Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX

Osteoporosis International, Sep 2015

Summary The aim of this study was to determine the efficacy of once-weekly teriparatide as a function of baseline fracture risk. Treatment with once-weekly teriparatide was associated with a statistically significant 79 % decrease in vertebral fractures, and in the cohort as a whole, efficacy was not related to baseline fracture risk. Introduction Previous studies have suggested that the efficacy of some interventions may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the antifracture efficacy of weekly teriparatide was dependent on the magnitude of fracture risk. Methods Baseline fracture probabilities (using FRAX) were computed from the primary data of a phase 3 study (TOWER) of the effects of weekly teriparatide in 542 men and postmenopausal women with osteoporosis. The outcome variable comprised morphometric vertebral fractures. Interactions between fracture probability and efficacy were explored by Poisson regression. Results The 10-year probability of major osteoporotic fractures (without BMD) ranged from 7.2 to 42.2 %. FRAX-based hip fracture probabilities ranged from 0.9 to 29.3 %. Treatment with teriparatide was associated with a 79 % (95 % CI 52–91 %) decrease in vertebral fractures assessed by semiquantitative morphometry. Relative risk reductions for the effect of teriparatide on the fracture outcome did not change significantly across the range of fracture probabilities (p = 0.28). In a subgroup analysis of 346 (64 %) participants who had FRAX probabilities calculated with the inclusion of BMD, there was a small but significant interaction (p = 0.028) between efficacy and baseline fracture probability such that high fracture probabilities were associated with lower efficacy. Conclusion Weekly teriparatide significantly decreased the risk of morphometric vertebral fractures in men and postmenopausal women with osteoporosis. Overall, the efficacy of teriparatide was not dependent on the level of fracture risk assessed by FRAX in the cohort as a whole.

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Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX

Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX N. C. Harvey 0 1 2 3 4 5 J. A. Kanis 0 1 2 3 4 5 A. Odén 0 1 2 3 4 5 T. Nakamura 0 1 2 3 4 5 M. Shiraki 0 1 2 3 4 5 T. Sugimoto 0 1 2 3 4 5 T. Kuroda 0 1 2 3 4 5 H. Johansson 0 1 2 3 4 5 E. V. McCloskey 0 1 2 3 4 5 0 National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655 , Japan 1 Centre for Metabolic Bone Diseases, University of Sheffield , Beech Hill Road, Sheffield S10 2RX , UK 2 MRC Lifecourse Epidemiology Unit, University of Southampton , Southampton SO16 6YD , UK 3 Medical Affairs Dept., Asahi-Kasei Pharma Corporation , 1-105 Kanda Jinbocho, Chiyoda-ku, Tokyo 101-8101 , Japan 4 Internal Medicine 1, Shimane University Faculty of Medicine , 89-1 Enya-cho, Izumo, Shimane 693-8501 , Japan 5 Research Institute and Practice for Involutional Diseases , 1610-1 Meisei, Misato, Azumino, Nagano 399-8101 , Japan Summary The aim of this study was to determine the efficacy of once-weekly teriparatide as a function of baseline fracture risk. Treatment with once-weekly teriparatide was associated with a statistically significant 79 % decrease in vertebral fractures, and in the cohort as a whole, efficacy was not related to baseline fracture risk. Introduction Previous studies have suggested that the efficacy of some interventions may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the antifracture efficacy of weekly teriparatide was dependent on the magnitude of fracture risk. Methods Baseline fracture probabilities (using FRAX) were computed from the primary data of a phase 3 study (TOWER) of the effects of weekly teriparatide in 542 men and postmenopausal women with osteoporosis. The outcome variable comprised morphometric vertebral fractures. Interactions between fracture probability and efficacy were explored by Poisson regression. Results The 10-year probability of major osteoporotic fractures (without BMD) ranged from 7.2 to 42.2 %. FRAXbased hip fracture probabilities ranged from 0.9 to 29.3 %. Treatment with teriparatide was associated with a 79 % (95 % CI 52-91 %) decrease in vertebral fractures assessed by semiquantitative morphometry. Relative risk reductions for the effect of teriparatide on the fracture outcome did not change significantly across the range of fracture probabilities (p= 0.28). In a subgroup analysis of 346 (64 %) participants who had FRAX probabilities calculated with the inclusion of BMD, there was a small but significant interaction (p= 0.028) between efficacy and baseline fracture probability such that high fracture probabilities were associated with lower efficacy. Conclusion Weekly teriparatide significantly decreased the risk of morphometric vertebral fractures in men and postmenopausal women with osteoporosis. Overall, the efficacy of teriparatide was not dependent on the level of fracture risk assessed by FRAX in the cohort as a whole. Epidemiology; FRAX; Osteoporosis; Randomised controlled trial; Teriparatide; Vertebral fracture - The continuous endogenous production of excess parathyroid hormone (PTH), as seen in primary or secondary hyperparathyroidism, or its exogenous administration, may give rise to deleterious consequences for the skeleton, particularly in cortical bone. However, intermittent administration of PTH (e.g., with daily or weekly subcutaneous injections) results in an increase of the number and activity of osteoblasts, leading to an increase in bone mass and in an improvement in skeletal architecture at both cancellous and cortical skeletal sites [1–3]. The intact molecule (amino acids 1–84) and the 1–34 N-terminal fragment (teriparatide) are used in the management of osteoporosis [4]. Treatment with either agent has been shown to reduce significantly the risk of vertebral fractures, whereas teriparatide has also been shown to have an effect on nonvertebral fractures [5–9]. Beneficial effects on nonvertebral fracture with teriparatide have been shown to persist for up to 30 months after stopping treatment [10]. Several studies have examined the interaction between FRAX-based probabilities at baseline and subsequent effectiveness. Three of these reanalyses of clinical trial data have shown greater efficacy against fracture in individuals at higher risk treated with clodronate or bazedoxifene [11–13] whereas others have shown stable benefits of strontium ranelate or raloxifene across a range of fracture probabilities (but with greater absolute risk reductions in those at higher risk) [13–15]. In a further preplanned analysis of the FREEDOM trial, greater efficacy against fracture was shown in individuals at higher risk treated with denosumab [16]. No data are available for teriparatide or PTH. Against this background, the aim of the present study was to seek interactions between teriparatide-induced effects on f (...truncated)


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N. C. Harvey, J. A. Kanis, A. Odén, T. Nakamura, M. Shiraki. Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX, Osteoporosis International, 2015, pp. 2347-2353, Volume 26, Issue 9, DOI: 10.1007/s00198-015-3129-7