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A recent study suggests that activin inhibits bone matrix mineralization, whereas treatment of mice with a soluble form of the activin type IIA receptor markedly increases bone mass and strength. To further extend these observations, we determined the skeletal effects of inhibiting activin signaling through the ActRIIA receptor in a large animal model with a hormonal profile and bone metabolism similar...
Sex steroid hormones are major determinants of bone morphology and quality and are responsible for sexually dimorphic skeletal traits. Hypogonadism results in suboptimal skeletal development and may lead to an increased risk of bone fracture later in life. The etiology of delayed puberty and/or hypothalamic amenorrhea is poorly understood, and experimental animal models addressing this issue are predominantly...
Femoral neck (FN) bone geometry is an important predictor of bone strength with high heritability. Previous studies have revealed certain candidate genes for FN bone geometry. However, the majority of the underlying genetic factors remain to be discovered. In this study, pathway-based genome-wide association analysis was performed to explore the joint effects of genes within biological pathways on...
In the Dosing IntraVenous Administration (DIVA) study, IV ibandronate injections (15–30 s duration) provided significantly greater gains in bone mineral density than daily oral ibandronate (P<0.001). Single transiliac bone biopsy was performed in a subgroup of women (n=109/1395) from DIVA to assess the impact of ibandronate on newly formed bone and bone remodeling. Patients received ibandronate...
Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone...
Glucocorticoid administration is required for many inflammatory and autoimmune diseases, but use of these drugs is associated with skeletal side effects including bone loss, fractures, and osteonecrosis. Fractures often occur without a reduction in bone mineral density, strongly suggesting that glucocorticoid excess adversely affects other aspects of bone strength. Although the primary effects of...
The strong association between body mass and skeletal robusticity has been attributed to increasing skeletal loading with increasing mass. However, it is unclear whether body mass is merely a coarse substitute for bone loading rather than a true independent predictor of bone strength. As indices of neuromuscular performance, impulse and peak power were determined from vertical ground reaction force...
Understanding the influence of total body fat mass (TBFM) on bone during the peri-pubertal years is critical for the development of future interventions aimed at improving bone strength and reducing fracture risk. Thus, we evaluated the relationship of TBFM to volumetric bone mineral density (vBMD), geometry, and strength at metaphyseal and diaphyseal sites of the femur and tibia of young girls. Data...
Both bone density and quality are important determinants of bone strength. Bone quality is prescribed by matrix characteristic including collagen cross-linking and bone structural characteristics and is important in reinforcement of bone strength. We investigated the effects of alfacalcidol (ALF), a prodrug of calcitriol, and alendronate (ALN), a bisphosphanate, on the mechanical properties and content...
Weight loss is claimed to cause bone loss. This prospective 12-month study evaluated effects of 3-month group-based weight loss with VLED on body composition, bone mass and strength (DXA and pQCT), muscle performance and biomarkers of bone turnover. The assessments were done at baseline and at 3 and 12 months. Sixty-two women of the recruited 75 obese (BMI>30) premenopausal women who completed...
Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism.Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body...
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