BOSTON, Massachusetts—The possibility that vitamin D deficiency might contribute to the incidence or progression of osteoarthritis (OA) is theoretically attractive (because of the relationship of vitamin D to healthy remodeling of subchondral bone) and has been supported by epidemiologic studies reporting a worse course of OA in subjects with low vitamin D levels.1,2 However, David T. Felson, MD, MPH, and colleagues report data from two longitudinal cohort studies that reach a different conclusion.3

"The findings indicate that vitamin D status is unrelated to the risk of joint space or cartilage loss in knee OA." —David T. Felson, MD, MPH.
"The findings indicate that vitamin D status is unrelated to the risk of joint space or cartilage loss in knee OA," writes Dr. Felson, of Boston University School of Medicine, in Massachusetts. His conclusion is based on data from 715 subjects in the Framingham Osteoarthritis Study and 277 subjects in the Boston Osteoarthritis of the Knee Study (BOKS).

Dr. Felson told CIAOMed that the lack of association between vitamin D status and knee OA progression was the investigators' most important finding. He also said that this analysis suggests that the conclusions from the McAlindon et al1 epidemiologic studies, which he coauthored, and those by Lane et al2 "were probably incorrect."

Patients from Framingham and BOKS cohorts

In the current study, the investigators measured 25(OH)D levels in subjects from the Framingham Osteoarthritis Study and from the BOKS study. Framingham patients had weight-bearing anteroposterior (AP) and lateral knee radiographs taken in the time period 1993–1994 and again in 2002–2005 (mean interval, 9 years), and blood was drawn for measurement of vitamin D status in 1992–2000. The BOKS patients all had symptomatic knee OA at study entry. They underwent fluoroscopically positioned semiflexed posteroanterior (PA) and lateral radiography of both knees and magnetic resonance imaging (MRIK) of the more symptomatic knee at baseline and again at 15 and 30 months. In these subjects, blood was drawn at each visit.

"Analyses focused on whether vitamin D levels, defined in tertiles or as deficient (25[OH]D<20 ng/mL) versus nondeficient, predicted worsening of OA," Dr. Felson writes.

This analyses showed no association of baseline 25(OH)D levels with radiographic worsening in either cohort.

"In fact, the risk of worsening was slightly, but not significantly, lower in persons with low levels of vitamin D than in persons with higher levels," the authors report. In addition, vitamin D levels in patients in the BOKS study were not related to cartilage loss seen on MRI.

Among the negative findings, the investigators report the following:

● No significant association of vitamin D level with disease worsening in the Framingham patients
● A higher risk of OA worsening among BOKS patients with high vitamin D levels
● No significant increase in joint space loss in Framingham patients with vitamin D deficiency
● No association of low vitamin D levels with osteophyte growth in either cohort
● No association between vitamin D levels and cartilage loss on MRI in the BOKS cohort

Nancy E. Lane, MD, lead author of the epidemologic study that measured incident changes of radiographic hip OA, is not convinced by the new study. Dr. Lane, director of the Aging Center and professor of medicine and rheumatology at the University of California at Davis Medical Center, in Sacramento, California, is a member of the CIAOMed Editorial Board.

Describing the Felson data as "interesting but not convincing," Dr. Lane said, "I believe vitamin D levels may influence cartilage change, but the time for the effect to be seen is probably greater [than the 4 years between vitamin D assay and radiography in the Framingham cohort.] Also, in the BOKS study, only 2-to-3 years of follow-up is probably just too short to be able to see an effect of vitamin D levels and risk of knee OA either up or down. This study sadly tells us very little," she added.

Dr. Lane's advice to clinicians is just to keep the patient's serum vitamin D levels in the normal range. "This will probably prevent, not accelerate OA," she said. Dr. Felson is essentially in agreement. With regard to a patient who has OA and is taking vitamin D supplements, Dr. Felson's advice would be to continue using vitamin D. "Vitamin D deficiency is common, and even if supplementing vitamin D does not help prevent cartilage loss, it could have other favorable health effects, like preventing osteoporosis or keeping muscles strong," he said.

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Reference

1. McAlindon TE, Felson DT, Zhang Y, et al. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med. 1996;125:353–359.
2. Lane NE, Gore LR, Cummings SR, et al, for the Study of Osteoporotic Fractures Research Group. Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: a longitudinal study. Arthritis Rheum. 1999;42:854–860.
3. Felson DT, Niu J, Clancy M, et al. Low levels of vitamin D and worsening of knee osteoarthritis. Results of two longitudinal studies. Arthritis Rheum. 2007;56:129–136.