Are Bisphosphonates Effective in the Treatment of Osteoarthritis Pain? A Meta-Analysis and Systematic Review

Abstract

ObjectiveOsteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment.MethodsLiterature databases were searched from inception to the 30th June 2012 for clinical trials of bisphosphonates to treat OA pain. Data was appraised and levels of evidence determined qualitatively using best evidence synthesis from the Cochrane Collaboration. The two largest studies were conducted with risedronate in the treatment of knee OA, for which meta-analyses were performed for pain and functional outcomes.ResultsOur searches found 13/297 eligible studies, which included a total of 3832 participants. The trials recruited participants with OA of the hand (n = 1), knee (n = 8), knee and spine (n = 3), or hip (n = 1). Our meta-analysis of the two largest knee studies using risedronate 15 mg showed odds ratios favouring placebo interventions for the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (1.73), WOMAC function (2.03), and WOMAC stiffness (1.82). However, 8 trials (61.5%) reported that bisphosphonates improve pain assessed by VAS scores and 2 (38.5%) reported significant improvement in WOMAC pain scores compared to control groups.ConclusionsThere is limited evidence that bisphosphonates are effective in the treatment of OA pain. Limitations of the studies we analysed included the differences in duration of bisphosphonate use, the dose and route of administration and the lack of long-term data on OA joint structure modification post-bisphosphonate therapy. Future more targeted studies are required to appreciate the value of bisphosphonates in treating osteoarthritis pain.Trial RegistrationPROSPERO Register CRD42012002541

MRI findings predict radiographic progression and development of erosions in hand osteoarthritis

“…Bisphosphonates target bone remodelling and can therefore reduce BMLs 35. Animal studies have shown conflicting evidence on whether bisphosphonates are preventing cartilage damage,40 41 and there is a lack of long-term data on OA joint structure modification postbisphosphonate therapy 42. The effect of bisphosphonates on structural progression in humans has been explored in one observational study only, showing a trend towards a beneficial effect that was not statistically significant 43.…”

Osteoarthritis and bone mineral density: are strong bones bad for joints?

“…However, in humans, two randomised controlled trials of risedronate for knee OA failed to demonstrate a significant reduction in JSN over time, 78,79 and similarly a recent systematic review concluded that there was limited evidence that bisphosphonates are an effective treatment option for pain in OA. 80 Following these negative studies, there has been a recent resurgence of interest in manipulating bone turnover for the treatment of OA following the publication of the SEKOIA trial of strontium ranelate for the treatment of knee OA. 81 This mixedgender, multicentre study demonstrated a reduction in the progression of JSN in the treatment group over a 3-year period, 81 and as such it has been heralded as the first positive Osteoarthritis and bone mineral density SA Hardcastle et al disease-modifying OA drug trial.…”

Hand Osteoarthritis — Clinical Presentation, Phenotypes and Management

“…intravenous clodronate in the treatment of hand OA with beneficial outcome for pain in their study [41]. However, a recent meta-analysis by our group did not show overall significant benefit overall for pain and function after use of bisphosphonates across several phenotype of OA, including hip, knee and hand [42]. Future studies targeted at specific stages of disease with proven synovitis and bone marrow lesions may be more helpful in establishing the potential future therapeutic use of bone-modulating agents in the clinic.…”