Evaluation of Clinical and Radiological Outcome of Fracture Proximal Humerus by Locking Compression Plate Taking into Consideration of Biomechanics of the Glenohumeral Joint

Vol 32 | Issue 1 | Jan – June 2017 | page: 50-55 | D C Srivastava, Sachin Yadav,  Alok Gupta


Authors: D C Srivastava [1], Sachin Yadav [1],  Alok Gupta [1] 

[1] Department Of Orthopaedics, M L N Medical College Allahabad.

Address of Correspondence
Dr. Ajai Singh
Department of Orthopaedics Surgery,
K. G. Medical University, Lucknow, India.
Email: as29762@gmail.com


Abstact

Introduction: Although several studies have repeatedly emphasized that PHILOS plating gives better functional outcomes for fracture proximal humerus and that many studies have speculated and concluded various risk factors for failure or poor functional outcomes, none of them gives a clear idea about the important parameters of the biomechanics of the glenohumeral joint and their restoration, while fixation with the PHILOS plate. Our aim of study is to assess and weigh the functional outcomes when PHILOS plating is done for fracture proximal humerus taking into consideration biomechanics of the glenohumeral joint.
Material and Methods: This was an open label prospective study of 30 patients of proximal humerus fracture who were treated with with PHILOS plate in SRN Hospital From Sept 2013 to June 2015. Cases were taken up according to inclusion and exclusion criteria. All the patients were managed by open reduction and internal fixation by PHILOS plate and all patients underwent a rehabilitation program. The patients were examined clinically and radiologically, assessed for range of motion and bony union and complication. Further follow ups were done at 6 weeks,12 weeks, 24 weeks,36 weeks and 1 year.
Results: All the patients were followed up for atleast for 12 months (range 12 to 20 months) with the mean follow up time was 16.5 months. All the fractures united clinically and radiologically around an average of 8 weeks (range7-11weeks). Constant scores were excellent to good in 21 patients (70%), fair in 5 patients (16.66%), poor in 4 patients (13.33%).
Conclusion: Management of proximal humerus fractures with PHILOS plate gives the most satisfactory functional outcome when fixation is done taking into account following parameters: Corrected neck-shaft angle, maintenance of retroversion of the humeral head and acromio-humeral head distance.
Keywords: Biomechanics, neck-shaft angle, retroversion of the humeral head, acromio-humeral head distance.


Introduction
Proximal humerus fractures account for approximately 4 – 5% of the all fractures [1,2,3]. The incidence of fracture is more common in the elderly because of decreased bone density. But it can occur in younger age group following high velocity trauma [3]. Because of increasing incidence of high velocity trauma, the fracture patterns in proximal humerus are becoming complicated. It has been always enigma of management because of numerous muscles attachment and paucity of space for fixing implant in fractures of proximal humerus. While for undisplaced fractures, literature strongly suggests nonoperative treatment [4,5,6] the treatment of displaced fractures is still controversial and challenging. The various methods to treat fractures of the proximal humerus are percutaneous cerclage wiring, k-wire fixation, tension band wiring, intramedullary nailing, plating, and humeral head replacement. Of these methods, recent clinical data have shown favorable results for the treatment of fractures with locking plates. Important for a successful stabilization of the fracture are in the order of anatomic reduction, medial cortical support, proximal humeral bone density, and patient age[7]. Although several studies have repeatedly emphasized that PHILOS plating gives better functional outcomes for fracture proximal humerus and that many studies have speculated and concluded various risk factors for failure or poor functional outcomes, none of them gives a clear idea about the important parameters of the biomechanics of the glenohumeral joint and their restoration, while fixation with the PHILOS plate. Restoration of the normal three-dimensional anatomy of the proximal humerus is desirable. This affects the lever arms of the deltoid and rotator cuff in the vertical plane and soft-tissue balance in the horizontal plane. Changes in this anatomy may produce abnormal kinematics by malpositioning the joint line and by moving the instant centres of rotation [8,9,10]. Our aim of study was to assess and weigh the functional outcomes when PHILOS plating was done for fracture proximal humerus taking into consideration biomechanics of the glenohumeral joint.

Material and Method
From SEPTEMBER 2013 to JUNE 2015, 35 consecutive patients with proximal humerus fractures fulfilling the inclusion criteria were treated with open reduction and internal fixation with PHILOS plate in SRN Hospital. This was an open label prospective study and the sampling technique was consecutive non-probability sampling. A total of 35 patients were included in the study out of which 5 patients could not be followed up for at least 1 year. Patients included in this study were based on the following inclusion criteria: all displaced two part, three part, four part proximal humeral fractures, age above 18, patient had fitness and willingness for surgery and willingness to undergo physiotherapy and posto-perative rehabilitation program. Exclusion criteria were: associated humerus shaft fracture and associated neurovascular injury and acute infection, pathological fractures, old fractures ( more than 3 months old), compound fractures, undisplaced fractures. On admission of the patient, the general condition of the patient and the vital signs were recorded. Methodical examination was done to rule out fractures at other sides. The local examination of injured shoulder was done for swelling, deformity loss of function and altered attitude. Any nerve injury was also looked for and noted. Local neurologic deficit of axillary nerve was also assessed by looking for anaesthetic patch over lateral aspect of shoulder. Radiograph of proximal humerus was taken and fractures were classified according to Neer’s classification.
Of the contralateral shoulder, True AP view and special view as described by Volkan oztuna et al11 were taken. On true AP view, Neck-shaft angle and acromio-humeral distance of the contralateral limb could be determined. Angle created at intersection of lines that are perpendicular to anatomic neck and parallel to shaft of humerus determines the neck shaft angle. Distance between undersurface of acromian and top of humeral head determines the acromio-humeral distance. Special view were taken as described by Volkan oztuna et al [11]. Posteroanterior semiaxial radiographs of humerus bones was taken. This method was performed while the subject was standing with their shoulder in 90° forward elevation and 20° abduction. The beam was positioned 1 m away from the shoulder and centered to the humeral head; and the fully supinated forearm was placed on the cassette. On special view as described by Volkan oztuna et al [11], humeral head retroversion is measured, determining the humeral anatomical neck axis, outlining a perpendicular line to the humeral head joint surface, and a line tangent to the trochlea, the humeral head retroversion angle being the acute angle formed by the intersection of both lines.
Of the 30 patients, there were 16 males (53%) and 14 females (47%). Overall mean age was 53.93 years (range 25 to 92 years). According to Neer’s classification: 12 patients (40%) had Neer’s two part fracture, 9 patients (30%) had Neer’s three part fracture and 9 patients (30%) had Neer’s four part fracture. Mean age of the patients with Two-part fractures was 55.17 years (range 27 to 92 years). Mean age of the patients with Three-part fractures was 49 years(range 25 to 81 years). Mean age of the patients with Four-part fractures was 57.22 years (range 32 to 89 years). 19 patients (63%) had right upper limb involvement and 11 patients (37%) had left upper limb involvement.
All the patients were managed by open reduction and internal fixation by PHILOS plate. Postoperatively all patients were immobilized in shoulder immobilizer, appropriate antibiotics and analgesics were used, immediate postoperative radiographs were taken to determine the bone alignment and maintenance of reduction, sutures were removed depending upon the condition of the surgical wound.


All patients underwent a rehabilitation program in which pendulum exercises were begun immediately depending on pain, passive range of motion were started at 1st week. The active range of motion were started at 2-4 weeks postoperatively, depending on stability of osteosynthesis and bone quality. At 4th to 6th week–immobilization was discontinued. Active assisted movements were started up to 90° abduction with no forced external Rotation. At 6th to 8th week-full range of movements with active exercises started. The patients were examined clinically and radiologically, assessed for range of motion and bony union and complication. Further follow ups were done at 6 weeks and 12 weeks and 24 weeks and 36 weeks and 1 year depending upon the condition of the patient. At 1 year, True AP view and special view of the operated limb as described by Volkan oztuna et al [11] were taken to measure neck-shaft angle, acromiohumeral head distance and retroversion angle of the humeral head of the operated limb. The final result were evaluated using the following score at 1 year follow up : CONSTANT AND MURLEY SCORING SYSTEM.
Surgical technique: General anesthesia was used in all patients. Patients were placed in supine position on operating table with wedge or a sandbag under the spine and medial border of scapula to push the affected side forward while allowing the arm to fall backward. Arm was draped free, because it had to be moved during the approach. A deltopectoral approach was used. Skin was infiltrated with local anaesthetic. The incision was started midway between coracoid and clavicle, and extended distally up to deltoid insertion. Cephalic vein was identified and retracted laterally. Plane was developed between deltoid and pectoralis major. Conjoint tendon was identified and retracted medially. The long head of biceps is the important landmark as it signifies rotator interval. Traction sutures were applied to tuberosity fragments using Ethibond 5 suture to hold and reduce fragments. K-wires were used in humeral head as joysticks and fixed temporarily with the humeral shaft. With the help of c-arm images displaced proximal humerus fracture was provisionally fixed with k-wires taking into consideration biomechanics of glenohumeral joint with the aim to achieve retroversion, neck shaft angle and acromiohumeral distance similar to those of contralateral limb, so that the head was not fixed in valgus or varus rotation in coronal plane and repair the rotator cuff mechanism so as to restore the length between undersurface of acromian and head of the humerus.
Intra operatively after provisionally fixing two, three and four part fracture proximal humerus by k-wires, abduct the arm if possible (as more clear images could be obtained) and flex the elbow to 90° such that horizontal line drawn parallel to the ground overlaps both the condyles of the humerus. In this position by C-ARM machine take an AP view of the shoulder. Now rotate the forearm externally or internally everytime by 10° and take subsequent C-ARM images. At that rotation of the forearm externally or internally where maximum diameter of the head of the humerus is visible will be the version angle of the head of the humerus. If the provisional fixation achieved by k-wires intra-operatively was satisfactory ensuring maximum correction of the various biomechanics parameters of the glenohumeral joint by c-arm images, rigid fixation with PHILOS plate was done and k-wires were removed. PHILOS plate was placed about 5 to 10 mm distal to the tip of greater tuberosity (confirmed under image intensifier) and just lateral to bicipital groove. First a standard 3.5 mm cortical screw was placed in oval hole and tightened lightly. Fracture reduction and plate position were reconfirmed under image before placing other screws. Locking screws were placed in humeral head using drill guide. Drilling was done under sequential fluoroscopic imaging to prevent intraarticular penetration. Subchondral screw position was confirmed under two image views. Finally screws were placed in humeral shaft. Tuberosity sutures were tied to the plate. The wound was closed over a suction drain, which was removed after 24 to 48 hours -postoperatively. Arm was supported with a sling.
Statistical analysis: All data were collected on a form with the patient’s details. Afterwards these data were filled into a Microsoft Excel-2010 sheet for simple calculations. Statistical analysis was performed over the data using the software SPSS 20.0 for Windows. Test used was the One-way ANOVA test and Post Hoc Bonferroni test for comparison and analysis of mean Constant score and mean Neer score between two part, three part and four part fractures which was considered significant at P <0.05.

Results
All the patients were follow up for 12 to 20 months with the mean follow up time was 16.5 months. All the fractures united clinically and radiologically at 8 weeks (range7-11weeks). Complications observed were avascular necrosis of the humerus head in 1 patient (3.33%), superficial infection in 2 patient (6.66%), anterior deltoid muscle atrophy in 3 patients (10%), transiently decreased radial nerve sensations in 3 patients (10%), subacromial impingement in 2 patients (6.66%).
In our study overall mean Constant Murley score (Table 1) was 73.1 (Range 35-96) with standard deviation of 16.34. Mean Constant Murley score for Two- part fracture was 83.33 with standard deviation of 11.51. Mean Constant Murley score for Three- part fracture was 75.67 with standard deviation of 8.94. Mean Constant Murley score for Four- part fracture was 56.89 with standard deviation of 15.67.
Pearson correlation coefficient between Constant Murley Score and Neer Score is 0.98 .
Difference in mean Constant Murley scores (Table 2) of Two-part fracture and Three part fracture was not significant (p value 0.503). Difference in mean Constant Murley scores of Two-part fracture and Four-part fracture was significant (p value 0.000). Difference in mean Constant Murley scores of Three-part fracture and Four-part fracture was significant (p value 0.009). Thus two-part fractures and three-part fractures are amenable to give better functional results than four part results even with the best technique and methods of fixation and post operative rehabilitation.

Grading Of Results (Table 3):In our study at one year follow up, constant scores were excellent to good in 21 patients (70%), fair in 5 patients (16.66%), poor in 4 patients (13.33%)

Comparison between various sub-scores of constant-murley score: (Table 4)There was no significant difference in pain, activities of daily living, strength and range of motion between Two-part fractures and Three- part fractures ( p value 0.335, 0.843, 0.582, 0.774 respectively). There was significant difference in pain, activities of daily living, strength and range of motion between Two-part fractures and Four- part fractures ( p value 0.000, 0.001, 0.000, 0.001 respectively). There was significant difference in pain, activities of daily living, strength and range of motion between Three-part fractures and Four- part fractures ( p value 0.025, 0.023, 0.023, 0.020 respectively)(Table 5).
There is no significant difference between mean acromio-humeral head distance in the uninjured limb and operated limb at one year follow up ( p value 0.92). There is no significant difference between mean neck-shaft angle in the uninjured limb and operated limb at one year follow up ( p value 0.42). There is no significant difference between mean retroversion angle of the humeral head in the uninjured limb and operated limb at one year follow up ( p value 0.08) (Table 6). Thus we have achieved fixation of the proximal humerus fracture with the PHILOS plate and restored the important three dimensional biomechanical parameters nearly as that of the contralateral normal limb.

Discussion
The treatment of proximal humerus fractures with PHILOS plate gives a satisfactory outcome when fixation is done taking into consideration biomechanics of glenohumeral joint. In our study the fixation of the proximal humerus fracture by PHILOS is done taking into consideration various biomechanical parameters of the glenohumeral joints, most important being acromio-humeral head distance, neck-shaft angle of the humerus and retroversion angle of the humeral head. It is observed that there is no significant difference in these biomechanical parameters at one year follow up between the operated limb and uninjured contralateral limb. Thus, we have achieved the various important biomechanical parameters of the injured limb with fracture proximal humerus after fixation with PHILOS plate at one year follow up nearly similar to those of contralateral uninjured limb. Overall mean Constant Murley score is 73.1 (Range 35-96) with standard deviation of 16.3398. Average age and sex adjusted Constant Murley score was 80.934. The functional outcome based on Constant Murley score at one year follow up, is excellent to good in 21 patients (70%), fair in 5 patients (16.66%), poor in 4 patients (13.33%).
It is observed that in young patients, internal fixation using the proximal humeral internal locking system (PHILOS) plate has yielded better functional outcome than in older patients. We speculate the role of osteoporosis in older patients that has lead to above finding. Functional outcome of two part and three part fracture promixal humerus fixed with PHILOS plate are significantly better when compared with four part fracture promixal humerus fixed with PHILOS plate. It is observed that there is no significant difference in pain, activities of daily living, strength and range of motion between Two-part fractures and Three- part fractures (p value 0.335, 0.843, 0.582, 0.774 respectively). While there is significant difference in pain, activities of daily living, strength and range of motion between Two-part fractures and Four- part fractures ( p value 0.000, 0.001, 0.000, 0.001 respectively) & between Three-part fractures and Four- part fractures ( p value 0.025, 0.023, 0.023, 0.020 respectively).

Conclusion
Proximal humerus fractures demands careful evaluation of type of fracture and higher surgical skills to restore three-dimensional anatomy of the gleno-humeral joint. Management of proximal humerus fractures with PHILOS plate gives the most satisfactory functional outcome when fixation is done taking into account following parameters:
A) Corrected neck-shaft angle has been associated with better functional outcome as it prevents lengthening of lever arm of the deltoid and supraspinatus muscles, abductor muscle dysfunction and subsequent subacromial impingement. Thereby associated with early restoration of range of motion especially abduction.
B) Maintenance of retroversion of the humeral head is associated with better functional outcome as it prevents shoulder subluxation and maintains the stability and range of motion especially in horizontal plane.
C) Acromio-humeral head distance if maintained is associated with better functional outcome as it facilitates rotator cuff mechanism and prevents impingement of the supraglenoid structures.
Adequate biomechanical stability is achieved by bone grafts in fractures of the base of the neck of humerus having gross metaphyseal communition and bone gap.


References

1. Gerald R. Williams and Kirk L. Wong: “Two-part and three part fractures-Management of proximal and distal humerus fracture”. Orthop Clin North Am, 2000;31 (1) : 1-21.
2. Anthony F. Depalma and Richards Cautilli. Fractures of the upper end of the humerus.Clin.ortho. 1971;20:73-93.
3. Neer CS II,Rockwood CA: Fractures and dislocations of the shoulder,in RockwoodCA, Green DP (eds):Fracture in adults, Philadelphia, PA, Lippincott, 1984:675-721.
4. Koval KJ, Gallagher MA, Marsicano JG, Cuomo F, McShinawy A, Zuckerman JD. Functional outcome after minimally displaced fractures of the proximal part of the humerus. J Bone Joint Surg Am. 1997;79:203–7.
5. Tejwani NC, Liporace F, Walsh M, France MA, Zuckerman JD, Egol KA. Functional outcome following one-part proximal humeral fractures: A prospective study. J Shoulder Elbow Surg. 2008;17:216–9.
6. Gaebler C, McQueen MM, Court-Brown CM. Minimally displaced proximal humeral fractures: Epidemiology and outcome in 507 cases. Acta Orthop Scand. 2003;74:580–5.
7. Krappinger D, Bizzotto N, Riedmann S, Kammerlander C, Hengg C, Kralinger FS. Predicting failure after surgical fixation of proximal humerus fractures. Injury. 2011;42(11):1283-8.
8. Fischer LP, Carret JP, Gonon GP, Dimnet J. Etude cin´ ´ ematique des mouvements de l’articulation scapulo-hum´erale (Articulatio Humeri). Rev Chir Orthop 1977;63(Suppl II):108-12.
9. Friedman RJ. Biomechanics of the shoulder following total shoulder replacement. In: Post M, Morrey BF, Hawkins RJ, eds. Surgery of the shoulder. St Louis, Mosby-Year Book, 1990:263-6.
10. Ballmer FT, Sidles JA, Lippitt SB, Matsen FA, III. Humeral head prosthetic arthroplasty: surgically relevant geometric considerations. J Shoulder Elbow Surg 1993;2:296-304.
11. Volkan Öztuna et al: Measurement of the humeral head retroversion angle, Archives of Orthopaedic and Trauma Surgery September 2002, 122, 7, 406-409.


