Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo
Patients at high risk of fracture due to metabolic diseases frequently undergo long-term antiresorptive therapy. However, in some patients, treatment is unsuccessful in preventing fractures or causes severe adverse health outcomes. Understanding load-driven bone remodelling, i.e., mechanoregulation,...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.677985/full |
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| author | Matthias Walle Francisco C. Marques Nicholas Ohs Michael Blauth Ralph Müller Caitlyn J. Collins |
| author_facet | Matthias Walle Francisco C. Marques Nicholas Ohs Michael Blauth Ralph Müller Caitlyn J. Collins |
| author_sort | Matthias Walle |
| collection | DOAJ |
| description | Patients at high risk of fracture due to metabolic diseases frequently undergo long-term antiresorptive therapy. However, in some patients, treatment is unsuccessful in preventing fractures or causes severe adverse health outcomes. Understanding load-driven bone remodelling, i.e., mechanoregulation, is critical to understand which patients are at risk for progressive bone degeneration and may enable better patient selection or adaptive therapeutic intervention strategies. Bone microarchitecture assessment using high-resolution peripheral quantitative computed tomography (HR-pQCT) combined with computed mechanical loads has successfully been used to investigate bone mechanoregulation at the trabecular level. To obtain the required mechanical loads that induce local variances in mechanical strain and cause bone remodelling, estimation of physiological loading is essential. Current models homogenise strain patterns throughout the bone to estimate load distribution in vivo, assuming that the bone structure is in biomechanical homoeostasis. Yet, this assumption may be flawed for investigating alterations in bone mechanoregulation. By further utilising available spatiotemporal information of time-lapsed bone imaging studies, we developed a mechanoregulation-based load estimation (MR) algorithm. MR calculates organ-scale loads by scaling and superimposing a set of predefined independent unit loads to optimise measured bone formation in high-, quiescence in medium-, and resorption in low-strain regions. We benchmarked our algorithm against a previously published load history (LH) algorithm using synthetic data, micro-CT images of murine vertebrae under defined experimental in vivo loadings, and HR-pQCT images from seven patients. Our algorithm consistently outperformed LH in all three datasets. In silico-generated time evolutions of distal radius geometries (n = 5) indicated significantly higher sensitivity, specificity, and accuracy for MR than LH (p < 0.01). This increased performance led to substantially better discrimination between physiological and extra-physiological loading in mice (n = 8). Moreover, a significantly (p < 0.01) higher association between remodelling events and computed local mechanical signals was found using MR [correct classification rate (CCR) = 0.42] than LH (CCR = 0.38) to estimate human distal radius loading. Future applications of MR may enable clinicians to link subtle changes in bone strength to changes in day-to-day loading, identifying weak spots in the bone microstructure for local intervention and personalised treatment approaches. |
| first_indexed | 2024-12-17T06:37:53Z |
| format | Article |
| id | doaj.art-eeaaabca5fc94e55b62ca2b4a5545104 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-17T06:37:53Z |
| publishDate | 2021-06-01 |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-eeaaabca5fc94e55b62ca2b4a55451042022-12-21T21:59:57ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-06-01910.3389/fbioe.2021.677985677985Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in VivoMatthias Walle0Francisco C. Marques1Nicholas Ohs2Michael Blauth3Ralph Müller4Caitlyn J. Collins5Institute for Biomechanics, ETH Zurich, Zurich, SwitzerlandInstitute for Biomechanics, ETH Zurich, Zurich, SwitzerlandInstitute for Biomechanics, ETH Zurich, Zurich, SwitzerlandDepartment for Trauma Surgery, Innsbruck University Hospital, Innsbruck, AustriaInstitute for Biomechanics, ETH Zurich, Zurich, SwitzerlandInstitute for Biomechanics, ETH Zurich, Zurich, SwitzerlandPatients at high risk of fracture due to metabolic diseases frequently undergo long-term antiresorptive therapy. However, in some patients, treatment is unsuccessful in preventing fractures or causes severe adverse health outcomes. Understanding load-driven bone remodelling, i.e., mechanoregulation, is critical to understand which patients are at risk for progressive bone degeneration and may enable better patient selection or adaptive therapeutic intervention strategies. Bone microarchitecture assessment using high-resolution peripheral quantitative computed tomography (HR-pQCT) combined with computed mechanical loads has successfully been used to investigate bone mechanoregulation at the trabecular level. To obtain the required mechanical loads that induce local variances in mechanical strain and cause bone remodelling, estimation of physiological loading is essential. Current models homogenise strain patterns throughout the bone to estimate load distribution in vivo, assuming that the bone structure is in biomechanical homoeostasis. Yet, this assumption may be flawed for investigating alterations in bone mechanoregulation. By further utilising available spatiotemporal information of time-lapsed bone imaging studies, we developed a mechanoregulation-based load estimation (MR) algorithm. MR calculates organ-scale loads by scaling and superimposing a set of predefined independent unit loads to optimise measured bone formation in high-, quiescence in medium-, and resorption in low-strain regions. We benchmarked our algorithm against a previously published load history (LH) algorithm using synthetic data, micro-CT images of murine vertebrae under defined experimental in vivo loadings, and HR-pQCT images from seven patients. Our algorithm consistently outperformed LH in all three datasets. In silico-generated time evolutions of distal radius geometries (n = 5) indicated significantly higher sensitivity, specificity, and accuracy for MR than LH (p < 0.01). This increased performance led to substantially better discrimination between physiological and extra-physiological loading in mice (n = 8). Moreover, a significantly (p < 0.01) higher association between remodelling events and computed local mechanical signals was found using MR [correct classification rate (CCR) = 0.42] than LH (CCR = 0.38) to estimate human distal radius loading. Future applications of MR may enable clinicians to link subtle changes in bone strength to changes in day-to-day loading, identifying weak spots in the bone microstructure for local intervention and personalised treatment approaches.https://www.frontiersin.org/articles/10.3389/fbioe.2021.677985/fullbone loading estimationmechanoregulationfinite element analysisbone remodellinghuman distal radiusmouse caudal vertebra |
| spellingShingle | Matthias Walle Francisco C. Marques Nicholas Ohs Michael Blauth Ralph Müller Caitlyn J. Collins Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo Frontiers in Bioengineering and Biotechnology bone loading estimation mechanoregulation finite element analysis bone remodelling human distal radius mouse caudal vertebra |
| title | Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo |
| title_full | Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo |
| title_fullStr | Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo |
| title_full_unstemmed | Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo |
| title_short | Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo |
| title_sort | bone mechanoregulation allows subject specific load estimation based on time lapsed micro ct and hr pqct in vivo |
| topic | bone loading estimation mechanoregulation finite element analysis bone remodelling human distal radius mouse caudal vertebra |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.677985/full |
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