Vitamin D Supplements Fail to Slow Knee Osteoarthritis

Janis C. Kelly

January 16, 2013

Vitamin D deficiency may increase osteoarthritis (OA) risk, but using supplements to bring serum 25-hydroxyvitamin D levels into the normal range does not slow progression for people with symptomatic OA, according to results of a study published in the January 9 issue of JAMA.

Timothy McAlindon, MD, MPH, from the Division of Rheumatology, Tufts Medical Center, Boston, Massachusetts, and colleagues report that 2 years of vitamin D supplementation did not reduce knee pain, prevent cartilage loss, maintain physical function, or preserve radiographic joint space width compared with placebo.

The authors write, "The basis for considering that vitamin D might influence the course of knee OA arose from its known role in bone health, the importance of systemic and local bone changes in OA, and epidemiologic observations from some studies suggesting slower rates of OA progression among those with higher vitamin D levels."

They continue, "Therefore, our goal was to determine through performance of a clinical trial whether vitamin D supplementation is associated with reductions in symptomatic and structural progression of knee OA."

Their 2-year randomized, placebo-controlled, double-blind trial of vitamin D supplementation enrolled 146 participants with symptomatic knee OA between March 2006 and June 2009. Participants were randomly assigned to receive either placebo or oral cholecalciferol, 2000 IU/day, with dose escalation to increase serum levels to more than 36 ng/mL.

Eighty-five percent of the participants completed the study. In the treatment group, 61.3% of the group (vs 8.3% of the placebo group) achieved target plasma 25-hydroxyvitamin D levels of at least 36 ng/mL by month 24 (95% confidence interval [CI] of difference, 39.3% - 66.7%; P < .001). Serum 25-hydroxyvitamin D levels increased by a mean of 16.1 ng/mL (95% CI, 13.7 - 18.6 ng/mL) in the treatment group and by a mean of 2.1 ng/mL (95% CI, 0.5 - 3.7 ng/mL; P < .001) in the placebo group.

The primary measured outcomes for the study were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0 - 20; 0 being no pain and 20 being extreme pain) and cartilage volume loss, measured by magnetic resonance imaging. Secondary outcomes included physical function, knee function (WOMAC function scale, 0 - 68; 0 being no difficulty and 68 being extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width.

At baseline, the treatment group had slightly worse knee pain and significantly worse knee function than the placebo group. In both groups, effects on WOMAC pain outcome were similar and nonsignificant. In addition, in both groups, cartilage volume decreased by about 4% and was consistent for the tibial and femoral segments. There was also no significant difference in change in cartilage thickness, bone marrow lesions, or radiographic joint space width between both groups.

Adverse event rates were similar for the 2 groups.

The authors note that epidemiologic data have shown both positive and negative associations between vitamin D levels and OA progression but conclude that the overall data, including the results of this trial, "suggest that vitamin D supplementation at a dose sufficient to elevate 25-hydroxyvitamin D levels to more than 36 ng/mL does not have major effects on clinical or structural outcomes in knee OA, at least in a US sample."

Michael F. Holick, PhD, MD, reviewed the study for Medscape Medical News. Dr. Holick, who is professor of medicine, physiology, and biophysics at Boston University School of Medicine in Massachusetts, is the author of more than 400 publications about the biochemistry, physiology, metabolism, and photobiology of vitamin D and the pathophysiology of vitamin D deficiency.

Dr. Holick told Medscape Medical News, "I am not at all surprised by the finding [of this clinical trial]. There was no reason to believe that once the disease was initiated, vitamin D would reduce progression or pain associated with it. The more important message is that from the initial study from Framingham there was an association with increased risk for osteoarthritis and vitamin D deficiency. That should be the message, rather than believing that vitamin D can reverse the disease. The message to clinicians is simple: Everyone should improve their vitamin D status to reduce risk of chronic illnesses, including osteoarthritis."

Medscape Medical News attempted unsuccessfully to reach the investigators for comment.

This study was funded by a grant from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Office of Dietary Supplements; a grant from the National Center for Research Resources; and a grant from the Houston Veterans Affairs Health Services Research and Development Service. Dr. McAlindon has reported that he serves as a consultant for Flexion, Bioberica, and sanofi-aventis; is a board member of Osteoarthritis Research Society International; and has a patent for conducting clinical trials over the Internet, dividends for which are paid to the University of Florida. One coauthor has reported that he serves as a consultant for Sunovian Pharmaceuticals and is an associate editor of Arthritis Care & Research. One coauthor has reported that she serves as a consultant to ImageIQ, Merck, Johnson & Johnson, and the National Institutes of Health; owns stock in Pfizer and General Electric; and is founder of NitroSci Pharmaceuticals. The other authors and Dr. Holick have disclosed no relevant financial relationships.

JAMA. 2013;309:155-162. Abstract

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