How to Cite this Article: Srivastava D C, Yadav S,  Gupta A. Evaluation of Clinical and Radiological Outcome of Fracture Proximal Humerus by Locking Compression Plate Taking into Consideration of Biomechanics of the Glenohumeral Joint. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):50-55.


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Therapeutic Efficacy of Intra-Articular Hyaluronic Acid in Osteoarthritis Knee

Vol 32 | Issue 1 | Jan – June 2017 | page: 44-49 | Chandra Prakash Pal, Ashwani Sadana, Amrit goyal,  Ravi mehrotra,  Pawan Kumar


Authors: Chandra Prakash Pal [1], Ashwani Sadana [1], Amrit goyal [1],  Ravi mehrotra [1],  Pawan Kumar [1]

[1] Department Of Orthopaedics, S.N. Medical College , Agra, India

Address of Correspondence
Dr. C P Pal
Department Of Orthopaedics, S.N. Medical College , Agra, India
Email: drcportho@gmail.com


Abstact

Objective: To evaluate the effect of intra articular hyaluronic acid for patients with knee osteoarthritis by analysing data from trial of intra articular hyaluronic acid versus placebo.
Material and method: This prospective study was conducted in department of orthopaedics, S.N. Medical College, Agra. Approval for study was taken by the local ethical committee. Objective was to evaluate the effect of intra articular hyaluronic acid for patients with knee osteoarthritis by analysing data from trial of intra articular hyaluronic acid versus placebo.
Osteoarthritic knees of 112 patients (65 female and 47 male) with age of 40-80 years taken, patients were randomized to five weekly injections of intra articular hyaluronic acid or normal saline (control) and were observed for 36 weeks. The primary efficacy measures were resting pain, weight-bearing pain. VAS Score and WOMAC (Western Ontario and McMaster University Osteoarthritis Index) during study weeks 0–36.
Results: The intra-articular injections produced a significant reduction in weight-bearing pain, resting pain, VAS Score and WOMAC scores after 12 weeks. Knee pain reduced and the function improved in most patients of hyaluronic acid group and these beneficial effects maintain till the last follow up. Adverse reactions were noted in 4 patients of Group1 and 3 patients of Group 2, out of which local reaction (swelling, redness, warmth, effusion, itching and Bruising) was common.
Conclusion: Viscosupplementation with intra-articular hyaluronic acid is a reasonable treat­ment for patients with mild-to-moderate osteoarthritis of the knee who have ongoing pain or are unable to toler­ate conservative treatment or joint replacement.
Key Words: Osteoarthritis, Knee, hyaluronic acid, VAS, WOMAC


Introduction
Osteoarthritis (OA) is an increasingly important public health problem [1]. It is slowly progressive, can cause symptoms ranging from mild to disabiling. Osteoarthritis is a common cause of knee pain especially in the elderly. It is characterised by loss of articular cartilage, subchondral sclerosis, joint deterioration and osteophyte formation [1]. The current treatment for knee OA consists of conservative treatment such as exercise, physical therapy, pharmacological agents and, in some cases surgical treatment [2,3]. While many of the commonly used conservative treatments have been recognised to be effective [4], there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA, although frequent and serious adverse effects of NSAIDs have been recognized [4] .
The normal adult knee contains approximately 3.0 mL of synovial fluid (SF), with a hyaluronic acid (HA) concentration of 2.5 to 4.0 mg/mL-1[5]. In osteoarthritic knee, the concentration and molecular weight of HA are decreased by 33% to 50% [6,7], resulting in less shock absorption, lubrication and protection of joints. The mechanism of action of hyaluronic acid injection is unclear but Basic science research suggests that intra-articular HA (IAHA) supplementation improves the viscoelasticity, flow characteristics of synovial fluid and also controls the arthritic disease process by promoting in vivo IAHA production and by providing an intra-articular anti-inflammatory effect[4,8,]. Preparations of HA can be divided into low and high-molecular-weight. Contra- indications to intra-articular HA include joint or skin infection, overlying skin disease, and allergy to chicken or eggs.
Numerous clinical trials and systemic reviews showed that patients treated with HA were doing better than untreated patients at the end of the treatment cycle and at the end of 6 months. Despite this, viscosupplementation for treatment of OA remains controversial and perhaps underused. Primary objective of this study was to determine whether HA injections improve pain and function in patients with OA in their knees.

Aims and Objectives
1. To evaluate the efficacy of intra-articular injection of hyaluronic acid in treatment of osteoarthritis of knee.
2. To compare against placebo the efficacy and safety of repeated injections of hyaluronic acid (HA) in osteoarthritis of knee.

Material And Method
This Randomised control study was carried out in the Department of Orthopaedics, S.N. Medical College, Agra. All consecutive patients were selected from the patients attending the outpatient department between 1st March 2014 to 30 October 2015. A detailed history, examination (General, systemic and local examination) along with investigation was carried out before doing procedure. Well informed consent was taken in all cases. Patients were selected on the basis of strict inclusion and exclusion criteria’s.
Inclusion criteria:
1. Age group 40 to 80 years
2. Osteoarthritis knee not responding or intolerant to traditional pharmacological and non-pharmacological treatment.
3. Patients with Osteoarthritis of knee whom any surgical intervention not contemplated due to associated medical problem or due to financial or other constraints.
Exclusion criteria:
1. Patients with known hypersensitivity to hyaluronate preparation.
2. infection or skin diseases in the area of the injection site.
3. Pregnant and lactating women.
4. Patients with rheumatoid arthritis.
5. Patients with severe osteoarthritis with a K/L grade of 4.
6. Patients who had either hematological, cardiac, renal or hepatic disorders.
7. All patients who did not came for follow up atleast for 24weeks.
All good clinical practice (GCP) guidelines were followed and. Approval for study was taken by the local ethical committee. 150 osteoarthritic knees of 112 patients with 38 bilateral affected, were randomized into two groups of 75 knees each. Group1 patients received five intraarticular injections of high molecular weight 2,700 kDa (25 mg) hyaluronic acid at weekly intervals, whereas in the control group, five intraarticular injections of 2 mL saline were administered similarly during a week period. Routine strict aseptic technique was adhered to during the administration of the injections into the joint. After giving the injections patients were advised to avoid excessive weight bearing and strenuous or prolonged (>1hr) exercises for the next 48 hrs. They were also informed that they might develop transient pain or swelling after the injection.
The patients were followed up at intervals of 4 weeks for three months and then at intervals of three months up to 36 weeks. In each follow up, patients were evaluated for their (1) Baseline characteristic, (2) Radiographic analysis of the knee, (3) Compliance with the treatment, (4) Clinical manifestations, and (5) Safety. The results were graded into excellent/ good / fair / poor according to the improvement in following scores.
1. Visual Analogue Score (VAS),
2. Western Ontario and Mc- Master University Osteoarthritis Index (WOMAC) score.

Results
112 patients were recruited for the study. Randomised into two Groups, majority of patients in both group were from 51-60 year age group accounting for 50.8% of all cases. Mean age of viscosupplementation group (group 1) and placebo group (group 2) was 57.4+9.05 and 58.6+10.1 respectively. There were 47 males and 65 females. Most patients did not have normal body weight. 47% were overweight, 25% were obese and 2.6% were morbidly obese according to their calculated BMI. On radiological evaluation, majority of patients (51.7%) were from KELLGREN LAWRENCE GRADE II.
Pain was assessed by use of the visual analogue score (VAS), revealed an average pain score for hyaluronic acid group was 76.3 pre-injection for standing and 82.4 for 30m walking. From this base line, the value dropped to 58.7 and 71.5 respectively at 4 weeks after fifth injection. There was continuous improvement, with the value 49.1 and 61.1 at 8 week, 34.1 and 42.4 at 12 week and 28.57 and 34.3 at 24 week. At last follow up at 36week, VAS Score with standing was 31.1 and 36.1 after 30m walk. For visual analogue pain score, hyaluronic acid was significantly effective than saline at 12 week, at 24 week, and 36week (p<0.05) (figure 1a &1b).
Knee pain and function was also assessed by the WOMAC (Western Ontario and McMaster Universities) instrument in both groups, with significant differences between the active treatments and placebo. WOMAC score for affected knee was 71.9 before treatment. From this base line, the value dropped to 59.02 at 4 weeks. There was continuous improvement, with the value 49.9, 33.2 and 28.2 at 8week, 12 week and at 24 weeks respectively and 28.8 at last follow up at 36week. For Western Ontario and McMaster Universities Osteoarthritis Index pain, hyaluronic acid was significantly more effective than saline at 12weeks, at 24 weeks and at 36 week (p<0.05). A significant benefit of hyaluronic acid versus saline also was observed for knee stiffness (p<0.05) and physical function (p <0.05) at 12week, 24week and at 36 week. Treatment with intraarticular hyaluronic acid improved knee pain and function with no significant differences between the active and placebo during first 8 weeks. Significant improvement (p<0.05) were reported with IA-HA as compared to placebo at 12 weeks, further improvement at 24 weeks and continued upto 36 week. According to WOMAC score, 30% patients reported with excellent improvement at last follow up after active treatment. 38% and 22% patients were found to be good and fair result, respectively. Only 10% patients were reported with poor result.(Table -1)
Treatment with intra-articular hyaluronic acid was shown to be safe form of treatment. During the follow up period of 36 weeks, adverse reactions were noted in 4 patients of Group 1 and 3 patients of Group 2, out of which most common was local reaction(swelling, redness, warmth, effusion, itching and Bruising). Patients recovered uneventfully with only analgesics and anti-inflammatory medications. No significant differences (p > 0.05) between the two groups were found.

Discussion
Pain was the single most important reason for the patients to seek medical attention for their knee problems. Activity related discomfort led to variable timing of presentation of these patients for medical treatment. There is variation in each individual pain threshold, some are able to withstand pain for longer duration than others. Intraarticular hyaluronic acid is not a new treatment for osteoarthritis. Many studies have shown that it is helpful in reducing the sign and symptoms of osteoarthritis. The patients age, sex, BMI, sign and symptoms of osteoarthritis, grading of osteoarthritis and adverse effects associated with intra-articular hyaluronic acid were taken into consideration in both groups of study.The safety and efficacy of several hyaluronic acid formulations have been investigated in patients with osteoarthritis of the knee [9].In present study patients were followed with regular interval up to 36 weeks. VAS and WOMAC score showed gradual but significant improvement in terms of pain at rest or after 30m walk at 12 weeks and sustained pain relief till the end of thirty six weeks. Only 11 (10%) patients were reported with poor results.
HA is a large glycosaminoglycan composed of repeating disaccharides of glucuronic acid and N-acetyl glucosamine that is naturally present in synovial fluid. Several protective properties of HA have been reported including shock absorption, traumatic energy dissipation, protective coating of the articular cartilage surface and lubrication [10,11]. Numerous clinical trials, meta-analyses and systematic reviews have indicated its clinical efficacy for knee osteoarthritis [12,13]. However, controversy remains regarding the efficacy of HA in treating knee osteoarthritis [14]. A recent meta-analysis concluded that the pain reduction by IA-HA is observed later than that of intra-articular corticosteroids [12]. In addition, the effects of IA-HA for knee osteoarthritis pain continued over six months post-intervention [13]. However, few studies have been conducted to clarify the early effects and safety of IA-HA in comparison to those of placebo. The results of this study clearly indicated that the early efficacy of IA-HA was not inferior in comparison to that of the placebo. A number of HA products with a variety of the molecular weights, ranging from approximately 600 to 6,000 kDa, have been developed as IA-HA for the treatment of osteoarthritis[14]. The considerable heterogeneity of outcomes between trials may be due in part to difference in hyaluronic acid products [15]. High-molecular-weight HA (>6,000 kDa) is suggested to have greater effects in comparison to lower-molecular-weight hyaluronic acid [14]. On the other hand, the intra-articular injection of high-molecular-weight hyaluronic acid (>6,000 kDa) showed a greater frequency of adverse events, such as pain flares, and hot and swollen knees, which typically occurred 24 to 72 hours after injection [16]. In our study we were reported only 4 cases with pain full, hot or swollen knees after injections. The molecular mechanisms underlying the efficacy of IA-HA for osteoarthritis remain unclear. It has recently been reported that HA inhibits the activities of matrix metalloproteinases and aggrecanases which are, at least in part, involved by pro-inflammatory cytokines, such as interleukin(IL)-1[13]. Therefore, hyaluronic acid is speculated to modify the structural damage of joints and the rate of osteoarthritis progression in addition to the symptom modifying effect [8], although further studies are required.
In our study, significant differences in Western Ontario and McMaster Universities Osteoarthritis Index scores were observed between group1 and group 2 patients throughout the study after 12 weeks. Hyaluronic acid ameliorated knee pain and stiffness and improved function and mobility (30m walk). After the series of five injections, the symptom relief advantages of hyaluronic acid at Week 12 was consistent with the durability of pain relief reported with other hyaluronic acid formulations[17].
It should be noted that hyaluronic acid injections can play a role in early management of osteoarthritis especially for those with allergies to glucosamine and also those with severe gastrointestinal tract disorders secondary to NSAIDS. At the other extreme, are the surgical candidates for knee replacement who are not fit for surgery, so would require intraarticular injections for symptomatic relief. Patients who benefited most from these injections were those with early, mild to moderate osteoarthritis. We believe that a treatment regime of five injections resulted in satisfactory outcome in current study but there is still room for improvement in the formula of hyaluronic preparation, duration of regime and perhaps also in technique for administering the injection.

Conclusion
Viscosupplementation with intra-articular hyaluronic acid is a reasonable treat­ment for patients with mild-to-moderate osteoarthritis of the knee who have ongoing pain or are unable to toler­ate conservative treatment or joint replacement. The effect lasts longer with high-molecular-weight prep­arations, and patients can experience improvement in clinical outcomes for up to 36 weeks. Intra-articular HA appears to have a slower onset of action than placebo but the effects seem to last longer. Patients should be warned of cost and of potential side effects, including local swelling.


References

1. Dieppe PA, Lohmander LS: Pathogenesis and management of pain in osteoarthritis. Lancet 2005, 365:965-973.
2. Carr AJ, Robertsson O,Graves S,Price AJ, Arden NK, Judge A, Beard DJ: Knee replacement. Lancet 2012, 379:1331-1340.
3. Ishijima M, Watari T, N aito K, Kaneko H,Futami I, Yoshimura-Ishida K, Tomonaga A, Yamaguchi H, Yamamoto T, Nagaoka I, Kurosawa H, Poole RA, Kaneko K: Relationship between biomarkers of cartilage, bone, synovial metabolism and knee pain provede insights into the origins of pain in early knee osteoarthritis.Arthritis Res Ther 2011, 13:R22.
4. Zhang W, Nuki G, Moskowitz RW, AbramsonS, Altmam RD, Arden NK, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P: OARSI recommendations for the management of hip and knee osteoarthritis part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010, 18:476-499.
5. Watterson JR, Esdaile JM. Viscosupplementation: therapeutic mechanisms and clinical potential in osteoarthritis of the knee. J. Am. Acad. Orthop. Surg. 2000; 8:277Y84.
6. Bressan E, Favero V, Gardin C, et al. Biopolymers for hard and soft engineered tissues: application in odontoiatric and plastic surgery field. Polymers. 2011; 3:509Y26.
7. Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action.Arthritis Res. Ther. 2003; 5:54Y67.
8. Goldberg VM et al: hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity. Osteoarthritis Cartilage 2005, 13:216-224.
9. Altman RD, Moskowitz R: Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: A randomized clinical trial. J Rheumatol25:2203–2212, 1998.
10. Julovi SM, Ito H et al: Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res2011, 29:258-264.
11. Strauss EJ, Hart JA, Miller MD, Altman RD, Rosen JE. Hyaluronic acid viscosupplementation and osteoarthritis: current uses and future directions. Am J Sports Med. 2009;37(8):1636–1644.
12. Bannuru RRet al,. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systemic review and meta-analysis. Arthritis Rheum 2009, 61:1704-1711.
13. Bannuru RR et al,. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis meta-analysis.Osteoarthritis Cartilage 2011, 19:611-619.
14. Lo GH et al.,Intr-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 2003, 290:3115-3121.
15. Balazs EA. The physical properties of synovial fluid and the specific role of hyaluronic acid. In: Helfet AJ, editor. Disorders of the Knee. Philadelphia (PA): J.B. Lippincott; 1982. p. 61Y74.
16. Reichenbach S et al: Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis. Arthritis Rheum2007, 57:1410-1418.
17. Adams ME, Atkinson MH, Lussier AJ, et al: The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: A Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cartilage3:213–225, 1995.


