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Dr. Wynn

Dr. Richard L. Wynn is Professor of Pharmacology at the University of Maryland Dental School. He holds a BS degree in pharmacy and a PhD degree in pharmacology. More »He chaired the Department of Pharmacology at the University of Maryland Dental School from 1980 to 1995. He is the lead author of the Drug Information Handbook for Dentistry, co-author of many other dental drug publications, author of over 300 refereed scientific journal articles, consultant to the Academy of General Dentistry, featured columnist, and a featured speaker presenting more than 500 courses in continuing dental education. One of his primary interests continues to be keeping dental professionals informed of all aspects of drug use in dental practice.

December 2012

Vitamin D Deficiency and Non-specific Musculoskeletal Pain

The University of Minnesota report of 2003 by G.A. Plotnikoff and J.M. Quigley stated that chronic nonspecific musculoskeletal pain is one consequence of vitamin D deficiency. Previous published reports from Europe had documented persistent nonspecific musculoskeletal pain in immigrant patients secondary to severe hypovitaminosis D. This 2003 study extended the European studies to include patients in the United States presumed to be vitamin D deficient. The primary study objective was to determine the prevalence of hypovitaminosis D in primary care patients with persistent, nonspecific musculoskeletal pain syndromes refractory to standard therapies.

The study consisted of 150 patients presenting to a University inner city primary care clinic in Minneapolis, complaining of persistent nonspecific musculoskeletal pain. Immigrant and nonimmigrant persons of both sexes, aged 10 to 65 years from 6 broad ethnic groups were screened for vitamin D status by measuring serum vitamin D levels. Of all patients, 93% (140 out of 150) had deficient vitamin D levels (mean of 12.08 ng/ml). Nonimmigrants had vitamin D levels as deficient as immigrants. Of all patients, 28% had severely deficient vitamin D levels (< 8.0 ng/ml) including 55% of whom were younger than 30 years.

The authors of the Minnesota report of 2003 concluded the following:

  1. All patients with persistent, nonspecific musculoskeletal pain were at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D.
  2. The risk extended to those considered at low risk for vitamin D deficiency (i.e., nonelderly, non housebound, or nonimmigrant persons of either sex).
  3. Nonimmigrant women of childbearing age with such pain appeared to be at greatest risk for misdiagnosis or delayed diagnosis.
  4. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screening all outpatients with such pain for vitamin D deficiency should be standard practice in clinical care.

The Mayo Clinic Editorial of 2003 stated that the take-home message from the Plotnikoff and Quigley report was that when patients with nonspecific skeleton-muscular pain are evaluated, their serum 25-hydroxyvitamin D levels should be obtained. Doctors should disregard the laboratory reported lower limit of the normal range (20 ng/ml). A serum 25-hydroxyvitamin D level of at least 20 ng/ml is only necessary to minimally satisfy the body's vitamin D requirements. Maintenance of a serum 25-hydroxyvitamin D level of 30-50 ng/ml is preferred.

Fast forwarding to 2009, a report by Atherton et al published in the Annals of Rheumatic Diseases suggested that low levels of vitamin D may contribute to chronic pain among women. The study objective was to examine the association between vitamin D status and chronic widespread pain in a nationwide population sample of white British adults.

Among the 7,000 men and women aged 45 that were studied, those who were smokers, non-drinkers, the overweight and the underweight all reported higher rates of chronic pain. Among the women in the study, vitamin D levels appeared to be important. Women with vitamin D serum levels less than 25 ng/ml had the highest rates of chronic pain at 14.4%. Women with high levels of vitamin D (75-99 ng/ml) had the lowest rates of chronic pain, at just over 8%. For women, the association between vitamin D serum levels and chronic pain persisted after adjusting for lifestyle and social factors. No evidence for an association between vitamin D levels and chronic pain was apparent in men after adjusting for the same factors. The authors also indicated that osteomalacia did not account for their findings in women. They concluded that vitamin D status was associated with chronic widespread pain in women but not in men.

The full report is found at Atherton K., Berry D.J., Parsons T. et al. Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from across-sectional population survey. Ann Rheum Dis 2009; 68(6):817-22.

In view of the findings described above, two questions remain of importance - do vitamin D supplements help in the management of persistent, nonspecific pain? And is there a mechanism proposed to explain the possible association between vitamin D deficiency and chronic widespread musculoskeletal pain?

To answer the first question, three studies suggest that vitamin D supplement might be of minor benefit in managing the pain described.

In a study by Arvold et al in 2009, it was reported that vitamin D deficient patients with musculoskeletal pain and symptoms of fibromyalgia pain showed mild short term improvement after receiving vitamin D3 supplements.

