Bisphosphonates therapy for osteoarthritis: a meta-analysis of randomized controlled trials

Abstract

High-turnover type bone metabolism derangement has been considered to be one of the major causes of osteoarthritis (OA). Bisphosphonates can attach to hydroxyapatite binding sites on bony surfaces, particularly those which are undergoing active bone resorption. To evaluate the effectiveness of bisphosphonates in OA treatment, literature databases were searched from inception to February 28, 2016 for clinical studies of bisphosphonates for OA treatment. All randomized controlled trials in which bisphosphonates therapy was compared with a placebo or a conventional medication, were selected. 15/1145 studies were eligible for analysis, which included 3566 participants. Bisphosphonates therapy improved pain, stiffness and function significantly in OA assessed by the Western Ontario and McMaster Universities Arthritis Index scale (MD = 4.59; 95 % CI 2.83–6.34; P < 0.00001; MD = 1.43; 95 % CI 0.83–2.23; P = 0.0005; MD = 2.01; 95 % CI 1.27–2.75; P < 0.00001). Bisphosphonates also reduced osteophyte score significantly (MD = −0.51; 95 % CI −0.84 to −0.19; P = 0.002). However, no significant differences were found in subjective improvement, osteoarthritis progression, the number of required acetaminophen treatment or joint replacement. In conclusion, bisphosphonates therapy is effective in relieving pain,stiffness and accelerating functional recovery in OA. Limitations of the studies we analysed included the differences in duration of bisphosphonates use, the doses and types of bisphosphonates and the lack of long-term data on OA joint structure modification after bisphosphonates therapy. More targeted studies are required to evaluate on the effectiveness of bisphosphonates for OA treatment.

Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials

“…In addition to the biphasic nature of bone remodeling in OA, the rates of bone remodeling even at the early OA stages may differ between individuals; a novel diagnostic approach may be required to assess those rates and predict whether a patient would be a good candidate for the treatment with antiresorptive agents 55 . Our efficacy results disagree with prior meta-analyses, which presented positive conclusions about the effectiveness of bisphosphonates in OA 37,38 . The first publication, by Davis et al, 2013 reviewed both RCTs and observational studies performed in the knee, hip or spine OA patients but used only three RCTs in its meta-analyses (Spector 2005 and North American and European cohorts from Bingham et al, 2006, all studying oral risedronate in knee OA) 37 .…”

“…The second, most recent meta-analysis on the topic, by Xing et al, 2016 also arrived at a positive verdict on the efficacy of bisphosphonates in OA 38 . However, this study had major methodological flaws.…”

“…Consistent with the Evidence-Based Research Network approach, we searched for existing systematic reviews on this topic and assessed the available systematic reviews for their scope, quality, and currency 35 . Prior meta-analyses on the efficacy of bisphosphonates in OA indicated that bisphosphonates may have a positive, albeit limited effect on symptomatology of OA 37,38 . However, the aforementioned analyses had numerous, major methodological flaws, such as overlooking the lack of statistical significance of their assessments or confounding their results with the inclusion of non-randomized trials, patient populations with assorted OA sites, active comparators, and less common outcomes.…”

Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis

“…In a one-year, placebo-controlled trial that included 59 patients with knee OA treated with zoledronic acid 5 mg intravenously as a single infusion, a significant reduction in visual analogue pain scores versus placebo was seen after six months, but not after 12 months; interestingly, a significant reduction in bone marrow lesions was detected with magnetic resonance imaging (MRI) [ 108 ]. In a recent meta-analysis of randomised controlled trials that compared bisphosphonate therapy with placebo or conventional medication, Xing et al assessed the efficacy of bisphosphonates in OA; 15 studies were eligible for analysis and they included 3566 participants (1517 on bisphosphonates) [ 109 ]. It was shown that bisphosphonate therapy leads to significant improvements in pain, stiffness and function in OA patients assessed using the WOMAC score.…”

Of mice and men: converging on a common molecular understanding of osteoarthritis

“…Blocking bone remodelling with a bisphosphonate early in murine osteoarthritis development appears to block pain without affecting structural disease, according well with clinical studies in osteoarthritis in which bisphosphonates are not disease-modifying when given in established disease. 156 , 157 …”