Vitamin D Supplementation in Orthopaedic Patients – An Indian Perspective

Vol 31 | Issue 2 | Aug – Dec 2016 | page: 33-37 | Chandra Prakash Pal, Vivek Mittal, Karuna Shankar Dinkar, Pawan Kumar, Ravi Mehrotra, Gaurav Deshwar


Authors: Chandra Prakash Pal [1], Vivek Mittal [1], Karuna Shankar Dinkar [1], Pawan Kumar [1], Ravi Mehrotra  [1], Gaurav Deshwar [1]

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

Address of Correspondence:

Dr. Pawan Kumar
Department of Orthopaedics, S N Medical College, Agra
Email: pawangangwar61@gmail.com


Abstract

Aim: Assessment of vitamin D role in vitamin D deficient adult Indian patients with orthopaedic complains
Material And Methods: This prospective study was conducted in department of orthopaedics in SN medical college Agra. 800 patients from both sex between 20 to 80 years were included in this study. These 800 patients were divided in two groups, group A of 400 patients was supplemented by 60000 IU/week orally active vitamin D for 3 months, while group B of 400 patients was supplemented by placebo for 3 months. Each patients was assessed clinically after 15 days and serum markers including 25(OH)D, total calcium, inorganic phosphate, intact parathyroid hormone(PTH-i), alkaline phosphates and 1,25(OH)2D were reassessed after 3 months .
Results: After 3 month of vitamin D supplementation parathyroid hormone (i-PTH) level decreased to 33.7 pg/ml from 41.2 in group A, while in placebo supplemented patients (group B), it remains 39.7pg/ml. insignificant difference (p<.3343) between two groups became significant (p<.0001), which shows parathyroid hormone decreased abruptly when vitamin D was supplemented adequately). Patients who were presented with pain in their hip region and later looser zone was identified in their x-rays. They are again assessed radiologically after 3months of vitamin D supplementation, their x-rays shows signs of healing on the site of looser zone.
Conclusion: Vitamin D is responsible for various neuro-muscular abnormalities like pain in multiple joints, muscle weakness( proximal muscles mostly involved) leads to imbalance and difficulty in walking and these signs and symptoms are directly related with serum 25(OH)D. After 60000 IU/week vitamin D supplementation in vitamin D deficient patients, 25(OH)D was elevated at significant level and all complains due to deficiency were subsided gradually.
Key Words: 25(OH)D, 60000IU/week vitamin D, visual analogue scale, looser zone


Introduction
Major role of vitamin D in humans is to increase the absorption of calcium and phosphate for mineralization of the skeleton. In adults with vitamin D deficiency, the newly formed bone matrix (the osteoid) is not mineralized, causing osteomalacia [1]. vitamin D synthesis takes place in the skin under the effect of sunlight. The India is situated between 8.4° N and 37.6° N latitude and has adequate sun exposure throughout the year. Despite this fact, there is widespread prevalence of hypovitaminosis D that may have an adverse impact on bone health [3–7]. Avoidance of sunlight, cultural and clothing practices, and skin pigment are factors contributing to vitamin D deficiency. Increasing urbanization that results in poor outdoor activity and greater pollution may further aggravate the problem [2-6]. Severe vitamin D deficiency results in clinically apparent metabolic bone disease, i.e., rickets and osteomalacia. Subclinical vitamin D deficiency or insufficiency can result in decrease in overall bone mass and, therefore, an increased risk of osteoporosis [3, 10]. Adequate replacement with vitamin D can increase the bone mass and decrease the risk of fractures [11].
Adequate dose and duration of vitamin D intake for the general population remains a subject of controversy. Experts now feel that 25-hydroxyvitamin D level of 30 ng/ml is required for maintaining optimal skeletal health [12]. The recommended doses of vitamin D (200–400 IU/day) intake are grossly inadequate to bring such low 25(OH)D levels to the desired levels [9–13]. This study was, therefore, undertaken to assess the efficacy and safety of cholecalciferol supplementation administered orally 60,000 IU/week for 3 months. This dose was chosen because this preparation is commonly and easily available in India, and the dose seems to be in agreement with the current suggestions available on vitamin D supplementation in the literature [10]. According to present studies, a dose as high as 10,000 IU/day is likely to pose no risk of adverse effects [14].

