Inhibitory effect of Astragalus polysaccharide on osteoporosis in ovariectomized rats by regulating FoxO3a /Wnt signaling pathway

Abstract Purpose: To investigate inhibitory effect of Astragalus polysaccharide (APS) on osteoporosis in ovariectomized rats by regulating FoxO3a/Wnt2 signaling pathway. Methods: Postmenopausal osteoporosis (PMOP) animal model was developed by excising the bilateral ovaries of rats. The model rats were administered with APS (200 mg/kg, 400 mg/kg, 800 mg/kg) by intragastric administration once daily for 12 weeks. Bone density, bone metabolism index and oxidative stress index were measured in all groups. Furthermore, the regulation of APS of FoxO3a / Wnt2 signaling pathway was observed. Results: APS has an estrogen-like effect, which can increase bone mass, lower serum ALP and BGP values, increase blood calcium content, and increase bone density of the femur and vertebrae in rats. At the same time, APS can increase the bone mineral content of the femur, increase the maximum stress, maximum load and elastic modulus of the ovariectomized rats, improve oxidative stress in rats by increasing the gene expression of β-catenin and Wnt2 mRNA and inhibiting the gene expression of FoxO3a mRNA. Conclusion: Astragalus polysaccharide can effectively alleviate oxidative stress-mediated osteoporosis in ovariectomized rats, which may be related to its regulation of FoxO3a/Wnt2/β-catenin pathway.

Behavioural and objective vestibular assessment in persons with osteoporosis and osteopenia: a preliminary investigation / Behavioural and objective vestibular assessment in persons with osteoporosis and osteopenia: a preliminary investigation

Abstract Introduction: Calcium is vital for the functioning of the inner ear hair cells as well as for the neurotransmitter release that triggers the generation of a nerve impulse. A reduction in calcium level could therefore impair the peripheric vestibular functioning. However, the outcome of balance assessment has rarely been explored in cases with osteopenia and osteoporosis, the medical conditions associated with reduction in calcium levels. Objective: The present study aimed to investigate the impact of osteopenia and osteoporosis on the outcomes of behavioural and objective vestibular assessment tests. Methods: The study included 12 individuals each in the healthy control group and osteopenia group, and 11 individuals were included in the osteoporosis group. The groups were divided based on the findings of bone mineral density. All the participants underwent behavioural tests (Fukuda stepping, tandem gait and subjective visual vertical) and objective assessment using cervical and ocular vestibular evoked myogenic potentials. Results: A significantly higher proportion of the individuals in the two clinical groups' demonstrated abnormal results on the behavioural balance assessment tests (p < 0.05) than the control group. However, there was no significant difference in latencies or amplitude of cervical vestibular evoked myogenic potential and oVEMP between the groups. The proportion of individuals with absence of ocular vestibular evoked myogenic potential was significantly higher in the osteoporosis group than the other two groups (p < 0.05). Conclusion: The findings of the present study confirm the presence of balance-related deficits in individuals with osteopenia and osteoporosis. Hence the clinical evaluations should include balance assessment as a mandatory aspect of the overall audiological assessment of individuals with osteopenia and osteoporosis.

Resumo: Introdução: O cálcio é vital para o funcionamento das células ciliadas, assim como para a liberação dos neurotransmissores que desencadeiam um impulso nervoso. Uma redução nos níveis de cálcio poderia, portanto, prejudicar o funcionamento vestibular periférico. No entanto, a avaliação do equilíbrio tem sido raramente explorada em casos de osteopenia e osteoporose, condições médicas associadas à redução dos níveis de cálcio. Objetivo: O presente estudo teve como objetivo investigar o impacto da osteopenia e da osteoporose nos resultados dos testes de avaliação comportamental e vestibular objetiva. Método: O estudo incluiu 12 indivíduos nos grupos controle e grupo de osteopenia e 11 indivíduos no grupo da osteoporose. Os grupos foram divididos com base nos achados da densidade mineral óssea. Todos os participantes foram submetidos a testes comportamentais (Prova dos Passos de Fukuda, Marcha em tandem e Vertical Visual Subjetiva) e à avaliação objetiva com o uso de potenciais evocados miogênicos vestibulares cervical e ocular (cVEMP e oVEMP). Resultados: Uma proporção significativamente maior de indivíduos nos dois grupos com condições clínicas mostrou resultados anormais nos testes de avaliação comportamental e do equilíbrio (p < 0,05) do que o grupo controle. Embora não tenha havido diferença significativa nas latências ou na amplitude de cVEMP e oVEMP entre os grupos, a proporção de indivíduos com ausência de oVEMP foi significativamente maior no grupo da osteoporose do que nos outros dois grupos (p < 0,05). Conclusão: Os resultados do presente estudo demonstram a presença de déficits de equilíbrio em indivíduos com osteopenia e osteoporose. Assim, as avaliações clínicas gerais e audiológicas de indivíduos com osteopenia e osteoporose deveriam incluir a avaliação do equilíbrio como um aspecto obrigatório.

