Iranian J Publ Iranian Health, J2008, supplementary issue on Osteoporosis Bone Turnover, No.1,Turnover, pp.49-54 No.1, pp.49-54 PublAHealth, 2008, A supplementary issue onand Osteoporosis and Bone
Association between Vitamin D Deficiency and Unexplained Musculoskeletal Pain Downloaded from http://journals.tums.ac.ir/ on Thursday, August 23, 2012
R Hafezi 1, A Hossein-nezhad 2, M Mirsafa 2, Zh Maghbooli 2, H Saghafi 2, F Karimi 2, *B Larijani 2 1
Assistant Professor of Physical Medicine & Rehabilitation, Baghiatallah University of Medical Sciences, Tehran, Iran 2 Endocrinology and Metabolism Research Center of Tehran University of Medical Sciences, Iran
Abstract Background: Vitamin D is an essential element for establishing bone and muscle structures. Unexplained musculoskeletal (MSK) pain is a common problem in elderly. The aim of this study is investigation of association between vitamin D deficiency and unexplained MSK pain. Methods: In order to quantify serum levels of vitamin D and other biochemical parameters, serum samples were taken from 1105 subjects aged from 17 to 79 years old, selected based on randomized clustered sampling from 50 blocks in Tehran Unexplained MSK pain was assessed based on the verbal rating scale. Results: Prevalence of MSK pain was 4.4% in the group with normal serum vitamin D, 4.9% in the group of mild vitamin D deficiency, 7.4% in the group of moderate vitamin D deficiency and 11.3% in the group of severe vitamin D deficiency. There was also a relative risk for unexplained MSK pain of severe vitamin D deficiency of 1.26 (95%CI: 1.01−1.72). Odds Ratio was 4.65 (CI95%:1.25−17.3) in this women. We found quite a high prevalence of unexplained MSK pain in people participated in our study. We also found a Conclusion: Positive relationship between BMI and unexplained MSK pain. Conclusion: vitamin D deficiency may be a major cause of unexplained MSK pain especially in older women.
Keywords: Vitamin D deficiency, Musculoskeletal pain, Elderly
Introduction Vitamin D is an essential element for formation and maintenance of bone structure (1). The main role of vitamin D is to promote calcium and phosphate absorption from the small intestine, the homeostasis of extracellular calcium and mineralization of the skeleton, either directly or through parathyroid hormone (2). Vitamin D deficiency results in secondary hyperparathyroidism and increased bone resorption leading to rickets and osteomalacia (1). Vitamin D also plays an important role in the physiology of muscles. Venning and colleagues showed in their study that more than one third of people aged over 65, fell each year. The point was that muscle weakness was the main risk factor. Poor muscle strength may be associated with vitamin D deficiency, which is common among elderly people due to the decreased capacity of the skin to synthesize the provitamin calcidiol (25-hydroxycholecalciferol) with age (3) .
MSK pain is one of the leading causes of chronic health problems. Studies suggest that a large number of adults suffer from MSK pain. The prevalence of MSK pain in the elderly is not accurately known, some studies suggest that older adults have an even higher prevalence of MSK pain, between 65%-85%, with 36% to 70% suffer from a back pain condition (4). In most cases, the exact cause of chronic musculoskeletal pain remains undetectable. Vitamin D deficiency might be a cause of unexplained musculoskeletal (MSK) pain regarding their correspondingly growing of their prevalence among elderly. Vitamin D deficiency is significant in urban population of Tehran (5). We aimed to verify if unexplained MSK pain associates with vitamin D deficiency in a randomized sample of the general population. The present study is part of a national project of prevention, diagnosis and treatment of osteoporosis that investigates the relationship be-
*Corresponding author: Tel: +98 21 84902476, Fax: +98 21 88220037, E-mail:
[email protected]
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R Hafezi et al: Association between Vitamin D…
tween various risk factors and bone mineral density in the population of Tehran.
