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Intravenous bisphosphonates do not improve knee pain or bone marrow lesions in people with knee osteoarthritis: a meta-analysis


Zhang, X and Cai, G and Jones, G and Laslett, LL, Intravenous bisphosphonates do not improve knee pain or bone marrow lesions in people with knee osteoarthritis: a meta-analysis, Rheumatology, 61, (6) pp. 2235-2242. ISSN 0080-2727 (2022) [Refereed Article]

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Copyright 2021 The Authors

DOI: doi:10.1093/rheumatology/keab786


Objective: To summarise effects of intravenous bisphosphonates (IVBP) in patients with symptomatic knee osteoarthritis (OA) and bone marrow lesions (BMLs), using a meta-analysis of randomized controlled trials (RCTs).

Methods: Literature databases were searched for placebo-controlled RCTs of IVBPs for knee OA from inception, and included validated pain and function scales, BML size, and incidence of adverse events. Efficacy was compared using standardized mean differences (SMD) and risk ratios (RR) with fixed-effect or random-effects models. Methodological quality was assessed using the Cochrane risk of bias tool, heterogeneity was assessed by I2 statistics.

Results: We included 428 patients in 4 RCTs of 224 months duration; most patients (84%) received zoledronic acid (ZA). Risk of bias was low-moderate. IVBP had large effect sizes on pain within 3 months (SMD= -2.33 (95% confidence interval= -3.02, -1.65)) mainly driven by neridronate (resulting in substantial heterogeneity, I2=92%) with no effect for ZA alone. Differences in knee function were statistically significant at 3 months (SMD=-0.22 (-0.43, -0.01), I2=0.2%). Effect sizes for pain did not reach statistical significance at any other time point. IVBPs improved a semi-quantitative measure of BML size within 6 months (SMD= -0.52 (-0.89, -0.14), I2=0%) but not at 12 months or two years. Adverse events (RR = 1.19 (1.00, 1.41) I2=52%), occurred more frequently with IVBP.

Conclusion: ZA has no effect on knee pain, possibly a short-term effect on BML size and higher rates of adverse events. Neridronate may improve pain in the short term, but this is based on a single trial.

Item Details

Item Type:Refereed Article
Keywords:bisphosphonates, knee, osteoarthritis, pain, trial, meta-analysis
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Rheumatology and arthritis
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Zhang, X (Mr Xu Zhang)
UTAS Author:Cai, G (Dr Guoqi Cai)
UTAS Author:Jones, G (Professor Graeme Jones)
UTAS Author:Laslett, LL (Dr Laura Laslett)
ID Code:147297
Year Published:2022 (online first 2021)
Funding Support:National Health and Medical Research Council (1070586)
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-25
Last Modified:2023-03-06

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