Hiperparatiroidismo primario asintomático en mujeres / Asymptomatic primary hyperparathyroidism in women

El hiperparatiroidismo primario puede tener diferentes características. Una de ellas es la forma asintomática. Esta es una variante leve del hiperparatiroidismo primario hipercalcémico, que se caracteriza por una calcemia no mayor a 1 mg/dl sobre el límite superior del método, hormona paratiroidea intacta (PTHi) elevada, ausencia de litiasis renal, deterioro de la función renal y de osteoporosis, edad menor de 50 años, y calciuria menor a 400 mg/día. No es una entidad quirúrgica, pero en su evolución puede llegar a serlo. Se estudiaron 24 mujeres postmenopáusicas, todas mayores de 50 años, con diagnóstico de hiperparatiroidismo asintomático, se describieron las manifestaciones clínicas, los cambios densitométricos, los parámetros bioquímicos y del remodelado óseo y se compararon los resultados con las variantes clásica y normocalcémica de la enfermedad. Se establecieron los criterios diagnósticos y se observó que solo 2 (8.3%) de las pacientes, durante un seguimiento de 44 ± 12 meses tuvo necesidad de paratiroidectomía. En definitiva, el hiperparatiroidismo primario asintomático es una alteración benigna, de seguimiento clínico periódico que, en pocas ocasiones, durante el seguimiento puede requerir cirugía.

Primary hyperparathyroidism may have different characteristics. One is the asymptomatic form. This is a mild variant of hypercalcemic hyperparathyroidism, characterized by a calcemia not greater than 1 mg/dl above the upper limit of the method, a high intact parathyroid hormone (iPTH), absence of renal stones, renal function impairement, and osteoporosis, less than 50 years of age, and less than 400 mg/day calciuria. It is not a surgical entity, but its evolution may require it. Twenty-four postmenopausal women, all older than 50 years, with a diagnosis of asymptomatic hyperparathyroidism, were studied. Clinical manifestations, densitometric changes, biochemical parameters and bone remodeling were analyzed and the results were compared with the classic and normocalcemic variants of the disease. Diagnostic criteria were established and observed that only 2 (8.3%) of patients, during a follow up of 44 ± 12 months, had need for a parathyroidectomy. In conclusion, the asymptomatic primary hyperparathyroidism is a benign disorder, of periodic clinical follow-up, which rarely may require surgery.

Osteoporosis: Parte I - Generalidades / Osteoporosis: Part I - Basic concepts

This review corresponds to a general analysis of osteoporosis, with emphasis in calcium metabolism, the role of Vitamin D, as well as osteoporosis physiopathology, diagnosis and treatment. The second part (Osteoporosis. Part II) will describe the importance of osteoporosis in several digestive diseases (liver and gastrointestinal tract).

En esta revisión abordamos el tema osteoporosis en forma general, desarrollando principalmente el metabolismo del calcio, el rol de la vitamina D; así como la fisiopatología, el diagnóstico y tratamiento de la osteoporosis. En la segunda parte (Osteoporosis. Parte II ) se describirá la importancia de la osteoporosis en diversas enfermedades digestivas (hepáticas y del tubo digestivo).

