caa a22 4500 357748336 20210129033014.0 cr unu---uuuuu 160304e201512 xx s 000 0 eng 0937-941X 10.1007/s00198-015-3179-x doi (BORIS)oai:boris.unibe.ch:76340 610 ddc 26068295 pmid 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 3years [Elektronische Daten] [S Ferrari, J D Adachi, Kurt Lippuner, C Zapalowski, P D Miller, J-Y Reginster, O Törring, D L Kendler, N S Daizadeh, A Wang, C D O'Malley, R B Wagman, C Libanati, E M Lewiecki] publishedVersion openAccess eu-repo Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7years, 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 3years 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 3years 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 3years 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 3years was associated with a further reduction in nonvertebral fracture rate that persisted through 7years 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. Ferrari S. joint author Adachi J D. joint author Lippuner Kurt joint author Zapalowski C. joint author Miller P D. joint author Reginster J-Y joint author Törring O. joint author Kendler D L. joint author Daizadeh N S. joint author Wang A. joint author O'Malley C D. joint author Wagman R B. joint author Libanati C. joint author Lewiecki E M. joint author Osteoporosis international 26(12), pp. 2763-2771 0937-941X 12103254X http://boris.unibe.ch/76340/1/art%253A10.1007%252Fs00198-015-3179-x.pdf text/html WWW-Backlink auf das Repository BK010053 XK010053 XK010000 1 info:eu-repo/semantics/article boris PeerReviewed boris peerstatus BORIS BORIS BORIS info:eu-repo/semantics/article openAccess BORIS 856 40 http://boris.unibe.ch/76340/1/art%253A10.1007%252Fs00198-015-3179-x.pdf text/html WWW-Backlink auf das Repository BORIS 700 1- Ferrari S. joint author BORIS 700 1- Adachi J D. joint author BORIS 700 1- Lippuner Kurt joint author BORIS 700 1- Zapalowski C. joint author BORIS 700 1- Miller P D. joint author BORIS 700 1- Reginster J-Y joint author BORIS 700 1- Törring O. joint author BORIS 700 1- Kendler D L. joint author BORIS 700 1- Daizadeh N S. joint author BORIS 700 1- Wang A. joint author BORIS 700 1- O'Malley C D. joint author BORIS 700 1- Wagman R B. joint author BORIS 700 1- Libanati C. joint author BORIS 700 1- Lewiecki E M. joint author BORIS 773 0- Osteoporosis international 26(12), pp. 2763-2771 0937-941X 12103254X SWISSBIB 357748336