Osteoporosis and autophagy: What is the relationship? / Osteoporose e autofagia: qual é a relação?

Summary Autophagy is a survival pathway wherein non-functional proteins and organelles are degraded in lysosomes for recycling and energy production. Therefore, autophagy is fundamental for the maintenance of cell viability, acting as a quality control process that prevents the accumulation of unnecessary structures and oxidative stress. Increasing evidence has shown that autophagy dysfunction is related to several pathologies including neurodegenerative diseases and cancer. Moreover, recent studies have shown that autophagy plays an important role for the maintenance of bone homeostasis. For instance, in vitro and animal and human studies indicate that autophagy dysfunction in bone cells is associated with the onset of bone diseases such as osteoporosis. This review had the purpose of discussing the issue to confirm whether a relationship between autophagy dysfunction and osteoporosis exits.

Resumo A autofagia é uma via de sobrevivência celular pela qual proteínas e organelas não funcionais são degradadas nos lisossomos, para reciclagem e geração de energia. Assim, a autofagia é fundamental para a manutenção da homeostase e viabilidade da célula, agindo como um controle de qualidade que evita o acúmulo de estruturas desnecessárias e o estresse oxidativo. Um número crescente de estudos tem demonstrado que disfunções na via autofágica estão relacionadas ao surgimento de diversas doenças, como as neurodegenerativas e o câncer. Estudos também têm indicado que a autofagia exerce um importante papel para a manutenção da homeostase óssea; por exemplo, estudos in vitro e em animais e humanos mostram que disfunções da autofagia nas células ósseas estão associadas ao surgimento de doenças ósseas, como a osteoporose. Nesta revisão, foram abordados esses estudos, a fim de melhor esclarecer se há uma relação entre disfunção autofágica e osteoporose.

In vivo bone response and interfacial properties of titanium-alloy implant with different designs in rabbit model with time.

Background: Using implants for dental applications are well-accepted procedures as one of the solutions for periodontal defect repair. Suitable design and materials, their reaction with the surrounding hard tissues and interfacial biomechanical properties are still considered to be the primary criteria which need to be addressed systematically. In the present study, a thorough and systemic approach was made to identify a suitable implant, considering the above criteria after both in vitro and in vivo animal trials. Materials and Methods: Titanium alloy (Ti-6Al-4V) implants, with thread and without thread models, were implanted to the mid-metaphysial portion of the tibia of the right hind leg of three white Australian Chinchilla rabbit species and their effects and response to the surrounding bone were investigated. Parameters studied included hematological and biochemical features (serum alkaline phosphatase and calcium), both preoperatively and postoperatively, consecutively for 7 days and after 1-3 months. The interfacial integrity and compositional variation along the interface were studied using scanning electron microscope (SEM) with energy dispersive analysis of X-ray (EDAX) and histopathology from 1 to 3 months consecutively. Finally, biomechanical properties were studied with the help of push-out test. Results: Bone remineralization started through the process of electro-physiological ionic exchanges, which helps in formation of osteoblastic cells in the area of bony injury. The SEM-EDAX results confirmed the initial stability for the Ti (with thread) implant, but the regeneration of new bone formation was faster in the case of Ti (Without thread) implant, and hence could be used for faster healing. These have also been substantiated through push-out and histopathlogical tests. Conclusion: From the physico-chemical and biomechanical observations, it was found that that smooth type implants were well accepted in the physiological condition although chances of elemental leaching from the surface were also observed. Increase of the surface roughness can help into the formation of physico-chemical bondage with the surrounding hard tissues.

Lipogranuloma with Osseous Metaplasia in the Breast That Developed after "Bu-Hwang" Oriental Medicine Treatment

A lipogranuloma is an inflammatory reactive process associated with exogenous or endogenous lipids, and it's occurrence in the breast has rarely been reported. Osseous metaplasia, which is used to describe bone formation in abnormal locations, can develop from several conditions such as trauma or a tumor. However, few studies have reported benign breast lesions that have been seen as osseous metaplasia. We present a case of a benign calcified breast lesion that developed after a traumatic treatment process called "Bu-Hwang", and it was confirmed as a lipogranuloma with osseous metaplasia. To the best of our knowledge, this is the first reported case of a lipogranuloma with osseous metaplasia in the breast.