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism

SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Vitamin D Activities for Health Outcomes

Reports describing significant health risks due to inadequate vitamin D status continue to generate considerable interest amongst the medical and lay communities alike. Recent research on the various molecular activities of the vitamin D system, including the nuclear vitamin D receptor and other receptors for 1,25-dihydroxyvitamin D and vitamin D metabolism, provides evidence that the vitamin D system carries out biological activities across a wide range of tissues similar to other nuclear receptor hormones. This knowledge provides physiological plausibility of the various health benefits claimed to be provided by vitamin D and supports the proposals for conducting clinical trials. The vitamin D system plays critical roles in the maintenance of plasma calcium and phosphate and bone mineral homeostasis. Recent evidence confirms that plasma calcium homeostasis is the critical factor modulating vitamin D activity. Vitamin D activities in the skeleton include stimulation or inhibition of bone resorption and inhibition or stimulation of bone formation. The three major bone cell types, which are osteoblasts, osteocytes and osteoclasts, can all respond to vitamin D via the classical nuclear vitamin D receptor and metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on the bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient.

Are skeletally mature female rats a suitable model to study osteoporosis? / Ratas esqueleticamente maduras são um modelo satisfatório para estudar osteoporose?

OBJECTIVE: To analyze if female Wistar rats at 56 weeks of age are a suitable model to study osteoporosis. MATERIALS AND METHODS: Female rats with 6 and 36 weeks of age (n = 8 per group) were kept over a 20-week period and fed a diet for mature rodents complete in terms of Ca, phosphorous, and vitamin D. Excised femurs were measured for bone mass using dual-energy x-ray absorptiometry, morphometry, and biomechanical properties. The following serum mar-kers of bone metabolism were analyzed: parathyroid hormone (PTH), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor Κappa B ligand (RANKL), C-terminal peptides of type I collagen (CTX-I), total calcium, and alkaline phosphatase (ALP) activity. RESULTS: Rats at 56 weeks of age showed important bone metabolism differences when compared with the younger group, such as, highest diaphysis energy to failure, lowest levels of OC, CTX-I, and ALP, and elevated PTH, even with adequate dietary Ca. CONCLUSION: Rats at 26-week-old rats may be too young to study age-related bone loss, whereas the 56-week-old rats may be good models to represent the early stages of age-related changes in bone metabolism.

OBJETIVO: Avaliar se ratas Wistar com 56 semanas de idade são um modelo satisfatório para estudar osteoporose. MATERIAIS E MÉTODOS: Ratas com 6 e 36 semanas de idade (n = 8 por grupo) foram criadas por um período de 20 semanas e alimentadas com dieta completa em Ca, fósforo e vitamina D para ratas adultas. Os fêmures foram analisados quanto à massa óssea pela técnica de absortiometria por dupla fonte de raios-X, morfometria e propriedades biomecânicas; os marcadores séricos do metabolismo ósseo analisados foram paratormônio (PTH), osteocalcina (OC), osteoprotegerina (OPG), fator receptor ativador nuclear Κappa B ligante (RANKL), peptídeos C-terminal de colágeno tipo I (CTX-I), cálcio total e atividade da fosfatase alcalina (FA). RESULTADOS: As ratas com 56 semanas de vida apresentaram uma importante diferença no metabolismo ósseo quando comparadas ao grupo das ratas jovens, como, por exemplo, maior energia para quebrar a diáfise do fêmur, menores níveis de OC, CTX-I e ALP e maiores níveis de PTH mesmo com dieta adequada em cálcio. CONCLUSÃO: As ratas com 26 semanas de vida podem ser consideradas muito jovens para estudar a perda óssea relacionada à idade, porém, as ratas com 56 semanas de vida podem representar um bom modelo dos estágios iniciais das alterações associadas à idade no metabolismo ósseo.

Osteoporose / Osteoporosis

As fraturas por osteoporose desempenham relevante problema de saúde pública em todo o mundo. No Brasil, embora existam poucos estudos sobre o impacto socioeconômico desses eventos em amostragem representativa da população, estima-se que cerca de 30% a 40% da população adulta seja de risco para fratura. Este artigo de revisão se propõe a discutir as abordagens mais recentes para o diagnóstico e tratamento precoce da osteoporose.