How to Cite this Article: Pal CP,  Sadana A, Goyal A, Mehrotra R, Kumar P. Therapeutic Efficacy of Intra-Articular  Hyaluronic Acid in Osteoarthritis  Knee. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):44-49.


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Comparative Study of Functional Outcome of Different Methods of Treatment of Fracture Talus and their Complications: A Prospective Study

Vol 32 | Issue 1 | Jan – June 2017 | page: 18-24| Dinesh Chandra Srivastava, Sachin Yadav, Manish Shukla, Alok Gupta, Ankur Singh, Rajeev Yadav


Authors: Dinesh Chandra.Srivastava [1], Sachin Yadav [1], Manish Shukla [1], Alok Gupta [1], Ankur Singh [1], Rajeev Yadav [1]

[1] Department of Orthopaedics, M L N Medical College Allahabad, UP, India

Address of Correspondence
Dr. Dinesh Chandra Srivastava
Department of Orthopaedics, M L N Medical College Allahabad, UP, India.
Email: srivastavadc1@rediffmail.com


Abstact

Introduction: Ankle injuries gain importance because body weight is transmitted through it and locomotion depends upon the stability of this joint. The Talus fractures are relatively uncommon injuries but they can be associated with significant complications. Talus is involved in about 2% of all lower extremity injury and 5-7% foot injury. There are several methods of treatment. The purpose of this study was to assess the functional outcomes and results of a comparative study of different method of treatment of Talus fractures by conservative modalities and by surgical methods.
Material and Methods: This was a prospective cohort study of the patients with Talus fractures who attended SRN Hospital, Allahabad from August 2014 to July 2016. Cases were taken up according to inclusion and exclusion criteria. A total of 37 patients of fracture of the Talus were admitted, out of which 7 patients were excluded as per exclusion criteria as they didn’t turn up at least at 6 month follow up. Each patient was followed up for interval of 3 weeks, 6 weeks, 12 weeks and 6 months duration but only thirty patients were included in this study who turned up for at least 6 months of follow up.
Results: All the patients were followed up at least for 6 months with the mean follow up time is 8.5 months. Total 30 patients were treated in our study out of which 12 patients were managed conservatively in which maximum number of patients 5(41.67%) had fair results, 3(25%) had good and poor results whereas only 1(8.33%) patient had excellent result. In operative group maximum number 7(38.89%) of cases had good results followed by excellent and fair results with 4(22.22%) of each whereas only 3(16.67%) had poor results
Conclusion: Anatomical reconstruction of articular surface, restoration of overall geometry of ankle and hind foot and stable fixation of the fracture fragments allow early rehabilitation. Non-invasive or conservative treatment should be reserved for stable and undisplaced fractures. Results of our study showed that the rate of complications associated with conservative managements of displaced fractures was much more as compare to open reduction and internal fixation. Minimally invasive surgical intervention gives better result than aggressive open reduction and internal fixation.
Keywords: Anatomical reconstruction, fracture Talus.


Introduction
Sir Robert Jones Said “Ankle is the most injured joint of the body but the least well treated. Ankle injuries gain importance because body weight is transmitted through it and locomotion depends upon the stability of this joint. The Talus fractures are relatively uncommon injuries but they can be associated with significant complications. Talus is involved in about 2% of all lower extremity injury and 5-7% foot injury[1]. The incidence of fracture Talus ranges from 0.1-0.85 of all body fractures. The Talus is the second largest tarsal bone[2]. 60% of this bone is cartilaginous. It has peculiar character that it is the only bone of body without muscle attachment. It lies between the tibia above and the calcaneum below.
The incidence of Talus fracture is rising due to increase in frequency of motor vehicle accidents and fall from height with component of dorsiflexion of ankle. Talus fractures are second in frequency among all tarsal bone fracture. Anatomical Classification of Talus Fracture: Talar neck fracture, Talar body fracture Talar head fracture, Lateral process fracture, Posterior process fracture. The most commonly used classification for talar neck fractures is that described by Hawkins with the modifications suggested by Canale and Kelly[1,3]. Type I- fracture refers to a fracture without associated dislocation, that is, an undisplaced fracture of the talar neck. The Hawkins II fracture refers to a talar neck fracture with associated dislocation of the subtalar joint. This is perhaps the most common type of talar neck fracture dislocation. Hawkins Type III fracture involves a dislocation at the ankle as well as at the subtalar joint. The Hawkins Type IV fracture was described by Canale and Kelly and implies associated subluxation or dislocation of the talonavicular joint. There are several methods of treatment , in conservative slab followed by cast or closed reduction percutaneous screw fixation and surgically using standard open reduction technique followed by K-wire fixation , lag screw fixation or plating . Every method of management has their own merits and demerits like osteonecrosis, arthritis (post-traumatic), non-union, malunion, infection. The purpose of this study is to assess the functional outcomes and results of a comparative study of different method of treatment of Talus fractures by conservative modalities and by surgical methods in the form of screws fixation, K-wire fixation, plating, arthrodesis to attain a proper anatomical alignment and stability of the ankle and hind foot joint , and appropriate definitive treatment based on the fracture pattern and soft tissue condition.

Material and Methods
Patients with Talus fractures who attended SRN Hospital, Allahabad from August 2014 to July 2016 were included in the study. A total of 37 patients of fracture of the Talus were admitted, out of which 7 patients were excluded as per exclusion criteria as they didn’t turn up at least at 6 month follow up. Patient included in the study are based on the following inclusion criteria: All patients in age group above 18 years presenting with fracture Talus which is confirmed radiologically, patients willing to complete a rigorous rehabilitation program, patients completing at least 6 month follow up. Exclusion criteria were: Patients with the Talus fracture with an active infection at the site of injury, with associated neurovascular disorder, compound fractures and patients who do not turn up at least at 6 month follow up.


On admission of the patient, the general condition of the patient and the vital signs were recorded. Methodical clinical examinations including both local and systemic were carried out. Fracture anatomy was assessed with X-rays and fractures were classified according to anatomical classification. Talar neck fractures are further classified by Hawkins Classification with the modifications suggested by Canale and Kelly. Of the 30 patients, 15 patients (50%) had talar neck fracture, 8 patients (26.67%) had talar body fracture, 4 patients (13.33%) had talar head fracture, 3 patients (10%) had posterior process fracture. Of the 15 patients with talar neck fracture, 6 patients (40%) had type I fracture (4 patients were treated conservatively and 2 were treated operatively ), 6 patients (40%) had type II fracture ( 1 patients were treated conservatively and 5 were treated operatively, 2 patients (13.33%) had type III fracture (all 2 treated operatively), 1 patient (6.67%) had type IV fracture (treated operatively). Thus of the 15 patients (50%) with talar neck fracture, 5 patients were treated conservatively and 10 were treated operatively. Of the 8 patients (26.67%) with talar body fracture, 3 patients were treated conservatively and 5 were treated operatively. Of the 4 patients (13.33%) with talar head fracture, 2 patients were treated conservatively and 2 were treated operatively. Of the 3 patients (10%) with posterior process fracture. 2 patients were treated conservatively and 1 was treated operatively. The following surgical procedures are used: Fixation with percutaneous screws, Open reduction with internal fixation by screws, Open reduction with internal fixation by plating, Blair fusion. Of the 10 patients with talar neck fracture treated operatively, 4 patients ( 2 patients with Hawkin’s Type I and 2 patients with Hawkin’s Type II) were treated with fixation with percutaneous screws, 5 patients ( 3 patients with Hawkin’s Type II and 2 patients with Hawkin’s Type III) were treated with open reduction with internal fixation by screws and 1 patient (with Hawkin’s Type IV) treated with open reduction with internal fixation by plating. Of the 5 patients with talar body fracture treated operatively, 1patients was treated with fixation with percutaneous screws , 2 patients were treated with open reduction with internal fixation by screws and 2 patient treated with Blair fusion. Of the 2 patients with talar head fracture treated operatively, 1 patient was treated with fixation with percutaneous screws , 1 patient was treated with open reduction with internal fixation by screws. 1 patient with posterior process fracture, treated operatively with percutaneous screws. From all the patients treated operatively informed written consent was taken for respective surgical procedure. Surgical procedures were carried out. Postoperative treatment incuded routine antibiotics, analgesic, regular cleaning and dressing of the wound. Post-operative evaluation is done by X-rays – AP and lat Views. Clinical and radiological assessment is done at 3 weeks, at 6 weeks, at 12 weeks and at 6 months. The functional assessment of the patient was done according to AOFAS -Ankle and Hind foot score.


Conservative Management :
After closed reduction, below knee POP slab was applied for 1 week, followed by below knee POP cast for 8 to 10 weeks with ankle in slight equinus position. Cast is removed after 8 to 10 weeks and short leg walking cast applied for 2 more months until clinical and X-rays sign of healing appears.

Surgical technique:
Fixation with closed reduction and fixation with percutaneous screws:
After closed reduction in anatomical position, first hold the reduction with two 2mm K -wire under C –Arm. After that fracture was fixed with two 4.5 mm partially threaded cannulated screws that weAre passed perpendicular to the fracture line. Reduction and placement of screws were checked under the C-Arm. Patients were given a non-weight bearing B/K POP slab with planter flexion for 8 -10 weeks and after 10 weeks below knee walking cast was given and partially weight bearing was allowed.
Open reduction with internal fixation by screws:
Approach used for the complete visualization of fracture Talus are Anteromedial, Anterolateral, Combined Anterolateral and Anteromedial, Posterolateral, Direct medial and direct lateral approach.
Anteromedial Approach: Expose the head and neck of Talus through incision 7.5 to 10cm long, beginning proximal and just anterior to the medial malleolus, curving distal ward and plantar ward toward the sole of the foot, and ending on the medial side of the body of the navicular, using the interval between the anterior and posterior tibial tendons. Avoid incising the posterior tibial tendon and neurovascular structures inferior to the medial malleolus. If the body of the Talus is extruded from the ankle mortise, osteotomy of the medial malleolus may make exposure and reduction easier. Expose the fracture and the anteromedial aspect of the neck and body of the Talus. Preserve as much soft tissue as possible around the head and neck of the Talus. Reduce the fracture, and irrigate the joint to remove bone fragments and debris. If the medical malleolus was osteotomized to improve exposure, reduce it and fix it with a malleolar screw or TBW.
Anterolateral approach: Expose the lateral neck through a 5-cm incision over the sinus tarsi, extending toward the base of the fourth metatarsal. Protect the dorsal intermediate cutaneous nerve in this region. After incising the inferior extensor retinaculum, reflect the extensor digitorum brevis plantarly to expose the fracture. Careful reduction is important because slight varus at the fracture still can produce mal-union that is quite disabling. Try to locate interdigitating fracture lines medially or laterally for a guide to reduction, even if a gap remains in the opposite cortex. Beginning just posterior to the articular surface of the head, on the medial or lateral aspect of the neck, drill two or three small Kirschner wires through the neck and into the body to hold the reduction. Depending on the available space for fixation, a 4.0 mm, 4.5 mm or 6.5 mm partially threaded cannulated screw can be used. In each case, care must be taken to countersink the screw head to provide a flat area for seating of the screw head. Alternatively, mini-fragment plates and screws can be placed, especially if there is excessive comminution or limited space for fixation in the head fragment. Check the final position with radiographs.
Posterolateral Approach: For placement of posterior-to-anterior screws, use the Henry approach from the lateral side of the Achilles tendon, and develop the interval between the flexor hallucis longus and the peroneal tendons. Place the guidewire above the lateral projection of the posterior process, and direct it toward the lateral talar head. Fluoroscopic guidance is essential to avoid the subtalar joint[4].
Open reduction with internal fixation by Plating :
With the K-wires placed appropriately and with image intensification verifying accurate reduction, a plate is contoured both medially and laterally through the anteromedial and anterolateral combined approaches. The medial plate will fit along the medial neck with screws into the head and the body, leaving the mid-portion overlying the comminution free of screws. With this fixation, medial talar neck shortening or collapse will not occur. Talus neck bone defect was filled with bone graft.
The lateral plate will fit along the lateral neck and process of talus. The fixation of the plate was done with mini-fragment 2.4 mm and 2.7 mm screws. The medial plate prevents loss of medial length, and the lateral plate acts as a tension band to resist fracture gapping.

Blair Fusion
Expose the ankle through an anterolateral incision, removed the fragments of the fractured body of the talus , and leave the talar head and neck undisturbed , sliding graft 2.5 cm wide and 5cm long from anterior aspect of distal tibia, cartilaginous tip is removed and introduced the graft into a previously prepared hole about 1.8cm deep in neck of the Talus. Pack the cancellous chips around the distal end of graft. Postoperative care ;a cast is applied from the groin to the toes with the knee in extension for 4 to 6 weeks ,after that short leg cast is applied , cast immobilization should be continued till the appearance of healing on X -rays.
Fixation of fracture talar head:
Displaced talar head fracture should always fixed. Anteromedial approach with medial malleolus osteotomy is used for better exposure of head .a 7.5 to 10 cm long incision beginning proximal and just anterior to medial malleolus curving downward and planter-ward towards the sole of foot and ending on medial side of the body of navicular bone .retract the soft tissues and tendon away from surgical view, reduced the fragments and hold with k-wire and fix with headless compression screws. And then medial malleoli fix with malleolar screws. Closed the incision after cleaning with normal saline, B/K POP slab given with strictly non weight bearing for 8 to 10 weeks after 12 days of postoperative stiches was removed and limb is kept in B/K POP slab.
Statistical analysis: Statistical analysis was performed using the software SPSS 21.0 for windows. Test used was the student t test for the comparison of the means which was considered significant at p < 0.05.

Results
All the patients were followed up at least for 6 months with the mean follow up time is 8.5 months. Total 30 patients were treated in our study out of which 12 patients were managed conservatively in which maximum number of patients 5(41.67%) had fair results, 3(25%) had good and poor results whereas only 1(8.33%) patient had excellent result. In operative group maximum number 7(38.89%) of cases had good results followed by excellent and fair results with 4(22.22%) of each whereas only 3(16.67%) had poor results.

Mean (AOFAS) Ankle and Hind foot Score improved in both the conservative and operative groups at 3, 6, 12 weeks and at 6 month follow up. p value at 12 weeks and 6 months were statistically significant, it means surgical fixation of the fracture Talus is better than conservative.

In our study 15 patients developed no complications (50%) after follow up of 3 weeks ,6 weeks, 12 weeks and 6 months. 6 patients developed AVN (20%) at 12 weeks and 6 months of follow up (2 in conservative and 4 in operated) ,10 patients developed osteoarthritis (5 out of 12 in conservative ,5 out of 18 1n surgical managed patients) at 12 weeks and 6 months. 2 patients developed malunion, all of those managed conservatively.2 developed non-union and 4 patients developed infection at 3weeks of follow up.

Discussion
Comparison of outcome of our study with different past studies. In Schulze series he studied 46 patients and found 26.08%( 12 patients) had Excellent, 30.43%(14 patients) had Good,23.91%(11 patients) had Fair result and 19.56%(9 patients) had poor result[5].
Comfort et al studied 36 patients and found 16.67%(6 patients) had Excellent result, 22.22%(8 patients) had Good result,47.23% (17 patients) had Fair result and 13.89%(5patients) had Poor results[6].
Hawkins et al studied 54 patients in his series and 25.92%(14 patients) had Excellent result, 24% (13 patients) had Good result, 35.18%(19 patients) had Fair result and 14.82% (8 patients) had poor result[1].

Increased knowledge about the normal and post traumatic anatomy and function of the ankle and hindfoot has led to demands for exact reduction and rigid fixation of the Talus fractures. Prompt operative treatment of displaced Talus fracture decrease morbidity and improves functional outcome.
The treatment of the Talus fracture with accurate closed reduction of fracture fragments and joints, percutaneous fixation or open reduction stable internal fixation using AO method and principles protection of remaining vascular supply and soft tissue was found to give a high percentage of excellent and good results.

Conclusion
Preoperative assessment of fracture anatomy, skin condition and regional vascularity should be assessed properly for good results. The aim of treatment for the fractures Talus is to make the ankle and hind foot stable and painless with near normal range of motion as well as gait .This required anatomical reconstruction of articular surface, restoration of overall geometry of ankle and hind foot and stable fixation of the fracture fragments to allow early rehabilitation. Although these goals are difficult to achieve in presence of substantial comminution and the loss of vascularity by trauma. The Talus fractures are not so common, but they lead to serious complications and invalidating disability. Early and accurate diagnosis of the Talus fractures is mandatory in order to provide adequate treatment and avoid major complications such as avascular necrosis and osteoarthritis. Before deciding the mode of treatment, it is necessary to evaluate the fracture anatomy, soft tissue condition and regional vascularity. CT and MRI are required for detailed fracture analysis and for the determination of fracture anatomy and mode of treatment. Non-invasive or conservative treatment is reserved for stable and undisplaced fractures. First Displaced and unstable fracture were tried by closed reduction, if reduction not achieved, open surgical reduction and fixation was done, with precaution to avoid damage to vascularity leads to good result and minimizes the complications. Despite the prompt and early reduction and fixation of the Talus fracture the long term complications are high specially in type3 and type4 neck fracture, comminuted head fracture and comminuted body fracture. Results of our study showed that the rate of complications associated with conservative managements of displaced fractures was much more as compare to open reduction and internal fixation. Conservative treatment in stable fracture leads to good result. Unstable fracture those managed by closed reduction, rigid fixation and early rehabilitation lead to good result. In cases of unstable fracture with open reduction and internal fixation, the probable results are govern by vascular damage of tissue, the degree of displacement and fracture comminution. Minimally invasive surgical intervention gives better result than aggressive open reduction and internal fixation.


