Refining Evaluation of Bone Mass and Adipose Distribution in Dunnigan Syndrome.

Familial partial lipodystrophies (FPLD) are rare diseases characterized by selective loss of subcutaneous adipose tissue at different sites. This cross-sectional observational study aimed to estimate adipose tissue in the bone marrow (BMAT), intra (IMCL) and extra-myocyte lipids (EMCL), and define the bone phenotype in the context of FPLD2/Dunnigan syndrome (DS). The subjects comprised 23 controls (C) and 18 DS patients, matched by age, weight and height. Blood samples, dual-energy X-ray absorptiometry for bone mineral density (BMD) and trabecular bone score (TBS) and 1H-spectroscopy using magnetic resonance to estimate BMAT in the lumbar spine, IMCL, EMCL and osteoclastogenesis were assessed. The prevalence of diabetes mellitus was 78% in DS patients. Glucose, HbA1c, triglycerides, insulin and HOMA-IR levels were elevated in DS, whereas HDLc, 25(OH)D, PTH and osteocalcin levels were reduced. BMD was similar between groups at all sites, except 1/3 radius, which was lower in DS group. TBS was reduced in DS. DS presented increased osteoclastogenesis and elevated BMAT, with greater saturation levels and higher IMCL than the C group. HOMA-IR and EMCL were negatively associated with TBS; osteocalcin and EMCL were correlated negatively with BMD. This study contributes to refining the estimation of adipose tissue in DS by showing increased adiposity in the lumbar spine and muscle tissue. DXA detected lower TBS and BMD in the 1/3 radius, suggesting impairment in bone quality and that bone mass is mainly affected in the cortical bone.

Population pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic control.

AIMS: Gabapentin (GBP) is widely used to treat neuropathic pain, including diabetic neuropathic pain. Our objective was to evaluate the role of diabetes and glycaemic control on GBP population pharmacokinetics. METHODS: A clinical trial was conducted in patients with neuropathic pain (n = 29) due to type 2 diabetes (n = 19) or lumbar/cervical disc herniation (n = 10). All participants were treated with a single oral dose GBP. Blood was sampled up to 24 hours after GBP administration. Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm. Weight, body mass index, sex, biomarkers of renal function and diabetes, and genotypes for the main genetic polymorphisms of SLC22A2 (rs316019) and SLC22A4 (rs1050152), the genes encoding the transporters for organic cations OCT2 and OCTN1, were tested as potential covariates. RESULTS: GBP drug disposition was described by a 1-compartment model with lag-time, first-order absorption and linear elimination. The total clearance was dependent on estimated glomerular filtration rate. Population estimates (between-subject variability in percentage) for lag time, first-order absorption rate, apparent volume of distribution and total clearance were 0.316 h (10.6%), 1.12 h-1 (10.7%), 140 L (7.7%) and 14.7 L/h (6.97%), respectively. No significant association was observed with hyperglycaemia, glycated haemoglobin, diabetes diagnosis, age, sex, weight, body mass index, SLC22A2 or SLC22A4 genotypes. CONCLUSION: This population pharmacokinetics model accurately estimated GBP concentrations in patients with neuropathic pain, using estimated glomerular filtrationrate as a covariate for total clearance. The distribution and excretion processes of GBP were not affected by hyperglycaemia or diabetes.

Association between the trunk muscle function performance and the presence of vertebral fracture in older women with low bone mass.

