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Dietary calcium intake and genetics have site-specific effects on peak trabecular bone mass and microarchitecture in male mice.

ABSTRACT: Trabecular bone (Tb) is used for rapid exchange of calcium (Ca) in times of physiologic need and the site-specific characteristics of Tb may explain why certain sites are more vulnerable to osteoporosis. We hypothesized that peak trabecular bone mass (PTBM) and Tb microarchitecture are differentially regulated by dietary Ca intake, genetics, or Gene-by-Diet (GxD) interactions at the distal femur and the fifth lumbar (L5) vertebra. Male mice from 62 genetically distinct lines were fed basal (0.5%) or low (0.25%) Ca diets from 4 to 12 wks of age. Afterwards, the right femur and L5 vertebra were removed and trabecular bone was analyzed by ?CT. In mice fed the basal diet, bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D) were significantly higher in the L5 vertebra than femur. Femur Tb had a weaker, more rod-like structure than the L5 vertebrae while mice fed the low Ca diet developed rod-like structures at both sites. Dietary Ca restriction also caused a greater relative reduction of Tb.N and Conn.D in the femur than L5 vertebra, i.e. it was more harmful to the integrity of Tb microarchitecture in femur. Genetics was a major determinant of Tb at both sites, e.g. heritability of BV/TV on the basal diet?=?0.65 (femur) and 0.68 (L5 vertebra). However, while GxD interactions altered the impact of dietary Ca restriction on Tb parameters at both sites, the effect was not uniform, e.g. some lines had site-specific responses to Ca restriction. The significance of our work is that there are site-specific effects of dietary Ca restriction and genetics that work independently and interactively to influence the attainment of PTBM and Tb microarchitecture.

SUBMITTER: Chanpaisaeng K

PROVIDER: S-EPMC6604851 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Dietary calcium intake and genetics have site-specific effects on peak trabecular bone mass and microarchitecture in male mice.

Chanpaisaeng Krittikan K Reyes Fernandez Perla C PC Fleet James C JC

Bone 20190509

Trabecular bone (Tb) is used for rapid exchange of calcium (Ca) in times of physiologic need and the site-specific characteristics of Tb may explain why certain sites are more vulnerable to osteoporosis. We hypothesized that peak trabecular bone mass (PTBM) and Tb microarchitecture are differentially regulated by dietary Ca intake, genetics, or Gene-by-Diet (GxD) interactions at the distal femur and the fifth lumbar (L5) vertebra. Male mice from 62 genetically distinct lines were fed basal (0.5% ...[more]

PMID: 31078711

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Project description:Adequate dietary calcium (Ca) intake is essential for bone accretion, peak bone mass (PBM) attainment, bone quality and strength during the mammalian growth period. Severe Ca deficiency during growing age results in secondary hyperparathyroidism (SHPT) and poor bone quality and strength. However, the impact of moderate Ca deficiency during rats early growth period on bone health and the reversibility with supplementing calcium later in adult life remains unclear. Female Sprague-Dawley (SD) rats (postnatal 28th day, P28) were initiated either with a moderate calcium-deficient diet (MCD, 0.25% w/w Ca) or a control diet (0.8% w/w Ca, control group) till P70. Thereafter, MCD rats were continued either with MCD diet or supplemented with calcium diet (0.8% w/w Ca, calcium supplemented group, CaS) till P150. Another group (control rats) were fed 0.8% w/w Ca containing diet from P28 till P150. MCD group, as compared to the control group, had significantly reduced serum ionized Ca and procollagen type 1 N-terminal propeptide (P1NP) at P70 while no significant change was observed in serum corrected Ca, inorganic phosphate (P), alkaline phosphatase (ALP), 25-hydroxy vitamin D [25(OH)D], intact parathyroid hormone (iPTH), and urinary C-terminal telopeptide of collagen 1 (CTX-1), Ca, and P. Femoral and tibial metaphysis in MCD rats had significantly reduced linear growth, cortical and trabecular volumetric BMD (vBMD), trabecular microarchitecture (BV/TV%, trabecular thickness, separation and number, structural model index and connectivity density), cortical thickness, and bone stiffness despite the absence of secondary hyperparathyroidism (SHPT). Continued MCD at P70-P150 results in persistence of compromised bone strength while calcium supplementation (CaS group) improved all the parameters related to bone strength and microarchitecture. Our results indicate that uncorrected moderate/subclinical calcium deficiency in growing rats can result in poor bone quality and strength despite the absence of SHPT. This finding could have relevance in children with poor calcium intake in childhood and adolescence.