References

1. Sanders DW. Fracture and dislocations of talus. In Rockwood and Greens Fracture in adults. 8th edition. Wolters Kluwer Health;2015:2593-4.
2. Canale ST, Beaty JH, Campbell operative orthopaedics. Edn International. 2012;4(12):4162-3.3
3. Hawkins LG: Fractures of the neck of the talus. J Bone Joint Surg Am 1970;52: 991-1002.
4. Trillat A, Bousquet G, Lapeyre B: Les fractures-sÈparations totales du col ou corps de líastragale: IntÈrÍt du vissage par voie postÈrieure. Rev Chir Orthop Reparatrice Appar Mot 1970;56:529-536.
5. Schulze W, Richter J, Russe O, Ingelfinger P, Muhr G. Surgical treatment of talus fractures. a retrospective study of 80 cases followed for 1-15 years. Acta Orthop Scand. 2002;73:344-351.
6. Comfort TH, et al. Long-term results of displaced talar neck fractures. Clinical Orthopedics. 1985;199:81-7


How to Cite this Article: Stive study. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):18-24.


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Valgus Reduction with Dynamic Hip Screw: The Answer to Unstable Peritrochanteric Fractures

Vol 32 | Issue 1 | Jan – June 2017 | page: 38-43 | Arunim Swarup, Karan Siwach, Abhay Shanker Dube, Avinash Rastogi,  Sunil Malhotra, Gaurav Dev Sharma


Authors: Arunim Swarup [1], Karan Siwach [1], Abhay Shanker Dube [1], Avinash Rastogi [1],  Sunil Malhotra [1], Gaurav Dev Sharma [1] 

[1] Department Of Orthopedics, Subharti Medical College, Meerut , India

Address of Correspondence
Dr. Karan Siwach
Department Of Orthopedics, Subharti Medical College, Meerut , India
Email: karansiwach@gmail.com


Abstact

Introduction: Peritrochanteric fractures are amongst the most common fractures sustained in elderly population. Numerous methods of fixation and implant choices are available for management of such fractures. The dynamic hip screw and sliding plate remains the most commonly used implant for surgical management in such fractures. Despite the widespread use of Dynamic hip screw akin to being considered as one of the most forgivable implant, many complications have been reported in the literature. Of these the most commonly described is screw cut out rates of 5-17%. Various attempts have been made to reduce these cut out rates and the most widely accepted method is Baumgartner method of screw placement with Tip apex distance less than 25 mm. The present study was conducted to evaluate the clinical and functional outcome of valgus reduction in peritrochanteric fractures fixed by 1350 Dynamic hip screw.
Materials and Methods: The 90 cases of peritrochanteric fractures (51 males and 39 females) with mean age of 65.4 years were treated with valgus reduction and internal fixation with Dynamic hip screw. Mean follow up was 28.03 months (range, 12-50 months).
Results: The mean neck shaft angle of hip was 1290 (range, 1180 to 1400). The mean neck shaft angle of operated hip was 1380 (range, 1270 to 1480). Union was achieved in all the patients. The average time of union was 9.3 weeks (range 8.1-14 weeks). No patient had cut out or implant failure. 78 patients had limb length equalization and 10 had shortening and five had limb lengthening at final follow up. Average Harris hip score was 94.8 points.
Conclusion: We advocate valgus reduction of peritrochanteric fractures to achieve reliable functional and radiologic outcome. Valgus reduction reduces the chance of shortening of the leg, and prevents implant cut out.
Keywords: Peritrochanteric fractures, valgus reduction, dynamic hip screw, screw cut out.


Introduction
Peritrochanteric fractures are common problems in elderly patients [1]. Operative treatment permits early mobilization and minimizes complications of prolonged recumbency [2]. Peritrochanteric fractures are treated with both extramedullary and intramedullary devices [3]. Each device has its own advantages and disadvantages. The advantage of extramedullary fixation such as dynamic hip screw (DHS) is relatively simple surgical technique, which is safe and very forgiving [3]. DHS remains the implant of choice because of its favorable results and low rate of non-union or hardware failure [4, 5] still high cut out rates (5-17%) have been reported in the literature which has led to the rise of intramedullary fixation for these fractures [4, 6, 7]. Moreover, osteoporosis, associated with trochanteric fractures in elderly patients, not only enhances the risk of fracture but also represents a problem in osteo synthesis of fractures in fracture treatment [1, 8].
Screw cut out can occur if the diaphyseal cervical angle or the neck shaft angle decreases, leading to the extrusion of the screw through the femoral head. Using the DHS with deliberate valgus reduction may theoretically result in a gap at the medial side of the fracture however the support is provided laterally by DHS combined with controlled collapse of the fracture by sliding of the screw in a stout barrel of the plate which results in medial continuity being maintained or restored in a valgus position and prevent varus collapse [9]. This study was done to evaluate the outcome of valgus reduction in intertrochanteric fractures fixed by 1350 DHS and to correlate its influence on union rate and functional outcome in unstable peritrochanteric fractures.

Materials and Methods
All patients presenting with peritrochanteric fractures to the author’s institute, a tertiary level center, from May 2007 to January 2015 were included in the present retrospective and prospective study. Patients included in this study were those who were above 40 years with peritrochanteric fracture managed by closed or open reduction and internal fixation by dynamic hip screw and with a minimum follow up of one year. 113 patients were treated with internal fixation and valgus reduction of the fracture. From amongst 113 cases, 23 cases were excluded as 19 patients expired during follow up and 4 developed infection. The 90 cases (51 males and 39 females) included for observation in this study were in the age group from 4th to 9th decade, youngest being 42 years old and oldest being 94 years old. The mean age was 65.4 years irrespective of their gender. The right hip was involved in 54 patients and the left in 36 patients. 78 patients suffered injury due to fall on the ground and 12 cases sustained road traffic high velocity injury. 59 patients had osteoporosis according to Singh’s index [10] assessed from antero-posterior radiograph of contralateral hip.
All fractures were broadly classified into stable and unstable fractures with all the authors coming to a consensus regarding the classification to minimize inter-observational variability (Table 1). The pre-operative anteroposterior skiagram of pelvis with both hips and lateral skiagrams of the fractured hip were studied to classify the fracture to identify the instability. The neck shaft angle of the contralateral hip in the anteroposterior skiagram were used as the reference for comparing the operated fracture. The mean time interval from injury to operation was 5.6(range, 2-11) days.

Surgical technique: All patients were operated on the fracture table keeping the patient in supine position under the image intensifier. The usual lateral approach was used with a modification during the use of triple reamer. After drilling and reaming with triple reamer, the entry point was over drilled superiorly and the hip screw was placed after tapping. Over the hip screw, the 1350 the barrel of the DHS plate was then put to make it appear abducted in relation to the shaft of femur. The foot piece was then loosened to abduct the limb till the shaft of femur could lie against the 1350 DHS plate to achieve a valgus at the fracture site at the cost of cancellous collapse of the fracture under the plate over the lateral aspect. The maintenance of valgus was confirmed by image intensifier before the 1350 DHS plate was fixed to shaft.
The post-operative evaluation included study of type of reduction, screw placement in the quadrant of the head as seen in the antero-posterior and lateral post-operative skiagram, TAD index [11], post-operative change in diaphyseal cervical angle, occurrence of any union related complications like varus mal-union, unacceptable fracture collapse, implant related complications like loosening, cut-out, intra-articular migration or breakage, time of clinico-radiological union and any anisomelia of lower limb. For example, figure 1 shows the pre-operative assessment of one of the patients with diaphyseal cervical angle of 1320 consequently, the post-operative skiagram and follow up at 1 year is shown in figure 2 and 3 respectively with cervical diaphyseal angle increased to 1410 by deliberate valgus reduction.


Functional assessment was done using the modified Harris hip score [24]. Isometric hip and knee strengthening exercises were educated. X-rays were done during follow up to assess union, controlled collapse and implant stability under the parameters described above.
The observations were recorded and individual data were noted and final follow up was taken at a minimum of 1 year on the aspects of functional outcome using Harris hip score. Correlations between the TAD Index and diaphyseal cervical angle, diaphyseal cervical angle and anisomelia and TAD index and anisomelia were calculated statistically using statistical tools like Chi-square test and Spearman’s correlation test.

Results
Mean follow up was 28.03 months (range, 12-50 months). The mean neck shaft angle of hip was 1290 (range, 1180 to 1400) in contralateral hip. The mean neck shaft angle of operated hip was 1380(range, 1270 to 1480) at final follow up. Table 2 shows number of patients in accordance to the range of neck shaft angle pre-operatively, post-operatively and at final follow up.
Average Harris hip score [24] (Table-3) was 94.8 points. 42 patients had an excellent Harris hip score, 35 patients scored good, 13 patients had fair score and none of the patients had a poor hip score. 54 patients had functional return to complete previous routine physical activities within 10 weeks, 40 patients showed signs of union after 10 weeks but within 12 weeks and 6 patients had a delayed fracture union after 12 weeks up to 14 weeks which can be contributed to delayed ambulation, poor nutrition, continued tobacco use and osteoporosis.

Discussion
There is a consensus for the treatment of stable inter-trochanteric fractures in the literature. However, the preferred treatment for unstable trochanteric fractures remains controversial [1].The diversity of fixation devices available for treatment of unstable trochanteric fractures illustrates the difficulties encountered in the actual treatment [1]. Even with the evolution of other modified sliding hip system and cephalo-medullary nail, the DHS continues to enjoy the preference by many surgeons for confident surgical management of peritrochanteric fractures. Osteopenia, age, and gender related variation may not allow the dynamic hip screw for ideal healing. The varus collapse, implant cutout in head region, intraarticular penetration due to sliding proportionate to collapse remain the major causes of unacceptable outcome in failures. Although the neck shaft angle is reported to vary in the population [12], 1350 DHS implant has continued to be the universal specification for surgeons. The present study evaluates the outcome of valgus reduction in intertrochanteric fractures fixed by 1350 DHS and correlates its influence on the functional outcomes and the rate of union. There was high incidence of unstable fractures in this study with 60% of fractures showing a posterior and medial wall comminution. All the fractures were reduced in valgus position and have shown excellent to good results with a 100 % union rate. Pajarinem J et al[13] also recommended that unstable intertrochanteric fractures should be initially reduced in slight valgus position.
Osteoporosis has been recognized as a major morbid factor in elderly age group. Based on Singh’s Index, this study showed that 34 females and 25 males (n=59, 65.5%) were osteopenic. This is consistent with the findings of Hartholt K et al [14] who studied that age adjusted incidence rate increased from 52.0 to 67.6 per 10,000 older persons especially in females. This observation is in contrast to study done by Dube et al [15] where osteoporosis was more common in males than in females.
Union was achieved in 100 % patients in the present study which is comparable to rates reported in literature (Table-5). The average Harris hip score [24] in present study was 94.8 points, with 46.6% of total patients in excellent grade, 38.8% in good grade, 14.4 % were in fair grade and none in poor grade. Results of present study were comparable with those in literature [1, 16, 17]. .
The diaphyseal cervical angle as measured in contralateral hip (1180-1400, mean-1290) was converted to deliberate valgus (1270-1480, mean-1380), the mean increase in valgus being 90. Majority of patients (n=52) had a mean increase in neck shaft angle of 100 which did not change significantly at the time of union. This finding was also confirmed by drawing the trabecular angle described by M J Parker et al [9] which also did not change significantly from time of fixation to time of union.
Several authors have reported significant incidence of screw cut out in their studies of trochanteric fractures. Andruszkow H et al [18] reported 3.4 % cut out of hip screw. Bruijn KD et al [19] reported 7% rate of screw cut-out in a study of 215 intertrochanteric hip fractures. Hsueh et al [20] reported 6.8 % cut out of hip screw in a large series of 937 patients. Parker MJ [9] reported that cut-out was significantly associated with a varus position the fracture and a superiorly or posteriorly placed lag screw within the femoral head. He also stressed the importance of trabecular angle being maintained in an optimal range for low rates of fixation failure. It was interesting to note that trabecular angle did not significantly change from the immediate post-operative period till the time of union and was maintained between the optimal range as recommended by Parker M.J et al [9]. This insignificant change in trabecular angle pertains to the fact that the 1350 DHS implant does not show migration during the post-operative phase till the time of union which might lead to decreased rates of failure due to implant migration. None of the case had fixation failure due to side plate pull-out in the present study. Incidence of screw cut-out was nil in the present study despite the fact that 55% patients had unstable fractures in the present study. Lateral wall impaction associated with valgus reduction also favours consolidation due to rise in compression forces [21]. A valgus reduction has the mechanical advantage of reducing the deforming forces across the fracture by reducing the distance between the plate and weight bearing axis [9]. This decreases the chances of implant failure.
The valgus reduction leads to lengthening of the lower limb. There was significant limb-length discrepancy observed in present study in the immediate post-operative period in twenty cases (28.8 %), all of which had a true lengthening of less than 1.5 cm each which required shoe raise of the contralateral unaffected limb. However, at final follow up, only 5 patients reported to have a significant limb lengthening. This was in accordance to a study conducted by C.Takeshi et al [21] which reported equalization of limb lengthening in majority of cases (70.5%) managed by valgus reduction. This was probably due to effect of impaction and collapse of fracture assisted by DHS. It was interesting to observe that none of the patients had a limb shortening at the immediate follow up, ten (11.1%) patients had significant limb shortening due to the controlled collapse achieved by 1350 DHS. Several authors have reported varying incidence of true shortening in their series. Ecker et al [22] have reported an average of 2cm of true shortening in 12 out of 62 cases. Leung et al [23] reported the mean femoral shortening of 4.9 mm (range 0-20.2 mm).Incidence of shortening of limb was less in the present study which may be because of valgus reduction achieved in present study. There was no significance (p=0.977) found statistically between the change in neck shaft angle and anisomelia at final follow up.
Parker MJ [9] have reported that valgus position would reduce the chance of shortening of the leg, as would occur if the fracture is allowed to unite in varus position. Using the 1350 DHS with a valgus reduction may theoretically result in gap at the medial side of the fracture, but support is provided laterally and this combined with compression and progressive controlled collapse of the fracture, results in medial continuity being restored in valgus position. This is in accordance with the observation by Parker MJ [9].

Conclusion
Although many devices can achieve rigid fixation for intertrochanteric fractures, the dynamic hip screw system is the most commonly used device. The commonest mechanical failure of fixation in using the DHS system is cutout of implant from the femoral head. Fractures considered stable have a much lower rate of complications than the unstable ones. The use of intramedullary devices has also been advocated for the management of unstable peritrochanteric fractures. Most of the cases in the present study were unstable and osteoporotic in which the outcome of deliberate valgus reduction in peritrochanteric fractures was analyzed to have diminished rates of screw cut out and facilitate consolidation. However, lateral wall comminution, reverse oblique type fractures and intertrochanteric fractures with subtrochanteric extension may still be fixed by an intramedullary device. Hence we advocate valgus reduction to achieve reliable functional and radiologic outcomes in all other stable and unstable type of peritrochanteric fractures.


References

1: Siwach RC, Rohilla R, Singh R, Singla R, Sangwan SS, Gogna P. Radiological and functional outcome in unstable, osteoporotic trochanteric fractures stabilized with dynamic helical hip system. Strat Traum Limb Recon 2013; 8:117-122.
2: Cleveland H, Bosworth DM, Thompson FR. Intertrochanteric fractures of the femur; a survey of treatment in traction and by internal fixation. J Bone Joint Surg 1947; 29:1049-67
3: Schipper IB, Marti RK, van der Werken C. Unstable trochanteric femoral fractures: extramedullary or intramedullary fixation. Review of literature. Injury 2004; 35:142-151
4: Hardy DC, Descamps PY, Krallis P, Fabeck L, Smets P, Bertens CL, et al. Use of an intramedullary hip-screw compared with a compression hip-screw with a plate for intertrochanteric femoral fractures: A prospective, randomized study of one hundred patients. J Bone Joint Surg Am 1998; 80:618-30
5: Adams CL, Robinson CM, Court-Brown CM, McQueen MM. Prospective randomized controlled trial of an intramedullary nail versus dynamic screw and plate for intertrochanteric fractures of the femur. J Orthop Trauma 2001; 15:394-400
6. Nordin S, Zulkifli O, Faisham WI (2001) Mechanical failure of Dynamic Hip Screw (DHS) fixation in intertrochanteric fracture of the femur. Med J Malaysia. 56(D):12-7
7. Simpson AH, Varty K, Dodd CA (1989) Sliding hip screws: modes of failure. Injury 20(4):227-231
8. Stromsoe K (2004) Fracture fixation problems in osteoporosis. Injury 35:107-113
9: Parker MJ: Valgus reduction of trochanteric fractures.Injury 1993 May; 24:313-316.
10: Singh M, Nagrath AR, Maini PS. Changes in trabecular pattern of the upper end of the femur as an index of osteoporosis. J Bone Joint Surg Am 1970; 52:457-67
11: Baumgaertner MR, Curtin SL, Lindskog DM and Keggi JM.: The value of the tip-apex distance in predicting failure of fixation of peritrochanteric fractures of the hip. J Bone & Joint Surgery (Am) 1995; 77:1058-1064.
12. Kaur P, Mathew S, George U. A study of neck shaft angle in the North–West Indian population on radiographs. International Journal of Basic and Applied Medical Sciences. 2013; 3(3):9-15.
13. Pajarinen J, Lindahl J, Savolainen V, Michelsson O, Hirvensalo O.: Femoral shaft medialisation and neck-shaft angle in unstable pertrochanteric femoral fractures. International Orthopaedics (SICOT) 2004; 28:347–353.
14. Hartholt KA et al: The Epidemic of Hip Fractures: Are We on the Right Track?. Plus One 2011 July; 6 (7).
15. Dube AS, Goel S, Rastogi A, Vashisht A, Swarop A. Implications of Surgery or Fracture Related Morbidity Factors in the Outcome of Pertrochanteric Fractures Managed by Dynamic Hip Screw. Journal of Medical Thesis 2014; Jan-Apr; 2(1)’24-30.
16. Kumar R, Singh RN, Singh BN. Comparative prospective study of proximal femoral nail and dynamic hip screw in treatment of intertrochanteric fracture femur. Journal Clinical Orthopedics and Trauma. 2012; 3(1):28-36.
17. Lee YS, Huang HL, Lo TY, Huang CR. Dynamic hip screw in the treatment of intertrochanteric fractures: a comparison of two fixation methods. Int Orthop .2007; 31(5):683-8.
18. Andruszkow H et al: Tip apex distance, hip screw placement, and neck shaft angle as potential risk factors for cut-out failure of hip screws after surgical treatment of intertrochanteric fractures. International Orthopaedics (SICOT) 2012; 36: 2347-2354.
19. Bruijn KD, Hartog DD, Tuinebreijer W, Roukema G. Reliability of predictors for screw cutout in intertrochanteric hip fractures. J Bone Joint Surg Am 2012; 94: 1266-72.
20. Hsueh KK, Fang CK, Chen CM, Su YP, Wu HF, and Chiu FY: Risk factors in cutout of sliding hip screw in intertrochanteric fractures: an evaluation of 937 patients. Int Orthop 2010 Dec; 34 (8):1273-1276.
21. Chikude T et al.: Cut Out Complications and Anisomelia of the Lower Limbs In Surgery With Valgus Reduction for Intertrochanteric Fractures. International Archives of Medicine. 2015 Apr 20; 8.
22. Ecker ML, Joyce JJ, Kohl JE. The treatment of trochanteric fractures using a compression hip screw. J Bone Joint Surg 1975; 87:23-7.
23. Leung F, Gudushauri P, Yuen G, Lau TW, Fang C, Chow SP: Dynamic hip screw blade fixation for intertrochanteric hip fractures. Journal of Orthopaedic Surgery 2012; 20(3):302-6.
24. Mahomed NN, Arndt DC, McGrory BJ, Harris WH. The Harris hip score: comparison of patient self-report with surgeon assessment. The Journal of arthroplasty. 2001 Aug 31; 16(5):575-80.


