Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures
- Autores
- Austin, Matthew; Yang, Yu Ching; Vittinghoff, Eric; Adami, Silvano; Boonen, Steven; Bauer, Douglas C; Bianchi, Gerolamo; Bolognese, Michael A.; Christiansen, Claus Bohn; Eastell, Richard; Grauer, Andreas; Hawkins, Federico; Kendler, David L.; Oliveri, María Beatriz; McClung, Michael R.; Reid, Ian R.; Siris, Ethel S.; Zanchetta, Jose; Zerbini, Cristiano A.F.; Libanati, Cesar; Cummings, Steven R.
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. Copyright © 2012 American Society for Bone and Mineral Research.
Fil: Austin, Matthew. Amgen Incorporated; Estados Unidos
Fil: Yang, Yu Ching. Amgen Incorporated; Estados Unidos
Fil: Vittinghoff, Eric. University of California; Estados Unidos
Fil: Adami, Silvano. Universita di Verona; Italia
Fil: Boonen, Steven. Katholikie Universiteit Leuven; Bélgica
Fil: Bauer, Douglas C. University of California; Estados Unidos
Fil: Bianchi, Gerolamo. Azienda Sanitaria Genovese; Italia
Fil: Bolognese, Michael A.. Bethesda Health Research Center; Estados Unidos
Fil: Christiansen, Claus Bohn. Center For Clinical And Basic Research As; Estados Unidos
Fil: Eastell, Richard. University Of Sheffield; Reino Unido
Fil: Grauer, Andreas. Amgen Incorporated; Estados Unidos
Fil: Hawkins, Federico. Hospital Universitario 12 de Octubre; España
Fil: Kendler, David L.. University of British Columbia; Canadá
Fil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: McClung, Michael R.. Oregon Osteoporosis Center; Estados Unidos
Fil: Reid, Ian R.. The University of Auckland; Nueva Zelanda
Fil: Siris, Ethel S.. Columbia University; Estados Unidos
Fil: Zanchetta, Jose. Universidad del Salvador; Argentina
Fil: Zerbini, Cristiano A.F.. Centro Paulista de Investigação Clinica; Brasil
Fil: Libanati, Cesar. Amgen Incorporated; Estados Unidos
Fil: Cummings, Steven R.. University of California; Estados Unidos - Materia
-
Bone Mineral Density
Denosumab
Fracture
Percent of Treatment Effect Explained
Surrogate - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/67431
Ver los metadatos del registro completo
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Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fracturesAustin, MatthewYang, Yu ChingVittinghoff, EricAdami, SilvanoBoonen, StevenBauer, Douglas CBianchi, GerolamoBolognese, Michael A.Christiansen, Claus BohnEastell, RichardGrauer, AndreasHawkins, FedericoKendler, David L.Oliveri, María BeatrizMcClung, Michael R.Reid, Ian R.Siris, Ethel S.Zanchetta, JoseZerbini, Cristiano A.F.Libanati, CesarCummings, Steven R.Bone Mineral DensityDenosumabFracturePercent of Treatment Effect ExplainedSurrogatehttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. Copyright © 2012 American Society for Bone and Mineral Research.Fil: Austin, Matthew. Amgen Incorporated; Estados UnidosFil: Yang, Yu Ching. Amgen Incorporated; Estados UnidosFil: Vittinghoff, Eric. University of California; Estados UnidosFil: Adami, Silvano. Universita di Verona; ItaliaFil: Boonen, Steven. Katholikie Universiteit Leuven; BélgicaFil: Bauer, Douglas C. University of California; Estados UnidosFil: Bianchi, Gerolamo. Azienda Sanitaria Genovese; ItaliaFil: Bolognese, Michael A.. Bethesda Health Research Center; Estados UnidosFil: Christiansen, Claus Bohn. Center For Clinical And Basic Research As; Estados UnidosFil: Eastell, Richard. University Of Sheffield; Reino UnidoFil: Grauer, Andreas. Amgen Incorporated; Estados UnidosFil: Hawkins, Federico. Hospital Universitario 12 de Octubre; EspañaFil: Kendler, David L.. University of British Columbia; CanadáFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: McClung, Michael R.. Oregon Osteoporosis Center; Estados UnidosFil: Reid, Ian R.. The University of Auckland; Nueva ZelandaFil: Siris, Ethel S.. Columbia University; Estados UnidosFil: Zanchetta, Jose. Universidad del Salvador; ArgentinaFil: Zerbini, Cristiano A.F.. Centro Paulista de Investigação Clinica; BrasilFil: Libanati, Cesar. Amgen Incorporated; Estados UnidosFil: Cummings, Steven R.. University of California; Estados UnidosAmerican Society for Bone and Mineral Research2012-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67431Austin, Matthew; Yang, Yu Ching; Vittinghoff, Eric; Adami, Silvano; Boonen, Steven; et al.; Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 27; 3; 3-2012; 687-6930884-0431CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jbmr.1472info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/jbmr.1472info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:44Zoai:ri.conicet.gov.ar:11336/67431instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:43:45.069CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| title |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| spellingShingle |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures Austin, Matthew Bone Mineral Density Denosumab Fracture Percent of Treatment Effect Explained Surrogate |
