David L Kendler1, Fernando Marin2, Cristiano A F Zerbini3, Luis A Russo4, Susan L Greenspan5, Vit Zikan6, Alicia Bagur7, Jorge Malouf-Sierra8, Péter Lakatos9, Astrid Fahrleitner-Pammer10, Eric Lespessailles11, Salvatore Minisola12, Jean Jacques Body13, Piet Geusens14, Rüdiger Möricke15, Pedro López-Romero2. 1. University of British Columbia, Vancouver, Canada. Electronic address: davidkendler@gmail.com. 2. Lilly Research Center, Madrid, Spain. 3. Centro Paulista de Investigaçao Clínica, São Paulo, Brazil. 4. CCBR Brasil Centro de Analises e Pesquisas Clinicas, Rio de Janeiro, Brazil. 5. Osteoporosis Center, University of Pittsburgh, Pittsburgh, PA, USA. 6. Department of Internal Medicine, General University Hospital, Prague, Czech Republic. 7. Centro de Osteopatías Comlit, Buenos Aires, Argentina. 8. Hospital Sant Pau, Barcelona, Spain. 9. Semmelweis University Medical School, Budapest, Hungary. 10. Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria. 11. University Orléans, Orléans, France. 12. Policlinico Umberto I, Rome, Italy. 13. CHU Brugmann, ULB, Brussels, Belgium. 14. Maastricht University Medical Center, Maastricht, Netherlands. 15. Institut Präventive Medizin & Klinische Forschung, Magdeburg, Germany.
Abstract
BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS:We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.
RCT Entities:
BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS: We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.
Authors: Michael A Clynes; Nicholas C Harvey; Elizabeth M Curtis; Nicholas R Fuggle; Elaine M Dennison; Cyrus Cooper Journal: Br Med Bull Date: 2020-05-15 Impact factor: 4.291
Authors: M Cellini; M Rotondi; M L Tanda; E Piantanida; L Chiovato; P Beck-Peccoz; Andrea Lania; G Mazziotti Journal: J Endocrinol Invest Date: 2020-07-21 Impact factor: 4.256