How to Cite this Article:  Swarup A, Siwach K, Dube  AS, Rastogi A, Malhotra S, Sharma GD. The Answer to Unstable Peritrochanteric Fractures. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):38-43.


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Osteomyelitis and Causing Microbes in Paediatric Patients and Current Recommendations in the Management

Vol 32 | Issue 1 | Jan – June 2017 | page: 2-6| Manish Yadav; Ajai Singh; Sabir Ali; Abbas Ali Mahdi; Rajeshwer Nath Srivastava


Authors: Manish Yadav [1]; Ajai Singh [1]; Sabir Ali [1]; Abbas Ali Mahdi [2]; Rajeshwer Nath Srivastava [1]

[1] Department Of Orthopaedic Surgery, K. G. Medical University, Lucknow, India.
[2] Department of Biochemistry, King George’s Medical University, Lucknow.

Address of Correspondence
Dr. Ajai Singh
Department of Orthopaedics Surgery,
K. G. Medical University, Lucknow, India.
Email: as29762@gmail.com


Abstact

The muscles and bone related infections are remains common cause of morbidity. In children, osteomyelitis is primarily hematogenous in origin and acute in nature. Methicillin resistant Staphylococcus aureus is the most common organism, but incidence of methicillin resistant S. aureus in the community is continuously rising. Owing to the emergence of community-associated methicillin-resistant S. aureus the overall management process must have to advance. The functional outcomes may become poor if there is poor quality of management. That is why management includes careful consideration about pathogenesis, microbiology, diagnostic options, surgical and medical treatment of osteomyelitis.
Keywords: Osteimyelitis, Microbes, Infection, Antimicrobial activity, Management.


Introduction
Osteomyelitis is the inflammatory infection of bone that are destroyed and followed by new bone formation [1], the initiation of OM is an acute infection that later develops into chronic conditions [2]. There are many diverse forms of this disease due to which it is considered as complicated. One of these diverse forms focuses on the source of the infection and distinguishes between infections arising from hematogenous seeding from the endosteal blood supply and infections arising as a consequence of an overlying soft tissue infection [1].
The incubation period of the infection is two weeks after the injury, the initial infection is known as the acute infection. When the disease has been present for more than one month it is termed as chronic OM. This chronic disease occurs if there is inadequate treatment of acute infection. In reality, there are no distinct subtypes; instead there is a spectrum of pathologic features that reflect balance between the type and severity of the cause of the inflammation, the immune system and local and systemic predisposing factors [3]. Sign and symptoms of acute and chronic osteomyelitis may vary, depending on the type (Fig 1) [4].



Diagnosis of osteomyelitis can be challenging task. Inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein tend to be elevated during osteomyelitis and decrease with effective therapy, but they are useful only to monitor response to therapy. MRI, CT scan, and 3-phase bone scan are marginally better than plain radiographs for diagnosing OM, but all have poor sensitivity and specificity. Bone biopsy with characteristic pathology and positive culture is the gold standard diagnosis. The presence of infected material immediately adjacent to bone should be treated as OM [5].
OM is a pyogenic bony infection, which means the formation of pus that result in inflammation; it can occur in almost every bone in the body, including the bones of the hand and wrist. As soon as the pathogen penetrates the tissue it replicates spreads more at the sites where the areas are least resistant. While intact cortex of bone provides at least a mechanical barrier to pathogen penetration, traumatized bone is easily infected. Local inflammation leads to increased tissue pressure, lower pH and oxygen tension, leading to the formation of microthrombi within the intraosseous vessels and bony necrosis [2].
In children, osteomyelitis is primarily hematogenous in origin and acute in nature. The principal cause of osteomyelitis in children is Staphylococcus aureus, and both the epidemiology and pathogenesis of S. aureus infections, including osteomyelitis, have changed in recent years owing to the emergence of community-associated methicillin-resistant S. aureus. This review focuses on advances in the diagnosis and overall management of acute hematogenous osteomyelitis in children.

Types of OM and important cause of infection in Paediatric Age Group:
OM can be classified according to the area of infection or area of skeleton where it is present. For example, OM of the jaws is different in several respects from OM present in long bones. Vertebral OM is another possible presentation. There are three types of osteomyelitis, the first is Acute OM; the infection develops within two weeks of an injury, initial infection, or the start of an underlying disease. Second one is Subacute OM; the infection develops within one or two months of an injury, initial infection, or the start of an underlying disease. Third one is Chronic OM; the bone infection starts at least two months after an injury, initial infection, or the start of an underlying disease [3].
The major causes for the root of infection are: hematogenous route i.e by the way of blood supply, direct inoculation, and local extension from contiguous infection, i.e from sexually transmitted infections, but the hematogenous route of infection represents only 20% of the cases of OM in adults, this route is the most common one in the pediatric population [5]. Estimates of the incidence of pediatric osteomyelitis vary, but pediatric OM is generally considered rare, the incidence is 6.0 per 1000 admitted patients [6]. Approximately 50% of cases of OM occur in the first 5 years of life. Boys are more likely than girls to be affected. The long bones of the lower extremities are most often involved, although any bone may be affected [7].
Puncture wounds to the foot may result in OM caused by mixed flora, including Pseudomonas, S. aureus, enteric gram-negative bacteria, and anaerobes. The source of bacteria is usually from moist colonized soles of tennis shoes. A series of cases describes OM of the metatarsals occurring as a result of toothpick puncture injuries. The organisms isolated included skin and environmental organisms; others have reported infection with mouth organisms as a result of toothpick injuries [8]. Anaerobes are a rare cause of pyogenic osteomyelitis in healthy children. Predominant organisms are Bacteroides, Fusobacterium, Clostridium, and Peptostreptococcus. Anaerobic osteomyelitis can occur as the result of a bite, chronic sinusitis, mastoiditis, or dental infection.

Infecting microbes and age group:
The type of infecting organism depends on the age of the child and underlying medical problem (Table 1) [8]. Staphylococcus aureus is the most common cause of OM in all age groups, accounting for 70% to 90% of infections [7]. In addition to S. aureus, young infants may develop OM caused by Streptococcus agalactiae or enteric gram-negative bacteria. Organisms other than S. aureus causing infection in older children include Streptococcus pyogenes, Streptococcus pneumoniae, and Kingella kingae [9]. S. pyogenes causes approximately 10% of cases of acute hematogenous osteomyelitis with a peak incidence of disease in preschool-age and early school–age children [10]. Children with S. pyogenes osteomyelitis often have a recent history of varicella infection and present with higher fever and white blood cell (WBC) counts compared with children infected with S. aureus. Children with osteomyelitis caused by S. pneumoniae are younger than children infected with S. aureus and S. pyogenes. They are more likely to have joint involvement [11].
The proportion of bone infections caused by S. pneumoniae is relatively small (approximately 1–4%); the impact of heptavalent pneumococcal conjugate vaccine on the incidence of OM is limited. K. kingae is reported as a pathogen with increasing frequency [12]. A cluster of bone and joint infections caused by K. kingae at a daycare center underscores the importance of this organism in children with musculoskeletal infections [13]. K. kingae is a fastidious gram-negative coccobacillary bacterium found in normal respiratory flora. Infection with this organism often is preceded by an upper respiratory tract infection or stomatitis; disrupted respiratory mucosa may facilitate invasion and hematogenous dissemination.

Current Recommendations in the Management
S. aureus is a virulent organism capable of causing significant tissue invasion and bone destruction. The rapid emergence of community associated methicillin resistant S. aureus (CA-MRSA) since the 1990’s has changed antimicrobial management for osteomyelitis; CA-MRSA are not susceptible to beta-lactam antibiotics, and therefore vancomycin must generally be included in empiric therapy for osteomyelitis when CA-MRSA is a potential pathogen [16, 17]. Though CA-MRSA isolates are often susceptible to clindamycin, trimethoprim-sulfamethoxazole, macrolides, and quinolones.
Management of OM should consist of a combined surgical and medical approach to achieve the most favorable outcome. Non-surgical cure is occasionally achieved in acute osteomyelitis, but should not be routinely attempted. Infected hardware should be removed, at least temporarily, whenever possible [18]. Temporary external fixation prior to hardware re-implantation should be considered. When hardware removal is not possible, chronic suppressive therapy after initial antimicrobial treatment is often necessary.
In general, bactericidal, parenteral antimicrobials are preferred for treatment of OM. Initial empiric therapy should include antimicrobials that are active against gram positive and gram negative bacteria. Many clinicians prefer vancomycin for gram positive coverage, with target troughs from 15 to 25 mcg/ml. Newer agents such as daptomycin and linezolid may be effective as well, though there is less experience with their use in osteomyelitis. In addition, empiric therapy should include gram negative coverage, such as a third or fourth-generation cephalosporin, or a flouroquinolone. Additional or alternative antimicrobials may be appropriate for specific situations according to suspected microbiology of the infection.
Once causative pathogens are identified, empiric therapy should be changed to pathogen specific therapy. Parenteral antimicrobials with less frequent dosing may be desirable for outpatient parenteral antimicrobial therapy. Switching to oral antimicrobials with excellent bioavailability is sometimes possible, but should be done cautiously and with consultative advice. Optimal duration of treatment has not been adequately studied. We commonly treat for 4 to 6 weeks, and sometimes longer based on severity and response to therapy.

Conclusion
On the basis of penetrating antibiotics, bone-to-tissue concentrations of first generation cephalosporins were 7% or less, and concentrations for vancomycin and quinolones were 12–15% [19]. Clindamycin concentrations in debrided bone have generally been above the minimum inhibitory concentration for isolated pathogens [20]. OM of the hand and wrist can result in significant morbidity and functional loss. As a result of which optimal management requires a multidisciplinary approach, involving surgeons and infectious diseases specialists to preserve function and maximize the positive outcome.


References

1. Lew DP, Waldvogel FA. Osteomyelitis. Lancet 2004; 12: 364:369
2. Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. Robbins Basic Pathology (8th ed.). Saunders Elsevier. 2007; pp. 810–811 ISBN 978-1-4160-2973-1
3. Burnett, M.W.; J.W. Bass; B.A. Cook. “Etiology of osteomyelitis complicating sickle cell disease.”. Pediatrics. (1998-02-01);101: 296–297
4. Nordqvist, Christian. “What is osteomyelitis? What causes osteomyelitis?.” Medical News Today. MediLexicon, Intl., 10 Sep. 2014. http://www.medicalnewstoday.com/articles.
5. Floyed RL, Steele RW. Culture-negative osteomyelitis. Pediatr Infect Dis J 2003; 22: 731– 736.
6. Mader JT, Shirtliff M, Calhoun JH. The host and the skeletal infection: classification and pathogenesis of acute bacterial bone and joint sepsis. Best Pract Res Clin Rheumatol 1999; 13: 1–20.
7. Arnold SR, Elias D, Buckingham SC, Thomas ED, Novais E, Arkader A, Howard C. Chang¬ing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-asso¬ciated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop 2006;26: 703–708.
8. Blyth MJ, Kincaid R, Craigen MA, Bennet GC. The changing epidemiology of acute and subacute haematogenous osteomyelitis in children. J Bone Joint Surg Br 2001;83:99– 102.
9. Imoisili MA, Bonwit AM, Bulas DI. Toothpick puncture injuries of the foot in children. Pediatr Infect Dis J 2004; 23: 80– 82.
10. Martínez-Aguilar G, Avalos-Mishaan A, Hulten K, Hammerman W, Mason EO Jr, Kaplan SL. Community-acquired, methicillinresistant and methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children. Pediatr Infect Dis J 2004; 23: 701– 706.
11. Yagupsky P. Kingella kingae: from medical rarity to an emerging paediatric pathogen. Lancet Infect Dis 2004; 4: 358 –367.
12. Ibia EO, Imoisili M, Pikis A. Group A beta-hemolytic streptococcal osteomyelitis in children. Pediatrics 2003; 112: 22–26.
13. Tan TQ, Mason EO Jr, Barson WJ, Wald ER, Schutze GE, Bradley JS, Arditi M, Givner LB, Yogev R, Kim KS, Kaplan SL. Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae. Pediatrics 1998; 102: 1369 –1375.
14. Centers for Disease Control and Prevention. Kingella kingae infections in children—United States, June 2001–November 2002. MMWR Morb Mortal Wkly Rep 2004; 53: 244.
15. Centers for Disease Control and Prevention. Osteomyelitis/septic arthritis caused by Kingella kingae among day care attendees—Minnesota, 2003. MMWR Morb Mortal Wkly Rep 2004; 53: 241– 243.
16. Barbieri RA, Freeland AE. Osteomyelitis of the hand. Hand Clin 1998; 14: 589–603.
17. Zetola N, Francis JS, Nuermberger EL, Bishai WR. Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis 2005; 5:2 75–286.
18. Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med 2004; 350: 1422–1429.
19. Stengel D, Bauwens K, Sehouli J, Ekkernkamp A, Porzsolt F. Systematic review and meta-analysis of antibiotic therapy for bone and joint infections. Lancet Infect Dis 2001; 1: 175–188.
20. Duckworth C, Fisher JF, Carter SA, Newman CL, Cogburn C, Nesbit RR, Wray CH. Tissue penetration of clindamycin in diabetic foot infections. J Antimicrob Chemother 1993; 31: 581–584.


How to Cite this Article: Yadav M, Singh A, Ali S, Mahdi A A, Srivastava R N. Osteomyelitis and Current Recommendations in the Management. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):2-6.


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Role of Bone Marrow Derived Autologous Mesenchymal Stem Cells in Fracture Healing in Rabbits

Vol 32 | Issue 1 | Jan – June 2017 | page: 7-13| Rajeev Kumar, Sandeep Kumar, Daljit Singh, Satish Chandra Goel


Authors: Rajeev Kumar [1], Sandeep Kumar [1], Daljit Singh [1], Satish Chandra Goel [1]

[1] Cedar Crest Hospital Abuja, Nigeria.
[2] Hamdard Institute of medical sciences and research New Delhi – India.
[3] Mahalapye District Hospital Mahalapye, Botswana
[4] Institute of medical sciences B.H.U, Varanasi – India.

Address of Correspondence
Dr. Rajeev Kumar
Affiliation Cedar Crest Hospital, Abuja, Nigeria
Email: kdrrajeev27@gmail.com


Abstact

Introduction: In patients with fractures, the bone marrow derived autologous stem cells have a therapeutic potential to accelerate the healing process and treat nonunion. It has become a clinical necessity to develop the novel therapeutic approaches to accelerate fracture healing. In our study we evaluated the effect of bone marrow derived autologous mesenchymal stem cells in fracture healing in rabbits by injecting them locally at the fracture site.
Method: For this study we osteotomised the mid shaft of the ulna in 28 rabbits and divided them into two groups. One group was injected with bone marrow derived autologous mesenchymal stem cells at the fracture site, whereas another group was not given any injection and served as control group. Both the groups were assessed radiologically, morphologically, volumetrically and histologically at 4, 8, 12 and 20 weeks.
Result: The analysis of the different parameters of our study showed that MSCs injected group showed enhanced fracture healing at 4, 8 and 12 weeks as compared to the control group, however, the results were similar at 20 weeks in both the groups.
Conclusion: Hence, it can be concluded that the injection of the bone marrow derived autologous mesenchymal stem cells locally at the fracture site hastens the process of fracture healing in the rabbits at earlier phases.
Keywords: Autologous stem cells, osteotomised, fracture healing.