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Material and Methods In order to quantify serum levels of vitamin D and other biochemical parameters, serum samples were taken from 1105 subjects aged from 17 to 79 yr old, selected based on randomized clustered sampling from 50 blocks in Tehran. Exclusion criteria were: known hepatic or renal disease, metabolic bone disease, malabsorption, sterility, oligomenorrhea, type I diabetes, hypercortisolism, malignancy, immobility for more than one-week, pregnancy, lactation, and medications influencing bone metabolism. The study protocol was approved by research ethics committee of Endocrinology and Metabolism Research Center (EMRC). After taking informed consent one fasting blood sample was taken from each participant in his or her place of residence. Sample centrifugation and serum extraction were done in the field. Then samples were sent to the laboratory of EMRC and were frozen immediately. Serum level of 25-hydroxy vitamin D (25(OH)D) was measured with RIA method (Biosource Europes.A,Ò). Normal range for serum vitamin D (25(OH)D) was 23 to 113 nmol/l. Interassay and Intrassy were 8%, 6·8% respectively. The subjects were asked to complete a questionnaire at the time of physical examination. Height and weight were measured at this time. 25(OH) D serum levels equal or less than 12·5 nmol/l were considered as severe vitamin D deficiency and levels between 12·5 nmol/l and 25 nmol/l were considered as moderate vitamin D deficiency. Levels between 25 nmol/l and 50 nmol/l were considered as mild vitamin D deficiency and Levels more than 50 nmol/l were considered as normal levels. Unexplained MSK pain was defined as pain in the upper and lower extremities and axial pain which were not secondary to other diseases or injuries or known conditions causing pain. Unexplained MSK pain was assessed based on the ver50
bal rating scale (VRS). SPSS software (version 12·5) was used for data analysis. Results were expressed as mean±SD. Student's t-test was used to find significant differences between means of variables in several groups. ANOVA was used to detect differences of means between groups. Chi square test was used to compare frequency of variables between groups. Finally after determination of primary relations between variables, logistic regression model was used to evaluate effect of severe vitamin D deficiency on MSK pain accompanies with other variables.
Results After recalling participants for completing the questionnaire and performing physical examination, 826 persons enrolled, (response rate was 74.7%). 39.1% of subjects were men and 60.9% were women. Characteristics of participants and concentrations of biochemical parameters are summarized in Table1. Prevalence of severe, moderate and mild vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. 4.9% of participants had unexplained MSK pain. The prevalence of unexplained MSK pain was 7% in participants aged over 50 yr and 3.8% in the others (Odds ratio= 1.9, 95%CI: 1.013.57, P= 0.03). The BMI and age of men were not significantly different between the groups with and without MSK pain .But women with MSK pain had higher BMI (29.3±3 vs. 27±5 kg/ m2) and were older (48·34±11.7 vs. 43.3±11.2 yr) than the others. Prevalence of MSK pain was 4.4% in the group with normal serum vitamin D, 4.9% in the group of mild vitamin D deficiency, 7.4% in the group of moderate vitamin D deficiency and 11.3% in the group of severe vitamin D deficiency (P= 0.03). Prevalence of MSK pain in men was not significantly different between vitamin D deficients and people with normal serum vitamin D concentrations. There was not significant difference of MSK pain prevalence between groups of vitamin D deficiency and normal serum levels of vitamin D in women younger than 50 yr old.
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Iranian J Publ Health, 2008, A supplementary issue on Osteoporosis and Bone Turnover, No.1, pp.49-54
In women older than 50 yr, prevalence of MSK pain was 3.3% in the group with normal serum vitamin D concentrations, 5.7% in the group with mild vitamin D deficiency, 20% in the group with moderate vitamin D deficiency and 26.7% in the group with severe vitamin D deficiency which was significantly different between these groups (P= 0.01). There was also a relative risk for unexplained MSK pain of severe vitamin D deficiency of 1.26 (95%CI: 1.01−1.72). Odds Ratio was 4.65 (CI95%:1.25−17.3) in this women. In a logistic regression model, after adjusting for age and BMI, sever vitamin D deficiency was a
predictor of unexplained MSK pain in women (P=0.03). Table 1: Characteristics of participants
Variables
Women Means±SD
Men Means±SD
P
Vitamin D (nmol/l)
32·80±43·04
33·34±48·19
0·874
Age (Years)
43·67±11·83
45·03±14·68
0·143
Height (cm)
156·36±7·09
169·28±7·66
0·000
Weight (Kg)
68·40±13·92
74·96±12·79
0·000
Fig. 1: Comparison of serum vitamin D concentrations in women with and without MSK pain in two age groups.
