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

in Annals of the Rheumatic Diseases (2013), 72(2), 179-86

BACKGROUND: Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its ... [more ▼]

BACKGROUND: Strontium 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. METHODS: Patients 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). RESULTS: The 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. CONCLUSIONS: Treatment 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. [less ▲]

Treatment of osteoporosis in men.

in BONE (2013), 53(1), 134-44

SUMMARY: Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline ... [more ▼]

SUMMARY: Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline) are discussed. INTRODUCTION: Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men and to provide a report by a panel of experts (the authors). METHODS: A debate with an expert panel on preselected topics was conducted. RESULTS AND CONCLUSIONS: Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds. Empirical data in men display similarities with data acquired in women, despite pathophysiological differences, which may not be clinically relevant. Men should receive treatment at a similar 10-year fracture probability as in women. The design of mixed studies may reduce the lag between comparable treatments for osteoporosis in women becoming available in men. [less ▲]

Structure modifying effects of strontium ranelate in knee osteoarthritis

in Osteoporosis International (2012, March), 23(S2), 58-59

Strontium ranelate and risk of venous thromboembolism (VTE) : an update of a retrospective cohort study in the UK general practice research database (GPRD)

in Osteoporosis International (2012, March), 23(S2), 364-365

Clinically meaningful effect of strontium ranelate on knee osteoarthritis symptoms

in Arthritis and Rheumatism (2012), 64(S10), 110

Antidepressant medications and osteoporosis

in BONE (2012), 51

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

in Annals of the Rheumatic Diseases (2012), 71(3), 693

A reappraisal of generic bisphosphonates in osteoporosis.

in Osteoporosis International (2012), 23

The competitive price of generic bisphosphonates has had a marked effect on practice guidelines, but an increasing body of evidence suggests that they have more limited effectiveness than generally ... [more ▼]

The competitive price of generic bisphosphonates has had a marked effect on practice guidelines, but an increasing body of evidence suggests that they have more limited effectiveness than generally assumed. INTRODUCTION: The purpose of this study is to review the impact of generic bisphosphonates on effectiveness in the treatment of osteoporosis. METHODS: This study is a literature review. RESULTS: A substantial body of evidence indicates that many generic formulations of alendronate are more poorly tolerated than the proprietary preparations which results in significantly poorer adherence and thus effectiveness. Poorer effectiveness may result from faster disintegration times of many generics that increase the likelihood of adherence of particulate matter to the oesophageal mucosa. Unfortunately, market authorisation, based on the bioequivalence of generics with a proprietary formulation, does not take into account the potential concerns about safety. The poor adherence of many generic products has implications for guideline development, cost-effectiveness and impact of treatment on the burden of disease. CONCLUSIONS: The impact of generic bisphosphonates requires formal testing to re-evaluate their role in the management of osteoporosis. [less ▲]

Partial adherence: a new perspective on health economic assessment in osteoporosis.

in Osteoporosis International (2011), 22(10), 2565-73

Partial adherence in osteoporosis increases the risk for fragility fracture and has considerable impact on cost-effectiveness. This review highlights a number of avenues for further research, such as ... [more ▼]

Partial adherence in osteoporosis increases the risk for fragility fracture and has considerable impact on cost-effectiveness. This review highlights a number of avenues for further research, such as improved definition of thresholds of compliance and persistence, as well as gap length, offset times, and fraction of benefit. INTRODUCTION: A number of economic models have been developed to evaluate osteoporosis therapies and support decisions regarding efficient allocation of health care resources. Adherence to treatment is seldom incorporated in these models, which may reduce their validity for decision-making since adherence is poor in real-world clinical practice. METHODS: An ad hoc working group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review key issues concerning the incorporation of partial adherence in health economic models. RESULTS: Observational data have shown that poor adherence is associated with an increase in the risk for fragility fracture. Health economic modelling indicates that full adherence is associated with more quality-adjusted life years gained than partial adherence, as well as higher treatment costs and lower fracture-related costs. Although adherence appears as an important driver of cost-effectiveness, the effect is dependent on a range of other variables, such as offset time, fraction of benefit, fracture risk, fracture efficacy, fracture-related costs, and drug cost, some of which are poorly defined. Current models used to evaluate cost-effectiveness in osteoporosis may oversimplify the contributions of compliance and persistence. CONCLUSION: Partial adherence has a significant impact on cost-effectiveness. Further research is required to optimise thresholds of compliance and persistence, the impact of gap length, offset times, and fraction of benefit. [less ▲]

Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database.

in Osteoporosis International (2010), 21

In a retrospective cohort study using the General Practice Research Database (GPRD), there was a greater association of venous thromboembolism (VTE) in osteoporotic than in non-osteoporotic female ... [more ▼]

In a retrospective cohort study using the General Practice Research Database (GPRD), there was a greater association of venous thromboembolism (VTE) in osteoporotic than in non-osteoporotic female patients. No greater association was shown in treated patients with strontium ranelate or alendronate compared to untreated osteoporotic female patients. INTRODUCTION: We explored the risk of VTE in usual practice in osteoporotic and non-osteoporotic women with and without anti-osteoporotic treatment. METHODS: A retrospective study was conducted using the GPRD in the UK. The cohorts consisted of untreated osteoporotic women (N = 11,546), osteoporotic women treated with alendronate (N = 20,084), or strontium ranelate (N = 2,408), and a sample of non-osteoporotic women (N = 115,009). Cohorts were compared using a Cox proportional hazards regression model. RESULTS: There was a significantly increased relative risk for VTE in untreated osteoporotic women versus non-osteoporotic women (annual incidence 5.6 and 3.2 per 1,000 patient-years, respectively; relative risk 1.75 [95% confidence interval (CI), 1.09-1.84]). Results were confirmed using adjusted models. The annual incidences of VTE in osteoporotic patients treated with strontium ranelate and alendronate were 7.0 and 7.2 per 1,000 patient-years, respectively, with no significant difference between untreated and treated patients whatever the treatment. Adjusted hazard ratios for treated versus untreated osteoporotic women were 1.09 (95% CI, 0.60-2.01) for strontium ranelate and 0.92 (95% CI, 0.63-1.33) for alendronate. CONCLUSION: This study shows a greater association of VTE in osteoporotic compared to non-osteoporotic patients, but does not show any greater association in treated patients with strontium ranelate or alendronate compared to untreated osteoporotic patients. [less ▲]