| title_short |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| title_full |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| title_fullStr |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| title_full_unstemmed |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| title_sort |
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures |
| dc.creator.none.fl_str_mv |
Austin, Matthew Yang, Yu Ching Vittinghoff, Eric Adami, Silvano Boonen, Steven Bauer, Douglas C Bianchi, Gerolamo Bolognese, Michael A. Christiansen, Claus Bohn Eastell, Richard Grauer, Andreas Hawkins, Federico Kendler, David L. Oliveri, María Beatriz McClung, Michael R. Reid, Ian R. Siris, Ethel S. Zanchetta, Jose Zerbini, Cristiano A.F. Libanati, Cesar Cummings, Steven R. |
| author |
Austin, Matthew |
| author_facet |
Austin, Matthew Yang, Yu Ching Vittinghoff, Eric Adami, Silvano Boonen, Steven Bauer, Douglas C Bianchi, Gerolamo Bolognese, Michael A. Christiansen, Claus Bohn Eastell, Richard Grauer, Andreas Hawkins, Federico Kendler, David L. Oliveri, María Beatriz McClung, Michael R. Reid, Ian R. Siris, Ethel S. Zanchetta, Jose Zerbini, Cristiano A.F. Libanati, Cesar Cummings, Steven R. |
| author_role |
author |
| author2 |
Yang, Yu Ching Vittinghoff, Eric Adami, Silvano Boonen, Steven Bauer, Douglas C Bianchi, Gerolamo Bolognese, Michael A. Christiansen, Claus Bohn Eastell, Richard Grauer, Andreas Hawkins, Federico Kendler, David L. Oliveri, María Beatriz McClung, Michael R. Reid, Ian R. Siris, Ethel S. Zanchetta, Jose Zerbini, Cristiano A.F. Libanati, Cesar Cummings, Steven R. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Bone Mineral Density Denosumab Fracture Percent of Treatment Effect Explained Surrogate |
| topic |
Bone Mineral Density Denosumab Fracture Percent of Treatment Effect Explained Surrogate |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. Copyright © 2012 American Society for Bone and Mineral Research. Fil: Austin, Matthew. Amgen Incorporated; Estados Unidos Fil: Yang, Yu Ching. Amgen Incorporated; Estados Unidos Fil: Vittinghoff, Eric. University of California; Estados Unidos Fil: Adami, Silvano. Universita di Verona; Italia Fil: Boonen, Steven. Katholikie Universiteit Leuven; Bélgica Fil: Bauer, Douglas C. University of California; Estados Unidos Fil: Bianchi, Gerolamo. Azienda Sanitaria Genovese; Italia Fil: Bolognese, Michael A.. Bethesda Health Research Center; Estados Unidos Fil: Christiansen, Claus Bohn. Center For Clinical And Basic Research As; Estados Unidos Fil: Eastell, Richard. University Of Sheffield; Reino Unido Fil: Grauer, Andreas. Amgen Incorporated; Estados Unidos Fil: Hawkins, Federico. Hospital Universitario 12 de Octubre; España Fil: Kendler, David L.. University of British Columbia; Canadá Fil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: McClung, Michael R.. Oregon Osteoporosis Center; Estados Unidos Fil: Reid, Ian R.. The University of Auckland; Nueva Zelanda Fil: Siris, Ethel S.. Columbia University; Estados Unidos Fil: Zanchetta, Jose. Universidad del Salvador; Argentina Fil: Zerbini, Cristiano A.F.. Centro Paulista de Investigação Clinica; Brasil Fil: Libanati, Cesar. Amgen Incorporated; Estados Unidos Fil: Cummings, Steven R.. University of California; Estados Unidos |
| description |
Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. Copyright © 2012 American Society for Bone and Mineral Research. |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2012-03 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/67431 Austin, Matthew; Yang, Yu Ching; Vittinghoff, Eric; Adami, Silvano; Boonen, Steven; et al.; Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 27; 3; 3-2012; 687-693 0884-0431 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/67431 |
| identifier_str_mv |
Austin, Matthew; Yang, Yu Ching; Vittinghoff, Eric; Adami, Silvano; Boonen, Steven; et al.; Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 27; 3; 3-2012; 687-693 0884-0431 CONICET Digital CONICET |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1002/jbmr.1472 info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/jbmr.1472 |
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American Society for Bone and Mineral Research |
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American Society for Bone and Mineral Research |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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