Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

Abstract

BackgroundStrontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis.MethodsPatients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372).ResultsThe intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated.ConclusionsTreatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.

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

“…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. However, in contrast to the radiographic findings, a small beneficial effect on symptoms in this trial was confined to the group taking the higher (2 g per day) dose.…”

“…However, in contrast to the radiographic findings, a small beneficial effect on symptoms in this trial was confined to the group taking the higher (2 g per day) dose. 81 As discussed by Lafeber and van Laar 82 in their accompanying editorial, a number of questions remain to be addressed before strontium can be adopted clinically as a treatment for OA, and recent concerns regarding the cardiovascular safety of this drug may prove prohibitive in the patient group most in need; 83 nevertheless, these results lend further support to the concept of using pharmacotherapies targeting bone to treat OA.…”

Update on biological therapies for knee injuries: osteoarthritis

“…In 2 studies by Reginster et al [39,40] comparing strontium ranelate with placebo in patients with OA, strontium ranelate seemed to have positive effects, with less degradation of joint space width in the knee, especially with a dosage of 2 g daily. Despite these positive results, however, studies with longer follow-up are needed to determine the drug's safety with longterm use.…”

Managing osetoarthritis

“…50,51 However, in light of emerging data on cardiovascular risks, the potential benefits may not be justifiable. 52 Commercial stem cell therapies have recently emerged for knee osteoarthritis.…”