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Byline: Haji Muhammad Aftab Alam, Syed Badshah Hussain Zaidi, Muhammad Kamran, Dilshad Ahmed Khan, Saqib Ur Rehman and Khalid Hussain


Objective: The study was conducted in Pakistani population to find association of vitamin D deficiency with persistent non-specific musculoskeletal pains by comparing with pain free controls.

Study Design: Case control study.

Material and Methods: Patients aged 12 years or more presenting to Medical OPD with persistent nonspecific musculoskeletal pains for more than 3 months were selected as cases, while healthy individuals served as controls.

Results: A total of 60 cases (patients with persistent non-specific pains) presenting to medical outpatients department at Military Hospital Rawalpindi and 60 controls were studied. Mean age of cases was 43.9 +- 14.0 years and amongst controls were 33.2 +- 17.8 years. Mean serum vitamin D level of 32.8 nmol/L was reported in cases whereas mean serum vitamin D level amongst controls was 26.7 +- 17.8 nmol/L. Hypovitaminosis D amongst cases and controls was 86.6% and 95% respectively. The proportion of vitamin D deficiency did not differ significantly as compared to controls. There was non-significant difference in proportion of deficiency amongst cases and controls.

Conclusion: Overall there was no association between persistent non-specific musculoskeletal pains and vitamin D deficiency.

Keywords: Age groups, Chronic nonspecific musculoskeletal pains, Hypovitaminosis D, Pakistan.


Persistent nonspecific musculoskeletal pains are frequently seen in medical and chiropractic clinics. Chronic non-specific musculoskeletal pain (CNSMSP) is defined as the pain of more than three days duration per week for more than three months. Hypovitaminosis D is defined by most experts as 25 hydroxyvitamin D level of <20 nanogram per milliliter1 and is affected by season, veiling technique of body, obesity and socioeconomic conditions.

In recent time association of vitamin D deficiency with various kinds of pains, especially persistent non-specific musculoskeletal pains is focus of interest. Although recent studies reveal Pakistani, Asian, Indian and Middle Eastern population to be severely vitamin D deficient2 with an estimated 76.6 to 92% deficiency amongst healthy Pakistani population3,4 and a similar level of deficiency amongst immigrants of Pakistani origin residing in western countries5, however, no data exists on Vitamin D deficiency in Pakistani population with persistent non-specific musculoskeletal pains.

Although most of studies reveal deficient vitamin D levels in patients of diffuse muscle pain6,7. However, other case control studies do not support this8,9 yet a positive association was shown between 25 (OH) D deficiency and skeletal pains in case control studies conducted by Heidari et al10 and McBeth et al11.

The rationale of doing this study was to find association between hypovitaminosis D in patients of persistent non-specific musculoskeletal pains in comparison with healthy pain free controls from different areas of Pakistan, since different studies done in western countries especially immigrants from South Asia, showed increased prevalence of vitamin D deficiency in patients of non-specific musculoskeletal pains without comparing pain free controls amongst immigrants from Pakistan12.

Table-I: Mean serum 25 (OH) D and frequency of hypovitaminosis D in cases (chronic non-specific musculoskeletal pains) compared with asymptomatic controls.

Group###n###Mean age###Mean vitamin D###*With###*Without

###(Years)###levels (nmol/L) hypovitaminosis D hypovitaminosis D

Cases###60###43.9 +- 14.0###32.8 +- 14.5###52###08

Control###60###33.2 +- 17.8###26.7 +- 17.8###57###03

Table-II: Gender wise distribution of frequency of serum 25 (OH) D deficiencies (<50nmol/L) in cases (Persistent nonspecific musculoskeletal pains) and controls.

Group###Gender###With hypovitaminosis D###Without hypovitaminosis D






The present case control study was conducted in the department of Medicine, Military Hospital Rawalpindi (Pakistan). Blood samples were analyzed at Armed Forces Institute of Pathology, Rawalpindi, by following the ethical guidelines of Military Hospital, Rawalpindi, Pakistan, from February 2012 to August 2012 over a period of 6 months. The sample size was calculated by WHO sample size calculator, as sixty patients from each group (cases and controls), by keeping confidence level of 95%, with anticipated population proportion (P1) of 93% and (P2) 76% with power of test 80. Consecutive non probability purposive sampling was selected during analysis. Inclusion criteria included all patients aged more than 12 years presenting to medical OPD, Military Hospital Rawalpindi, with persistent non-specific musculoskeletal pains for more than 3 months, while healthy asymptomatic individuals were declared as control.

