Hypovitaminosis D

Research Title: Hypovitaminosis D in non-elderly, non-disabled, immigrant and non-immigrant primary care outpatients with persistent non-specific musculoskeletal pain

Principal Investigator: Gregory A. Plotnikoff, MD, MTS, Center for Spirituality and Healing, University of Minnesota 

Co-Investigator: Joanna Quigley, Carleton College

Source:  University of Minnesota Departments of Internal Medicine and Pediatrics and the Center for Spirituality and Healing (www.csh.umn.edu) Minneapolis, Minnesota USA

Introduction

Vitamin D deficiency is prevalent throughout the developed world in elderly, homebound and southern-to-northern latitude immigrant patients. Although several factors are known to contribute to Vitamin D deficiency, such as race, age and lack of sun exposure (due to sunscreen, work hours, pollution, clothing, season, and latitude), Vitamin D status is presumed to be adequate in all young, ambulatory, non-immigrant patients. Vitamin D deficiency is widely considered to be asymptomatic in adults. However, this deficiency has been associated with non-specific bone pain and muscle weakness.

Purpose

To determine the incidence of hypovitaminosis D in non-elderly, non-disabled immigrant and non-immigrant patients with persistent, non-specific musculoskeletal pain syndrome refractory to standard therapies.

Method

Serum 25-hydroxyvitamin D3 levels were obtained by radioimmunoassay in 142 immigrant (n=78) and non-immigrant (n=64) patients between the ages of 10 and 65 who presented in 2000-2002 to a primary-care community clinic with more than 2 months of non-diagnostic, refractory musculoskeletal pain.

The subjects in this study did not have any known medical condition that would result in decreased production, absorption or hydroxylation of Vitamin D. Nor were they known to have any condition associated with decreased action or increased clearance of 1,25-dihydroxyvitamin D3. As numerous studies demonstrate, 20 ng/ml is the inflection point for PTH secretion; the lower threshold of normal serum 25-OH-Vitamin D3 levels was defined as 20 ng/ml.

Results

The incidence of hypovitaminosis D is unexpectedly high in this population of non-elderly, non-disabled primary-care patients with persistent, non-specific musculoskeletal pain refractory to standard pharmaceutical agents. One hundred percent (n=32) of East African immigrants, 100% of Hispanic immigrants (n=5) and 88% (36/41) of South East Asian immigrants with such pain demonstrated serum values = 20ng/ml (= 50nmol/L). Surprisingly, 100% of African American (n=20), 100% of Native American (n=10), and 82% of Caucasian (28/34) persistent pain patients also demonstrated hypovitaminosis D. Five subjects with severe pain had unmeasurable serum 25-OH-vitamin D3 levels (<3 ng/ml).

Hypovitaminosis D is not limited to southern-to-northern latitude immigrant populations. Contrary to expectations, Vitamin D deficiency may be as, or even more common in non-immigrant patients with persistent, non-specific, musculoskeletal pain. Although 17% (7/41) of the South East Asian subjects and 28% (9/32) of the East African subjects demonstrated profound or severe deficiency, 47% (14/30) of the African-American and Native American subjects did so as well. Non-immigrant patients account for 45% of the 142 subjects but represent 62.5% (5/8) of subjects with profound deficiency and 55% (18/33) of subjects with severe deficiency.

The degree of severity appears to be gender neutral. Twenty-eight percent (40/142) of the subjects are male and they represent 12/40 (30%) of the subjects with profound or severe deficiency. There is a marked discrepancy, however, between Muslim East African males and females.

The severity of the deficiency is disproportionate for age. Although 32/142 subjects (22.5%) are less than 30 years old, they represent 18/41 (44%) of the subjects with profound or severe deficiency. And although 100% of the subjects under age 30 and over age 60 were deficient, the younger subjects demonstrated significantly lower serum levels. Of the patients 30 or younger, 56% (18/32) demonstrated severe (= 8ng/ml, n=12) or profound (= 4ng/ml, n=6) deficiency. In contrast, only 9% (1/11) of the subjects over age 60 demonstrated such low serum levels. Four of the five subjects with unmeasurable serum 25-OH-Vitamin D3 levels are less than 35 years of age.

Season of measurement does not appear to significantly impact the measurements. Fisher exact test analysis of the 4 x 4 contingency table results in a p=0.46.

Discussion

Vitamin D deficiency in adults is considered to be both a rare and an occult disease. Widely recognized risk factors for Vitamin D deficiency in adults include advanced age, physical disability and immigrant status. This study suggests that hypovitaminosis D in healthy adults may not be rare and may result in non-specific musculoskeletal symptoms. Young, ambulatory, non-immigrant patients may also be deficient, even profoundly deficient.

Vitamin D is crucial for the prevention of osteoporosis, osteomalacia and fractures in the elderly. This study suggests that young people with persistent, non-specific musculoskeletal pain are at unexpectedly high-risk for loss of skeletal integrity.

This study suggests that all patients with persistent, non-specific musculoskeletal pain should be screened for hypovitaminosis D. Patients with unrecognized severe deficiency may be at risk for misdiagnosis and mistreatment of their pain condition.

This study also suggests that Vitamin D intake should be assessed and encouraged as part of routine preventive care in both immigrant and non-immigrant populations. Muslim women who adhere to traditional dress codes that require covering the head, arms and legs may require additional daily supplementation to prevent deficiency.

Conclusion

At 45º north, both immigrant and non-immigrant, young, ambulatory outpatients with persistent non-specific musculoskeletal pain demonstrated unexpectedly low serum Vitamin D levels. This is true for both genders, across all races and all age groups studied. Persistent, non-specific pain in primary-care patients may be attributable to hypovitaminosis D osteopathy. Such patients appear to be at high-risk for osteoporosis and other consequences of hypovitaminosis D. Screening for vitamin D deficiency should become a more standard practice in clinical care. Supplementation may be a very feasible and cost-effective public health intervention.

Several questions that now need to be answered include: 1) What is the background prevalence of hypovitaminosis D in young, asymptomatic outpatients?; 2) What is the prevalence of hypovitaminosis D in women of child-bearing age?; 3) Does pre-natal vitamin supplementation provide sufficient vitamin D?; and 4) Does Vitamin D replenishment result in decreased musculoskeletal symptoms?