Densidade mineral óssea de adolescentes saudáveis do sexo feminino

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Contribuição da aplicação do ultrassom de baixa potência na prevenção de osteopenia em tíbias de ratos sob ausência de carga

Este trabalho objetivou verificar se o ultrassom de baixa potência (US) previne a ocorrência de osteopenia em tíbias de ratos sob ausência de carga. Foram utilizados 45 Rattus novergicus albinus, Wistar adultos, machos, distribuídos em cinco grupos iguais: C - animais-controle livres em gaiolas por 21 dias; S - animais suspensos pela cauda por 21 dias; ST - suspensos pela cauda por 21 dias e concomitantemente tratados com US; S→C - suspensos por 21 dias e depois permanecendo livres em gaiolas por mais 21 dias; S→CT - suspensos por 21 dias e depois permanecendo livres em gaiolas por mais 21 dias e concomitantemente tratados com US. O tratamento foi realizado com US de 1,5MHz, ciclo de trabalho 1:4, 30mW/cm², na tíbia direita, por 15 sessões de 20 minutos cada, cinco sessões por semana. Ainda vivos, os animais foram submetidos a exame de densitometria óssea para verificação da densidade mineral óssea (DMO) e do conteúdo mineral ósseo (CMO). Após a eutanásia dos animais, as tíbias foram desarticuladas, dissecadas e submetidas a ensaio mecânico destrutivo para análise da força máxima (Fmáx) e da rigidez (R). Foram avaliados também o comprimento (L) e o diâmetro (D) no ponto médio da tíbia. O grupo S apresentou valores de DMO, CMO, Fmáx, R, L e D menores em relação ao grupo C, demonstrando que a suspensão pela cauda é prejudicial a estas variáveis. O tratamento dos animais suspensos com o US, grupo ST, elevou os valores de CMO e DMO em relação aos do grupo S, igualando-os aos do grupo C. A Fmáx, R e L do grupo ST aumentou em relação ao grupo S e também em relação ao grupo C (p<0,05). Nenhuma diferença significativa foi encontrada entre as variáveis analisadas para os grupos S→CT e S→C (p>0,05). Os resultados obtidos neste estudo permitem concluir que o US de baixa potência contribuiu na prevenção e reversão da ocorrência da osteopenia nos animais submetidos à suspensão pela cauda, demonstrando que a ausência do estímulo mecânico causada pela impossibilidade da deambulação pode ser minimizada pela ação mecânica deste.

Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist

OBJECTIVES: Idiopathic central precocious puberty and its postponement with a (gonadotropin-releasing hormone) GnRH agonist are complex conditions, the final effects of which on bone mass are difficult to define. We evaluated bone mass, body composition, and bone remodeling in two groups of girls with idiopathic central precocious puberty, namely one group that was assessed at diagnosis and a second group that was assessed three years after GnRH agonist treatment. METHODS: The precocious puberty diagnosis and precocious puberty treatment groups consisted of 12 girls matched for age and weight to corresponding control groups of 12 (CD) and 14 (CT) girls, respectively. Bone mineral density and body composition were assessed by dual X-ray absorptiometry. Lumbar spine bone mineral density was estimated after correction for bone age and the mathematical calculation of volumetric bone mineral density. CONEP: CAAE-0311.0.004.000-06. RESULTS: Lumbar spine bone mineral density was slightly increased in individuals diagnosed with precocious puberty compared with controls; however, after correction for bone age, this tendency disappeared (CD = -0.74 +/- 0.9 vs. precocious puberty diagnosis = -1.73 +/- 1.2). The bone mineral density values of girls in the precocious puberty treatment group did not differ from those observed in the CT group. CONCLUSION: There is an increase in bone mineral density in girls diagnosed with idiopathic central precocious puberty. Our data indicate that the increase in bone mineral density in girls with idiopathic central precocious puberty is insufficient to compensate for the marked advancement in bone age observed at diagnosis. GnRH agonist treatment seems to have no detrimental effect on bone mineral density.

Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide

Os glicocorticoides (GC) são prescritos por praticamente todas as especialidades médicas, e cerca de 0,5% da população geral do Reino Unido utiliza esses medicamentos. Com o aumento da sobrevida dos pacientes com doenças reumatológicas, a morbidade secundária ao uso dessa medicação representa um aspecto importante que deve ser considerado no manejo de nossos pacientes. As incidências de fraturas vertebrais e não vertebrais são elevadas, variando de 30%-50% em pessoas que usam GC por mais de três meses. Assim, a osteoporose e as fraturas por fragilidade devem ser prevenidas e tratadas em todos os pacientes que iniciarão ou que já estejam em uso desses esteroides. Diversas recomendações elaboradas por várias sociedades internacionais têm sido descritas na literatura, porém não há consenso entre elas. Recentemente, o Americam College of Rheumatology publicou novas recomendações, porém elas são fundamentadas na FRAX (WHO Fracture Risk Assessment Tool) para analisar o risco de cada indivíduo e, dessa maneira, não podem ser completamente utilizadas pela população brasileira. Dessa forma, a Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia, em conjunto com a Associação Médica Brasileira e a Associação Brasileira de Medicina Física e Reabilitação, implementou as diretrizes brasileiras de osteoporose induzida por glicocorticoide (OPIG), baseando-se na melhor evidência científica disponível e/ou experiência de experts. DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIA: A revisão bibliográfica de artigos científicos desta diretriz foi realizada na base de dados MEDLINE. A busca de evidência partiu de cenários clínicos reais, e utilizou as seguintes palavras-chave (MeSH terms): Osteoporosis, Osteoporosis/chemically induced*= (Glucocorticoids= Adrenal Cortex Hormones, Steroids), Glucocorticoids, Glucocorticoids/administration and dosage, Glucocorticoids/therapeutic use, Glucocorticoids/adverse effects, Prednisone/adverse effects, Dose-Response Relationship, Drug, Bone Density/drug effects, Bone Density Conservation Agents/pharmacological action, Osteoporosis/ prevention&control, Calcium, Vitamin D, Vitamin D deficiency, Calcitriol, Receptors, Calcitriol; 1-hydroxycholecalciferol, Hydroxycholecalciferols, 25-Hydroxyvitamin D3 1-alpha-hydroxylase OR Steroid Hydroxylases, Prevention and Control, Spinal fractures/prevention & control, Fractures, Spontaneous, Lumbar Vertebrae/injuries, Lifestyle, Alcohol Drinking, Smoking OR tobacco use disorder, Movement, Resistance Training, Exercise Therapy, Bone density OR Bone and Bones, Dual-Energy X-Ray Absorptiometry OR Absorptiometry Photon OR DXA, Densitometry, Radiography, (Diphosphonates Alendronate OR Risedronate Pamidronate OR propanolamines OR Ibandronate OR Zoledronic acid, Teriparatide OR PTH 1-34, Men AND premenopause, pregnancy, pregnancy outcome maternal, fetus, lactation, breast-feeding, teratogens, Children (6-12 anos), adolescence (13-18 anos). GRAU DE RECOMENDAÇÃO E FORÇA DE EVIDÊNCIA: A) Estudos experimentais e observacionais de melhor consistência; B) Estudos experimentais e observacionais de menor consistência; C) Relatos de casos (estudos não controlados); D) Opinião desprovida de avaliação crítica, com base em consensos, estudos fisiológicos ou modelos animais. OBJETIVO: Estabelecer as diretrizes para a prevenção e o tratamento da OPIG.

