Effects of Raloxifene and tibial loading on bone mass and mechanics in male and female mice

Berman, Alycia G.; Damrath, John G.; Hatch, Jennifer M.; Pulliam, Alexis; Powell, Katherine M.; Hinton, Madicyn J.; Wallace, Joseph M.

doi:10.1080/03008207.2020.1865938

Cited by 11 publications

(13 citation statements)

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“…4.2 Bone is sexually dimorphic across many length-scales, including the metabolome Our results build on previous work that mouse bone properties are sexually dimorphic (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) . We observed that male mice have greater femur trabecular bone microarchitecture and have higher serum biomarkers of bone formation.…”

Section: Discussionsupporting

confidence: 71%

“…The purpose of this study was to (1) evaluate differences in the metabolomes of whole bone (i.e., cortical and trabecular bone and marrow), isolated cortical bone, and bone marrow (2) assess if the cortical bone metabolome is sexually dimorphic, and (3) determine if metabolomic differences correspond with whole bone strength, a sexually dimorphic cortical bone material property.…”

Section: Introductionmentioning

confidence: 99%

“…Sex differences exist in mouse bone tissue across several length scales (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) . In C57Bl/6 mice, females and males frequently exhibit different whole bone material properties (1,5,6,8,10) Females can have statistically significantly higher bone strength (5) , although more commonly studies report data that suggest that females have increased strength for females but do not specifically test sex differences (1,5,10) . In other work with BALB/c mice, 6 months old females have higher modulus and tougher femurs than males, but femur strength does not differ (17) .…”

Section: Introductionmentioning

confidence: 99%

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The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

Welhaven

Vahidi

Walk

et al. 2021

Preprint

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The material properties of bone tissue depend on the activity of remodeling bone cells, but the impact of bone cell metabolism on bone tissue is uncertain. To date, the metabolome of bone has not been evaluated for cortical bone, bone marrow, or whole bone including both tissue types. Furthermore, it is of particular interest whether the cortical bone metabolome reflects the sexual dimorphism observed in cortical bone material properties. We hypothesized that the metabolome of cortical bone differs from that of bone marrow, and that the cortical bone metabolome is sexually dimorphic. We first evaluated the metabolic profiles of isolated cortical bone, bone marrow, and whole bone for 20-week female C57Bl/6 mice (n = 10). We then compared metabolic profiles for isolated cortical bone from a separate group of 20-week female and male C57Bl6/mice (n = 10 / sex). Femurs from the same mice were evaluated for flexural material properties. Strength groupings (high strength males, high strength females, low strength males) were utilized to inform comparisons in the isolated humerus cortical bone metabolome. The metabolome of isolated cortical bone, bone marrow, and whole bone are distinct. The isolated cortical bone metabolome is also distinct between males and females. The female mice show evidence of lipid metabolism, whereas male mice show evidence of amino acid metabolism. Finally, 12 metabolic pathways were differentially regulated between bones that differed in strength. High-strength bones from both male and female mice included metabolites associated with tryptophan and purine metabolism. Taken together, these data demonstrate the power of metabolomics to provide insight into the effects of metabolism on bone physiology. These data add to an intricate picture of bone as an organ that is sexually dimorphic both in material and metabolomic profiles.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

Welhaven

Vahidi

Walk

et al. 2021

Preprint

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“…Figure 4 A showed that bone volume (BV/TV) was similar and comparable for G2 (CFD + CaCO 3 ) and G3–G5 (CFD + ICa + ), but higher than G1 (CFD) for all supplemented groups. The BV/TV is an essential microstructural parameter of the new generation of bone, which was documented in papers [ 49 , 50 , 51 ]. This is a relevant result because ICa + can promote de novo bone production in the mice model implemented, i.e., calcium supplementation with CaCO 3 or ICa + for 6 weeks preserved a similar microstructure of the mice’s bone tissue.…”

Section: Resultsmentioning

confidence: 99%

“…This is a relevant result because ICa + can promote de novo bone production in the mice model implemented, i.e., calcium supplementation with CaCO 3 or ICa + for 6 weeks preserved a similar microstructure of the mice’s bone tissue. There are experiments with similar time of treatment, such as six weeks, as shown by Berman et al [ 49 ] with Raloxifene (a selective estrogen receptor modulator), which demonstrated efficacy in preventing osteoclastic activity and promoting osteoblastic activity.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of an Ionic Calcium Fiber Supplement and Its Impact on Bone Health Preservation in a Dietary Calcium Deficiency Mice Model

et al. 2022

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ionic calcium can help in the prevention of the process of osseous decalcification. This study aimed to evaluate the physicochemical properties and toxic effects of ionic calcium-fiber supplement (ICa+) and its impact on bone health preservation in mice C57/BL6 fed a calcium-deficient diet. Physicochemical properties include FTIR, apparent calcium solubility estimated by the calcium ratio obtained by ionization chromatography and atomic absorption. In vitro genotoxicity and cytotoxicity of the ICa+ were assessed. Twenty-five 7-week-old C57/BL6 mice were fed calcium-free diet (CFD) or CFD plus CaCO3 (1.33 mg Ca) or CFD plus ICa+ (1.33–6.66 mg Ca) for six weeks. After that, bone mass and microstructure parameters were assessed. Histological staining was performed to determine calcium deposits. ICa+ (100%) exhibited an apparent calcium solubility higher than CaCO3 (12.3%). ICa+ showed no cytotoxic and genotoxic in vitro activities. Histomorphometry analysis showed that the ICa+ treated group displayed a higher trabecular number than the trabecular space. Also, the ratio BV/TV was increased compared with all treatments. Ionic calcium-fiber supplementation prevents bone deterioration compared to mice fed a calcium-deficient diet.

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The Cortical Bone Metabolome of C57BL/6J Mice Is Sexually Dimorphic

et al. 2022

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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 lowerstrength 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.

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Effects of Raloxifene and tibial loading on bone mass and mechanics in male and female mice

Cited by 11 publications

References 50 publications

The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

Evaluation of an Ionic Calcium Fiber Supplement and Its Impact on Bone Health Preservation in a Dietary Calcium Deficiency Mice Model

The Cortical Bone Metabolome of C57BL/6J Mice Is Sexually Dimorphic

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