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.
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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: 57 (6 ULg)
The Effect of 3 or 6 Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension.
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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)
Long-term denosumab treatment of postmenopausal women with osteoporosis: results from the first year extension study of the FREEDOM trial
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in Arthritis and Rheumatism (2010, October), 62(10), 903Detailed reference viewed: 73 (1 ULg)
Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study.
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in Journal of Rheumatology (2008), 35(3), 488-97
OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was ... [more ▼]
OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was designed to identify the optimal ibandronate IV injection schedule for the treatment of postmenopausal osteoporosis by comparing the efficacy and tolerability of 2- and 3-monthly injections with the previously evaluated daily oral ibandronate regimen. We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years. METHODS: This randomized, double-blind, double-dummy, noninferiority study recruited 1395 women (aged 55-80 yrs; > or = 5 yrs since menopause) with osteoporosis [mean lumbar spine (L2-L4) BMD T-score < -2.5 and > or = -5.0]. Patients received IV ibandronate (2 mg every 2 mo or 3 mg every 3 mo) plus daily oral placebo, or 2.5 mg daily oral ibandronate plus 2- or 3-monthly IV placebo. Supplemental vitamin D (400 IU) and calcium (500 mg) were provided throughout the 2-year study. RESULTS: At 2 years, the 2- and 3-monthly IV regimens achieved statistically noninferior and also superior increases in lumbar spine BMD compared with the daily regimen (6.4% and 6.3% vs 4.8%, respectively; p < 0.001). Greater increases were also obtained with IV ibandronate versus daily in proximal femur BMD. Serum concentrations of the biochemical marker of bone resorption C-telopeptide of the alpha-chain of type I collagen were reduced to a similar extent in all treatment arms (53.4%-59.9%). The tolerability profile of the IV regimens was similar to that observed with daily oral therapy. CONCLUSION: Ibandronate IV injections are an effective and well tolerated treatment for postmenopausal osteoporosis and provide a useful alternative to oral dosing. [less ▲]Detailed reference viewed: 19 (4 ULg)