Obesity, Type 2 Diabetes and Bone in Adults.

In an increasingly obese and ageing population, type 2 diabetes (T2DM) and osteoporotic fracture are major public health concerns. Understanding how obesity and type 2 diabetes modulate fracture risk is important to identify and treat people at risk of fracture. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable to osteoporosis in the general population. Most available evidence indicates lower risk of proximal femur and vertebral fracture in obese adults. However the risk of some fractures (proximal humerus, femur and ankle) is higher, and a significant number fractures occur in obese people. BMI is positively associated with BMD and the mechanisms of this association in vivo may include increased loading, adipokines such as leptin, and higher aromatase activity. However, some fat depots could have negative effects on bone; cytokines from visceral fat are pro-resorptive and high intramuscular fat content is associated with poorer muscle function, attenuating loading effects and increasing falls risk. T2DM is also associated with higher bone mineral density (BMD), but increased overall and hip fracture risk. There are some similarities between bone in obesity and T2DM, but T2DM seems to have additional harmful effects and emerging evidence suggests that glycation of collagen may be an important factor. Higher BMD but higher fracture risk presents challenges in fracture prediction in obesity and T2DM. Dual energy X-ray absorptiometry underestimates risk, standard clinical risk factors may not capture all relevant information, and risk is under-recognised by clinicians. However, the limited available evidence suggests that osteoporosis treatment does reduce fracture risk in obesity and T2DM with generally similar efficacy to other patients

Influência do status de vitamina D na absorção intestinal do estrôncio.

Introdução: O estroncio e o calcio sao metais alcalinoterrosos com multiplas semelhancas. Estudos sugeriram que ambos utilizam a mesma via de absorcao intestinal, o que motivou o uso do estroncio para avaliacao indireta da absorcao intestinal do calcio. Extensa investigacao ja foi realizada sobre os fatores que regulam a absorcao intestinal do calcio, destacando-se o papel da vitamina D, entretanto pouco se sabe sobre a regulacao da absorcao do estroncio. A influencia deste sobre a homeostase do calcio tambem nao esta esclarecida. Como o paratormonio (PTH) e o principal regulador da homeostase do calcio, torna-se importante avaliar o seu comportamento na presenca do estroncio. Assim, os objetivos deste trabalho sao avaliar a influencia do status de vitamina D na absorcao intestinal do ranelato de estroncio e descrever o comportamento do PTH diante da sobrecarga oral desse mineral. Pacientes e metodos: Cinquenta pacientes do sexo feminino na pos-menopausa com osteopenia ou osteoporose com funcao renal normal, em acompanhamento no ambulatorio de Doencas Osteometabolicas, foram recrutadas e divididas em dois grupos de acordo com seu status de vitamina D: 25 suficientes (SUF) e 25 deficientes (DEF). Foram considerados SUF niveis de 25(OH) vitamina D maiores que 30 ng/mL e DEF, niveis menores que 20 ng/mL. Apos coleta de exames para avaliacao inicial em jejum (incluindo dosagem serica de Sr), cada paciente recebeu 1 gr de ranelato de estroncio dissolvido em 200 mL de agua deionizada. A seguir, foram colhidas amostras para dosagem serica de estroncio e PTH apos 30, 60, 120 e 240 minutos. As 25 pacientes DEF em vitamina D foram tratadas e submetidas a novo teste apos alcancar niveis maiores que 30 ng/mL. A absorcao intestinal do estroncio foi avaliada atraves da fracao absorvida (FA) em cada tempo e da area total sob a curva concentracao de Sr x tempo. Para calculo da FA foi utilizada a formula: FA= (Sr t- Sr0) x 15% peso Dose administrada de Sr Sendo Sr t a concentracao serica de Sr no tempo selecionado e Sr0 a concentracao basal de Sr (tempo 0). Resultados: Os dois grupos, DEF e SUF, eram semelhantes, exceto pelos niveis de 25OHD (15,4 ± 5,4 x 39,36 ± 7,32ng/mL p<0,001), 1,25(OH)2D (24,97 ± 4,64 x 36,3 ± 10,2 pg/mL p< 0,001) e dose de colecalciferol em uso (808,76 ± 689,5 x 1712,4 ± 724,8 UI/d p< 0,001). O tratamento da defiCiência de vitamina D resultou em aumento significativo de 1,25(OH)2D ( 24,97 ± 4,64 x 34,62 ± 9,14 pg/mL p< 0,001) e reducao de PTH (73,87 ± 37,50 x 58,24 ± 20,13 pg/mL p=0,006). Nao houve diferenca na absorcao de estroncio entre DEF e SUF. O tratamento do grupo deficiente tampouco resultou em aumento da absorcao. A sobrecarga de estroncio associou-se com diminuicao significativa dos niveis de PTH seguida de recuperacao, nas pacientes DEF e SUF. Nao houve diferenca na magnitude da variacao do PTH nos dois grupos. Conclusao: A correcao da defiCiência de vitamina D foi eficaz para elevar seu metabolito ativo 1,25(OH)2D e reduzir PTH. A inGestão oral de Sr associou-se a queda aguda nos niveis de PTH. O tratamento da defiCiência de vitamina D e recomendado, entretanto os dados demonstram que o status da vitamina D parece nao ser determinante na absorcao intestinal do ranelato de estroncio.BV UNIFESP: Teses e dissertaçõe

