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ABSTRACT Cortical bone quality, which is sexually dimorphic, depends on bone turnover and therefore on the activities of remodeling bone cells. However, sex differences in cortical bone metabolism are not yet defined. Adding to the uncertainty about cortical bone metabolism, the metabolomes of whole bone, isolated cortical bone without marrow, and bone marrow have not been compared. We hypothesized that the metabolome of isolated cortical bone would be distinct from that of bone marrow and would reveal sex differences. Metabolite profiles from liquid chromatography–mass spectrometry (LC‐MS) of whole bone, isolated cortical bone, and bone marrow were generated from humeri from 20‐week‐old female C57Bl/6J mice. The cortical bone metabolomes were then compared for 20‐week‐old female and male C57Bl/6J mice. Femurs from male and female mice were evaluated for flexural material properties and were then categorized into bone strength groups. The metabolome of isolated cortical bone was distinct from both whole bone and bone marrow. We also found sex differences in the isolated cortical bone metabolome. Based on metabolite pathway analysis, females had higher lipid metabolism, and males had higher amino acid metabolism. High‐strength bones, regardless of sex, had greater tryptophan and purine metabolism. For males, high‐strength bones had upregulated nucleotide metabolism, whereas lower‐strength bones had greater pentose phosphate pathway metabolism. Because the higher‐strength groups (females compared with males, high‐strength males compared with lower‐strength males) had higher serum type I collagen cross‐linked C‐telopeptide (CTX1)/procollagen type 1 N propeptide (P1NP), we estimate that the metabolomic signature of bone strength in our study at least partially reflects differences in bone turnover. These data provide novel insight into bone bioenergetics and the sexual dimorphic nature of bone material properties in C57Bl/6 mice. © 2022 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Age and Sex Differences in Load‐Induced Tibial Cortical Bone Surface Strain Maps
ABSTRACT Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano‐adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load‐related strains vary with age and sex. In this study, full‐field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old (aged 10, 22 weeks, and 20 months, respectively), male and female C57BL/6J mice with load applied using a noninvasive murine tibial model. Strain maps indicate a nonuniform strain field across the tibial surface, with axial compressive loads resulting in tension on the medial side of the tibia because of its curved shape. The load‐induced surface strain patterns and magnitudes show sexually dimorphic changes with aging. A comparison of the average and peak tensile strains indicates that the magnitude of strain at a given load generally increases during maturation, with tibias in female mice having higher strains than in males. The data further reveal that postmaturation aging is linked to sexually dimorphic changes in average and maximum strains. The strain maps reported here allow for loading male and female C57BL/6J mouse legs in vivo at the observed ages to create similar increases in bone surface average or peak strain to more accurately explore bone mechano‐adaptation differences with age and sex. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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- Award ID(s):
- 1829310
- PAR ID:
- 10449829
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- JBMR Plus
- Volume:
- 5
- Issue:
- 3
- ISSN:
- 2473-4039
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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