Intra-articular clodronate for the treatment of knee osteoarthritis: dose ranging study vs hyaluronic acid.

OBJECTIVE Bisphosphonates may have a chondroprotective effect in patients with knee OA (KOA), but the results of clinical trials with oral bisphosphonates have been contradictory. In this Phase 2 randomized, partially blind clinical trial, we tested the efficacy of IA clodronate vs HA in patients with primary KOA. METHODS One hundred and fifty men or women aged 50-75 years suffering from KOA were randomized to one of five IA therapies: (i) clodronate 0.5 mg one IA injection/week for 4 weeks; (ii) clodronate 1 mg one IA injection/week for 4 weeks; (iii) clodronate 2 mg one IA injection/week for 4 weeks; (iv) clodronate 1 mg two IA injections/week for 2 weeks (clodronate 1 + 1 mg); and (v) HA 20 mg one IA injection/week for 4 weeks. RESULTS Visual analogue scores (VASs) for different types of pain and the Lequesne index significantly improved in all treatment groups after the first injection and continued to improve even 2-4 weeks after the last injection without significant difference among the groups. A significant (P = 0.03) linear trend for a dose-response (0.5-2 mg clodronate) relationship was found for active movement VAS pain. Both joint extension and mobility scores improved significantly at all time points in all treatment groups without statistical differences among them. CONCLUSIONS This study indicates that IA clodronate provides symptomatic and functional improvements at least as good as those obtained with HA. Trial Registration. Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali - Agenzia Italiana del Farmaco. Comitato Etico Azienda Ospedaliera Universitaria Senese number CLIO 22/02 http://oss-sper-clin.agenziafarmaco.it.