Materials and Methods
This prospective study was conducted on patients attending the orthopaedic OPD and emergency department of S.N. medical college, Agra from November 2013 to October 2015. 800 patients from both sex between 20 to 80 years were included in this study. All participants were recruited after taking written informed voluntary consent. The study subjects were recruited after a careful history, general and systemic physical examination. The questionnaire recorded information on age, co-morbidity status(such as diabetes mellitus, hypertension and Ischemic heart disease) and medication use including oral vitamin D supplementation.
Nutritional status was assessed by estimating the average composition of the daily diet in terms of energy, carbohydrate, protein, fat, calcium, and phytate (phytin-P) by use of a semi-quantitative food-frequency questionnaire and published data on the nutrient composition of Indian food.
Direct sunlight exposure was assessed by documenting average duration of exposure and percentage of the surface area of the body exposed daily. The average duration of cloud free sunshine during the years of study (2013-15) was 7.4 h/day in winter months (October to March) and 9.5 h/day in summer (April to September), according to the data provided by the Meteorology Department of U.P. Patients were selected on the basis of strict inclusion and exclusion criteria’s-
Inclusion Crieteria
1. Orthopaedic patients from both sex from age group 20 yrs to 80 yrs coming to orthopedic OPD and emergency department.
2. Subjects with any signs and symptoms of musculoskeletal problems including bone and joint pain, fracture and acute soft tissue injury, degenerative joint disease, metabolic bone, proximal myopathy disease etc.
Exclusion crieteria
1. Age <20 yrs and > 80 years.
2. Pregnant and lactating women
3. Drugs that can affect bone mineral metabolism, glucocorticoids, antitubercular therapy, antiepileptics, levothyroxine, hormone replacement therapy, biophosphonates, teriparatide etc.
4. Patient with history of surgery, hospitalization, or major medical illness within the past one year.
5. Diabetes mellitus patient, cancer patient, hepatic, renal, dermatological disorders and alcoholic persons.
6. Person taking vitamins and mineral supplementation since last 6 months.
Serum 25(OH)D concentrations will be estimated by using a radioimmunoassay. Serum marker measured included total calcium (Ca), inorganic phosphate, intact parathyroid hormone (PTH-i), alkaline phosphates and 1,25(OH)2D. Intact PTH was determined by a two site binding immunoradiometric assay. The normal values, standardized in our laboratory, are as follows: serum calcium 8.5–10.5 mg/dl, serum phosphorus 2.5–4.5 mg/dl; serum alkaline phosphatase 6–15 KAU/dl. Serum 25-hydroxyvitamin D3 (reference range 9–37.6 ng/ml) and serum intact PTH (13–54 ng/L). The subjects were classified as vitamin D-deficient, insufficient or sufficient on the basis of 25(OH)D concentrations of <20ng/mL, 21-29ng/ml and 30-100 ng/mL respectively, according to recent consensus [to convert to nmol/L, multiply by 2. 800 patients were divided in two groups, group A of 400 patients was supplemented by 60000 IU/week orally active vitamin D and 1000 mg calcium in two devided doses daily for 3 months, while group B of 400 patients was supplemented by placebo for 3 months. Each patients was assessed clinically after 15 days and serum markers including 25(OH)D, total calcium, inorganic phosphate, intact parathyroid hormone(PTH-i), alkaline phosphates and 1,25(OH)2D were reassessed after 3 months .
Statistical analysis – The data was categorised either in n (%) and means ± SD. Paired t test was used to compare changes in biochemical parameters before and after supplementation in group A and group B.. A p-value of < 0.05 was taken to be statistically significant.

