Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2015 Nov;26(11):2677-84.
doi: 10.1007/s00198-015-3173-3. Epub 2015 Jun 20.

FRAX and the effect of teriparatide on vertebral and non-vertebral fracture

N C Harvey  1 , J A Kanis  2 , A Odén  3 , R T Burge  4 , B H Mitlak  4 , H Johansson  3 , E V McCloskey  3
Affiliations
Randomized Controlled Trial

FRAX and the effect of teriparatide on vertebral and non-vertebral fracture

N C Harvey et al. Osteoporos Int. 2015 Nov.

Abstract

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.

Keywords: BMD; Epidemiology; FRAX; Fracture; Interaction; Osteoporosis; Randomised controlled trial; Teriparatide.

PubMed Disclaimer

Conflict of interest statement

Disclosures

NH has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare and Internis Pharma. JA Kanis has received consulting fees, advisory board fees, lecture fees, and/or grant support from the majority of companies concerned with skeletal metabolism. EVM has received consultancy, lecture fees, research grant support and/or honoraria from ActiveSignal, Alliance for Better Bone Health, AMGEN, Bayer, Consilient Healthcare, GE Lunar, Hologic, Internis Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Servier, Tethys, UCB and Univadis. RTB and BHM are employees and shareholders of Eli Lilly and Company.

Figures

Figure 1
Figure 1
Hazard ratio (HR) between treatments (teriparatide versus placebo) for morphometric vertebral fractures according to baseline 10-year probability of a major osteoporotic fracture calculated with inclusion of BMD.
Figure 2
Figure 2
Hazard ratio (HR) between treatments (teriparatide versus placebo) for non-vertebral fracture according to baseline 10-year probability of a major osteoporotic fracture calculated with inclusion of BMD.
Figure 3
Figure 3
Hazard ratio (HR) between treatments (teriparatide versus placebo) for morphometric vertebral fractures according to baseline 10-year probability of a major osteoporotic fracture calculated without inclusion of BMD.
Figure 4
Figure 4
Hazard ratio (HR) between treatments (bazedoxifene versus placebo) for morphometric vertebral fractures according to baseline 10-year probability of a major osteoporotic fracture calculated with inclusion of BMD (left 2 panels). Baseline probability was set at the 10th and 90th percentile of fracture probability. The two right hand panels show the equivalent hazard ratios for teriparatide.
See this image and copyright information in PMC

References

    1. Hingorani AD, Windt DA, Riley RD, et al. PROGRESS Group Prognosis research strategy (PROGRESS) 4: stratified medicine research. BMJ. 2013 Feb 5;346:e5793. doi: 10.1136/bmj.e5793. - DOI - PMC - PubMed
    1. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y, on behalf of the Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis International. 2013;24:23–57. - PMC - PubMed
    1. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434–1441. - PubMed
    1. Prince R, Sipos A, Hossain A, et al. Sustained non vertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res. 2005;20:1507–1513. - PubMed
    1. Kanis JA, on behalf of the World Health Organization Scientific Group . Assessment of osteoporosis at the primary health-care level Technical Report. WHO Collaborating Centre, University of Sheffield; UK: 2008.

Publication types

MeSH terms

Substances

LinkOut - more resources