Tuesday, November 16, 2010

Study Suggests Vitamin D May Not Benefit Knee OA

Conference NotesIn prior research reports [here] and blogposts [here] we have advocated for vitamin D supplementation as helping to relieve the pain of musculoskeletal and certain other conditions. However, in fair balance, new research raises important doubts about benefits of vitamin D specifically for lessening symptoms or slowing progression of knee osteoarthritis (OA).

According to research presented November 8, 2010, at the American College of Rheumatology Annual Scientific Meeting in Atlanta, Georgia, investigators in Boston enrolled 146 persons with symptoms of knee OA in a study to examine disease-modifying effects of vitamin D supplementation [McAlindon et al. 2010]. Participants were 57% female, 79% Caucasian, mean age 62 years and, on average, they were borderline obese (mean body mass index = 30.7 [BMI definitions here]). Although more than half (56%) were taking vitamin D supplements in unspecified amounts, their average vitamin D level was insufficient (mean=22.3 ng/mL).

During the trial funded by the U.S. National Institutes of Health subjects were randomly assigned to receive either placebo or 2000 IU/day of vitamin D, which was escalated as needed in 2000 IU increments at 3, 6, and 9 months to achieve a targeted vitamin D serum level of >30 ng/mL. Participants were equally distributed across the two groups by disease severity and both researchers and subjects were blinded to treatment condition (vitamin D vs placebo). Assessments included the WOMAC Index (Western Ontario and McMaster Osteoarthritis Index) at each visit, which is a 24-item self-report questionnaire focusing on joint pain, stiffness, and loss of function related to OA of the knee and hip. At the beginning of the study and at 12 months followup the researchers performed on each participant physical function tests, X-rays, tests of knee cartilage volume and thickness, and bone marrow lesion volume analyses taken from MRIs to determine if any changes had occurred.

At the end of the study, the participants in the vitamin D group had an average vitamin D level increase of 15 ng/mL compared with only 1.8 ng/mL in the placebo group, but researchers found no substantial or statistically significant differences between the two groups in any of the various outcomes measured. Therefore, they concluded that the vitamin D supplement intervention in this population of subjects was not advantageous for relieving OA symptoms or disease progression.

COMMENTARY: This was a long-term, well-designed, adequately powered trial to detect clinically important benefits of vitamin D supplementation for knee OA. Although it is available only in abstract form at present, it is the sort of research that we have been saying all along is necessary to confirm benefits of vitamin D for alleviating painful musculoskeletal conditions; therefore, the lack of positive outcomes is disappointing. However, there are some points worth considering.

The stepped strategy for increasing vitamin D levels via 2000 IU/day increments appeared to be effective and relatively safe. For example, the authors reported comparable adverse events in both groups, which were not specified but were unrelated to vitamin D therapy. However, the magnitude of serum vitamin D increases may not have been adequate to alleviate pain or disease progression (some practitioners advocate achieving 40-60 ng/mL 25[OH]D3 in persons with pain [eg, see blogpost here]). There was, indeed, a favorable change from baseline WOMAC pain scores in the vitamin D group — 78% greater than in the placebo group — however, the improvements were small in both cases and not significantly different between groups statistically. The researchers do not report on analgesic use, and it could be important to know if vitamin D supplementation resulted in a decreased need for pain medications during the trial. Many of the subjects were obese, which is a common comorbidity in hip and/or knee OA, and this might have played a role in curtailing vitamin D efficacy; the authors did not report a subgroup analysis comparing only subjects across groups who had more normal BMI scores.

Much of the prior research on vitamin D has included rather heterogenous groups of subjects with “widespread” and/or nonspecific pain, some involving various types of arthritis, and the optimal level of 25(OH)D3 for affording pain relief has not been clearly defined. Interestingly, Timothy McAlindon (lead author of the present study) and colleagues had previously (in 1996) reported that two-thirds of subjects with knee OA in an observational study had vitamin D levels <33 ng/mL. This was the only examination specifically of vitamin D in knee OA that we know of until this new research was reported. It is possible that OA of large weight-bearing joints, the knee or hip, particularly in overweight persons, is resistant to treatment with dietary supplements, as research on glucosamine and/or chondroitin for this condition has similarly demonstrated a lack of efficacy [eg, see blogpost here].

In sum… until further high-quality research is conducted, it may be prudent to temper expectations for what might be achieved via vitamin D supplementation for OA of the knee (and probably the hip). It still seems reasonable based on prior research that achieving more optimal vitamin D levels in patients with musculoskeletal pain conditions could be generally advantageous, with a favorable safety profile and modest cost; however, the extent and quality of benefits may depend on individual patient factors that need better definition.

REFERENCE: McAlindon TE, Dawson-Hughes B, Driban J, et al. Clinical Trial of Vitamin D To Reduce Pain and Structural Progression of Knee Osteoarthritis (OA). Arthritis & Rheumatism. 2010(Oct);62(10 Suppl):abstract 706 [conference abstracts PDF here see pp.S294-295].