Exploration of the role of serum factors in maintaining bone mass during hibernation in black bears

Disuse osteoporosis is a condition in which reduced mechanical loading (e.g. bed-rest, immobilization, or paralysis) results in unbalanced bone turnover. The American black bear is a unique, naturally occurring model for the prevention of disuse osteoporosis. Bears remain mostly inactive for up to half a year of hibernation annually, yet they do not lose bone mechanical strength or structural properties throughout hibernation. The long-term goal of this study is to determine the biological mechanism through which bears maintain bone during hibernation. This mechanism could pinpoint new signaling pathway targets for the development of drugs for osteoporosis prevention. In this study, bone specific alkaline phosphatase (BSALP), a marker of osteoblast activity, and tartrate resistant acid phosphatase (TRACP), a marker of osteoclast number, were quantified in the serum of hibernating and active black bears. BSALP and TRACP decreased during hibernation, suggesting a balanced reduction in bone turnover. This decrease in BSALP and TRACP were correlated positively to serum adiponectin and inversely to serum neuropeptide Y, suggesting a possible role of these hormones in suppressing bone turnover during hibernation. Osteocalcin (OCN) and undercarboxylated OCN increased dramatically in the serum of hibernating bears. These increases were inversely correlated with adiponectin, glucose, and serotonin, suggesting that OCN may have a unique role in energy homeostasis during hibernation. Finally, MC3T3-E1 osteoblasts were cultured in the serum from active and hibernating bears, and seasonal cell responses were quantified. Cells cultured in serum from hibernating bears had a reduced caspase-3/7 response, and more living cells, after apoptotic threat. The caspase-3/7 response was positively correlated to serum adiponectin and to gene expression of OCN and Runx2, suggesting that reduced caspase-3/7 activity may be related to the reduced differentiation potential of osteoblasts in hibernation serum, and that adiponectin is a potential effector hormone. In summary, the activities of osteoblasts and osteoclasts are reduced during hibernation in bears. This reduced turnover is due, in part, to hormonal control. Further study of potential effectors adiponectin and neuropeptide Y may provide insight into the biological mechanism through which bears maintain bone throughout hibernation.

Desenvolvimento de protótipo de aplicativo móvel em Android® para o controle e acompanhamento nutricional da saúde óssea em mulheres menopáusicas

Following a drop in estrogen in the period of menopause some women begin to lose bone mass more than 1% per year reaching the end of five years with loss greater than 25%. In this regard, factors such as older age, low calcium intake and premature menopause favor the onset of osteoporosis. Preventive methods such as nutritional counseling to a proper diet and the support of technology through applications that assess dietary intake are essential. Thus, this study aimed to develop an application for Android® platform focused on the evaluation of nutritional and organic conditions involved in bone health and risks for developing osteoporosis in postmenopausal women. To achieve this goal we proceeded to a study of 72 women aged 46-79 years, from the physical exercise for bone health of the Laboratory for Research in Biochemistry and Densitometry the Federal Technological University of Paraná program. Data were collected in the second half of 2014 through tests Bone Densitometry and Body Composition, Blood Tests, Anthropometric data and Nutrition Assessment. The study included women with a current diagnosis of osteopenia or osteoporosis primary, aged more than 45 years postmenopausal. For the assessment of bone mineral density and body composition used the device Absorptiometry Dual Energy X-ray (DXA) brand Hologic Discovery TM Model A. For anthropometric assessment was included to body mass, height, abdominal circumference, Waist circumference and hip circumference. The instrument for assessing food consumption was used Recall 24 hours a day (24HR). The estimated intake of energy and nutrients was carried from the tabulation of the food eaten in the Software Diet Pro 4®. In a sub sample of 30 women with osteopenia / osteoporosis serum calcium and alkaline phosphatase tests were performed. The results demonstrated a group of women (n = 30) average calcium intake of 570mg / day (± 340). The analysis showed a mean serum calcium within the normal range (10,20mg / dl ± 0.32) and average values and slightly increased alkaline phosphatase (105.40 U / L ± 23.70). Furthermore, there was a significant correlation between the consumption of protein and the optimal daily intake of calcium (0.375 p-value 0.05). Based on these findings, we developed an application early stage in Android® platform operating system Google®, being called OsteoNutri. We chose to use Java Eclipse® where it was executed Android® version of the project; choice of application icons and setting the visual editor for building the application layouts. The DroidDraw® was used for development of the three application GUIs. For practical tests we used a cell compatible with the version that was created (4.4 or higher). The prototype was developed in conjunction with the Group and Instrumentation Applications Development (GDAI) of the Federal Technological University of Paraná. So this application can be considered an important tool in dietary control, allowing closer control consumption of calcium and dietary proteins.