Os glicocorticoides e seus efeitos no crescimento e na mineralização óssea / Effects of glucocorticoids on growth and bone mineralization

OBJETIVO: Revisar os mecanismos de ações dos glicocorticoides e sua capacidade de induzir osteoporose e déficits de crescimento. FONTES DOS DADOS: A revisão bibliográfica de artigos científicos foi realizada na base de dados MEDLINE e utilizou as palavras-chave agrupadas nas sintaxes “glicocorticoides”, “mineralização óssea”, “crescimento” e “efeitos colaterais”, nos últimos 10 anos, e das referências destes nos reportamos para as publicações mais antigas, mas com os estudos fundamentais para a compreensão do assunto. SÍNTESE DOS DADOS: Destacam-se ações dos glicocorticoides sobre hormônios e citocinas responsáveis pelo crescimento longitudinal. Os efeitos finais dos glicocorticoides sobre o esqueleto são determinados por ações sistêmicas no metabolismo ósseo e por ações diretas desses esteroides nas células ósseas, levando a mudanças no número e função das mesmas e favorecendo a perda óssea. Discutem-se os mecanismos indutores da recuperação dos canais de crescimento e recuperação da massa óssea após a descontinuação dos glicocorticoides; os métodos diagnósticos do metabolismo e mineralização óssea; assim como medidas terapêuticas e preventivas das alterações óssea induzidas pelos glicocorticoides. CONCLUSÃO: A monitorização de cada paciente é essencial para identificação e potencial reversão dos danos associados ao uso crônico de glicocorticoides.

OBJECTIVE: To review the various mechanisms of glucocorticoid action and the ability of these agents to induce osteoporosis and growth deficits. SOURCES: A review of the scientific literature was conducted on the basis of a MEDLINE search using the keywords and descriptors “glucocorticoids,” “bone mineralization,” “growth,” and “side effects” and limited to articles published in the last decade. The references cited by these articles were used to identify relevant older publications, with an emphasis on landmark studies essential to an understanding of the topic. SUMMARY OF THE FINDINGS: Emphasis was placed on the actions of glucocorticoids on the hormones and cytokines that modulate linear growth. The end effects of glucocorticoids on the skeletal system are the result of systemic effects on bone metabolism and of direct actions on bone cells, which alter bone cell counts and predispose to bone loss. The mechanisms underlying catch-up growth and bone mass recovery after discontinuation of glucocorticoid treatment are discussed, followed by a review of diagnostic methods available for assessment of bone metabolism and mineralization and of measures for prevention and management of glucocorticoid-induced bone changes. CONCLUSION: Patient monitoring on a case-by-case basis plays an essential role in detection and, potentially, reversal of the damage associated with chronic glucocorticoid therapy.

Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-b) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats. METHODS: Thirty female Sprague-Dawley rats weighing 200-250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 mg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing. RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02). CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.

Osteoporosis and inflammation / Osteoporose e inflamação

Several inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, celiac disease, cystic fibrosis and chronic obstructive pulmonary disease have been associated to bone resorption. The link between osteoclast, macrophage colony stimulating factor and pro-inflammatory cytokines, especially tumor necrosis factor-α and interleukin-1 explain the association between inflammation and osteoporosis. These diseases are related to osteoporosis and high fracture risk independent of other risk factors common to inflammatory diseases such as reduced physical activity, poor nutritional status, hypovitaminosis D, decrease in calcium intake and glucocorticoid treatment. Erythrocyte sedimentation rate and C-reactive protein should always be performed, but the indication about when to perform the densitometry test should be analyzed for each disease. Bisphosphonates are nowadays the best choice of therapy but new medications such as denosumab, IL-1 receptor antagonist, and TNF-α antibody have risen as new potential treatments for osteoporosis secondary to inflammation.

Diversas doenças inflamatórias têm sido associadas à reabsorção óssea, como a artrite reumatoide, o lúpus eritematoso sistêmico, a doença inflamatória intestinal, a doença celíaca, a fibrose cística e a doença pulmonar obstrutiva crônica. A ligação entre osteoclastos, fator estimulador de colônia de macrófagos e citocinas pró-inflamatórias, principalmente o fator de necrose tumoral-α e interleucina-1, explica a associação entre a inflamação e a osteoporose. Essas doenças estão relacionadas com osteoporose e aumento do risco de fratura, independentemente de outros fatores de risco comuns às doenças inflamatórias, tais como redução da atividade física, estado nutricional, hipovitaminose D, diminuição da ingestão de cálcio e uso de glicocorticoides. A velocidade de hemossedimentação e proteína C-reativa devem ser sempre realizadas, mas a indicação do exame de densitometria óssea deve ser analisada em cada doença. Os bisfosfonatos são atualmente a melhor opção de terapia, mas novos medicamentos, tais como denosumabe, antagonista do receptor de IL-1 e anticorpos anti-TNF-α, surgem como novos potenciais tratamentos para a osteoporose secundária à inflamação.

