N C Harvey1, J A Kanis2, A Odén3, R T Burge4, B H Mitlak4, H Johansson3, E V McCloskey3. 1. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK. 2. Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK. w.j.pontefract@sheffield.ac.uk. 3. Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK. 4. Bone, Muscle and Joint Platform, Eli Lilly and Company, Indianapolis, IN, USA.
Abstract
UNLABELLED: Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here, we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. INTRODUCTION: Daily administration of 20 or 40 μg teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. METHODS: One thousand six hundred thirty-seven postmenopausal women in the pivotal phase three trial, randomly assigned to receive placebo (n = 544), teriparatide 20 μg per day (n = 541) or teriparatide 40 μg per day (n = 552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40 μg teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. RESULTS: The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2 %. Treatment with teriparatide was associated with a 37 % decrease in all non-vertebral fractures (95 % CI 10-56 %) and a 56 % decrease in low-energy non-vertebral fractures (95 % CI 24-75 %) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66 % (95 % CI 50-77 %). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p > 0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. CONCLUSION: We conclude that teriparatide significantly decreases the risk of non-vertebral and morphometric vertebral fractures in women by a similar extent, irrespective of baseline fracture probability.
UNLABELLED: Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here, we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. INTRODUCTION: Daily administration of 20 or 40 μg teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. METHODS: One thousand six hundred thirty-seven postmenopausal women in the pivotal phase three trial, randomly assigned to receive placebo (n = 544), teriparatide 20 μg per day (n = 541) or teriparatide 40 μg per day (n = 552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40 μg teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. RESULTS: The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2 %. Treatment with teriparatide was associated with a 37 % decrease in all non-vertebral fractures (95 % CI 10-56 %) and a 56 % decrease in low-energy non-vertebral fractures (95 % CI 24-75 %) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66 % (95 % CI 50-77 %). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p > 0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. CONCLUSION: We conclude that teriparatide significantly decreases the risk of non-vertebral and morphometric vertebral fractures in women by a similar extent, irrespective of baseline fracture probability.
Authors: Eugene V McCloskey; Monique Beneton; Diane Charlesworth; Karthik Kayan; Dominic deTakats; Abhijit Dey; Jane Orgee; Robert Ashford; Martin Forster; Jennifer Cliffe; Linda Kersh; John Brazier; Jon Nichol; Sakari Aropuu; Tarja Jalava; John A Kanis Journal: J Bone Miner Res Date: 2007-01 Impact factor: 6.741
Authors: E V McCloskey; H Johansson; A Oden; S Vasireddy; K Kayan; K Pande; T Jalava; J A Kanis Journal: Osteoporos Int Date: 2008-11-11 Impact factor: 4.507
Authors: Aroon D Hingorani; Daniëlle A van der Windt; Richard D Riley; Keith Abrams; Karel G M Moons; Ewout W Steyerberg; Sara Schroter; Willi Sauerbrei; Douglas G Altman; Harry Hemingway Journal: BMJ Date: 2013-02-05
Authors: Mattias Lorentzon; Helena Johansson; Nicholas C Harvey; Enwu Liu; Liesbeth Vandenput; Carolyn J Crandall; Jane A Cauley; Meryl S LeBoff; Eugene V McCloskey; John A Kanis Journal: Osteoporos Int Date: 2022-07-14 Impact factor: 5.071
Authors: Eugene V McCloskey; Helena Johansson; Anders Oden; Nicholas C Harvey; Hai Jiang; Sara Modin; Lorraine Fitzpatrick; John A Kanis Journal: J Bone Miner Res Date: 2017-06-26 Impact factor: 6.741
Authors: Liesbeth Vandenput; Dan Mellström; Andreas Kindmark; Helena Johansson; Mattias Lorentzon; Jason Leung; Inga Redlund-Johnell; Björn E Rosengren; Magnus K Karlsson; Yi-Xiang Wang; Timothy Kwok; Claes Ohlsson Journal: J Bone Miner Res Date: 2016-01-20 Impact factor: 6.741
Authors: J A Kanis; C Cooper; R Rizzoli; B Abrahamsen; N M Al-Daghri; M L Brandi; J Cannata-Andia; B Cortet; H P Dimai; S Ferrari; P Hadji; N C Harvey; M Kraenzlin; A Kurth; E McCloskey; S Minisola; T Thomas; J-Y Reginster Journal: Osteoporos Int Date: 2017-04-27 Impact factor: 4.507
Authors: Eugene McCloskey; Helena Johansson; Nicholas C Harvey; Lee Shepstone; Elizabeth Lenaghan; Ric Fordham; Ian Harvey; Amanda Howe; Cyrus Cooper; Shane Clarke; Neil Gittoes; Alison Heawood; Richard Holland; Tarnya Marshall; Terence W O'Neill; Tim J Peters; Niamh Redmond; David Torgerson; John A Kanis Journal: J Bone Miner Res Date: 2018-03-23 Impact factor: 6.741
Authors: E V McCloskey; N C Harvey; H Johansson; M Lorentzon; L Vandenput; E Liu; J A Kanis Journal: Osteoporos Int Date: 2020-10-14 Impact factor: 5.071