Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficent osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis (due to osteoclast defect) and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization). Osteopetrorickets, the paradoxical association of insufficient mineralization in the context of a positive total body calcium balance, is thought to occur due to the inability of the osteoclasts to maintain normal calcium–phosphorus homeostasis. However, osteoclast-specific Snx10 knockout had no effect on calcium balance, and therefore led to severe osteopetrosis without rickets. Moreover, supplementation with calcium gluconate rescued mice from the rachitic phenotype and dramatically extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis that has previously gone unrecognized. We conclude that tissue-specific effects of Snx10 mutation need to be considered in clinical approaches to this disease entity. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. These studies established an essential role for Snx10 in bone homeostasis and underscore the importance of gastric acidification in calcium uptake.

We assessed and compared the effects of swimming, jumping, and vibration therapies on the prevention of bone loss because of unloading. Eighty Wistar rats were randomly divided into eight groups: S, permanent hind limb-suspended rats; CON, control rats; S + Swim, unloading interrupted by swimming exercise; S + C(Swim), suspension interrupted by regular weight-bearing with the same duration as in the S + Swim protocol; S + Jump, unloading interrupted by jumping exercise; S + C(Jump), suspension interrupted for regular weight-bearing as in the S + Jump group; S + Vibr, unloading interrupted by vibration; and S + C(Vibr), suspension with interruptions for regular weight-bearing with the same protocol as that used for the S + Vibr rats. At the end of the experiment, the bone mineral density, bone strength, histomorphometric parameters, and serum levels of the bone markers were analyzed. The hind limb-suspended rats exhibited bone quality loss. In contrast, the trained rats showed a significant increase in bone mass, bone strength, bone formation, and serum levels of bone markers compared with the respective controls. Although we did not find a significant difference among the three physical exercises, the osteogenic effect of vibration was slightly lower than that of swimming and jumping. Thus, all physical exercises were efficient in preventing bone loss because of unloading and preserving bone quality.

The potential hazardous effects of secondhand smoke on fracture healing in rodents should stimulate future clinical studies in human passive smokers.

Spaceflight results in reduced mechanical loading of the skeleton, which leads to dramatic bone loss. Low bone mass is associated with increased fracture risk, and this combination may compromise future, long-term, spaceflight missions. Here, we examined the systemic effects of spaceflight and fracture surgery/healing on several non-injured bones within the axial and appendicular skeleton. Forty C57BL/6, male mice were randomized into the following groups: (1) Sham surgery mice housed on the earth (Ground + Sham); (2) Femoral segmental bone defect surgery mice housed on the earth (Ground + Surgery); (3) Sham surgery mice housed in spaceflight (Flight + Sham); and (4) Femoral segmental bone defect surgery mice housed in spaceflight (Flight + Surgery). Mice were 9 weeks old at the time of launch and were euthanized approximately 4 weeks after launch. Micro-computed tomography (μCT) was used to evaluate standard bone parameters in the tibia, humerus, sternebra, vertebrae, ribs, calvarium, mandible, and incisor. One intriguing finding was that both spaceflight and surgery resulted in virtually identical losses in tibial trabecular bone volume fraction, BV/TV (24-28% reduction). Another important finding was that surgery markedly changed tibial cortical bone geometry. Understanding how spaceflight, surgery, and their combination impact non-injured bones will improve treatment strategies for astronauts and terrestrial humans alike.

Standing frame and electrical stimulation may have potential as future therapeutic modalities to treat or prevent bone loss after SCI.

Diabetes Mellitus is a condition that predisposes a higher risk for the development of osteoporosis. The objective of this study was to investigate the influence of boron supplementation on bone microstructure and strength in control and non-obese diabetic mice for 30days. The animals were supplemented with 40μg/0,5ml of boron solution and controls received 0,5ml of distilled water daily. We evaluated the biochemical parameters: total calcium, phosphorus, magnesium and boron; bone analysis: bone computed microtomography, and biomechanical assay with a three point test on the femur. This study consisted of 28 animals divided into four groups: Group water control - Ctrl (n=10), Group boron control - Ctrl±B (n=8), Group diabetic water - Diab (n=5) and Group diabetic boron - Diab±B (n=5). The results showed that cortical bone volume and the trabecular bone volume fraction were higher for Diab±B and Ctrl±B compared to the Diab and Ctrl groups (p≤0,05). The trabecular specific bone surface was greater for the Diab±B group, and the trabecular thickness and structure model index had the worst values for the Diab group. The boron serum concentrations were higher for the Diab±B group compared to non-supplemented groups. The magnesium concentration was lower for Diab and Diab±B compared with controls. The biomechanical test on the femur revealed maintenance of parameters of the bone strength in animals Diab±B compared to the Diab group and controls. The results suggest that boron supplementation improves parameters related to bone strength and microstructure of cortical and trabecular bone in diabetic animals and the controls that were supplemented.

Vibration therapy improved bone quality and the quality of the fracture bone callus in ovariectomized rats.

RESUMO: Os nervos periféricos sofrem constantes lesões de origem traumática, o que resulta em perdas funcionais. A terapia com laser de baixa potência vem sendo utilizada para minimizar os efeitos maléficos da inflamação e acelerar o processo de cicatrização dos tecidos lesados. Este estudo teve como objetivo verificar o efeito da irradiação do laser 830 nm no comportamento do nervo isquiático de ratos submetido a esmagamento. Foram utilizados 20 ratos, todos tendo tido o nervo isquiático esmagado, divididos em 4 grupos (n=5): P7 e P14, tratamento placebo por 7 e 14 dias; L7 e L14, tratamento por laser (dosagem de 4 J/cm²) por 7 e 14 dias. Os animais dos grupos P7 e P14 foram submetidos aos mesmos procedimentos, mas com o laser desligado. Os parâmetros analisados foram presença de infiltrado inflamatório e fibroblastos, destruição da bainha de mielina e degeneração axonal. Na análise estatística foi observada diferença estatística com relação a três parâmetros: os animais do grupo L14 apresentaram maior quantidade de fibroblastos (p=0,0001), menor degeneração da bainha de mielina (p=0,007) e menor quantidade de infiltrado inflamatório (p=0,001). A aplicação do laser de baixa potência contribuiu para a redução do processo inflamatório decorrente da lesão do nervo isquiático de ratos. DESCRITORES: Nervo ciático; Regeneração nervosa; Síndromes de compressão nervosa/reabilitação; Terapia a laser de baixa intensidade ABSTRACT: Peripheral nerves are commonly subject to traumatic injuries, leading to functional loss. Low-power laser therapy has been used in order to minimize harmful effects of inflammation and to accelerate healing of injured tissues. The purpose of this study was to assess the effect of 830 nm-laser irradiation on rat sciatic nerves submitted to crush. Twenty male Wistar rats had their sciatic nerve crushed and were divided into 4 groups (n=5): Sham7 and Sham14, placebo-treated for 7 and 14 days; L7 and L14, laser-treated (at 4 J/cm²) for 7 and 14 days. Sham group animals were submitted to the same procedures, but with the laser turned off. Assessed parameters were inflammatory infiltrates, fibroblasts, myelin sheath destruction, and axonal degeneration. The statistical analysis showed significant differences in three parameters: L14 animals showed more fibroblasts (p=0.0001), lesser myelin sheath degeneration (p=0.007), and lesser inflammatory infiltrates (p=0.001). Low-power laser therapy hence contributed to reduce the inflammatory process due to rat sciatic nerve injury.