Adult primary care patients were screened for vitamin D deficiency. Participants completed a questionnaire documenting a variety of symptoms, vitamin D intake and selected medical conditions. Those (N=100) with vitamin D deficiency (10-12 ng/ml) participated in a randomized controlled trial of vitamin D replacement and the change in symptoms. They received 50,000 units of vitamin D3 weekly or a placebo for 8 weeks. The treated group showed significantly greater improvement in fibromyalgia assessment scores than the placebo group. Those with severe deficiency (<10 ng/ml) (N=38) were treated with the same vitamin D regimen and this group had no symptom improvement with the vitamin D treatment.

The complete report is found at Arvold D.S. et al. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial Endocr Pract 2009; 15(3): 203-212.

In another study out of the Netherlands by Schreuder et al, they found an improvement in self assessment pain 6 weeks after administration of a single high dose of 150,000 units of vitamin D3 in non-Western immigrants having vitamin D deficiency. This study was a semi-crossover randomized controlled trial between February 2008 and February 2010 in primary care in 84 non-Western immigrants visiting their general practitioner for nonspecific musculoskeletal pain. At baseline, patients received either placebo or vitamin D with an oral dose of 150,000 units (specially prepared by the pharmacy). At 6 weeks, those in the original vitamin D group were randomized a second time to receive vitamin D (again) or switch to placebo, whereas patients in the original placebo group were all switched to vitamin D. The outcome was self assessed change in pain after the first 6 weeks.

The results showed that patients in the vitamin D group were significantly more likely than those in the placebo group to report pain relief 6 weeks after treatment (35% vs. 20%). The former were also more likely to report an improved ability to walk stairs. In addition, in a nonsignificant trend, patients receiving vitamin D again at the 6 week point, were more likely to have an improvement when measured at the 12 week point compared to those patients receiving the placebo.

That complete report is found at Schreuder F. et al. Vitamin D supplementation for nonspecific musculoskeletal pain in non-Western immigrants: a randomized controlled trial. Ann Fam Med 2012 10(6):547-55.

The third study was by Huang et al from the Atlanta VA Medical Center in Decatur GA and Emory University School of Medicine. They found that standardized vitamin D supplementation in veterans with multiple areas of chronic pain can be effective in improving their pain levels, sleep, and various aspects of quality of life. A case series was performed as an outpatient vitamin D supplementation quality improvement project. A total of 28 U.S. veterans with multiple areas of chronic pain and low serum vitamin D level (<30 ng/ml) concentrations at baseline were identified from May 2009 to November 2010. Study subjects were supplemented with vitamin D 1,200 units daily if vitamin D serum levels were in the insufficient range (20-29 ng/ml) or 50,000 units weekly if serum levels were in the deficient range (<20 ng/ml). Standard outcome measures were assessed before and after supplementation including pain assessed by the 0 to 10 pain score.

The results showed that pain, sleep and quality of life all improved. The improvements remained significant in pain score, sleep latency and duration, and bodily pain after controlling for age, sex, race, body mass index, season, baseline serum concentration subgroup, and whether or not participants received additional intervention during the vitamin D supplementation.

That complete report is found at Huang W. et al. Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation. Clin J Pain 2012 June 13.

Is there a mechanism proposed to explain the possible association between vitamin D deficiency and chronic widespread musculoskeletal pain?

There is an interesting report found at Tague S.E. et al. Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. Journal of Neuroscience 2011 (31(39):13728-13738. They prefaced their study by stating that a substantial body of clinical data implicates vitamin D deficiency in nonspecific musculoskeletal pain. Previous findings have shown that pain sensing nerves express vitamin D receptors, suggesting responsiveness to vitamin D supplementation. In their study, rats receiving vitamin D deficient diets for 2 - 4 weeks showed deep muscle hypersensitivity. The muscle hypersensitivity was accompanied by continued vitamin D deficiency and occurred before onset of any overt muscle or bone pathology. Further evaluation of skeletal muscle innervations showed increased numbers of pain-conducting axons without changes in skeletal muscle motor innervations. Their findings suggested that vitamin D deficiency can lead to pain receptor hyper-innervations of skeletal muscle which in turn is likely to contribute to muscular hypersensitivity and musculoskeletal pain.

Final comments - from Mayo clinic editorial of 2003

Many experts agree that a substantial body of clinical data implicates vitamin D deficiency in nonspecific musculoskeletal pain. Prevention of vitamin D deficiency not only may preserve bone and muscle health, but may help prevent many chronic diseases and preserve overall health and well being.