Naringin Prevents Bone Damage in the Experimental Metabolic Syndrome Induced by a Fructose Rich Diet

We have analyzed the effect of naringin (NAR), a flavonoid from citric fruits, on bone quality and bone biomechanical properties as well as the redox state of bone marrow in rats fed a fructose rich diet (FRD), an experimental model to mimic human metabolic syndrome. NAR blocked the enhancement in the number of osteoclasts and adipocytes and the decrease in the number of osteocytes and osteocalcin (+) cells caused by FRD. The trabecular number was significantly higher in the FRD+NAR group. FRD induced a decrease in femoral trabecular and cortical bone mineral density, which was blocked by NAR. The fracture and ultimate loads were also decreased by the FRD and FRD+NAR groups. NAR increased the number of nodes to terminal trabecula, the number of nodes to node trabecula, the number of nodes, and the number of nodes with two terminals, and decreased the Dist (mean size of branches) value. Bone marrow catalase activity was decreased by the FRD, an effect prevented by NAR. In conclusion, FRD produces detrimental effects on long bones, which are associated with oxidative stress in bone marrow. Most of these changes are avoided by NAR through its antioxidant properties and promotion of bone formation. Novelty bullets: • Fructose rich diet produces detrimental effects on long bones, which are associated with oxidative stress in bone marrow. • Most of these changes are avoided by Naringin through its antioxidant properties and promotion of bone formation.

The Mid-Diaphysis Is a Poor Predictor of Humeral Fracture Risk Indicating That Predisposing Factors Are Recent

The incidence of spontaneous humeral fractures in first-lactation dairy heifers in New Zealand has emphasised the need to understand the thoracic limb bone growth of dairy heifers. Previous research has indicated that a predisposing factor to spontaneous humeral fracture is nutrition. In addition, it has been hypothesised that liver copper concentration affects bone strength and may be a potential factor associated with humeral fracture risk. The aim of this study was to compare bone morphology in the mid-diaphysis of the metacarpus and humerus of heifers affected and unaffected by spontaneous humeral fractures, and determine the effect of copper status at death on bone morphology. The metacarpus and humerus were collected from heifers affected and unaffected by humeral fractures, and scanned using peripheral quantitative computed tomography (pQCT). The mid-diaphysis of the humerus of the affected group had reduced cortical bone mineral density and a trend for reduced cortical content and total bone content, which contributed to a reduced stress–strain index. The trend for reduced bone length in affected humeri provides additional support for the hypothesis of inhibited humeral growth. Heifers with low copper liver concentrations had reduced humerus lengths and reduced cortical bone mineral densities. These data support the hypothesis that the developmental window for humeral fracture is recent, and possibly associated with periods of inadequate nutrition.

Tissue selective effects of bazedoxifene on the musculoskeletal system in female mice

The actions of selective estrogen receptor modulators are tissue dependent. The primary objective of the current study was to determine the tissue selective effects of bazedoxifene (BZA) on the musculoskeletal system of ovariectomized (OVX) female mice, focusing on strengths of muscle-bone pairs in the lower hindlimb. Treatment with BZA after ovariectomy (OVX+BZA) did not prevent body or fat mass gains (p<0.05). In vivo plantarflexor muscle isometric torque was not affected by treatment with BZA (p=0.522). Soleus muscle peak isometric, concentric and eccentric tetanic force production were greater in OVX+BZA mice compared to OVX+E2 mice (p≤0.048) with no effect on maximal isometric specific force (p=0.228). Tibia from OVX+BZA mice had greater cortical cross-sectional area and moment of inertia than OVX mice treated with placebo (p<0.001), but there was no impact of BZA treatment on cortical bone mineral density, cortical thickness, tibial bone ultimate load or stiffness (p≥0.086). Overall, these results indicate that BZA may be an estrogen receptor agonist in skeletal muscle, as it has previously been shown in bone, providing minor benefits to the musculoskeletal system.

Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity

Obesity remodels bone and increases bone marrow adipocytes (BMAT), which negatively regulate hematopoiesis and bone. Reduced BMAT could restore altered hematopoiesis and bone features. We analyzed the potential of erythropoietin (EPO), the cytokine required for erythropoiesis, to inhibit BMAT in C57BL6/J mice fed four weeks of a high-fat diet (HFD). Acute EPO administration markedly decreased BMAT in regular chow diet (RCD) and HFD-fed mice, without affecting whole body fat mass. Micro-CT analysis showed EPO reduced trabecular bone in RCD- and HFD-fed mice, but EPO-treated HFD-fed mice maintained cortical bone mineral density and cortical bone volume, which was reduced on RCD. Despite achieving similar increased hematocrits with BMAT loss in RCD- and HFD-fed mice treated with EPO, decreased bone marrow cellularity was only observed in RCD-fed mice concomitant with an increasing percentage of bone marrow erythroid cells. In contrast, in HFD-fed mice, EPO increased endothelial cells and stromal progenitors with a trend toward the normalization of marrow homeostasis. EPO administration increased c-terminal FGF23 and intact serum FGF23 only in HFD-fed mice. These data demonstrate the distinct EPO responses of bone and marrow in normal and obese states, accompanying EPO-induced loss of BMAT.

Effect of Nano-Montmorillonite on Osteoblast Differentiation, Mineral Density, and Osteoclast Differentiation in Bone Formation

Calcium-type montmorillonite, a phyllosilicate mineral, has diverse health benefits when introduced into the gastrointestinal tract or applied to the skin. However, the predominant use of this layered material has thus far been in traditional industries, despite its potential application in the pharmaceutical industry. We investigated the effects and mechanism of nano-montmorillonite (NM) on osteoblast and osteoclast differentiation in vivo and in vitro. We examined the osteogenic effects of NM with high calcium content (3.66 wt%) on alkaline phosphatase (ALP) activity, mineralization, bone microarchitecture, and expression level of osteoblast and osteoclast related genes in Ca-deficient ovariectomized (OVX) rats. Micro-computed tomography of OVX rats revealed that NM attenuated the low-Ca-associated changes in trabecular and cortical bone mineral density. It improved ALP activity and mineralization, as well as the expression of osteoblast and osteoclast differentiation associated genes. NM also activated the expression of runt-related transcription factor 2, osteocalcin, bone morphogenetic protein 2, and type 1 collagen via phosphorylated small mothers against decapentaplegic homolog 1/5/8 signaling. Further, NM repressed the expression of receptor activator for cathepsin K, nuclear factor kappa-B ligand and tartrate-resistant acid phosphatase. Therefore, NM inhibits osteoclastogenesis, stimulates osteoblastogenesis, and alleviates osteoporosis.

Effect of prenatal calcium supplementation on bone during pregnancy and 1 y postpartum

ABSTRACT Background Low calcium intake during pregnancy may cause maternal skeletal calcium mobilization to meet fetal needs. The Recommended Dietary Allowance (RDA) for calcium in nonpregnant, pregnant, or lactating women aged 19–50 y is 1000 mg/d; most women in the United States report consuming 60–80% of the calcium RDA. An insufficient calcium intake could increase maternal bone loss during pregnancy and reduce bone recovery postpartum. Objectives The aim of this study was to determine the effect of maternal calcium supplementation on peripheral cortical and trabecular bone loss during pregnancy and bone gain postpartum. Methods A total of 64 women were enrolled in the study at 16 wk of gestation and randomly assigned to receive 1000 mg Ca/d or placebo for the remainder of the pregnancy. Measurements were performed at 16, 26, and 36 wk of pregnancy and at 4 and 12 mo postpartum for serum 25-hydroxyvitamin D and markers of bone turnover. Trabecular and cortical bone mineral density (BMD) and content were assessed at the tibia and radius by peripheral quantitative computed tomography. Results Mean ± SD daily calcium intake at baseline was 733 ± 350 mg; only 25% of the women met the RDA. Thirty women (47% of those enrolled) remained in the study at 12 mo postpartum. After controlling for baseline bone value, serum 25-hydroxyvitamin D concentrations, length of breastfeeding, and body mass index, the calcium group had significantly greater increases in radial total BMD (P = 0.02) and tibial cortical BMD (P = 0.03) at 12 mo postpartum than the placebo group. Trabecular and total BMD at the tibia trended toward higher values (P &lt; 0.06) in the calcium group than in the placebo group in the same models. Conclusions These data show that supplemental calcium provided during pregnancy may improve bone recovery postpartum in women consuming a typical US diet. A larger study is warranted to solidify the conclusions. This trial was registered at clinicaltrials.gov as NCT01145573.