The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study

The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. INTRODUCTION: This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. METHODS: Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. RESULTS: Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. CONCLUSIONS: Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile

Evaluation of patients with a recent clinical fracture and osteoporosis, a multidisciplinary approach

The aetiology of osteoporotic fractures is multifactorial, but little is known about the way to evaluate patients with a recent clinical fracture for the presence of secondary osteoporosis

Treatment Satisfaction in Postmenopausal Women Previously Treated with Bisphosphonates Who Transitioned to Denosumab Vs Ibandronate Therapy in an Open-Label Study

Background/Purpose: Higher treatment satisfaction is associated with greater persistence with osteoporosis therapy in postmenopausal women (Barrett-Connor OI 2012). Greater satisfaction has been reported with subcutaneous injections of denosumab compared with oral alendronate tablets in a randomized, cross-over study where subjects received both treatments (Freemantle OI 2012). In this open-label trial, we evaluated treatment satisfaction in postmenopausal women with low bone mineral density (BMD) who were sub-optimally treated with prior bisphosphonate therapy and were transitioned to denosumab or ibandronate. Methods: This was a multicenter, randomized, open-label, parallel-group study in which postmenopausal women aged 55 and older were randomized 1:1 to receive open-label denosumab 60 mg subcutaneously every 6 months or ibandronate 150 mg orally every month for 12 months. The treatment satisfaction questionnaire for medication (TSQM) version 1.4 was given at baseline and months 6 and 12 or at time of early termination. TSQM is a validated tool that measures the subject’s perception of the 4 domains of treatment satisfaction: the medication’s effectiveness, convenience, side effects, and global satisfaction (Atkinson Health Qual Life Outcomes 2004). Each TSQM domain score is between 0 and 100 and a higher score indicates a more preferred health status. Treatment comparisons of change in TSQM from baseline to months 6 and 12 were analyzed using an ANCOVA model fitted with treatment group and adjusted for baseline TSQM domain score. Results: The study population included 833 women (417 denosumab; 416 ibandronate) with a mean (SD) age of 66.7 (8.0) years and mean (SD) BMD T-scores of –1.8 (0.7) at the total hip, 2.1 (0.7) at the femoral neck, and –2.5 (0.8) at the lumbar spine. Compared with the TSQM scores at baseline, subjects in both treatment groups reported greater satisfaction in all domains of the TSQM at month 6 and at month 12. However, subjects who transitioned to denosumab therapy had significantly greater improvements among all domains than did subjects who transitioned to ibandronate therapy at month 6 (P 0.0004 in all domains; data not shown) and at month 12 (P 0.0003 in all domains; Table 1).Table 1. TSQM Change From Baseline to Month 12 TSQM Domain Treatment n LS Mean 95% CI P-value* Effectiveness Ibandronate 332 17.9 15.6, 20.2 0.0001 Denosumab 378 24.1 22.0, 26.3 Convenience Ibandronate 338 16.7 14.9, 18.6 0.0001 Denosumab 384 26.3 24.6, 28.0 Side Effects Ibandronate 337 4.2 2.7, 5.8 0.0003 Denosumab 385 8.1 6.7, 9.6 Global Satisfaction Ibandronate 337 14.9 12.8, 17.1 0.0001 Denosumab 382 26.4 24.4, 28.4 n number of subjects with non-missing TSQM domain at baseline and at month 12. LS least squares. CI confidence interval. *P-value from treatment comparison based on an ANCOVA model fitted with treatment group and adjusted for baseline TSQM domain score. Conclusion: In summary, postmenopausal women with low BMD who were sub-optimally treated with prior bisphosphonate therapy reported greater satisfaction if they transitioned to denosumab vs ibandronate in an open-label study. Greater treatment satisfaction may lead to better adherence to therapy and thus improvements in treatment efficac

Relationship between changes in bone mineral density and incidence of fracture with 6 years of Denosumab treatment

Bone and mineral researc

Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: Efficacy and safety results from a randomized open-label study

Denosumab has been shown to reduce new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. In subjects who were treatment-naive or previously treated with alendronate, denosumab was associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers when compared with alendronate-treated subjects. This trial was designed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy. In this randomized, open-label study, postmenopausal women aged >= 55 years received denosumab 60 mg subcutaneously every 6 months or risedronate 150 mg orally every month for 12 months. Endpoints included percentage change from baseline in total hip BMD (primary endpoint), femoral neck, and lumbar spine BMD at month 12, and percentage change from baseline in sCTX-1 at months 1 and 6. Safety was also assessed. A total of 870 subjects were randomized (435, risedronate; 435, denosumab) who had a mean (SD) age of 67.7 (6.9) years, mean (SD) BMD T-scores of -1.6 (0.9), -1.9 (0.7), and -2.2 (1.2) at the total hip, femoral neck, and lumbar spine, respectively, and median sCTX-1 of 03 ng/mL at baseline. At month 12, denosumab significantly increased BMD compared with risedronate at the total hip (2.0% vs 0.5%), femoral neck (1.4% vs 0%), and lumbar spine (3.4% vs 1.1%; p<0.0001 at all sites). Denosumab signi In postmenopausal women who were suboptimally adherent to alendronate therapy, transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved