Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Ferrari, S; Adachi, J D; Lippuner, Kurt; Zapalowski, C; Miller, P D; Reginster, J-Y; Törring, O; Kendler, D L; Daizadeh, N S; Wang, A; O'Malley, C D; Wagman, R B; Libanati, C; Lewiecki, E M (2015). Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years. Osteoporosis international, 26(12), pp. 2763-2771. Springer 10.1007/s00198-015-3179-x

[img]
Preview
Text
art%3A10.1007%2Fs00198-015-3179-x.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC).

Download (360kB) | Preview

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Osteoporosis

UniBE Contributor:

Lippuner, Kurt

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0937-941X

Publisher:

Springer

Language:

English

Submitter:

Romain Perrelet

Date Deposited:

03 Mar 2016 09:07

Last Modified:

07 Mar 2016 14:20

Publisher DOI:

10.1007/s00198-015-3179-x

PubMed ID:

26068295

Uncontrolled Keywords:

Denosumab; Fracture threshold; Hip bone mineral density; Long-term osteoporosis therapy; Nonvertebral fracture; Treatment to goal

BORIS DOI:

10.7892/boris.76340

URI:

https://boris.unibe.ch/id/eprint/76340

Actions (login required)

Edit item Edit item
Provide Feedback