 

Table 1

Table 1: Sex wise distribution: Females are more vitamin D deficient than males because of more indoor activity, more illiterate and due to post menopausal effect

                                                                                                 

Table 2

Table 2: Biochemical parameters in vitamin D deficient and insufficient patients as compare to vitamin D sufficient individual.

                                                                                                

Table 3

Table 3: Parameters after 3 month of 60000IU/week vitamin D and placebo supplementation

                                                                                                

Table 4

Table 4: Changes in visual analogue scale after 3 month of vitamin D supplementation.

                                                                                                

Results
Out of 800 patients included in our study, 264(33%) were males and 536(67%) female, among which patients 729 (90.2%) had vitamin D level <20 ng/ml, named as vitamin D deficient and 71 patients (9.8%) had vitamin D 21-29 ng/ml, called vitamin D insufficient. Initially there was no significant difference ( p<.1506) in 25(OH) D in group A and group B, but after 3 month of vitamin D ( in group A) and placebo ( in group B) supplementation the difference was significant (p<.0001), which shows significant increment in 25(OH)D level after 60000 IU/week vitamin D supplementation for 3 months. After 3 month of vitamin D supplementation parathyroid hormone (i-PTH) level decreased to 33.7 pg/ml from 41.2 in group A, while in placebo supplemented patients (group B), it remains 39.7pg/ml. insignificant difference (p<.3343) between two groups became significant (p<.0001), which shows parathyroid hormone decreased abruptly when vitamin D was supplemented adequately. Calcium was also elevated in vitamin D supplemented group ( group A) up to the significant level, while group B (placebo supplemented group) patient were remained calcium deficient . The difference between these two groups became significant( p<.0005 from p<.2676). There was no significant difference in phosphorus in group A and group B patients ( p<.2770), after vitamin D supplementation this difference became significant ( p< .0001) , that shows rise in phosphorous values in supplemented group while no change in placebo supplemented group.
After vitamin D supplementation alkaline phosphatase was decreased and difference between two groups became significant (p-value changes into .0001 from .0775). Patients who were presented with pain in their hip region and later looser zone was identified in their x-rays. They are again assessed radiologically after 3months of vitamin D supplementation, their x-rays shows signs of healing on the site of looser zone. Complain of their pain was also subsided gradually. After supplementation of 60000IU/week vitamin D, changes in visual analogue scale at the end of 2nd, 4th, 6th, 8th, 10th and 12th week in vitamin D supplemented group was 78, 45, 35, 30, 20, 15 respectively while in placebo group it was 82, 80, 78, 70, 70 respectively.

Figure 1: Looser zone in 32 years female

Figure 1: Looser zone in 32 years female

Figure 2: Looser zone healing after 3 months vitamin D ( 60000IU/week) supplementation

Figure 2: Looser zone healing after 3 months vitamin D ( 60000IU/week) supplementation

