Objectives: A recent meta-analysis suggested that bisphosphonates may be beneficial for patients with knee osteoarthritis (OA) and high bone turnover. This study aimed to summarise effects of intravenous bisphosphonates (IVBP) on knee pain, function, bone marrow lesion (BML) size, and safety outcomes in randomised controlled trials (RCTs) of older adults with symptomatic knee OA and a marker of high bone turnover (BMLs), compared to placebo.
Methods: Web of Science, PubMed, EMBASE, MEDLINE were searched for RCTs of IVBP’s for knee OA. Methodological quality was assesed using the Cochrane risk of bias tool. Outcomes included change in knee pain (visual analog scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)), knee function (WOMAC, Knee injury and osteoarthritis outcome score (KOOS)), BML size, and incidence of adverse events. Efficacy was compared using standard mean difference (SMD) and risk ratios (RR) with fixed-effect or random-effects models.
Results: 428 patients in 4 RCTs of 2-24 months duration were included. Two studies used zoledronic acid alone, one zoledronic acid plus intravenous methylprednisolone and one neridronate. Risk of bias of included studies was low-moderate. IVBP improved knee function within 3 months (3m) (SMD= -0.22 (95% CI -0.43,-0.01)) but not 6m (-0.15 (-0.53,0.23)) or 12m (-0.10 (-0.34,0.15)). IVBP did not improve knee pain (VAS: SMD= -0.21 (-0.57,0.15) at 6m, -0.06 (-0.30,0.19) at 12m; WOMAC: 0.21 (-0.62,0.21) at 6m, -0.03 (-0.28,0.21) at 12m), or BML size (SMD= -0.15 (-0.36,0.06) at 6m). Adverse effects (RR= 1.19 (1.0,1.41) occurred more frequently with IVBP. Heterogeneity was observed in all analyses excepting BML size.
Conclusion: IVBP gave more frequent adverse effects with no concomitant improvement in knee pain, or BML size compared to placebo. Overall, there was no benefit of IVBPs for treating people with knee pain and osteoarthritis.