Background/Purpose: Bone marrow lesions (BMLs) are important contributors to pain and progression of knee OA. There has been recent interest in bisphosphonates as a potential disease modifier through amelioration of BMLs; however, there is theoretical concern that long-term suppression of bone turnover may be detrimental to healing of BMLs. One randomized controlled trial demonstrated beneficial effects of intravenous zoledronic acid on BML volume at 6 months, though this effect was no longer statistically significant at 12 months. We sought to determine the effect of commonly prescribed oral bisphosphonates on BML volume over 12 months.

Methods: We identified women in the Osteoarthritis Initiative who newly initiated an oral bisphosphonate (alendronate or risedronate) and who had a MRI at the visit at which they reported initiating a bisphosphonate as well as the following clinic visit (i.e., 12 months later) after initiation. We excluded women who reported use of other bone-active agents, such as PTH, calcitonin, or raloxifene. We propensity-score matched (see Table for covariates) bisphosphonate initiators to women who did not initiate bisphosphonate use with greedy matching, and used multiple imputation to address missing covariate data. BML volume was assessed using the sagittal turbo spin echo fat-suppressed intermediate-weighted MR images (slice thickness 3mm). A validated semi-automated process was used to segment the subchondral OA-related BMLs in the distal femur and proximal tibia to determine the total volume of BMLs based upon the number of voxels (0.382 mm³) within the outlined region of interest (intra- and inter-reader reliability: 0.96, 0.97, respectively). We evaluated the mean change in BML volume over 12 months among the bisphosphonate initiators compared with the non-initiators using multiple linear regression, as well as by proportion with changes in BMLs over 12 months.

Results: We identified 145 bisphosphonate initiators, who were well-matched to their comparators (mean age 65, mean BMI 26.2). A similar proportion of bisphosphonate initiators and non-initiators had BMLs at their index visit (51% vs. 47%, p=0.3). The proportion of subjects with decrease, increased, or unchanged BML volumes over time were similar in both groups, though there was a trend towards decreased BMLs in the bisphosphonate initiators (Table). However, mean change in total BML volume for the whole sample, regardless of presence of baseline BMLs, was not significantly different between the two groups (difference in mean change in total BML volume: 98.8mm3, 95% CI -156.6 to +354.2, p=0.4).

Conclusion: In this ‘real-world’ setting of women starting bisphosphonates, we found no clear evidence of benefit or harm of oral bisphosphonate use over a 12-month period on BML volume. Longer term follow-up is likely necessary to better appreciate the effects of bisphosphonates on BMLs in knee OA.