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R Hafezi et al: Association between Vitamin D…
Fig. 2: Comparison prevalence of MSK pain in different degree of Vitamin D deficiency
Discussion Unexplained MSK pain is a common problem especially in elderly people. We found quite a high prevalence of unexplained MSK pain in people participated in our study. The prevalence of MSK pain in the elderly is not accurately known, some studies suggest that older adults have an even higher prevalence of MSK pain, between 65%-85% (6). Jan Tore Gran reported that Chronic widespread MSK pain occurs in approximately 10% of general population, women being significantly more often affected than men. Although all ages are suffered, the peak prevalence appears to be among those in the age group 50-74 yr (7). Data analyzed in that study where gathered from different independent studies from several countries including: Finland, Norway, South Africa, Denmark, USA, Sweden, Canada, Pakistan, Mexico, Spain, and England. Brochet and colleagues mentioned that the frequency of persistent MSK pain increased slightly with age in both sexes but was higher in 52
women. Their study population was from Southwestern France. We also found a Positive relationship between BMI and unexplained MSK pain. This finding is similar to other studies (8). Sievert and colleagues showed that women with MSK pain had a higher BMI (9). A repot from Johns Hopkins Arthritis Center indicated that the prevalence of significant knee, hip, and back pain increases with increased levels of BMI (10). Vitamin D deficiency is a quite common public health problem all over the world. Hashemipour and colleagues demonstrated that vitamin D deficiency has a high prevalence in Iranian population and has been identified as an important public health problem (1). Plotnikoff and colleagues mentioned that 100% of African- Americans, East Africans, Hispanics and American Indians in their Minnesota-based study had vitamin D deficiency (11). We found a positive relationship between Vitamin D deficiency and unexplained MSK pain. The
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Iranian J Publ Health, 2008, A supplementary issue on Osteoporosis and Bone Turnover, No.1, pp.49-54
largest cross-sectional study demonstrating the association of persistent, nonspecific MSK pain with severe hypovitaminosis D was recently carried out by Plotnikoff and Quigley (11). A mechanism for the MSK pain caused by hypovitaminosis D has been proposed. Insufficient calcium phosphate for mineralization of the expanding collagen matrix of bone cause arubbery matrix. This newly formed matrix dose not provide sufficient support; instead hydrates and expands, causing an outward pressure under the periosteom. As it is richly innervated with sensory pain fibers gentle pressure on superficial bones such as the sternum, anterior tibia, radius, and ulna can lead to an anguishing pain (12). Vitamin D metabolites have been found to affect muscle metabolism in three ways: mediating gene transcription, through rapid pathways not involving DNA synthesis, and by the allelic variant of the Vitamin D receptor (VDR). Both in animal models and in humans, VDR has been found in skeletal muscle cells that specifically binds 1, 25-Dihydroxyvitamin D3 (1, 25(OH) D3). In cultured myoblasts, this ligand-receptor interaction, which modulates transcription complex, was found to influence muscle cell calcium uptake, phosphate transport across the muscle cell membrane, and phospholipid metabolism and to mediate cell proliferation and subsequently differentiation into mature muscle fibers (13). Studies showed that most of people with unexplained MSK pain, responded positively to vitamin D supplementation (14). De la Jara and colleagues mentioned that the impact of treatment in female asylum seekers with unexplained MSK pain and vitamin D deficiency is beneficial, with a rapid resolution of symptoms and reductions in both the use of medical services and the prescription of analgesic drugs. They addressed that physicians should be aware of the importance of vitamin D deficiency and the impact of rapid diagnosis and treatment (14). In conclusion, vitamin D deficiency may propose to play a role in unexplained MSK pain especially in older women.
Acknowledgements We acknowledge with gratitude the efforts of EMRC laboratory staff specially Mr Mazaher Rahmani for his assistance in this study. The research has been granted by EMRC, which should be acknowledged to pave the way for young researchers.
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