Discussion
This study was conducted on 800 patients coming to OPD and Emergency in department of orthopaedics of S.N. Medical College to evaluate the role of vitamin D supplementation in vitamin D deficient adult Indian orthopaedic population. Indians obtained most of their vitamin D through adequate sun exposure, however, darker skin pigmentation and the changes. Which have accompanied India’s modernization, including increased hours spent working indoors and pollution, limit sun exposure for many. The “adequacy of exposure to sunlight of an individual’s bare skin” required to synthesize vitamin D is grossly ill understood. Darker skin has high melanin content which acts as a natural sunscreen. Therefore, darker skin produces a significantly lesser amount of vitamin D when compared with the individuals with fairer skin, such as Caucasians. Thus, for Indian skin tone, minimum “direct sun exposure” required daily is more than 45 min to bare face, arms and legs to sun’s UV rays (wavelength 290–310 nm).
Inadequate sun exposure results in reduced vitamin D synthesis and ultimately poor vitamin D status if not compensated by dietary intake. Dietary vitamin D intake is very low in India because of low consumption of vitamin D rich foods absence of fortification and low use of supplements. Females are more prone to vitamin D deficiency as compare to men. As in our study out of 800 patients 536(67%) are females because most of women in India are house bound, living in crowded localities and with covered-up style of clothing and purdah and thus, deprived, of sun exposure, are at the highest risk of developing vitamin D deficiency.
In our study most of vitamin D deficients are in 60-80 years of age (47%) group, older people are prone to develop vitamin D deficiency because of various risk factors: decreased dietary intake, diminished sunlight exposure, reduced skin thickness, impaired intestinal absorption, and impaired hydroxylation in the liver and kidneys.
Dose of vitamin D for treating complications related with vitamin D deficiency are not fixed, many societies and studies suggest various regimens with different doses but in most of studies 50,000 IU/ week for 6-8 weeks is optimal dose for deficiency correction, as in 1998 Malabanan et al reported that ergocalciferol in a dosage of 50,000 IU once a week for 8 was an effective regimen to improve vitamin D status and decrease PTH levels in patients managed in an osteoporosis. In our study we found that after 3 month of 60,000 IU/week vitamin D supplementation, there is significant (p<.0001) rise in 25(OH) D, which shows repletion of vitamin D pool in body. Similar relation was found by Close et al. (2013), they examined young, United Kingdom based athletes (n = 30), and examined the effects that vitamin D supplementation (20–40,000 IU/week for 12 weeks) had on muscle performance (1-RM bench press, leg press and vertical jump height). Subjects were assigned to a placebo, 20,000 IU/week or 40,000 IU/week of vitamin D for 12 weeks. Muscle performance and 25(OH)D was measured at six and 12 weeks, revealing that six weeks of supplementation was enough to correct vitamin D deficiency, however, it was not enough to obtain optimal vitamin D levels >40 ng/mL. serum 25(OH)D levels significantly increased over this time, from an average of 20.43 ng/mL to 31.65–39.26 ng/mL. In our study we found that pain due to loosers zone was gradually decreased after vitamin supplementation. Evidence of healing was also identified radiologically, similar association was found by Abderhaman Ghazali, Patrice Fardellone, André Pruna et al. (1999), they found that looser’s zones (always associated with subperiosteal resorption) did not occur with plasma 25(OH)D of more than 40 nmol/liter, and subperiosteal resorption did not occur with plasma 25OHD of more than 100 nmol/liter., due to vitamin D deficiency most our patients were presented with musculoskelton and joint pain, we assessed response of vitamin D in these patients on the basis of visual analogue scale. We divided scale 0-100 and response of vitamin D was assessed every second week. Patients who was supplemented with vitamin D shows gradually decreased values on visual analogue scale, while in placebo group value was not changed.
Conclusion
Worldwide, vitamin D is predominantly obtained through exposure to UVB radiation in the form of sunlight and cutaneous vitamin D production. Latitude, cultural dress habits, season, sun avoidance, and sunscreen protection can all limit vitamin D production. Gastrointestinal, hepatic, and renal disease may be related to low vitamin D levels, but hypovitaminosis D most commonly results from inadequate intake. As by previous study and researches, vitamin D is responsible for various neuro-muscular abnormalities like pain in multiple joints, muscle weakness( proximal muscles mostly involved) leads to imbalance and difficulty in walking and these signs and symptoms are directly related with serum 25(OH)D. This study demonstrates that vitamin D supplementation has clinically beneficial effects on neuromuscular function in adults. After 60000 IU/week vitamin D supplementation in vitamin D deficient patients, 25(OH)D was elevated at significant level. Patients who was presenting with pain in their hip region during climbing stairs, rising up from stairs , these patients after 60000 IU/week supplementation shows positive response, their complains gradually decreases. While in placebo group their was no change in their complains.


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How to Cite this Article: Pal CP, Mittal V, Dinkar KS, Kumar P, Kumar P, Mehrotra R, Deshwar G. Vitamin D Supplementation in Orthopaedic Patients – An Indian  Perspective. Journal of Bone and Joint Diseases  Aug-Dec 2016;31(2):33-37 .

Dr CP Pal

Dr CP Pal


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