Nutritional aspects of the prevention and treatment of osteoporosis

Osteoporosis is a global health problem characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Nutrition plays a critical role in reducing the risk of osteoporosis through its effect on all of these fragility factors, especially on the development and maintenance of bone mass. An adequate calcium, vitamin D and protein intake resulted in reduced bone remodeling, better calcium retention, reduced age-related bone loss, and reduced fracture risk. Recent evidence indicates that a healthy dietary pattern including dairy products (mainly fat free), fruit and vegetables and adequate amounts of meat, fish and poultry is positively related to bone health. Furthermore, mineral and vitamin supplementation should be closely monitored by health professionals since it could have adverse effects and be insufficient to ensure optimal protection of bone health.

Nutrional aspects of the prevention and treatment of osteoporosis

A osteoporose é um problema de saúde global, caracterizada por baixa massa óssea e deterioração da microarquitetura do tecido ósseo, com consequente aumento da fragilidade óssea e suscetibilidade a fraturas. A nutrição desempenha um papel fundamental na redução do risco de osteoporose por seu efeito sobre todos os fatores relacionados à fragilidade óssea, principalmente no desenvolvimento e na manutenção da massa óssea. Uma adequada ingestão de cálcio, vitamina D e proteína leva à redução da remodelação óssea, à maior retenção de cálcio, à redução da perda óssea relacionada à idade e à redução do risco de fraturas. Evidências recentes indicam que uma alimentação saudável, incluindo a ingestão de produtos lácteos (principalmente os desnatados), frutas e verduras, e uma quantidade adequada de carnes, peixes e aves, está relacionada positivamente com a saúde óssea. Além disso, a suplementação de vitaminas e minerais deve ser monitorada de perto, por profissionais de saúde, uma vez que pode ter efeitos adversos e ser insuficiente para assegurar uma eficaz proteção à saúde óssea

Denosumab for prevention of fractures in postmenopausal women with osteoporosis.

BACKGROUND: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis. METHODS: We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures. RESULTS: As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001)--a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04)--a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01)--a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab. CONCLUSIONS: Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.)

La substitution hormonale et ses dérivés dans la prévention et le traitement de l'ostéoporose [Hormone replacement therapy and its derivatives in the prevention and treatment of osteoporosis]

Hormone replacement therapy (HRT) is an established approach for the treatment and the prevention of osteoporosis. Many studies with bone mineral density as primary outcome have shown significant efficacy. Observational studies have indicated a significant reduction of hip fracture risk in cohorts of women who maintained HRT therapy. The Women's Health Initiative is the first prospective randomised controlled study which showed a positive effect of HRT in terms of reduction of vertebral and hip fractures risk. Unfortunately, this study has been interrupted after 5.2 years because of the unsupportable increase of risk of cardiovascular disease and breast cancer. Compliance with HRT, however, is typically poor because of the potential side effects and possible increased risk of breast or endometrial cancer. Nevertheless, there is now evidence that lower doses of estrogens in elderly women may prevent bone loss while minimizing the side effects seen with higher doses. Combination therapies using low doses estrogen should probably be reserved for patients who continue to fracture on single therapy. Selective estrogen receptor modulators (SERMs) are very interesting drugs. The goal of these agents is to maximize the beneficial effect of estrogen on bone and to minimize or antagonize the deleterious effects on the breast and endometrium. Raloxifene, approved for the prevention and the treatment of osteoporosis, has been shown to reduce the risks of vertebral fracture in large clinical trials. However, they don't reduce non vertebral fractures. Tibolone is a synthetic steroid that increased bone mineral density at lumbar spine and femoral neck. But no trial has been performed with fractures as end point.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.