Exclusion criteria included patients with clinical stigmata of osteoarthritis, rheumatoid arthritis, hypothyroidism/ hyper-thyroidism, fibromyalgia, having liver enzymes more than three times upper limit of normal, blood urea more than two times upper limit of normal, using vitamin D supplements or anticonvulsants and patients having diarrhea of more than six months duration.

From each patient after obtaining verbal informed consent, serum was collected for measurement of vitamin D levels by chemiluminescent immunoassay (CLIA) using Liaison Diasorin Italy 2229 machine, at Armed Forces Institute of Pathology, Rawalpindi. Data were analyzed using SPSS version 14.

Descriptive statistics were calculated for both qualitative and quantitative variables. Qualitative variables were gender and hypovitaminosis D and were presented as frequency/percentages. Quantitative variables included age and vitamin D levels and these were presented as mean +- SD. Tables and charts were made for qualitative variables. Chi square test and Fisher's exact test was applied where necessary. A p-values 0.05, table-I) difference between vitamin D level and hypovitaminosis D among cases and control.

Table-III: Comparison of age wise distribution of mean Serum 25 (OH) D and frequency of serum 25(OH) D deficiency (0.05, table-II) difference between vitamin D level and hypovitaminosis D during gender wise comparison among females. However, there was severe hypovitaminosis D among males of control group. There was no male entry in case group.

Patients were stratified according to age groups and were compared with age matched controls. Three patients presented in age group 13-19 years and were compared with 6 age matched controls. Ten cases and 21 age matched controls were studied in age group 20-29. In age group 30-39 years, 17 cases and 21 age matched controls were studied. There were 13 cases and 4 age matched controls in age group 40-49 and 12 cases and 4 age matched controls in age group 50-59 years. In age group 60-69 years, there were 3 cases and 4 age matched controls. There were only 2 cases in age group 70-79 years and no age matched controls were available. The results of stratification have been described in tabulated form in table-III. The results show non-significant association between cases and control at 95% probability level.


The study revealed that there was overall deficiency of vitamin D amongst cases and controls and that indicates healthy Pakistani population has severe hypovitaminosis D. This was the reason of non-association between 25 (OH) D levels and CNSMSP as indicated from statistical tests.

Prevalence of severe vitamin D deficiency in healthy asymptomatic controls in our study i.e. mean serum vitamin D 32.8 nmol/l in cases, and 26.7 nmol/l in controls, and hypovitaminosis D of 86.6% in cases and 95% in controls correlates with studies done in different parts of Pakistan, where Sheikh et al3 revealed deficiency of 84.3% (defined by 65 years, however a weak association is found in our study. Similarly, our study correlates with study of Plotnikoff et al16 on patients of persistent non-specific musculos-keletal pains in Minneapolis who found out that overall 93% cases had deficiency of vitamin D; however no controls were included in the study.

The findings of severe vitamin D deficiency amongst patients of Study conducted at Oslo et al17 showed an overall 58% prevalence of vitamin D deficiency in patients presenting with non-specific musculoskeletal pains, headache and fatigue including 83% deficiency amongst South Asian immigrants, however no controls from asymptomatic South Asians immigrants were studied. Helliwell et al14 in Bradford revealed high levels of persistent pain biochemical osteomalacia, and disability especially amongst immigrants from Mirpur area of Pakistan, which was unrelated to diagnosis, biochemical status or treatment with calcium or vitamin D. The larger randomized placebo-controlled trials, preferably by stratification with baseline vitamin D status and response to treatment with vitamin D should be carried out in Pakistani patients presenting with persistent non-specific musculoskeletal pains.

Moreover future studies on vitamin D in Pakistani population should focus on comparison of vitamin D deficiency in different conditions with controls rather than simply finding frequency of vitamin D deficiency.


The study concluded that there was no association between 25 (OH) D levels and chronic non-specific musculoskeletal pain.


Authors acknowledge the efforts of Major Gen (R) Farooq Ahmed Khan, HI (M), Professor of Pathology, Consultant Chemical Pathologist and Endocrinologist, ex-Comdt Armed Forces Institute of pathology (AFIP), Rawalpindi Pakistan for his valuable contribution in carrying out the tests.


This study has no conflict of interest to declare by any author.


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Publication:Pakistan Armed Forces Medical Journal
Geographic Code:9PAKI
Date:Jun 30, 2017

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