Introduction
In 10-20% of the fractures, the fracture healing process is impaired which leads to non union and delayed union [1, 2]. Such factors have led to the quest for modalities which can enhance fracture healing. Fracture healing takes place through various stages as hematoma formation, inflammation, angiogenesis, callus formation, and bone remodeling. The healing cascade is coordinated by the interaction of different set of molecules with the local and circulating cells i.e. mitogens (TGF B), Insulin like growth factor (IGF), morphogens (BMPs), effectors of inflammation(IL-1 , IL-6, COX -2), fibroblast growth factor(FGF), platelet derived growth factor(PGDF) and angiogenic factors(VEGF and angiopoietins). These factors affect the proliferation and differentiation of MSCs [3].
MSCs are the pluripotent mesodermal cells which have the potential to differentiate into the different tissues. In the presence of the lineage specific growth factors these MSC have been induced to differentiate into bone in tissue culture [4, 5]. The fracture repair process is initiated by the Mesenchymal stem cells which results in the formation of callus i.e. cartilaginous template .This callus is thereafter replaced by the new bone which repairs the
gap[6]. In various experimental studies it has been established that the MSCs isolated from the bone marrow of rats [7, 8], dogs [9] and humans [4, 5] can differentiate into osteoblasts. In one animal study it had been demonstrated that Mesenchymal Stem Cells (MSCs) accelerates the bone formation [10].
Our study has also been performed to evaluate the role of autologous bone marrow derived mesenchymal stem cells in fracture healing in rabbits.
*The work was carried out in the Experimental Medicine and Surgery Research Laboratory Section of the Institute of Medical Sciences, Banaras Hindu University, Varanasi, India in collaboration with Blood Bank and Pathology Department, IMS, BHU, Varanasi.

Material and methods
This study has been performed to assess the effect of stem cells in fracture healing. This work has been carried out in the experimental medicine and surgery research laboratory section in IMS, BHU in collaboration with blood bank. Autologous stem cells injection was given in animals with surgically created transverse midshaft ulnar osteotomy and describes the healing observed clinicoradiologically and histologically.
Animals:
The study was conducted on healthy mature rabbits irrespective of sex, weighing approx 1.5 kg or more. The experiments are protected under section of prevention of cruelty for Animals Act (1960). Approval was obtained by the ethical committee of Institute of Medical Sciences, BHU.
Experimental Design:
The study was conducted on 28 adult rabbits. Each rabbit was anaesthetized by a dose of 20 mg/kg of ketamine + 0.4 mg/kg of Midazolam I/M. Both upper limbs were shaved and cleaned with chlorhexidine, spirit and betadine. Rabbit was placed in prone position on operating table. Length of ulna was measured from tip of olecranon to wrist. Mid shaft of ulna was exposed through an incision over ulnar aspect of forearm. Few drill holes were drilled with 1 mm k wire to create fracture and minimal periosteal stripping was taken care
of. Transverse osteotomy of mid shaft of ulna was created using osteotome and hammer. Local antibiotic (Chloramphenicol) was instilled before closure. Wound was closed by using interrupted 3-0 vicryl and skin closure done using prolene 3-0. Sterile dressing was done. Skin sutures were removed 10 days after the operation. Post operative intramuscular amikacin was given at dose of 20 mg/kg body weight and ceftriaxone at dose of 40 mg/kg body weight was given for 5 days.
After operation animals were divided into two groups-
(A) TEST GROUP (20 rabbits) – 1ml of final stem cell suspension was given after 10 days of fracture.
(B) CONTROL GROUP (8 rabbits) – With no stem cells injection
Proposed Plan: Both the groups were sacrificed at 4, 8, 12 and 20 weeks comprising 2 rabbits in each of the control group and 5 rabbits in each of the test group.
Marrows stem cell harvesting:
After giving adequate anaesthesia painting and draping was done for bilateral proximal tibia and bone marrow aspiration needle 16G was introduced into tibia. Trocar was removed and 1ml of heparin containing 2500 IU was taken into 10ml syringe and 10ml of bone marrow was aspirated and specimen was immediately transported to the laboratory.

Stem Cell Isolation:
Ficoll-Hipaque (sigma) density 1.077 15ml solution was taken in sterile centrifuge tube and then 10ml marrow aspirate was diluted with 20ml of normal saline. Centrifugation was done at spin speed 1500 rpm at 220C temperature for 30 minutes using heraeus centrifuger (6000i). After centrifugation plasma layer was carefully aspirated and discarded without disturbing the plasma Ficoll interface. Mono Nuclear Cell (MNC) layer was transferred into another sterile tube using sterile pipette and Phosphate Buffered Saline (PBS) was added to the cell suspension and washed thrice by centrifugating at a spin speed of 1500 rpm at 220C temperature for 10 minutes before a final re-suspension in phosphate buffered saline to make 1ml of final stem cell suspension.

Post-experimental schedule:
Animals were kept in wire cages and fed on standard rabbit diet containing about 6% protein and 60% non nitrogenous extract. All animals were observed daily for 1 week for any signs of wound infection. Wound healing was observed for 6-10 days for any signs of infection and the suture removal was done on the 10th day after operation. Test rabbits were given 1.0 ml of stem cells injection over the fracture site on 10th day post-operation. In Control group stem cells injection was not given.

Parameters of study:
1. Radiological examination:
Rabbits were examined radiologically at 0, 4, 8, 12 and 20 weeks by using a standard anteroposterior and lateral skiagram of the operated limb. Fracture gap, bridge bone formation, degree of callus formation and fracture end sclerosis, if any, was observed and noted.
2. Gross examination at autopsy:
Rabbits were sacrificed by giving overdose of ketamine and succinyl choline intramuscularly. Mobility at fracture site was tested. Specimen was obtained and gross findings were observed like type and amount of callus, status of bony union and any abnormal mobility after removing the soft tissue as much as possible from the specimen.
3. Volumetrically measuring the size of callus:
Callus size was measured by taking multiple readings with the help of VERNIER CALIPER and assuming the cross section to be ellipsoid. Major and minor radii were measured at fracture callus site in test group and control group.
4. Histological examination:
Five and two rabbits each from the control group and the MSCs injected groups respectively were sacrificed at 4, 8, 12 and 20 weeks interval. The specimens for histological examination were decalcified using decalcification solution and studied for fracture union. The specimens were washed with water and dehydrated by passing for 12 hrs in each of the graded increasing concentrations of ethanol separately of 30%, 50%, 70%, 90% and through absolute alcohol. The specimen was subsequently treated with xylol solution mounted in liquid paraffin wax, cut into thin sections of 5-8 microns thickness which were made by cutting with microtome and were transferred to xylol to remove the paraffin. Next they were kept on bovine albumin coated slides. They were finally stained with haematoxyline and eosine. Thereafter, the fracture callus was assessed for degree of cellularity, amount of callus, cartilage, bone matrix formation, woven bone and mature bone formation and medullary repair and any remodeling and cortical repair etc. Rankit score, a five degree scoring system based on the observation of Allens et al [11] was used to score the degree of fracture repair and healing. As per this scoring system the GRADE 4 : Complete bone union (Fracture site bridged by well formed bony trabeculae); GRADE 3 : Less than complete bony union as evidenced by presence of small amount of cartilage in fracture callus; GRADE 2 : Complete cartilaginous union(Well formed plate of hyaline cartilage uniting the fragments); GRADE 1 : Incomplete cartilaginous union (as evidenced by retention of fibrous elements in plate); GRADE 0 : Pseudoarthrosis formation or non union seen as inconvertible cavity within cartilage plate between fracture fragments containing blood or other fluid and/ or lined by low cuboidal mesothelia.

Results
Post-operatively fracture healing was assessed in both groups at regular intervals of 4wks, 8wks, 12 wks and 20wks by radiological examination, gross examination at autopsy (morphological examination), volumetric study measuring callus size and histopathological examination. Within 6 to 10 days the wound was healed in all the cases and as absorbable sutures were used for wound closure hence there was no need of suture removal.

Radiological Examination
Radiographs were taken to assess callus formation, fracture gap, fracture end sclerosis, bridging bone formation, remodeling in both the groups. At 4 weeks – In the control group, minimal amount of bridging callus was seen with fracture gap clearly visible in all the rabbits. In the MSCs treated group, there was mild to moderate amount of bridging callus with fracture gap faintly visible in all the rabbits. As compared to the control group the amount of bridging bone callus appeared more in the test group radiologically and also quantitatively which have been detailed further. At 8 weeks – In the control group, the minimal amount of callus increased in all the rabbits. The fracture line was faintly visible with minimal fracture end sclerosis. In the MSCs treated group, after 8 weeks of treatment there was complete bony union with fair amount of bridging callus. No fracture gap was visible in most of the rabbits with faintly visible fracture line in all the rabbits. In control group the healing was better than the control groups. At 12 weeks – There was minimal amount of callus in all the rabbits. The fracture line was still visible with faintly visible fracture end sclerosis. In the MSCs treated group, good amount of callus formation was seen; no fracture gap was visible with complete bony union in all the rabbits. Remodeling and repair of the medullary canal was observed better in this group. At 20 weeks – in control group, the fracture union & variable amount of remodeling was observed (Fig. – 1 ).
In the MSCs treated group at 20 weeks very good amount of callus with complete bony union was present. Remodeling and repair of medullary canal was observed better than the control group.(Fig.- 2)In both the groups bridging bone formation was increased with the time though remodeling was started earlier in MSCs treated groups .

Morphological Examination (Gross examination at autopsy) AND VOLUMETRIC ANALYSIS
All rabbits at the end of experiment were sacrificed as planned by giving lethal dose of succinyl choline and bilateral ulnas were harvested and morphological changes at the fracture site were observed. At 4 weeks – In the control group, the fracture callus was immature and soft. Also the fracture callus was sufficient in amount. In MSCs treated group, minimal to sufficient amount of bridging callus was seen in all the rabbits. Union was mostly cartilaginous and incomplete.

At 8 weeks – In both the groups the amount of callus and maturity of callus was increased. In the control group, there was average amount of osteocartilagenous callus. In the MSCs treated group, all the rabbits showed good amount of osteocartilagenous callus with mostly nearly complete bony union. No abnormal mobility was seen in any of the samples. At 12 weeks, in the control group, there was average amount of osteocartilagenous callus in both the rabbits with nearly complete bony union. In MSCs treated group there was good amount of bony callus with complete bony union. At 20 weeks – there was decrease in amount of callus in both the groups compared to amount of callus seen at 12 weeks – probably due to maturation of callus and remodeling process (Fig.-3, 4).

Histological Analysis
Histological sections were taken and grading of fracture healing was done on five degree grading system, Rankit score. At 4 weeks, MSCs treated group showed much higher stages of healing and lesser amount of fibrous tissue as compared to the control groups. New bone formation was more as compared to the control group. Similar observations were made at 8 and 12 weeks (Fig. – 5) . At 20 weeks there was no difference among the MSCs treated group and the control groups with respect to the histological evidence of healing was observed.

Discussion
The clonogenic, multipotential precursor cells in the bone marrow were first described in the original work by Friedenstein at al [12]. These cells were termed as colony forming unit fibroblasts (CFU – Fs).They are currently termed as Mesenchymal stem cells and denote the pluripotent mesenchymal progenitor cells[13]. The bone marrow mainly consists of two types of cells i.e. stromal cells and hematopoietic cells. Due to their ability to diffentiate as mesenchymal or stromal cells, the stem cells for non hematopoietic tissues are referred as mesenchymal stem cells [14]. Mesenchymal stem cells can be isolated from the bone marrow and other adult tissues [15]. In bony compartment, they can be found in the bone marrow, endosteum, periosteum, thin connective tissue linings of the surface of the bones, and the mineralized bones. Mesenchymal stem cells play a significant role in bone healing [16].
Many studies have been done to establish the role of MSCs in fracture healing. In a study, Niemeyer et al[17] used xenogenic based bone marrow derived MSCs and autologous ovine bone marrow derived MSCs and implanted into a 3cm long sheep tibia bone defect. The results showed improved bone healing in the autologous cells as compared to the human cells. Also, Ai et al [18] did a study on bone healing rate after the xenograft of mineralized bone and together with an allograft of bone marrow derived MSCs in the tibial bone defect of a rabbit model. Comparative study showed that stem cells produced more bone like tissue in the defect area than controls. MSCs have also been injected at the injured site in many of the studies to evaluate the effect of MSCs on fracture healing, similar method have been used in our study. Shao et al [19] injected the bone marrow derived MSCs to the experimentally induced gap of the callus in a model of rabbit. The results of bone union were better in the test group than the control group. The use of MSCs resulted in increased bone formation and bone density at the distraction site. The objective of this study was to further elucidate the role of bone marrow derived MSCs which has been claimed to enhance the role of fracture healing process. Our study also demonstrates that bone marrow derived autologous mesenchymal stem cell when locally administered at the fracture site enhances the bone healing. Our results showed that bone marrow derived MSCs injected animals had increased radiological, morphological, volumetric and histological differences in fracture healing at 4,8 and 12 weeks as compared to the control groups. The results were found similar at 20 weeks in both the groups. Our results are in agreement with the earlier observation of Shao et al [19]. Other studies have also been performed to see the efficacy of MSCs in tissue regeneration. Giannotti et al [20] in a case series treated the upper limb fractures showing pseudoarthrosis and delayed consolidation with the use of bone marrow derived MSCs.
The site of non union had been revitalized in all the cases by micro fractures and drilling, and a rigid plate had been used for synthesis. All the cases were healed and the same was confirmed radiographically.
In another study, Qu et al [21] investigated the effect of MSCs derived from human cord blood on bone nonunion of the femoral and tibial fracture. The results evaluated the accelerated bone healing with use of the human cord blood MSCs.
In stem cell therapy the most standard methods are the direct injection or cell seedling (Cell + Scaffold) and transplantation of the graft. Similar standard method has been followed in our study by injecting bone marrow derived autologous Mesenchymal stem cells at fracture site with favorable results.
In view of increasing the osteogenic potential of the stem cells, different methods have been conducted to differentiate the stem cells. In another study done by Qi et al [22], they investigated the fracture healing of an osteotomy in a model in a rat tibia, the effects of simvastatin locally applied from calcium sulphate combined with a MSC sheet were observed. In the cell treated group complete bone union was obtained after 8 weeks whereas there was no bone union in the control group at this time. These studies and their results opens a new avenue in the acceleration of fracture healing process , but further studies are needed in this area to demonstrate a beneficial effect for therapeutics for human beings.
Though the number of the animals used in our study in both the groups were small, on the basis of the findings it may be concluded that the bone marrow derived MSCs favorably hastens the process of fracture healing, especially in the early stages. The biological response of the use of MSCs on humans may vary, so caution must be exercised when extrapolating these data on human beings. Also, further investigations are required to establish the role of MSCs in fracture healing in human beings.
As conclusion our study showed that the stem cells injected group showed better healing at four, eight and twelve weeks of treatment as compared with the control group. Though, the number of control rabbits in each group was smaller than the test group and the overall number of rabbits per group was smaller, still on basis of findings, it can be concluded stem cells hastens the process of fracture healing.

Clinical Relevance
Role of autologous BMD –MSCs as an enhancer of fracture healing could be extended to humans, it would be of great benefit to all fracture patients as healing time would be shortened, which would eliminate the disadvantages of long-term immobilization of the involved bone and morbidity relating to long-term immobilization can be reduced by early fracture healing.