Obesity, diabetes mellitus and last but not least, osteoporosis / Obesidade, diabete melito e osteoporose

Knowledge about the influence of bone on intermediary metabolism corresponds to a developing area that has gained prominence. The old concept of bone and adipose tissues as inert metabolic tissues, with minor contributions to metabolic adaptations has been reconsidered in light of findings that bone is involved in the development of insulin sensitivity. Similarly adipose tissue exerts important influences on bone mass development and maintenance. Moreover, the use of drugs in the treatment of metabolic disorders such as diabetes mellitus can impact bone metabolism. These networks linking osteoporosis to obesity and diabetes mellitus have reinvigorated investigations in the pathophysiology of osteoporosis. The present review examines this aspect and calls attention to health care providers and potential treatments of skeletal disorder.

O estudo sobre a influência do tecido ósseo no metabolismo intermediário corresponde a uma área em desenvolvimento que tem ganho recente destaque. O conceito prévio de que os tecidos ósseo e adiposo seriam metabolicamente inativos foi reconsiderado à luz de estudos que mostram que metabólitos ósseos podem influenciar a sensibilidade à insulina. Da mesma forma, o tecido adiposo exerce influência importante no desenvolvimento e na manutenção da massa óssea. Além disso, o uso de drogas no tratamento de doenças metabólicas como o diabetes melito pode afetar o metabolismo ósseo. A rede de conexões existentes que ligam a osteoporose à obesidade e ao diabetes melito tem revigorado investigações sobre a fisiopatologia da osteoporose. A presente revisão analisa esse aspecto e destaca a necessidade de atenção para esses pontos por parte de serviços de saúde voltados para o atendimento de diabetes melito e da obesidade quanto ao potencial impacto sobre o tecido ósseo.

Efectos de la cirugía bariátrica sobre el metabolismo óseo / Effects of bariatric surgery on bone health

There is concern about the long term complications of bariatric surgery and among these, the derangements in bone metabolism that could increase the risk of osteopororosis. Most studies show an elevated bone turnover in operated patients with loss of bone mass, that are partially explained by the development of a secondary hyperparathyroidism. We have shown that, among postmenopausal women, bone resorption remains elevated, even five years after the operation, although not associated to loss of bone mass. The pathophysiology of these alterations is complex and includes an reduction in mechanical load and calcium absorption and postoperative changes in signaling hormones that have an effect on bone, coming from adipose tissue (estrogens, leptin and adiponectin), liver (insulin like growth factor-1), pancreas (insulin and amylin) or the bowel (ghrelin, glucagon-like peptide 2, peptide YY, gastric inhibitory polypeptide). Available evidence suggest that bariatric surgery should be considered a risk factor for osteoporosis. We recommend the incorporation of bone health in pre operative evaluation. We also give suggestions to prevent the adverse effects of bariatric surgery on bone health.

Changes in bone histology due to capacitive electric field stimulation of ovariectomized rat.

Background & objectives: Postmenopausal osteoporosis leads to a significant decline in bone mass. That complicates the treatment outcome. The objective of the present study was to find out the effects of pulsed modulated low level electric field capacitively coupled on bone histology of induced osteoporotic rats, for screening the potential therapy for osteoporosis. Methods: Osteopororosis was induced by performed by bilateral ovariectomy of female Wistar rats. After one month of surgery electric field stimulation was delivered to one leg of experimatal rats while the other was sham exposed. After 60 days of exposure treated rats were sacrificed and femur and tibia bones were segregated into (i) control (CON), (ii) ovariectomized (OVX) and (iii) ovariectomized + electrical stimulation (OVX+ES). Results: Histopathological analyses showed that capacitively coupled pulsed electric field exposure treatment augmented and restored the bone marrow cell population. Immunohistological localization of alkaline phosphatase (ALP) showed the increased activity of this enzyme after electrostimulation, which showed an enhanced osteoblast differentiation. Collagen histochemistry showed high amount of collagen fiber in exposed rats bones than that of osteoporotic bones. Electron microscopic study revealed the enhancement of microstructural composition and compactness in cortical and trabecular part of treated bones. Interpretation & conclusions: Our results suggest that capacitively coupled pulsed electric field exposure treatment of specified parameters is efficacious in attenuating the effects of ovariectomy induced osteoporosis and restore the bone loss.

