Top

Published in:

Open Access 01-09-2015 | Original Article

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

Authors: N. C. Harvey, J. A. Kanis, A. Odén, T. Nakamura, M. Shiraki, T. Sugimoto, T. Kuroda, H. Johansson, E. V. McCloskey

Published in: Osteoporosis International | Issue 9/2015

Abstract

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.

Reeve J, Meunier PJ, Parsons JA et al (1980) Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. Br Med J 280:1340–1344PubMedCentralPubMedCrossRef

Devogelaer JP, Boutsen Y, Manicourt DH (2010) Biologicals in osteoporosis: teriparatide and parathyroid hormone in women and men. Curr Osteoporos Rep 8:154–161PubMedCrossRef

Resmini G, Iolascon G (2011) New insights into the role of teriparatide. Aging Clin Exp Res 23(2 Suppl):30–32PubMed

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) (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57PubMedCrossRef

Vescini F, Grimaldi F (2012) PTH 1-84: bone rebuilding as a target for the therapy of severe osteoporosis. Clin Cases Miner Bone Metab 9:31–36PubMedCentralPubMed

Fujita T, Fukunaga M, Itabashi A, Tsutani K, Nakamura T (2014) Once-weekly injection of low-dose teriparatide (28.2 μg) reduced the risk of vertebral fracture in patients with primary osteoporosis. Calcif Tissue Int 94(2):170–175PubMedCentralPubMedCrossRef

Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRef

Shrader SP, Ragucci KR (2005) Parathyroid hormone (1-84) and treatment of osteoporosis. Ann Pharmacother 39:1511–1516PubMedCrossRef

Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga M, Hagino H, Sone T, Yoshikawa H, Nishizawa Y, Fujita T, Shiraki M (2012) Randomized Teriparatide [human parathyroid hormone (TERIPARATIDE) 1-34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk. J Clin Endocrinol Metab 97:3097–3106PubMedCrossRef

10.

Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, Halse J, Lindsay R, Dalsky GP, Mitlak BH (2005) Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 20:1507–1513PubMedCrossRef

11.

McCloskey EV, Johansson H, Oden A, Vasireddy S, Kayan K, Pande K, Jalava T, Kanis JA (2009) Ten-year fracture probability identifies women who will benefit from clodronate therapy–additional results from a double-blind, placebo-controlled randomised study. Osteoporos Int 20:811–817PubMedCrossRef

12.

Kanis JA, Johansson H, Oden A et al (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX. Bone 44:1049–1054PubMedCrossRef

13.

Kim K, Svedbom A, Luo X, Sutradhar S, Kanis JA (2014) Comparative cost-effectiveness of bazedoxifene and raloxifene in the treatment of postmenopausal osteoporosis in Europe using the FRAX algorithm. Osteoporos Int 25:325–337PubMedCrossRef

14.

Kanis JA, Johansson H, Odén A et al (2010) A meta-analysis of the efficacy of raloxifene on all clinical and vertebral fractures and its dependency on FRAX. Bone 47:729–735PubMedCrossRef

15.

Kanis JA, Jönsson B, Odén A, McCloskey EV (2011) A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®. Osteoporos Int 22:2347–2355, with erratum Osteoporos Int. 22: 2357-2358PubMedCrossRef

16.

McCloskey EV, Johansson H, Oden A, Austin M, Siris E, Wang A, Lewiecki EM, Lorenc R, Libanati C, Kanis JA (2012) Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX. J Bone Miner Res 27:1480–1486PubMedCrossRef

17.

Committee for Medicinal Products for Human Use (CHMP) (2006) Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. Ref CPMP/EWP/552/95Rev.2. London, CHMP. Nov 2006

18.

Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison f semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. J Bone Miner Res 11:984–996PubMedCrossRef

19.

Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–489PubMedCrossRef

20.

Kanis JA on behalf of the World Health Organization Scientific Group (2008a) Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK. Accessible at http://www.shef.ac.uk/FRAX

21.

Kanis JA, Johnell O, Odén A, Johansson H, McCloskey E (2008) FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397PubMedCentralPubMedCrossRef

22.

Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward's triangle. Osteoporos Int 12:438–444PubMedCrossRef

23.

Breslow NE, Day NE (1987) Statistical Methods in Cancer Research. IARC Scientific Publications No 32 Volume II:p 131-135

24.

Nakano T, Shiraki M, Sugimoto T, Kishimoto H, Ito M, Fukunaga M, Hagino H, Sone T, Kuroda T, Nakamura T (2013) Once-weekly teriparatide reduces the risk of vertebral fracture in patients with various fracture risks: subgroup analysis of the Teriparatide Once-Weekly Efficacy Research (TOWER) trial. J Bone Miner MetabNov 9. [Epub ahead of print] PubMed

25.

McCloskey EV, Spector TD, Eyres KS, Fern ED, O'Rourke N, Vasikaran S, Kanis JA (1993) The assessment of vertebral deformity: a method for use in population studies and clinical trials. Osteoporos Int 3(3):138–147PubMedCrossRef

Title: Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX
Authors: N. C. Harvey
J. A. Kanis
A. Odén
T. Nakamura
M. Shiraki
T. Sugimoto
T. Kuroda
H. Johansson
E. V. McCloskey
Publication date: 01-09-2015
Publisher: Springer London
Published in: Osteoporosis International / Issue 9/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-015-3129-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2015

The relationship between serum 25(OH)D and bone density and microarchitecture as measured by HR-pQCT

Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status

Burden of high fracture probability worldwide: secular increases 2010–2040

Meeting international standards of secondary fracture prevention: a survey on Fracture Liaison Services in the Netherlands

Unexpected action of lanthanum carbonate

Efficacy of bisphosphonates against osteoporosis in adult men: a meta-analysis of randomized controlled trials