Dataset Information

Estimation of Long-Term Efficacy of Denosumab Treatment in Postmenopausal Women With Osteoporosis: A FRAX- and Virtual Twin-Based Post Hoc Analysis From the FREEDOM and FREEDOM Extension Trials.

ABSTRACT: The 3-year placebo-controlled FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial established the antifracture efficacy of denosumab in postmenopausal women with osteoporosis. The 7-year open-label extension demonstrated that denosumab treatment for up to 10?years was associated with low rates of adverse events and low fracture incidence. The extension lacked a long-term control group, thus limiting the ability to fully evaluate long-term efficacy. This analysis provides a quantitative estimate of the long-term antifracture efficacy of denosumab based on two approaches: comparison with FRAX®- (Fracture Risk Assessment Tool-) and virtual twin-estimated 10-year fracture rates. Subjects who were randomized to denosumab in the FREEDOM trial, continued into the Extension study, completed the 10-year visit, and missed ?1 dose in the FREEDOM trial and ?1 dose in the Extension (n = 1278) were included in the analysis. The 10-year observed cumulative incidence of major osteoporotic fracture (MOF) and hip fractures was compared with the 10-year fracture probability predicted at baseline by FRAX, a computer-based fracture risk algorithm, and with that estimated for a hypothetical cohort of 10-year placebo controls (virtual twins). The observed 10-year fracture incidence was lower than the 10-year probability predicted by FRAX for both MOF (10.75% [95% CI, 9.05 to 12.46] versus 15.63% [95% CI, 15.08 to 16.18], respectively), and hip fractures (1.17% [95% CI, 0.58 to 1.76] versus 5.62% [95% CI, 5.28 to 5.97], respectively). The observed fracture incidence was also lower than the fracture rate estimated in a hypothetical cohort of 10-year placebo controls for MOF (23.13% [95% CI, 17.76 to 28.87]; relative risk 0.49 [95% CI, 0.36 to 0.64]). These data support the long-term efficacy of denosumab in reducing MOF and hip fractures in postmenopausal women with osteoporosis. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

SUBMITTER: Siris E

PROVIDER: S-EPMC7117843 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Estimation of Long-Term Efficacy of Denosumab Treatment in Postmenopausal Women With Osteoporosis: A FRAX- and Virtual Twin-Based Post Hoc Analysis From the FREEDOM and FREEDOM Extension Trials.

Siris Ethel E McDermott Michele M Pannacciulli Nicola N Miller Paul D PD Lewiecki E Michael EM Chapurlat Roland R Jódar-Gimeno Esteban E Huang Shuang S Kanis John A JA

JBMR plus 20200224 4

The 3-year placebo-controlled FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial established the antifracture efficacy of denosumab in postmenopausal women with osteoporosis. The 7-year open-label extension demonstrated that denosumab treatment for up to 10 years was associated with low rates of adverse events and low fracture incidence. The extension lacked a long-term control group, thus limiting the ability to fully evaluate long-term efficacy. This anal ...[more]

PMID: 32258966

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Project description:Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone.The purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent.Preplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 ?g daily), denosumab (60 mg every 6 months), or both medications for 24 months.Participants were 94 postmenopausal women with osteoporosis.Lumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured.At 24 months, lumbar spine BMD increased more in the combination group (12.9 ± 5.0%) than in either the teriparatide (9.5 ± 5.9%, P = .01) or denosumab (8.3 ± 3.4%, P = .008) groups. Femoral neck BMD also increased more in the combination group (6.8 ± 3.6%) than in either the teriparatide (2.8 ± 3.9%, P = .003) or denosumab (4.1 ± 3.8%, P = .008) groups. Similarly, total hip BMD increased more in the combination group (6.3 ± 2.6%) than in the teriparatide (2.0 ± 3.0%) or denosumab (3.2 ± 2.5%) groups (P < .001 for both). Although spine and hip BMD continued to increase in the second year in all groups, these year 2 increases did not differ among groups. Serum C-telopeptide and N-terminal propeptide of type 1 procollagen were equally suppressed in the denosumab and combination groups, whereas osteocalcin decreased more in the denosumab group than in the combination group, a difference that persisted, but lessened, in the second year of therapy.Two years of concomitant teriparatide and denosumab therapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy. The combination of these agents may prove to be an important treatment option in patients at high risk of fracture.

Dataset Information

Estimation of Long-Term Efficacy of Denosumab Treatment in Postmenopausal Women With Osteoporosis: A FRAX- and Virtual Twin-Based Post Hoc Analysis From the FREEDOM and FREEDOM Extension Trials.

Publications

Estimation of Long-Term Efficacy of Denosumab Treatment in Postmenopausal Women With Osteoporosis: A FRAX- and Virtual Twin-Based Post Hoc Analysis From the FREEDOM and FREEDOM Extension Trials.

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