Longitudinal loss of bone mineral density from the femoral neck was associated with prevalent knee osteoarthritis in an observational cohort study, lending support to the notion that osteoporosis treatments are worth further investigation for the prevention of osteoarthritis progression.
The study, led by Dr. Ji Y. Lee of the division of rheumatology at Tufts Medical Center, Boston, builds on previous research that loss of bone mineral density (BMD) is associated with the progression of radiographic joint space narrowing. The current study is the first to examine the relationship between BMD and knee osteoarthritis (OA) progression as measured by cartilage volume and thickness on MRI, providing a more sensitive measure of changes in knee cartilage (Arthritis Rheum. 2013 March 12 [doi:10.1002/art.37926]).
The study contrasts with previous research, which has shown a positive relationship between BMD and incident or prevalent radiographically measured knee OA. Other past studies have found no relationship between BMD and radiographic progression of OA or a paradoxical opposite relationship in which low BMD predicted radiographic progression, according to Dr. Lee and associates.
Because previous studies included patients who already had OA, there may have been selection bias (collider confounding) in which the variables of interest – BMD and cartilage volume and thickness – were affected by the same factors. Dr. Lee and colleagues hoped to avoid this selection bias by studying the effect of risk factors that change after disease onset – in this case, change in BMD.
The investigators analyzed a cohort of 127 patients with prevalent knee OA, defined as a Kellgren-Lawrence grade of 2 or more. The patients had at least two MRI scans over a 2-year period, but most had three scans: at baseline and at 1 and 2 years. The patients (41% men) had a mean age of 63 years and mean body mass index (BMI) of 30 kg/m2. Baseline BMD averaged across two femoral neck measurements was 0.95 g/cm2.
In multivariate linear regression models – adjusted for baseline values of age, gender, BMI, alignment status, and vitamin D treatment – BMD loss of 0.1 g/cm2 was associated with a 1.25% per year loss of cartilage volume. For patients who lost BMD at a rate considered to be significant (calculated by the investigators to be a loss of at least 4.7% from baseline), cartilage volume loss was 1.02% per year greater than for patients without BMD loss.
The models also showed that a BMD loss of 0.1 g/cm2 was associated with a significant loss of cartilage thickness at the tibia (0.028 mm/year). Those who lost at least 4.7% of BMD lost a mean of 0.021 mm in tibial cartilage thickness per year, compared with those who did not lose BMD, the investigators reported.
Baseline BMD, however, was not significantly associated with any cartilage outcomes in the study.
The biological mechanisms conjectured to link systemic BMD to cartilage loss in knee OA include the possibility that "BMD health might provide an environment that supports optimal subchondral bone turnover and remodeling in response to OA stressors, thus favoring joint stabilization" and the beneficial effect that optimal bone health might have on cartilage health via "humoral mechanisms," Dr. Lee and colleagues wrote. "Systemic BMD could also be a marker for a range of covariates that mediate or confound the relationship, such as systemic inflammation, circulating growth factors or hormones, physical activity, or frailty."
The original trial from which the observational cohort was derived, the Randomized Controlled Trial of Vitamin D for Knee OA, was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. None of the authors had financial disclosures to report.