References

1. Einhorn TA. Enhancement of fracture-healing. J Bone Joint Surg Am. 1995; 77:940–956.
2. Marsh D. Concepts of fracture union, delayed union, and nonunion. Clin Orthop. 1998 Oct ;( 355 Suppl ):S22–30.
3. Dimitriou R, Eleftherios T and Giannoudis P. Current concepts of molecular aspects of bone healing. Injury. 2005; 36:1392−1404.
4. Haynesworth, S. E., J. Goshima, V. M. Goldberg, A. I. Caplan. Characterization of cells with osteogenic potential from human marrow. Bone. 1992; 13:81–88.
5. Jaiswal, N., S. E. Haynes worth, A. I. Caplan, S. P. Bruder. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J. Cell. Biochem. 1997; 64:295–312.
6. Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. 1998 Oct ;( 355 Suppl):S7–21.
7. Maniatopoulos, C., J. Sodek, A. H. Melcher. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res. 1988; 254:317–330.
8.Okumura, M., H. Ohgushi, Y. Dohi, T. Katuda, S. Tamai, H. K. Koerten, S. Tabata. Osteoblastic phenotype expression on the surface of hydroxyapatite ceramics. J. Biomed. Mater. Res.1997; 37:122–129.
9. Kadiyala, S., R. G. Young, M. A. Thiede, S. P. Bruder. Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant. 1997; 6:125–134.
10. Bruder SP, Kraus KH, Goldberg VM, Kadiyala S. The effect of implants loaded with autologous mesenchymal stem cells on healing of canine segmental bone defects. J Bone Joint Surg Am. 1998; 80: 985–996.
11. Allen H L, Wase A and bear W T, Indomethacin and aspirin; Effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat, Acta Orthop Scand. 1980; 51:595.
12. Friedenstein AY, Chailakhyan RK and Lalykina KS. ‘The development of fibroblast colonies in monolayer cultures of guinea pig bone marrow and spleen cells’, Cell tissue kinetics. 1970; 3: 392-403.
13. Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R, Harman S, Gingerich DA, Harman R. Effect of Intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of Chronic osteoarthritis of the elbow joint in dogs. Vet Ther. 2008; Fall; 9(3):192-200.
14. Obermeyer TS, Yonick D, Laying K, Stock SR, Nauer R, Strotman P, Shankar R, Gamelli R, Stover M, Callaci JJ. Mesenchymal stem cells facilitate fracture repair in an alcohol-induced impaired healing model. J Orthop Trauma. 2012; Dec; 26(12):712-8.
15. da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006; 119:2204–2213.
16. Colnot C: Cell sources for bone tissue engineering: insights from basic science. Tissue Eng Part B Rev 2011; 17: 449.
17. Niemeyer P, Schönberger TS, Hahn J, Kasten P, Fellenberg J, Suedkamp N, Mehlhorn AT, Milz S, Pearce S. Xenogenic transplantation of human mesenchymal stem cells in a critical size defect of the sheep tibia for bone regeneration. Tissue Eng Part A. 2010 Jan; 16 (1):33-43.
18. Ai J, Ebrahimi S, Khoshzaban A, Jafarzadeh Kashi TS, Mehrabani D. Tissue engineering using human mineralized bone xenograft and bone marrow mesenchymal stem cells allograft in healing of tibial fracture of experimental rabbit model. Iran Red Crescent Med J. 2012 Feb; 14 (2):96-103.
19. Shao Z, Liu B, Peng Q, Liu W, Liu Y, Liu R, Xu Y, Liu L. Transplantation of osteoblast-like cells to the distracted callus in the rabbit mandible. Plast Reconstr Surg. 2007 Feb; 119(2):500-7.
20. Giannotti S, Bottai V, Ghilardi M, Dell’osso G, Fazzi R, Trombi L, Petrini M, Guido G. Treatment of pseudoarthrosis of the upper limb using expanded mesenchymal stem cells: a pilot study. Eur Rev Med Pharmacol Sci. 2013 Jan; 17(2):224-7.
21. Qu Z, Mi S, Fang G. [Clinical study on treatment of bone nonunion with MSCs derived from human umbilical Cord ] [Article in Chinese]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Mar; 23(3):345-7.
22. Qi Y, Zhao T, Yan W, Xu K, Shi Z, Wang J. Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model. Cytotherapy. 2013 Jan; 15(1):44-56.


How to Cite this Article: Kumar R, Kumar S, Singh D, Goel S C. Role of bone marrow derived autologous mesenchymal stem cells in fracture healing in rabbits. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):7-13.


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Non Secretory Multiple Myeloma Presenting as Pathological Fracture Bilateral Humerii: A case report

Vol 32 | Issue 1 | Jan – June 2017 | page: 69-71 | Mohd Faizan, Ziaul Hoda Shaan,  Latif  Z. Jilani, Mazhar Abbas


Authors: Mohd Faizan [1], Ziaul Hoda Shaan [2],  Latif  Z. Jilani [3], Mazhar Abbas [1] 

[1] Department of Orthopaedic Surgery, J.N. Medical College, A.M.U, Aligarh,202002.

Address of Correspondence
Dr. Ziaul Hoda Shaan
Department of Orthopaedic Surgery, JNMCH AMU, Aligarh,
Email – shaan.hoda007@gmail.com


Abstact

Non Secretory Multiple Myeloma (NSMM) is a rare variant of multiple myeloma which is characterised by the absence of monoclonal gamma-globulins in blood or urine. The patients usually present with multiple lytic lesions in bones with pain, anaemia, hypercalcemia, normal renal function, and positive clonal proliferation of plasma cells and atypical plasma cells in bone marrow biopsy. We present a case report of a 45 year old female with bilateral pathological fracture of humerus. Skeletal survey showed multiple lytic lesions throughout the body with absence of monoclonal gamma globulins on serum immunoelectrophoresis. Bilateral plating was done for humeral fractures and chemotherapy was instituted. Fractures united and patient’s condition improved.
Keywords: Non Secretory Multiple Myeloma, Pathological Fracture, Managemente.


Introduction
Plasma cell neoplasms comprise of spectrum of diseases characterized by clonal proliferation and accumulation of terminally differentiated B cells. This spectrum comprise of conditions as benign as Monoclonal Gammopathy of Undetermined Significance (MGUS); indolent conditions like Waldenström’s macroglobulinemia on the one end and more malignant disorders like multiple myeloma and plasma cell leukemia on the other. These disorders have a common feature on serum protein electrophoresis that is the production of single monoclonal peak (M component). Among patients with multiple myeloma, 70% have their M component comprising IgG and 20% having IgA. Production of monoclonal light chains only represents 5 – 10%. Less than 1% of patients produce monoclonal IgD, IgE, IgM or have non-secretory myeloma [1]. Non Secretory Multiple Myeloma (NSMM) comprise of 1-5% of all multiple myeloma cases [2]. It presents with diagnostic difficulty as there is absence of detectable monoclonal proteins in the serum as well as urine [1]. The plasma cells are unable to secrete the monoclonal immunoglobulin into the blood. Immunoglobulin is typically present in the cytoplasm of neoplastic plasma cells as confirmed by immunofluorescence study. We report this case due to it being very rare and presenting a diagnostic challenge to the treating surgeon.

Case Report
We hereby report a case of 45 years old female who came to us with the complaints of pain to right arm following trivial trauma. For this X-ray of right whole arm AP and lateral view was done which showed pathological fracture of right humerus mid 1/3rd through a lytic lesion in the bone (fig.1). This prompted us to investigate the cause of lesion. We did the skeletal survey of the patient which revealed multiple punched out lesion in the calvarial bone, also lytic lesions were seen in multiple dorsolumbar vertebrae, proximal femur, ilium, ischium and opposite humerus. Blood investigations were done which mainly revealed anaemia and thrombocytopenia.


Laboratory results: Hg:9.6 g/dl WBC:7.6 x 103/uL , hematocrit:19.6% MCV: 91.6 fl MCH:27.5 pg, MCHC: 30.2 g/dL, PLT- 56 x 103/uL ,AST: 19 U/L, ALT:12 U/L, BUN:7.0 mg/dL, Creatinin: 0.9 mg/dL, Uric acid:5.6 mg/dL, Calcium: 3.05 mmol/L, Protein:6.40 g/dL, albumin: 3.91 g/dL globulin: 2.49 g/dL. MR imaging of dorsolumbar spine was done which showed anterior wedge collapse of D6 vertebra and decreased height of D9 and D10 vertebrae with altered signal intensity in the body and posterior element of vertebrae and bilateral ribs at multiple levels, sacrum, bilateral ilium and right humerus both showing heterogenous enhancement on post contrast sequence. Serum immunoelectrophoresis was done which showed no M spike, normal A:G ratio. Histopathological examination of the tru-cut biopsy from the lytic lesion showed sheets of plasma cells with interspersed capillaries which confirmed the diagnosis of non-secretory multiple myeloma. For the fracture of right humerus excision of lesion with open reduction and internal fixation with narrow DCP was done and the fracture united uneventfully. Two years later the patient again presented with pathological fracture of of left humerus for which she was again operated and lesion excision with open reduction and internal fixation with narrow DCP was done (Fig.2). The patient was put on Melphalan and prednisolone combination chemotherapy. Patient had subjective improvement and both fractures united in subsequent follow ups.

Discussion
NSMM primarily manifests as multiple lytic lesions of bone, anemia, hypercalcemia and thrombocytopenia. Mainly skull, ribs, humerus and sternum are involved [3]. The clinical manifestations of NSMM are similar to plasma cell myeloma, except the lower incidence of renal insufficiency and a better prognosis [4]. The diagnosis of non-secretory multiple myeloma is mainly made on the basis of multiple lytic bone lesion, anemia, hypercalemia, and a normal serum and urine protein electrophoresis and immuno-electrophoresis. At times it becomes difficult to make diagnosis of NSMM due to lower percentage of plasma cell in marrow and the bone marrow aspirate obtained from routine sites like sternum and hip often only showed a picture consistent with generalized medullary reaction against chronic infection or metastasis [5].


It is a subject of debate that why is there an absence of detectable monoclonal M-protein in patients with NSMM. Intracellular immunoglobulin can be detected in plasma cells implying defective immunoglobulin secretion or abnormal Ig structure which is not capable of being transmitted by the secretory pathway [6].
NSMM patients are treated the same way as those of secretors. Melphalan-Prednisolone combination chemotherapy remains a standard regimen for symptomatic patients over 70-year old and younger patients who are not candidate for transplantation. More aggressive chemotherapies do not show superiority over Melphalan. VAD regimen is less myelotoxic, can be used as initial treatment for myeloma patients who are candidates for transplantation. Biphosphonates are recommended for patients with bone lysis. Zolendronic acid 4 mg or Pamidronate 90 mg is given every 3-4 weeks. Clinical judgment regarding the palliative benefit of intravenous biphosphonate and the inconvenience of using biphos-phonate injection must be kept in mind. Intermittent evaluation for albuminuria and azotemia should be performed in patients on chronic biphosphonate treatment.
Fractures are generally believed to be common in patients with multiple myeloma as a result of lytic bone lesions, generalized bone loss, and/or elevated bone turnover from excessive cytokine production, but the actual risk of pathologic versus osteoporotic fractures has not been quantified. At diagnosis, pathologic fractures are the presenting feature in 30% of cases of Multiple Myeloma [7]. But risk of pathological fracture in patients with NSSM have not been quantified yet.

Conclusion
In the presence of multiple lytic lesion on skeletal survey, we should not exclude the diagnosis of multiple myeloma merely on the absence of immunoglobulins in blood or urine. We should confirm the diagnosis of multiple myeloma on bone marrow biopsy. We should keep the diagnosis of non secretory multiple myeloma in presence of lutic lesion and absence of M-spike on immunoelectrophoresis.


References

1. Riedel DA, Pottern LM. The epidemiology of multiple myeloma. Hematol Oncol Clin North Am 1992; 6: 225-30.
2. Grogan TM, Van Camp B, Kyle RA, Muller-Hermelink HK, Harris NL. Plasma Cell Neoplasma. Pathology & Genetics Tumours of Haematopoietic and Lymphoid Tissues. ES Jaffe, NL Harris, H Stein, JW Vardiman eds. WHO Classification of Tumor IARC Press, Lyon. 2001: 142-56.
3. Dave SS, Dunbar CE. Multiple myeloma. Handbook of Clinical Hematology. Rodgers DP, Young NS eds. Lippincott Williams & Wilkins Philadelphia, 2005.
4. Smith DB, Harris M, Gowland E, Chang J, Scarffe JH. Non-secretory multiple myeloma: a report of 13 cases with a review of the literature. Hematol Oncol. 1986 Oct-Dec;4(4):307-13.


How to Cite this Article: Faizan M, Shaan Z H,  Jilani L Z, bbas M. Non Secretory Multiple Myeloma Presenting as Pathological Fracture Bilateral Humerii: A case report. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):69-71.


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Indexing of Journal of Bone and Joint Diseases

Vol 32 | Issue 1 |Jan – June 2017 | page: 1 | Sanjay Dhawan, Ashok Shyam


Authors: Sanjay Dhawan [1], Ashok Shyam [2,3]

[1] Dhawan Orthocare, 14 Dwarika Puram  Byepass Agra, India.
[2] Sancheti Institute for Orthopaedics and Rehabilitation, Pune.
[3] Indian Orthopaedic Research Group, Thane, India.

Address of Correspondence
Dr. Sanjay Dhawan,
Dhawan Orthocare, 14 Dwarika Puram
Byepass Agra, India.
Email: sanjaydhawanorth@gmail.com


Editorial

Dear Colleagues,
Indexing of a journal is of prime importance since the recognition by the medical council of India depends on publication in an Indexed journal. The Journal of Bone and Joint Diseases is one of the oldest orthopaedic journals in the country, however till now it has a much localised feel and restricted readership. With advent of online version last year, the outreach of the journal has greately increased. The online format has also made it easier to submit the journal content for online assessment and indexing.
The journal content was submitted to Index Copernicus for assessment in July 2016. After a good six months of review the journal is now indexed with Index Copernicus. The ICV value is calculated to be more than 72. This is very good factor considering journal is online only since one year. Probably the long and regular history of journal publication has helped journal get indexed and also get a very good ICV Score. Journal articles can also be found with Google Scholar and are open access for any indexing body to review.
As per MCI guidelines any journal that is indexed with Index Copernicus and has a print version is to be considered as Indexed journal. JBJD comes out with print version of every issue and as mentioned above is now indexed with Index Copernicus, thus fulfilling the MCI criteria. With this indexing now every article published in JBJD will add additional value to the academic value of every author specially in terms of applying for promotions and fellowships.
JBJD team will further strive to make the journal better and continue to climb on the ladder of improved indexing, however even currently it joins one of the few elite orthopaedic journals that fulfil the MCI criteria of Indexing
We invite our members to write in details if they have any query regarding indexing and abstracting of the journal.

Long Live UPOA
Long Live IOA
Yours truly,

Dr Sanjay Dhawan Dr Ashok Shyam
Editor – JBJD Associate Edito – JBJD

How to Cite this Article: Dhawan S, Shyam AK. Indexing of Journal of Bone and Joint Diseases. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):1.


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Intraprosthetic Dislocation Following Bipolar Hemiarthroplasty after 4 Years with Squatting and Sitting Cross Legged: A Case Report

Vol 32 | Issue 1 | Jan – June 2017 | page: 66-68 | Pramod Bhilare, Md Sehal Khan Abid, Md Talha Khan Abid, Neeraj Mishra, Sarang Patki, Pravin Bande


Authors: Pramod Bhilare [1], Md Sehal Khan Abid [1], Md Talha Khan Abid [2], Neeraj Mishra [1], Sarang Patki [1], Pravin Bande [1]

[1] BARC Hospital, Mumbai.

Address of Correspondence
Dr. Md Sehal Khan Abid
Room No. 27, RMO Quarters, BARC Hospital, Anushaktinagar
Mumbai 85
E mail – drsehalkhanabid@gmail.com


Abstact

Case Report: A 64 year old female sustained injury to her left hip four years back and was diagnosed as subcapital fracture neck of femur for which bipolar hemiarthroplasty left hip was done. Post Op she was asymptomatic for almost 4 years and reported after 4 years of surgery with click heard at her left hip and painful limp on the affected side while attempting to get up from squatting position. Radiographs of the hip was taken which showed intraprosthetic dislocation. The patient was operated with Southern approach with extended trochanteric osteotomy and a revision Total hip Arthroplasty was done. Implant which was retrieved had a failed anti dissociation mechanism.In most reported cases only implant related factors have been considered and discussed with no emphasis on any patient related factors. The current case would be the first to be documented with no history of any dislocation or closed reduction maneuvers in immediate post operative period, and is associated with squatting and sitting cross legged after years of uneventful hip
Conclusion:Long term follow up comparison studies between simple unipolar and bipolar prostheses has shown no significant difference in the functional outcome and complication rates. Hence the common use of bipolar implants with a unique complication of intraprosthetic dislocation becomes questionable especially in a developing country like India with a lower economic status of most people. Proper implant selection with individualized approach is a must to avoid long term debility and pain and to ensure patient’s satisfaction and early return to function.
Keywords: Intraprosthetic dislocation, bipolar hemiarthroplasty, neck of femur fracture.


Introduction
Intraprosthetic dislocation is rare entity but a unique complication of bipolar arthroplasties. But when they do occur, they usually co-exist with dislocation of the prosthesis from the native acetabulum. There have been relatively few prior reports of this serious complication which have highlighted upon the exact mechanism of occurrence of this entity. The most common and widely highlighted mechanisms behind component dissociation is dislocation in immediate post op period with an attempted closed reduction. If the femoral head component locks against the acetabular rim during dislocation, and the component sizing is not accurate, simultaneous dissociation can occur. Other possible etiology could be as a result of a weak or defective polyethylene locking ring. A defective locking ring can allow slippage to occur such that dissociation may take place even without traditional extraacetabular dislocation. We are here reporting a unique case with intra prosthetic dislocation in which no earlier known mechanism has played a role. The post op period of this patient was uneventful and she started squatting and sitting cross legged leading to intraprosthetic dislocation after four years of surgery.

Case Report
A 64 year old female sustained injury to her left hip four years back and was diagnosed as subcapital fracture neck of femur. Hemiarthroplasty left hip was done with an uncemented modular bipolar prosthesis by Southern approach. The fixation was stable and the post operative period was uneventful. Patient was mobilized initially non weight bearing with the help of walker for 4 weeks and then full weight bearing later on. She was on regular follow up every 3 months till one year after which she stopped visiting the hospital. She reported after 4 years of surgery with click heard at her left hip and painful limp on the affected side while attempting to get up from squatting position. On extracting detailed history, she admitted that she started squatting and sitting cross legged in last one year. Radiographs of the hip was taken which showed intraprosthetic dislocation (Fig. 1). The patient was operated with Southern approach with extended trochanteric osteotomy and a revision Total hip Arthroplasty was done (Fig 2). Implant which was retrieved had a failed anti dissociation mechanism (Fig 3).

