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Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study
Atypical femur fractures (AFFs) are well‐established serious complication of long‐term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case‐control study to investigate bone tissu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441274/ https://www.ncbi.nlm.nih.gov/pubmed/34532612 http://dx.doi.org/10.1002/jbm4.10523 |
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author | Griffin, Lanny V. Warner, Elizabeth Palnitkar, Saroj Qiu, Shijing Honasoge, Mahalakshmi Griffin, Shawna G. Divine, George Rao, Sudhaker D. |
author_facet | Griffin, Lanny V. Warner, Elizabeth Palnitkar, Saroj Qiu, Shijing Honasoge, Mahalakshmi Griffin, Shawna G. Divine, George Rao, Sudhaker D. |
author_sort | Griffin, Lanny V. |
collection | PubMed |
description | Atypical femur fractures (AFFs) are well‐established serious complication of long‐term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case‐control study to investigate bone tissue nanomechanical properties and prevailing bone microstructure and tissue‐level remodeling status as assessed by bone histomorphometry. We hypothesized that there would be differences in nanomechanical properties between patients with and without AFF and that bone microstructure and remodeling would be related to nanomechanical properties. Thirty‐two full‐thickness transiliac bone biopsies were obtained from age‐ and sex‐matched patients on long‐term bisphosphonate therapy with (n = 16) and without an AFF (n = 16). Standard histomorphometric measurements were made in each sample on three different bone envelopes (cancellous, intracortical, and endosteal). Iliac bone wall thickness was significantly lower on all three bone surfaces in patients with AFF than in those without AFF. Surface‐based bone formation rate was suppressed similarly in both groups in comparison to healthy premenopausal and postmenopausal women, with no significant difference between the two groups. Nanoindentation was used to assess material properties of cortical and cancellous bone separately. Elastic modulus was higher in cortical than in cancellous bone in patients with AFF as well as compared to the elastic modulus of cortical bone from non‐AFF patients. However, the elastic modulus of the cancellous bone was not different between AFF and non‐AFF groups or between cortical and cancellous bone of non‐AFF patients. Resistance to plastic deformation was decreased in cortical bone in both AFF and non‐AFF groups compared to cancellous bone, but to a greater extent in AFF patients. We conclude that long‐term bisphosphonate therapy is associated with prolonged suppression of bone turnover resulting in altered cortical remodeling and tissue nanomechanical properties leading to AFF. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
format | Online Article Text |
id | pubmed-8441274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84412742021-09-15 Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study Griffin, Lanny V. Warner, Elizabeth Palnitkar, Saroj Qiu, Shijing Honasoge, Mahalakshmi Griffin, Shawna G. Divine, George Rao, Sudhaker D. JBMR Plus Original Articles Atypical femur fractures (AFFs) are well‐established serious complication of long‐term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case‐control study to investigate bone tissue nanomechanical properties and prevailing bone microstructure and tissue‐level remodeling status as assessed by bone histomorphometry. We hypothesized that there would be differences in nanomechanical properties between patients with and without AFF and that bone microstructure and remodeling would be related to nanomechanical properties. Thirty‐two full‐thickness transiliac bone biopsies were obtained from age‐ and sex‐matched patients on long‐term bisphosphonate therapy with (n = 16) and without an AFF (n = 16). Standard histomorphometric measurements were made in each sample on three different bone envelopes (cancellous, intracortical, and endosteal). Iliac bone wall thickness was significantly lower on all three bone surfaces in patients with AFF than in those without AFF. Surface‐based bone formation rate was suppressed similarly in both groups in comparison to healthy premenopausal and postmenopausal women, with no significant difference between the two groups. Nanoindentation was used to assess material properties of cortical and cancellous bone separately. Elastic modulus was higher in cortical than in cancellous bone in patients with AFF as well as compared to the elastic modulus of cortical bone from non‐AFF patients. However, the elastic modulus of the cancellous bone was not different between AFF and non‐AFF groups or between cortical and cancellous bone of non‐AFF patients. Resistance to plastic deformation was decreased in cortical bone in both AFF and non‐AFF groups compared to cancellous bone, but to a greater extent in AFF patients. We conclude that long‐term bisphosphonate therapy is associated with prolonged suppression of bone turnover resulting in altered cortical remodeling and tissue nanomechanical properties leading to AFF. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. John Wiley & Sons, Inc. 2021-08-12 /pmc/articles/PMC8441274/ /pubmed/34532612 http://dx.doi.org/10.1002/jbm4.10523 Text en © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Griffin, Lanny V. Warner, Elizabeth Palnitkar, Saroj Qiu, Shijing Honasoge, Mahalakshmi Griffin, Shawna G. Divine, George Rao, Sudhaker D. Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study |
title | Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study |
title_full | Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study |
title_fullStr | Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study |
title_full_unstemmed | Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study |
title_short | Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case‐Control Study |
title_sort | bone nanomechanical properties and relationship to bone turnover and architecture in patients with atypical femur fractures: a prospective nested case‐control study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441274/ https://www.ncbi.nlm.nih.gov/pubmed/34532612 http://dx.doi.org/10.1002/jbm4.10523 |
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