A 24-month Study Evaluating the Efficacy and Safety of Denosumab for the Treatment of Men With Low Bone Mineral Density: Results From the ADAMO Trial.
; ; et al
in The Journal of clinical endocrinology and metabolism (2015), 100(4), 1335-1342
Context: One in 4 men in the US aged >50 will suffer an osteoporosis-related fracture. Less data are available on osteoporosis treatment in men than women. Objective: Evaluate denosumab therapy in men ... [more ▼]
Context: One in 4 men in the US aged >50 will suffer an osteoporosis-related fracture. Less data are available on osteoporosis treatment in men than women. Objective: Evaluate denosumab therapy in men with low BMD. Design: Phase 3 study with two treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. Setting: Multicenter in North America and Europe. Participants: 228 men entered the open-label phase and 219 completed the study. Intervention: Men from the original denosumab (long-term) and placebo (crossover) groups received denosumab 60 mg SC every 6 months. Main Outcome Measures: BMD, serum C-telopeptide (sCTX), and safety. Results: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine; 0.9% total hip; 1.3% femoral neck; 1.3% trochanter; and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P<0.01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to the long-term denosumab group during the first treatment year. Significant reductions in sCTX were observed following denosumab administration. Adverse events rates were similar between groups and no new safety signals identified. Conclusions: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and men with prostate cancer on androgen deprivation therapy. [less ▲]Detailed reference viewed: 59 (6 ULg)
Clinically meaningful effect of strontium ranelate on symptoms in knee osteoarthritis: a responder analysis
Bruyère, Olivier ; Reginster, Jean-Yves ; et al
in Rheumatology (2014), 53
Objectives. The aim of this study was to assess the efficacy of strontium ranelate in improving symptoms in knee OA. Methods. Symptoms were assessed over 3 years in patients with primary knee OA receiving ... [more ▼]
Objectives. The aim of this study was to assess the efficacy of strontium ranelate in improving symptoms in knee OA. Methods. Symptoms were assessed over 3 years in patients with primary knee OA receiving strontium ranelate 2 g/day (n = 454), 1 g/day (n = 445) or placebo (n = 472) in the Strontium Ranelate Efficacy in Knee Osteoarthritis Trial. Clinical response was evaluated using WOMAC subscores, minimal perceptible clinical improvement (MPCI), minimal clinically important improvement (MCII) and a modified OMERACT Osteoarthritis Research Society International (OARSI) responder definition. Patients who withdrew prematurely from the study were considered non-responders. Results. There was no significant effect on symptoms for strontium ranelate 1 g/day. At the dosage of 2 g/day, strontium ranelate was associated with greater response than placebo in terms of 520% improvement in WOMAC pain from baseline to the last visit (58% vs 47%, P = 0.002) and 550% improvement in WOMAC pain (42% vs 36%, P = 0.083). Significant differences were found in MPCI response for WOMAC pain (52% vs 40%, P<0.001), stiffness (47% vs 39%, P = 0.009) and physical function (46% vs 37%, P = 0.009) and in MCII response for WOMAC physical function (46% vs 37%, P = 0.013). There were also more OMERACT-OARSI-like responders with strontium ranelate (44% vs 35%, P = 0.004). The treatment placebo difference in MPCI response for WOMAC pain was significant after 6 months (P = 0.024), while that in MPCI and MCII response for WOMAC physical function reached significance after 12 months (P = 0.027 and P = 0.019, respectively). Conclusion. Treatment with strontium ranelate 2 g/day over 3 years is associated with a clinically meaningful improvement in pain from 6 months as well as physical function and stiffness as assessed by the number of responders above thresholds of clinical relevance. [less ▲]Detailed reference viewed: 35 (14 ULg)
What is the predictive value of MRI for the occurrence of hard clinical endpoints in knee osteoarthritis?
; ; et al
in Osteoporosis International (2013, April), 24(Suppl.1), 84-85Detailed reference viewed: 14 (0 ULg)
What is the value of biomarkers for drug development in osteoarthritis?
; ; et al
in Osteoporosis International (2013, April), 24(Suppl.1), 77-78Detailed reference viewed: 27 (5 ULg)
The Effect of 3 or 6 Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension.
; ; et al
in The Journal of clinical endocrinology and metabolism (2013)
Context:The FREEDOM extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years.Objective:Report results from the first 3 years of the extension, representing up to 6 years ... [more ▼]
Context:The FREEDOM extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years.Objective:Report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure.Design, Setting, and Participants: Multicenter, international, open-label study of 4550 women.Intervention:Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (cross-over).Main Outcome Measures:Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety.Results:Reductions in BTMs were maintained (long-term) or achieved rapidly (cross-over) following denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the cross-over group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below rates projected for a "virtual placebo" cohort. In the cross-over group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of ONJ confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture.Conclusion:Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low. [less ▲]Detailed reference viewed: 29 (2 ULg)
Assessment of joint space narrowing in knee osteoarthritis has good long-term intercentre reproducibility when read in pairs with a semi-automated device
; DEROISY, Rita ; et al
in Osteoporosis International (2012, March), 23(Suppl. 2), 247-248Detailed reference viewed: 23 (8 ULg)
Long-term (3 years) reproducibility for the radiological assessment of knee osteoarthritis
DEROISY, Rita ; Bruyère, Olivier ; et al
in Osteoporosis International (2012, March), 23(Suppl. 2), 219-220Detailed reference viewed: 17 (5 ULg)
Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis: rationale and design of randomised, double-blind, placebo-controlled trial.
; REGINSTER, Jean-Yves ; et al
in Current Medical Research & Opinion (2012), 28(2), 231-9
Abstract Objective: The osteoporosis drug strontium ranelate dissociates bone remodelling processes. It also inhibits subchondral bone resorption and stimulates cartilage matrix formation in vitro ... [more ▼]
Abstract Objective: The osteoporosis drug strontium ranelate dissociates bone remodelling processes. It also inhibits subchondral bone resorption and stimulates cartilage matrix formation in vitro. Exploratory studies in the osteoporosis trials report that strontium ranelate reduces biomarkers of cartilage degradation, and attenuates the progression and clinical symptoms of spinal osteoarthritis, suggesting symptom- and structure-modifying activity in osteoarthritis. We describe the rationale and design of a randomised trial evaluating the efficacy and safety of strontium ranelate in knee osteoarthritis. Research design, methods, and results: This double-blind, placebo-controlled trial (98 centres, 18 countries) includes ambulatory Caucasian men and women aged >/=50 years with primary knee osteoarthritis of the medial tibiofemoral compartment (Kellgren and Lawrence grade 2 or 3), joint space width (JSW) 2.5 to 5 mm, and knee pain on most days in the previous month (intensity >/=40 mm on a visual analogue scale). Patients are randomly allocated to three groups (strontium ranelate 1 or 2 g/day, or placebo). Follow-up is expected to last 3 years. The primary endpoint is radiographic change in JSW from baseline in each group versus placebo. The main clinical secondary endpoint is WOMAC score at the knee. Safety is assessed at every visit. It is estimated that 1600 patients are required to establish statistical significance with power >90% (0.2 mm +/- 10% between-group difference in change in JSW over 3 years). Recruitment started in April 2006. The results are expected in spring 2012. Clinical trial registration: The trial is registered on www.controlled-trials.com (number ISRCTN41323372). Conclusions: This randomised, double blind, placebo-controlled study will establish the potential of strontium ranelate in improving structure and symptoms in patients with knee osteoarthritis. [less ▲]Detailed reference viewed: 159 (14 ULg)