Project description:Obesity is declared as a chronic multifaceted health problem, and young adults may be particularly vulnerable to weight gain. This study aims to identify the role of dietary calcium intake and the muscle strength index in handling excess of fat mass in young adults and to examine if the relationship between dietary calcium intake and fat mass percentage is mediated by muscle strength. A cross-sectional study including 355 Spanish college students (aged 21.05 ± 3.11) was performed during the 2017-2018 academic year. Pearson correlation coefficients were estimated to determine the relationship between dietary calcium intake, fat mass percentage, body mass index, muscle strength components, and total energy intake. ANCOVA models were used to analyze the differences in the muscle strength index by total dietary calcium intake categories, as well as the differences in % fat mass by total dietary calcium intake and muscle strength index categories, controlling for different sets of confounders. A mediator analysis was conducted to test if the relationship between dietary calcium intake and fat mass percentage was explained by muscle strength. Data on the fat mass percentage, dietary calcium intake, and muscle strength index as the sum of the standardized z-score of the standing long jump and z-score of handgrip/weight were collected. The muscle strength index was significantly better in young adults with higher dietary calcium intake. Moreover, the fat mass percentage was significantly lower in those with a higher dietary calcium intake and a better muscle strength index. Finally, the relationship between dietary calcium intake and fat mass percentage was fully mediated by muscle strength (z = -1.90; p < 0.05), explaining 33.33% of this relationship. This study suggests that both a major dietary calcium intake and muscle strength are associated with fat mass percentage. Moreover, muscle strength mediates the link between dietary calcium intake and fat mass percentage. Therefore, both high dietary calcium intake and exercise activities aimed at improving muscle strength levels may help to prevent the cardiometabolic risk associated with an excess of fat mass in young people.

Project description:In a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to one of three different doses of abaloparatide-SC, subcutaneous teriparatide, or placebo for 24 weeks, abaloparatide-SC resulted in improvements in skeletal microarchitecture as measured by the trabecular bone score. INTRODUCTION:Subcutaneous abaloparatide (abaloparatide-SC) increases total hip and lumbar spine bone mineral density and reduces vertebral and non-vertebral fractures. In this study, we analyzed the extent to which abaloparatide-SC improves skeletal microarchitecture, assessed indirectly by trabecular bone score (TBS). METHODS:This is a post hoc analysis of a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to abaloparatide-SC (20, 40, or 80 ?g), subcutaneous teriparatide (20 ?g), or placebo for 24 weeks. TBS was measured from lumbar spine dual X-ray absorptiometry (DXA) images in 138 women for whom the DXA device was TBS software compatible. Assessments were made at baseline, 12 and 24 weeks. Between-group differences were assessed by generalized estimating equations adjusted for relevant baseline characteristics, and a pre-determined least significant change analysis was performed. RESULTS:After 24 weeks, TBS increased significantly by 2.27, 3.14, and 4.21% versus baseline in participants on 20, 40, and 80 ?g abaloparatide-SC daily, respectively, and by 2.21% in those on teriparatide (p?<?0.05 for each). The TBS in the placebo group declined by 1.08%. The TBS increase in each treatment group was significantly higher than placebo at 24 weeks (p?<?0.0001 for each) after adjustment for age, BMI, and baseline TBS. A dose-response was observed at 24 weeks across the three doses of abaloparatide-SC and placebo (p?=?0.02). The increase in TBS in the abaloparatide-SC 80 ?g group was significantly greater than TPTD (p?<?0.03). CONCLUSIONS:These results are consistent with an effect of abaloparatide-SC to improve lumbar spine skeletal microarchitecture, as assessed by TBS.

Dataset Information

Dietary calcium intake and genetics have site-specific effects on peak trabecular bone mass and microarchitecture in male mice.

Publications

Dietary calcium intake and genetics have site-specific effects on peak trabecular bone mass and microarchitecture in male mice.

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