Bone regeneration after demineralized bone matrix and castor oil (Ricinus communis) polyurethane implantation

Innocuous biocompatible materials have been searched to repair or reconstruct bone defects. Their goal is to restore the function of live or dead tissues. This study compared connective tissue and bone reaction when exposed to demineralized bovine bone matrix and a polyurethane resin derived from castor bean (Ricinus communis). Forty-five rats were assigned to 3 groups of 15 animals (control, bovine bone and polyurethane). A cylindrical defect was created on mandible base and filled with bovine bone matrix and the polyurethane. Control group received no treatment. Analyses were performed after 15, 45 and 60 days (5 animals each). Histological analysis revealed connective tissue tolerance to bovine bone with local inflammatory response similar to that of the control group. After 15 days, all groups demonstrated similar outcomes, with mild inflammatory reaction, probably due to the surgical procedure rather than to the material. In the polymer group, after 60 days, scarce multinucleated cells could still be observed. In general, all groups showed good stability and osteogenic connective tissue with blood vessels into the surgical area. The results suggest biocompatibility of both materials, seen by their integration into rat mandible. Moreover, the polyurethane seems to be an alternative in bone reconstruction and it is an inexhaustible source of biomaterial.

Influence of simvastatin on bone regeneration of tibial defects and blood cholesterol level in rats

The purpose of this study was to evaluate the effects of simvastatin, by oral or subcutaneous administration, on tibial defects regeneration and blood cholesterol level in rats. A surgical defect was made on the right tibia of 40 male animals assigned to 4 groups (n=10), based on two routes of administration and on the use or not of simvastatin: subcutaneous injection of simvastatin (7 mg/kg) (group AT) or only the vehicle of drug suspension (group AC), above the defect area, for 5 days; and 20 mg/kg of simvastatin macerated on water (group BT) or only water (group BC), orally, daily, during the whole observation period. The animals were sacrificed after 15 or 30 days, when blood samples were analyzed to check plasma cholesterol levels. Tibiae were removed and, after decalcification and routine laboratorial processing, histological and histomorphometrical analyses were carried out. ANOVA was used for statistical analysis at 5 percent signficance level. The histological and histomorphometrical analyses showed significant differences only between the experimental periods (p<0.05). Animals sacrificed after 30 days showed better bone repair (p<0.05). There was no statistically significant difference (p>0.05) for blood cholesterol levels between the groups. In conclusion, simvastatin administration either orally or subcutaneously did not improve bone repair of experimental tibial defects and did not alter blood cholesterol levels in rats.

Este estudo avaliou a influência da sinvastatina, administrada por via oral ou subcutânea, na reparação de defeitos ósseos em tíbia e nos níveis de colesterol sangüíneo, em ratos. Foram realizados defeitos cirúrgicos nas tíbias direitas de 40 ratos machos, distribuídos em 4 grupos (n=10), tomando-se como base duas vias de administração e o uso ou não de sinvastatina: injeção subcutânea de sinvastatina (7 mg/kg) (grupo AT) ou apenas do veículo de suspensão da droga (grupo AC), sobre a região do defeito, durante 5 dias; 20 mg/kg de sinvastatina (grupo BT) ou água filtrada (grupo BC) via oral, diariamente, durante todo o período de observação. Os animais foram sacrificados após 15 ou 30 dias, quando amostras sangüíneas foram colhidas para análise do nível de colesterol. As tíbias foram removidas e, após descalcificação e procedimentos laboratoriais de rotina, procedeu-se à análise histológica e histomorfométrica. Para avaliação estatística utilizou-se ANOVA com nível de significância de 5 por cento. As análises histomorfométrica e histológica mostraram diferença entre os grupos apenas com relação ao período experimental (p<0,05), apresentando os melhores resultados os animais sacrificados em 30 dias (p<0,05). Quanto ao nível de colesterol sangüíneo, não houve diferença estatisticamente significante entre os grupos analisados (p>0,05). Concluiu-se que, nas condições utilizadas, a sinvastatina, administrada via oral ou subcutânea, não exerceu efeito estimulador sobre o reparo ósseo de defeitos experimentais em tíbias de ratos e não alterou os níveis de colesterol sangüíneo.