Bone density after teriparatide in patients with or without prior antiresorptive treatment: one-year results from the EUROFORS study*

Abstract

Objective: Recombinant teriparatide, a bone anabolic agent, is given to treatment-naïve and pre-treated patients with severe osteoporosis, but few data exist comparing the response to teriparatide in these groups. EUROFORS (the EUROpean study of FORSteo‡) enrolled postmenopausal women with established osteoporosis who were either treatment-naïve or had prior antiresorptive (AR) treatment with or without documented inadequate clinical response. The objective of the secondary analysis described here was to evaluate the interim bone mineral density (BMD) response in these groups after one year of open-label teriparatide therapy.

Research design and methods: Postmenopausal women with established osteoporosis who enrolled in a prospective, randomized, controlled trial received open-label teriparatide 20 µg/day for the first year. With respect to their prior osteoporosis treatment history, they were retrospectively allocated to one of three groups: treatment-naïve (n = 204), prior treatment with an antiresorptive drug (AR-pretreated) (n = 240), or prior antiresorptive treatment with inadequate response (inadequate AR-responders) (n = 421). BMD was measured by dual energy x-ray absorptiometry.

Results: Lumbar spine BMD increased from baseline (p < 0.001) in the three groups (mean, 95% CI); treatment-naïve: 8.4% (7.4%, 9.3%); AR-pretreated: 7.1% (6.3%, 7.9%); inadequate AR-responders: 6.2% (5.6%, 6.9%). Total hip BMD increased from baseline in the treatment-naïve (p < 0.001): 1.8% (1.1%, 2.5%) but did not change in the AR-pretreated: 0.4% (−0.2%, 1.1%) or inadequate AR-responders: −0.3% (−0.9%, 0.2%). Treatment-emergent adverse events were similar in the three groups.

Conclusion: One year of teriparatide significantly (p < 0.001) increased spine BMD in all groups, and total hip BMD in the treatment-naïve group. Because of the limitations of this interim analysis (most importantly, the short duration of treatment and lack of a control group), further study is needed to determine the optimal treatment duration to reach the potential BMD gains at the proximal femur in patients with prior antiresorptive drug use (mostly bisphosphonates).

Clinical trial registration: clinicaltrials.gov, nct00191425

Key words: :

• Antiresorptive therapy
• Bone mineral density
• Osteoporosis
• Postmenopausal women
• Teriparatide

* Details of the EUROFORS investigators are included following the Acknowledgments

† These results were presented at the American Society for Bone and Mineral Research annual meeting, Nashville, TN, USA, September 2005; the abstract was published in the Journal of Bone and Mineral Research, 2005;20(Suppl 1):S174

‡ Forsteo (recombinant teriparatide), Eli Lilly and Company, Indianapolis, IN, USA

* Forsteo (recombinant teriparatide), Eli Lilly and Company, Indianapolis, IN USA

* Details of the EUROFORS investigators are included following the Acknowledgments

† These results were presented at the American Society for Bone and Mineral Research annual meeting, Nashville, TN, USA, September 2005; the abstract was published in the Journal of Bone and Mineral Research, 2005;20(Suppl 1):S174

‡ Forsteo (recombinant teriparatide), Eli Lilly and Company, Indianapolis, IN, USA

* Forsteo (recombinant teriparatide), Eli Lilly and Company, Indianapolis, IN USA

Acknowledgements

Declaration of interest: This study was funded by Lilly Research Laboratories, Eli Lilly and Company. H.M. receives speaker honoraria and grants (both research and travel) from Eli Lilly and Company. M.A. receives consultancies and speaker honoraria from Eli Lilly. B.O.-P., M.E.S. and G.S. report no conflicts. F.M., G.P.D., and T.N. are full-time employees of Eli Lilly and Company and report stock ownership. The authors thank the following employees of Eli Lilly and Company for technical assistance: Petra Ochs and Frederico Machado (study coordination); Ruth Alonso, David López, Laura Briones (data management); Alain Frix (study drug coordination), Tracey Nicholson (statistical support), Clare Barker (statistical analyst), Melinda Rance and Mary Ellen Perron (graphs).

The EUROFORS investigators

Austria: L. Erlacher, G. Finkenstedt, B. Obermayer-Pietsch; Belgium: S. Boonen, Y. Boutson, P. Geusens, J.-M. Kaufman, F. Raeman, F. van den Bosch. Denmark: K. Brixen, J.-E. B. Jensen, B. Langdahl. France: C. Alexandre, M. Audran, C. L. Benhamou, C. Cormier, B. Cortet, A. Daragon, P. Fardellone, J.-L. Kuntz, M. Laroche, C. Roux, C. Ribot, M. C. de Vernejoul, G. Weryha. Germany: K. Badenhoop, E. Blind, T. Brabant, H.-G. Dammann, J. Feldkamp, F. Flohr, H. G. Fritz, R. R. Fritzen, P. Hadji, U. Haschke, H.-J. Heberling, G. Hein, T. Hennigs, F. Jakob, P. Kaps, C. Kasperk, J. Kekow, H.-P. Kruse, H. W. Minne, H. Moenig, R. Möricke, H. Radspieler, J. D. Ringe, M. Runge, S. S. Scharla, J. Semler, W. Spieler, N. Vollmann, A. Wagenitz. Greece: A. Avramides, G. Lyritis. Iceland: B. Gudbjörnsson, G. Sigurðsson. Portugal: J. C. Branco, A. Malcata, J. Melo-Gomes, M. E. Simões. Spain: J. Babio, J. del Pino, J. de Toro, C. Díaz-Lopez, C. González, J. González de la Vera, E. Rejón, J. A. Román, X. Sans. United Kingdom: K. Adams, A. Bhalla, M. Brown, J. Compston, C. Cooper, S. Doherty, R. Eastell, I. Fogelman, W. Fraser, D. Hosking, R. Keen, T. O’Neill, S. Orme, T. Palferman, D. Reid, P. Ryan, P. Selby, M. Stone, H. Taggart, P. Thompson, T. Wheatley, A. Woolf.

Notes

* Details of the EUROFORS investigators are included following the Acknowledgments

† These results were presented at the American Society for Bone and Mineral Research annual meeting, Nashville, TN, USA, September 2005; the abstract was published in the Journal of Bone and Mineral Research, 2005;20(Suppl 1):S174

‡ Forsteo (recombinant teriparatide), Eli Lilly and Company, Indianapolis, IN, USA

* Forsteo (recombinant teriparatide), Eli Lilly and Company, Indianapolis, IN USA