Discussion
Hemiarthroplasty using unipolar femoral endoprosthesis was commonly associated with painful loosening and erosion at the implant acetabular interface [1]. It was in the early 1970s that bipolar femoral prostheses were introduced with an idea to answer these complications associated with unipolar prosthesis. Bipolar design allows movement to occur at patient’s native acetabulum and the prosthesis as well as within the prosthesis [2]. The theoretical advantages are less wear and tear as well as lower risk of dislocation, with variable head and neck size and an increased range of motion [3,4,5]. However recent studies have not shown any significant difference in functional outcome and complication rates in long term follow up [2,4,6]. Intraprosthetic dislocation (IPD) has come to lime light since last decade with the advent of dual mobility cups used in THRs with reported incidence is approximately 1.9% to 5.2% [8]. Philippot et al reported that intraprosthetic dislocation has been associated with cup loosening, extrinsic blocking of the polyethylene liner or polyethylene wear [7]. IPD is a still rare complication with bipolar hemiarthroplasty with reported incidence in literature is less than 1%. Various mechanisms have been highlighted in previously reported cases as mentioned in the table 1.


Majority of documented cases of intraprosthetic dislocation in bipolar had a history of early postoperative dislocation and a closed reduction maneuver done. This could lead to the ‘bottle opener’ effect wherein the cup locks on the posterior actabular rim while traction is applied and damage the anti dissociation mechanism in the modern bipolar implants [5]. ‘Bubble sign’ could be seen on plain radiographs where the liner has lost its attachment with the cup. In above mentioned cases only implant related factors have been considered and discussed with no emphasis on any patient related factors. The current case would be the first to be documented with no history of any dislocation or closed reduction maneuvers in immediate post operative period, and is associated with squatting and sitting cross legged after years of uneventful hip. When such a dislocation occurs the treatment of choice is open reduction or a conversion into a total hip arthroplasty. THR solves the future alignment problems and avoids need for further surgery keeping in mind the usual age of these patients.
The effect on economic and health conditions of these intraprosthetic dislocations are catastrophic. These patients with revision surgery have a longer hospital stay with more costly medical co morbidities. Revision arthroplasty is a cumbersome job for the operating surgeon with possibility of bone loss, peri prosthetic fractures and increased rates of infection.

Conclusion
Long term follow up comparison studies between simple unipolar and bipolar prostheses has shown no significant difference in the functional outcome and complication rates [2,4,6]. Hence the common use of bipolar implants with a unique complication of intraprosthetic dislocation becomes questionable especially in a developing country like India with a lower economic status of most people. Proper implant selection with individualized approach is a must to avoid long term debility and pain and to ensure patient’s satisfaction and early return to function.


References

1. Cornell CN, Levine D, O’Doherty J, Lyden J. Unipolar versus bipolar hemiarthroplasty for the treatment of femoral neck fractures in the elderly. Clin Orthop Relat Res 1998:67-71.
2. Parker MJ, Gurusamy K. Arthroplasties (with and without bone cement) for proximal femoral fractures in adults. Cochrane Database Syst Rev 2006; 3:CD001706.
3. Goldhill VB, Lyden JP, Cornell CN, Bochner RM. Bipolar hemiarthroplasty for fracture of the femoral neck. J Orthop Trauma 1991; 5:318-324.
4. Ong BC, Maurer SG, Aharonoff GB, Zuckerman JD, Koval KJ. Unipolar versus bipolar hemiarthroplasty: functional outcome after femoral neck fracture at a minimum of thirty-six months of follow-up. J Orthop Trauma 2002; 16:317-322.
5. Star MJ, Colwell CW, Jr., Donaldson WF, 3rd, Walker RH. Dissociation of modular hip arthroplasty components after dislocation. A report of three cases at differing dissociation levels. Clin Orthop Relat Res 1992:111-115.
6. Raia FJ, Chapman CB, Herrera MF, Schweppe MW, Michelsen CB, Rosenwasser MP. Unipolar or bipolar hemiarthroplasty for femoral neck fractures in the elderly? Clin Orthop Relat Res 2003:259-265.
7. Philippot R, Adam P, Farizon F, Fessy MH, Bousquet G. Survivor of cementless dual mobility sockets: ten-year follow-up [In French]. Rev Chir Orthop Reparatrice Appar Mot. 2006 Jun;92(4): 326-331.
8. Kwon MS, Kuskowski M, Mulhall KJ, Macaulay W, Brown TE,Saleh KJ. Does surgical approach affect total hip arthroplasty dislocation rates? Clin Orthop Relat Res. 2006 Jun;447:34-38.
9. Georgiou G, Siapkara A, Dimitrakopoulou A, Provelengios S, Dounis E. Dissociation of bipolar hemiarthroplasty of the hip after dislocation: a report of five different cases and review of literature. Injury. 2006; 37(2):162–168.
10. Hasegawa M, Sudo A, Uchida A. Disassembly of bipolar cup with self¬centering system: a report of seven cases. Clin Orthop Relat Res. 2004; 425:163–167.
11. Lee HH, Lo YC, Lin LC, Wu SS. Disassembly and dislocation of a bipolar hip prosthesis. J Formos Med Assoc. 2008; 107(1):84–88.
12. Lawson KA, Meneses JJ, Pedersen RA. Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development. 1991; 113(3):891–911.


How to Cite this Article: Bhilare P, Abid MSK, Patki S, Mishra N, Bande P. Intraprosthetic Dislocation Following Bipolar Hemiarthroplasty after 4 Years with Squatting and Sitting Cross Legged: A Case Report. Journal of Bone and Joint Diseases  Jan – June 2017;32(1):66-68.


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Role of Total Urinary Hydroxyproline for the Assessment of Fracture Union

Vol 32 | Issue 1 | Jan – June 2017 | page: 32-37 | Sabir Ali, Ajai Singh, Manish Yadav, Abbas Ali Mahdi, Rajeshwer Nath Srivastava


Authors: Sabir Ali [1], Ajai Singh [1], Manish Yadav [1], Abbas Ali Mahdi [2], Rajeshwer Nath Srivastava [1] 

[1] Department of Orthopaedic Surgery, K. G. Medical University, Lucknow, INDIA.
[2] Department of Biochemistry, K. G. Medical University, Lucknow, INDIA.

Address of Correspondence
Dr. Ajai Singh
Department of Orthopaedics Surgery,
K. G. Medical University, Lucknow, India.
Email: as29762@gmail.com


Abstact

Introduction: Predicting the fracture healing outcomes early is one of the most important and fundamental clinical determinations made in Orthopaedics. However, till date there are no methods yet.
Materials and methods: In this cohort study, after ethical clearance and informed consent formalities, total 107 patients were analysed. The serial estimation of total urine hydroxyproline was done at different follow-ups and further correlates it with the fracture healing progression measured using RUST score.
Results: As per 24th week of radiological follow-up, these patients were divided into two groups: Normal healing (n=91) and Impaired healing (n=16) groups. The total urinary hydroxyproline levels were measured at different follow-ups showed statistically significant difference between normal and impaired healing groups, except at baseline. A statistically significant positive correlation between total urinary hydroxyproline levels with fracture healing progression.
Conclusion: The serial monitoring of total urinary hydroxyproline levels can be used as an adjunct to clinical and radiological evidence of fracture healing to predict the outcomes early.
Keywords: Total Urinary Hydroxyproline, Fracture Healing, Impaired Healing.


Introduction
Fractures are common orthopaedic problem occurs most in long bones. Amongst all long bones, shaft of tibia is one of the commonest bones that are prone to fractures. Also due to lesser soft tissue coverage on anterior aspect, such fractures have relatively higher incidence of impaired healing amounting to 2 – 10% [1-2]. Non-union fracture is a dreaded complication with devastating outcomes for the patients that have required involving multiple surgical procedures, pain, morbidity, prolonged hospital stay and functional and psychosocial disability [3]. Ability in prompt identification of patients who are at high risk of non-union will enable early appropriate targeted treatment intervention leading to a successful outcome. Such approach would benefit not only the patient’s wellbeing but also the health care system in terms of the cost implications associated with long lasting treatment interventions and prolonged hospital stay.
Hydroxyproline is released by the breakdown of collagen in the tissues, especially during bone resorption, it degraded into free amino acid that circulates in plasma, and is almost entirely reabsorbed by the kidney. At last it completely oxidized in the liver and degraded to carbon dioxide and urea [4-5]. As the hydroxyproline released during degradation of collagen cannot be reutilized in collagen synthesis, these excreted in the urine and act as a definitive indicator of bone matrix turnover [6-8]. In the present study, we plan to analyzed the serial estimation of total urinary hydroxyproline throughout the initial phase of healing in patients with diaphyseal tibial fracture.

Materials and Methods
This is a prospective cohort study conducted between 2011 to 2015 at our institutional trauma center. After obtaining ethical clearance (Ref. Code: 55 E.C.M. IIB/P6) from institutional ethical review committee and informed consent formalities, the demographic data of all enrolled patients were collected.
As per inclusion-exclusion criteria, total 119 patients of both sexes of aged between 18 and 40 years with simple, fresh (less than 03 days) traumatic diaphyseal fractures of both bones leg managed conservatively were included in the study. Also the patients included in the study were suggested to avoid diets rich in collagen. All patients included in this study were managed conservatively (reduction -setting and above knee plaster cast under general/regional anesthesia). Prior to the management, the clinical and radiological examinations were done. They were admitted for next 24-48 hours and then discharged with a standard advice.
Total urinary hydroxyproline level were estimated from the 24 hours urinary samples according to the method of Bergman and Loxley, 1970 [9] at 04th day (baseline) and 06th & 10th weeks of post-fracture follow-ups.
The clinico-radiological examination was done at 06th, 10th, 16th, 20th, 24th post fracture weeks. The radiological progression of healing was evaluated using RUST scoring system [10-11]. The x-rays for RUST score were examined separately by two orthopaedic surgeons blindly and findings were noted separately. The average of scores was taken for final decision/analysis. The clinic-radiological evaluation at 24th week was used to label the healing as normal or impaired. Patients with normal bony healing were defined with RUST score ≥ 7 by the end of 24th week along with painless (no tenderness), motionless (no abnormal mobility) with presence of transmitted movements at fracture site. Otherwise they were labeled as impaired healing [10-11]. The clinical & radiological status (RUST Score) of union based on 24th week was then analysed against total urinary hydroxyproline level.

Statistical Analysis:
Statistical analysis was performed using SPSS software (SPSS Inc., Chicago, IL, USA) for Windows program (15.0 version). The continuous variables were evaluated by mean (±standard deviation) or range value when required. For comparison of the means between the two groups, analysis by Student’s t-test (unpaired) with 95% confidence interval. The correlation analysis was done using Spearman correlation coefficient. A P < 0.05 or 0.001 was regarded as significant.

Results
Out of 128 patients, 09 were excluded as per inclusion-exclusion criteria. Out of these 119 patients who were enrolled in our study, 12 patients were lost to follow-up. So, only 107 patients were analysed. The baseline characteristics of the patients showed in Table-1, which do not show any statistically significant difference.


As per clinico-radiological status of fracture healing at 24th week, these 107 patients were divided into: Normal Healing (n = 91) and Impaired Healing (n = 16) groups. Mean RUST score at 06th, 10th, 16th, 20th, and 24th weeks of post fracture follow-up were 6.32±0.49, 7.89±0.46, 8.41±0.60, 10.22±0.90 and 11.08±0.86 respectively in normal healing patients and 4.34±0.39, 4.65±0.43, 5.06±0.47, 5.62±0.46, 5.87±0.59 respectively in impaired healing patients. The mean time of healing in normal healing patients was 17.2 ± 3.7 weeks. Mean RUST score were significantly higher at each of the radiological follow-ups in normal healing as compare to impaired healing groups (p <0.0001) [Fig-1].


Total urinary hydroxyproline level at 04th day and 06th & 10th weeks after post-fracture follow-ups were 11.24±2.25, 13.62±3.11 and 10.63±2.79 respectively in normal healing patients and 10.89±2.08, 3.87±1.92 and 2.12±0.93 respectively in impaired healing patients.

The peak total urinary hydroxyproline level was obtained at 04th day (baseline) of post fracture. Significant positive correlation was found between the peak mean total urinary hydroxyproline level (at 04th day) with the fracture healing progression at all different follow up measured using RUST scoring [Table-3; Fig-2].

Discussion
Bone turnover is probably faster than in soft tissues, whereas nearly half of human collagen remains in bone. Excretion of hydroxyproline in urine is regarded as a marker of bone resorption. Approximately 50% of urinary hydroxyproline is derived from bone collagen breakdown [12]. Increased production of collagen is allied with increase in the hydroxyproline [13-14]. In the present study, we plan to analyzed the serial estimation of total urinary hydroxyproline throughout the initial phase of healing, hypothesizing that the total urinary hydroxyproline level might be altered and showed difference in level while compared between normal and impaired healing patients.
In the present study we observed that the total urinary hydroxyproline levels were measured at different follow-ups during the fracture healing progression showed statistically significant difference between normal and impaired healing groups, except at baseline value. Furthermore, statistically significant positive correlation between total urinary hydroxyproline levels with fracture healing progression (RUST score) were also observed.
Increase in the hydroxyproline also found soon after fracture that associated with an increased production of collagen. These modifications represent the changes in levels of total and free hydroxyproline excretion in urine [15-16]. In a recent study by Das., et al. [17], in patients with long bone fractures, significant differences were observed between normal union and nonunion groups in case of urinary hydroxyproline levels after treatment with a positive correlation between urinary hydroxyproline in normal united group. Mukhopadhyay., et al.[7] in their study also observed significant difference in total urinary hydroxyproline between normal union and nonunion groups, showed positive correlation with fracture healing. Our study observations relies on the results obtained by Das et al., [17] and Mukhopadhyay et al.,[7]. Thus, concluded that the serial monitoring of urinary hydroxyproline reflect the actual status of bone turnover in real time [18]. However, small sample size was the limitation of the present study.

Conclusion
Serial monitoring of biochemical marker of bone turnover like urinary hydroxyproline, reflect the actual status of fracture healing progression. Thus, quantification of total urinary hydroxyproline might be used as a complementary assessment tool to assess the fracture healing progression in parallel to clinic-radiological examination. By this, we can accurately assess the healing progression at real time and also may early predict the impaired healing, which could be helpful in performing early interventional procedures. Thus, this approach would benefit not only the patient’s wellbeing but also to the total health care system in terms of the substantial cost associated with long lasting treatment interventions and prolonged hospital stay. However, further multicentric studies were recommended.

Funding
This study was funded by Indian Council of Medical Research, New Delhi (No5/4-5/12/Trauma/2011-NCD-I).

Conflict of interest
The authors have no conflict of interests in this article.

Acknowledgements
This study was supported by Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India and funded by funded by Indian Council of Medical Research, New Delhi.


References

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2. Reed L. K., Mormino M. A. Distal tibia nonunions. Foot and Ankle Clinics 2008 13(4),725–735.
3. Marsh D. Concepts of fracture union, delayed union, and nonunion. Clinical Orthopaedics and Related Research 1998; (355, supplement),S22–S30.
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7. Mukhopadhyay M, Sinha R, Pal M, Bhattacharyya S, Dan A, Roy MM. Role of common biochemical markers for the assessment of fracture union. Indian Journal Clinical of Biochemistry 2011; 26(3): 274-278.
8. Jakob C, Zavrski I, Heider U, Brux B, Eucker J, Langelotz C, Sinha P, Possinger K, Sezer O Bone resorption parameters [carboxy-terminal telopeptide of type-I collagen (ICTP), amino-terminal collagen type-I telopeptide (NTx), and deoxypyridinoline (Dpd)] in MGUS and multiple myeloma. European Journal of Haematology 2002 69(1): 37-42.
9. Bergman I, Loxley R. The determination of hydroxyproline in urinary hydrolysates. Clin Chim Acta. 1979; 96:125–30.
10. Sabir Ali, Ajai Singh, Avinash Agarwal, Anit Parihar, A A Mahdi, R. N. Srivastava. Reliability of the RUST Score for the Assessment of Union in Simple Diaphyseal Tibial Fractures. Int J Biomed Res. 2014; 05 (05): 333-335.
11. Whelan DB, Bhandari M, Stephen D, Kreder H, McKee MD, Zdero R, Schemitsch EH. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. Journal of Trauma and Acute Care Surgery 2010; 68(3):629–632.
12. Lowry M, Hall DE, Brosnan JT. Hydmxyproline metabolism by the rat kidney: distribution of renal enzymes of hydroxyproline catabolism and renal conversion of hydroxyproline to glycine and serine. Metabolism 1985; 34(10): 955-961.
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14. Block RJ, Weiss KW, Almquist HJ, Carroll DB, Gordon WG, Saperstein S. Amino Acid Handbook; Methods and Results of Protein Analysis. Springfield 1956; 3(record: 19571404492): 346.
15. Hodgkinson A and Thompson T. Measurement of the fasting urinary hydroxyproline: creatinine ratio in normal adults and its variation with age and sex. Journal of Clinical Pathology 1982; 35(8): 807-811.
16. Deacon AC, Hulme P, Hesp R, Green JR, Tellez M, Reeve J. Estimation of whole body bone resorption rate: a comparison of urinary total hydroxyproline excretion with two radioisotopic tracer methods in osteoporosis. Clinical Chemistry Acta 1987; 166(2-3): 297-306.
17. Soumi Das, Soumya Ghosh, Keya Pal, Arunima Chaudhuri, Soma Datta .Changes in biochemical markers in blood and urine in case of malunion and nonunion after fracture of long bones. Saudi Journal of Sports Medicine 2015; 15(3): 269-275.
18. Manish Yadav, Sabir Ali, Ajai Singh, Abbas Ali Mahdi. Hydroxyproline for the Assessment of Fracture Union. EC Orthopaedics 2016; 3(4): 368-376.


How to Cite this Article: Ali S, Singh A, Yadav M, Mahdi A A, Srivastava R N. Role of Total Urinary Hydroxyproline for the Assessment of Fracture Union. Journal of Bone and Joint Diseases  Jan – June 2017;32(1): 32-37.


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