Efeitos sobre o tecido ósseo e cartilagem articular provocados pela imobilização e remobilização em ratos Wistar / Effects of immobilization and remobilization on bone tissue and cartilage in Wistar rats

Longos períodos de imobilização conduzem à perda óssea e de propriedades do osso, e sua recuperação depende de vários fatores; além disso, a imobilização pode causar ulcerações no tecido cartilaginoso articular devido a alterações como perda de proteoglicanas, de massa e volume totais da cartilagem. O objetivo deste estudo foi verificar alterações histológicas, do tecido ósseo periarticular e da cartilagem articular, provocadas pela imobilização e remobilização de membros posteriores de ratos Wistar. Foram utilizados 12 ratos Wistar, divididos em dois grupos: GI - (n = 6): 15 dias com o membro posterior esquerdo imobilizado em plantiflexão, sendo o membro direito o controle; GR - (n = 6): período de 15 dias de remobilização livre na gaiola, associado a três séries diárias de alongamento do músculo sóleo esquerdo por 30 segundos. Foram avaliados no tecido ósseo as medidas de espessura do osso cortical, diâmetro do canal medular e número de osteócitos; no tecido cartilaginoso, foram mensurados a espessura média da cartilagem e o número de condrócitos. Como resultado, observou-se que para GI não houve alterações significativas na espessura do osso (p = 0,1156) nem no diâmetro do canal medular (p = 0,5698), mas diminuição significativa dos osteócitos em relação ao contralateral (p = 0,0005); em GR também houve decréscimo no número de osteócitos (p = 0,0001), mas as diferenças na espessura (p = 0,1343) e diâmetro do canal medular (p = 0,6456) mantiveram-se não significantes. Para os dados de cartilagem articular não houve diferenças significativas para as amostras, tanto na espessura da cartilagem para GI (p = 0,6640) e GR (p = 0,1633), quanto no número de condrócitos em GI (p = 0,9429) e GR (p = 0,1634). Conclui-se que duas semanas de imobilização e remobilização produziram apenas diminuição significativa no número de osteócitos nos ratos imobilizados; esse número continuou a diminuir mesmo nos animais remobilizados.

Long immobilization periods lead to bone and properties loss, and its recovery depends on many factors. Besides that, immobilization can cause ulcerations in the articular cartilage tissue due to alterations, such as loss of proteoglycans and total cartilage mass and volume. The aim of this study was to verify histological alterations of the periarticular bone tissue and articular cartilage caused by immobilization as well as remobilization of hinder limbs of Wistar rats. Twelve Wistar rats were divided in two groups: GI - (n=6): 15 days with the left hinder limb immobilized at plantiflexion, with the right limb being the control; GR - (n=6): used a 15 day-period of free remobilization in the cage, associated with 3 daily stretching bouts of the left soleus muscle for 30 seconds. The measures of the cortical bone thickness, diameter of the medular channel and number of condrocites were evaluated; in the cartilage tissue, the cartilage mean thickness and the number of condrocites were measured. The results showed that for GI there were no significant alterations in the bone thickness (p=0.1156), nor in the medular channel diameter (p=0.5698), but there was significant decrease of the osteocytes compared with the counter-lateral side (p=0.0005); in GR decrease in the number of osteocytes (p=0.0001) was also observed, but the differences in thickness (p=0.1343) and medular channel diameter (p=0.6456) remained non-significant. There were no significant differences for the articular cartilage data for the samples, neither in the cartilage thickness for GI (p=0.6640) and GR (p=0.1633); concerning the number of condrocites in GI (p=0.9429) and GR (p=0.1634). It is concluded hence that two weeks of immobilization and remobilization produced only significant decrease in the number of osteocytes in the immobilized rats and continued to decrease even in the remobilized animals.

