{"doi":"10.1242/jeb.085522","title":"Load-induced changes in bone stiffness and cancellous and cortical bone mass following tibial compression diminish with age in female mice","abstract":"<jats:title>Abstract</jats:title><jats:p>The vertebrate skeleton is an adaptive structure that responds to mechanical stimuli by increasing bone mass under increased mechanical loads. Although experimental animal models have shown the anabolic cortical bone response to applied load decreases with age, no consensus exists regarding whether this adaptive mechanism is affected by age in cancellous bone, the tissue most impacted by age-related bone loss. We used an established murine in vivo tibial loading model to characterize the load-induced cancellous, cortical, and whole bone responses to mechanical stimuli in growing and mature female mice at 6, 10, and 16wks of age. The effects of applied load on tibial morphology and stiffness were determined using microcomputed tomography and in vivo bone strains measured at the medial tibial midshaft during applied loading. At all ages, two weeks of applied load produced larger midshaft cortical cross-sectional properties (+13-72%) and greater cancellous bone volume (+21-107%) and thicker trabeculae (+31-68%) in the proximal metaphyses of the loaded tibiae. The relative anabolic response decreased from 6wks to 16wks of age in both the cancellous and cortical envelopes. Load-induced tibial stresses decreased more in 6wk old mice following loading, which corresponded to increased in vivo tibial stiffness. Stiffness in the loaded tibiae of 16wk old mice decreased despite moderately increased cortical cross-sectional geometry, suggesting load-induced changes in bone material properties. This study shows that the cancellous and cortical anabolic responses to mechanical stimuli decline with age into adulthood and that cortical cross-sectional geometry alone does not necessarily predict whole bone functional stiffness.</jats:p>","journal":"Journal of Experimental Biology","year":2014,"id":686397,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1793208,"name":"Maureen E. Lynch","orcid":null,"position":1,"is_corresponding":false},{"id":1793209,"name":"Marjolein C.H. van der Meulen","orcid":null,"position":2,"is_corresponding":false},{"id":381480,"name":"Russell P. Main","orcid":"0000-0001-7607-1647","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Load-induced changes in bone stiffness and cancellous and cortical bone mass following tibial compression diminish with age in female mice","abstract":"The vertebrate skeleton is an adaptive structure that responds to mechanical stimuli by increasing bone mass under increased mechanical loads. Although experimental animal models have shown the anabolic cortical bone response to applied load decreases with age, no consensus exists regarding whether this adaptive mechanism is affected by age in cancellous bone, the tissue most impacted by age-related bone loss. We used an established murine in vivo tibial loading model to characterize the load-induced cancellous, cortical and whole-bone responses to mechanical stimuli in growing and mature female mice at 6, 10 and 16 weeks of age. The effects of applied load on tibial morphology and stiffness were determined using microcomputed tomography and in vivo bone strains measured at the medial tibial midshaft during applied loading. At all ages, 2 weeks of applied load produced larger midshaft cortical cross-sectional properties (+13-72%) and greater cancellous bone volume (+21-107%) and thicker trabeculae (+31-68%) in the proximal metaphyses of the loaded tibiae. The relative anabolic response decreased from 6 to 16 weeks of age in both the cancellous and cortical envelopes. Load-induced tibial stresses decreased more in 6-week-old mice following loading, which corresponded to increased in vivo tibial stiffness. Stiffness in the loaded tibiae of 16-week-old mice decreased despite moderately increased cortical cross-sectional geometry, suggesting load-induced changes in bone material properties. This study shows that the cancellous and cortical anabolic responses to mechanical stimuli decline with age into adulthood and that cortical cross-sectional geometry alone does not necessarily predict whole-bone functional stiffness.","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24577445","pmcid":"PMC4020944","openalex_id":"https://openalex.org/W2159876918","authors":[],"funders":[{"funder_name":"NIAMS NIH HHS","grant_id":"F32-AR054676","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG028664","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01-AG028664","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"F32 AR054676","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"P30 AR046121","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"P30-AR46121","title":null}],"total_grants":6,"fwci":3.9106,"citation_percentile":0.93631172,"influential_citations":0,"citation_trend":[{"year":2015,"count":8},{"year":2016,"count":3},{"year":2017,"count":5},{"year":2018,"count":3},{"year":2019,"count":11},{"year":2020,"count":4},{"year":2021,"count":3},{"year":2022,"count":2},{"year":2023,"count":8},{"year":2024,"count":4},{"year":2025,"count":5}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://doi.org/10.1242/jeb.085522","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24577445","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4020944","host_type":"repository"},{"url":"http://jeb.biologists.org/cgi/content/short/217/10/1775","host_type":"repository"}],"fields_of_study":["Bone health and osteoporosis research","Spaceflight effects on biology","Bone fractures and treatments","Aging","Animals","Bone Density","Female","Mice","Mice, Inbred C57BL","Stress, Mechanical","Tibia","Weight-Bearing","X-Ray Microtomography"],"mesh_terms":["Aging","Animals","Female","Mice, Inbred C57BL","Stress, Mechanical","Tibia","Bone Density","Weight-Bearing","Mice","X-Ray Microtomography"],"keywords":["Cancellous bone","Cortical bone","Tibia","Anabolism","Mechanical load","Anatomy","X-ray microtomography","Bone mass","In vivo","Chemistry","Medicine","Materials science","Biology","Endocrinology","Osteoporosis","Mouse","Bone","Stiffness","Cortical","Load","Cancellous"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T19:23:00.369276Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}