Bone remodeling and responsiveness to mechanical stimuli in individuals with type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) has been linked to increased osteocyte apoptosis, local accumulation of mineralized lacunar spaces, and microdamage suggesting an impairment of the mechanoregulation network in affected individuals. Diabetic neuropathy might exacerbate this dysfunction through direct effects on bone turnover, and indirect effects on balance, muscle strength, and gait. However, the in vivo effects of impaired bone mechanoregulation on bone remodeling in humans remain underexplored. This longitudinal cohort study assessed consenting participants with T1DM and varying degree of distal symmetric sensorimotor polyneuropathy (T1DM, n = 20, median age 46.5 yr, eight female) and controls (CTRL; n = 9, median age 59.0 yr, four female) at baseline and 4-yr follow-up. Nerve conduction in participants with T1DM was tested using DPNCheck and bone remodeling was quantified with longitudinal high-resolution peripheral quantitative-computed tomography (HR-pQCT, 82 μm) at the standard distal sites. Local trabecular bone formation (Tb.F) and resorption (Tb.R) sites were captured by implementing 3D rigid image registration of HR-pQCT images, and the mechanical environment across the bone microarchitecture at these sites was simulated using micro-finite element analysis. We calculated odds ratios to determine the likelihood of bone formation (ORF) and resorption (ORR) with increasing/decreasing strain in percent as markers for mechanoregulation. At the distal radius, Tb.F was 47% lower and Tb.R was 59% lower in T1DM participants compared with CTRL (P < .05). Tb.F correlated positively with nerve conduction amplitude (R = 0.69, P < .05) in participants with T1DM and negatively with glycated hemoglobin (HbA1c) (R = -0.45, P < .05). Additionally, ORF was 34% lower and ORR was 18% lower in T1DM compared with CTRL (P < .05). Our findings represent in vivo evidence suggesting that bone remodeling in individuals with T1DM is in a state of low responsiveness to mechanical stimuli, resulting in impaired bone formation and resorption rates; these correlate to the degree of neuropathy and level of diabetes control

An updated hip fracture incidence rate for Brazil : the Brazilian Validation Osteoporosis Study (BRAVOS)

Hip fracture incidence rates in three representative geographic areas in Brazil over a period of 2 years (2010-2012) were assessed for the first time. Estimated incidence rates varied regionally, and markedly differed from those previously reported. Thus, national guidelines as well as FRAX Brazil should be revised in light of this new data. Purpose: To determine the annual incidence of hip fractures in individuals aged 50 years and over, living in 3 cities located in different regions of the country. To investigate the age, gender, and regional differences in fracture rates. Based on the obtained data, to estimate the national incidence of hip fractures resulting from osteoporosis, in order to improve prevention strategies. Methods: Retrospective, observational study including all patients aged ≥ 50 years admitted in hospitals because of a hip fracture in three cities (Belem, Joinville, and Vitoria) from representative geographic areas in Brazil from 2010 to 2012. Data were obtained from medical records in those cities. We analyzed incidence rates (crude and age- and gender-standardized rates) for hip fractures. Results: There were 1025 (310 in men and 715 in women) hip fractures in the over 50-year-old merged population from the three cities. The crude incidence rate for hip fracture was 103.3/100,000 (95% confidence interval [CI = 97.0; 109.7), in men 77.4/100,000 (95% CI = 68.8; 86.0), and in women 125.2/100,000 (95% CI = 116.0; 134.4). Incidence standardized for age and gender was 105.9 cases per 100,000 persons per year (95% CI = 99.4; 112.4); 78.5 cases per 100,000 (95% CI = 69.8; 87.3) in men and 130.6 cases 100,000 in women (95% CI = 121.0, 140.2) per year. Belem, located in the equatorial region (latitude 1° 27' S), had significantly lower crude and age-adjusted incidence than Joinville (latitude 26° 18' S) and Vitoria (latitude 20° 19' S), which were no different from each other. The incidence of fractures increased exponentially with age, and women had about twice the risk of fractures than men. Conclusions: Hip fracture mainly affects elderly women and presents great variability in incidence between the different regions in Brazil. The incidence of hip fractures in Brazil differed markedly from that reported previously, so that national guidelines and the FRAX model for Brazil should be revised