Dietary calcium intake - a critical reappraisal.

The clinical implications of calcium deficiency include rickets, poor bone mass accrual as well as abnormal foetal programming during pregnancy, poor peak bone mass due to poor accrual in childhood and adolescence, postmenopausal osteoporosis and osteoporosis of the elderly. Serum calcium is maintained within a narrow normal range, chiefly by resorption from the skeleton and alteration of urinary calcium loss and absorption from gut. Absorption is dependent on vitamin D sufficiency, presence of calcium binders in diet (such as phosphate, oxalate and phytate), age group and physiological state. A 2004 WHO expert panel has examined available data on calcium balance studies as well as calcium deficiency states and recommended daily calcium intake in the adult to be 1000 mg per day, with adjustments suggested for other age groups and physiological states. Daily calcium intake in India, both the reality and the recommendations, are far lower than the Western data. A reappraisal of dietary calcium recommendations may be necessary for India.

The use of biochemical markers of bone turnover in osteoporosis

OBJECTIVE: Present evidence-based recommendations on the use of biochemical markers of bone turnover in the management of osteoporosis. METHODS: The English literature from 1999 to 2005 was reviewed by using data sources from MEDLINE. RESULTS: Measurement of biochemical markers of bone turnover helps us identify a high bone turnover rate. Elevated levels of these markers points towards a pathology and at an accelerated loss of bone mass. Its main utility is in documenting the response to therapy. They have a limited role in the follow-up of patients with osteoporosis. To be useful, bone markers must be measured at baseline and periodically after the beginning of therapy. A fall of on fifty (50%) percent in the levels of resorption markers between the third and sixth month of therapy predicts a good response. Bone markers can not be used to establish the diagnosis of osteoporosis. Neither do they measure bone mass. Markers are not capable of predicting future loss of bone mass in an individual nor do they correlate with the occurrence of previous fractures. The greatest limitation of these measurements is not being able to measure bone remodeling in the individual subject. Bone resorption markers are more frequently used than those of formation. The levels of the markers can identify the failures to the therapy and responses to therapy. Lack of reduction in the resorption markers could indicate lack of compliance with therapy, problems of absorption of the medication or lack in response to treatment. There may be problems with the measurement and the interpretation of results of bone remodeling markers. Variability between individuals and intra-individual variability exist as well as inter-assay and intra-assay variability. CONCLUSION: Biochemical markers of bone turnover along with measurements of bone density can help optimize the management of osteoporosis. The use of the bone markers is not recommended in a routine form, but they can be of utility in situations of poor compliance with the therapy or when there are difficulties in the management of the treatment of osteoporosis.

Bone metabolism and vascular calcification

Osteoporosis and atherosclerosis are chronic degenerative diseases which have been considered to be independent and whose common characteristic is increasing incidence with age. At present, growing evidence indicates the existence of a correlation between cardiovascular disease and osteoporosis, irrespective of age. The morbidity and mortality of osteoporosis is mainly related to the occurrence of fractures. Atherosclerosis shows a high rate of morbidity and especially mortality because of its clinical repercussions such as angina pectoris, acute myocardial infarction, stroke, and peripheral vascular insufficiency. Atherosclerotic disease is characterized by the accumulation of lipid material in the arterial wall resulting from autoimmune and inflammatory mechanisms. More than 90 percent of these fatty plaques undergo calcification. The correlation between osteoporosis and atherosclerosis is being established by studies of the underlying physiopathological mechanisms, which seem to coincide in many biochemical pathways, and of the risk factors for vascular disease, which have also been associated with a higher incidence of low-bone mineral density. In addition, there is evidence indicating an action of antiresorptive drugs on the reduction of cardiovascular risks and the effect of statins, antihypertensives and insulin on bone mass increase. The mechanism of arterial calcification resembles the process of osteogenesis, involving various cells, proteins and cytokines that lead to tissue mineralization. The authors review the factors responsible for atherosclerotic disease that correlate with low-bone mineral density.