BACKGROUND: Despite the clinical importance, it has remained unclear which changes in the trunk muscle function parameters are more associated with the presence of vertebral fracture (VF). AIMS: The aim of this study was to verify the association between the trunk muscle function performance and the presence of VF in older women with low bone mass. The secondary aim was to evaluate the correlation between trunk muscle function and both fall history and muscle mass. METHODS: This cross-sectional study was composed by 94 women over 60 years within value of T-Score lumbar spine BMD <- 1.0 DP. Multidimensional evaluations were performed: appendicular skeletal muscle mass index (ASMI) was determined by the total body DEXA; the radiographic evaluations measured the degree of thoracic kyphosis and classification of VF. The trunk muscle function parameters, such as peak torque (PT), rate of torque development (RTD) and torque steadiness (TS) were evaluated by isokinetic dynamometer. The trunk muscle endurance was evaluated by the timed loaded standing test. The adjusted multivariate logistic regression model and multivariate linear regression were performed to verify the association between the variables studied. RESULTS: The results showed that the trunk muscle function parameter with greater association with the presence of VF is TS extensors (OR = 1.70; p < 0.001). The other two significant muscle parameters were: RTD30 flexors (OR = 0.31; p = 0.033) and PT extensors (OR = 0.13; p = 0.009). No statistical association was found between the presence of VF and the ASMI and trunk muscle endurance. No correlation between trunk muscle function and fall history was observed. There was a weak correlation between ASMI and extensor PT (R2 = 0.21; p = 0.027) and extensor RTD30 (R2 = 0.21; p = 0.026). CONCLUSIONS: This study demonstrated that deficit in trunk muscle function has shown a strong association with the presence of VF, highlighting issues heretofore unexplored regarding the association between VF with muscle power and motor control.

Male and female cats have different regional body compositions and energy requirements for weight loss and weight maintenance.

Body composition and energy requirements are different between males and females in several species, and both interfere with weight loss. The aim of this study was to compare the total and regional body composition and energy requirements in obese male (n = 8) and female (n = 8) cats, during weight loss and weight maintenance over 17 subsequent weeks after regimen. The total and regional (thoracic and pelvic limbs, and trunk) body composition was assessed by dual-energy X-ray absorptiometry (DXA). Females exhibited a higher fat mass (FM) than males (p < 0.05), and the trunk was the site with greater fat accumulation regardless of gender. A 23.0 ± 2.8% reduction in body weight was followed by a 50.3 ± 9.4% and a 37.0 ± 8.9% reduction in fat in the trunk region in males and females respectively. Lean mass (LM) mobilization was also increased in the trunk (p < 0.05), and the loss of LM was associated with a reduction in bone mass. The energy intake to achieve the same rate of weight loss was 12.9 ± 3.4% higher in males (p < 0.05). The cats exhibited a gradual increase in energy requirements to maintain their body weight after weight loss (p < 0.05). It was concluded that obese cats mainly accumulate fat in the trunk. The reduction in lean mass after the regimen also occurred in the trunk, with no modifications in the skeletal muscle mass of the limbs. Neutered male cats have higher energy requirements than neutered females, and gender should be considered during obesity management in cats.

High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin-induced type 1 diabetic mice.

There is a growing and alarming prevalence of obesity and the metabolic syndrome in type I diabetic patients (T1DM), particularly in adolescence. In general, low bone mass, higher fracture risk, and increased marrow adipose tissue (MAT) are features of diabetic osteopathy in insulin-deficient subjects. On the other hand, type 2 diabetes (T2DM) is associated with normal or high bone mass, a greater risk of peripheral fractures, and no change in MAT. Therefore, we sought to determine the effect of weight gain on bone turnover in insulin-deficient mice. We evaluated the impact of a 6-week high-fat (HFD) rich in medium chain fatty acids or low-fat diet (LFD) on bone mass and MAT in a streptozotocin (STZ)-induced model using male C57BL/6J mice at 8 weeks of age. Dietary intervention was initiated after diabetes confirmation. At the endpoint, lower non-fasting glucose levels were observed in diabetic mice fed with high fat diet compared to diabetic mice fed the low fat diet (STZ-LFD). Compared to euglycemic controls, the STZ-LFD had marked polydipsia and polyphagia, as well as reduced lean mass, fat mass, and bone parameters. Interestingly, STZ-HFD mice had higher bone mass, namely less cortical bone loss and more trabecular bone than STZ-LFD. Thus, we found that a HFD, rich in medium chain fatty acids, protects against bone loss in a T1DM mouse model. Whether this may also translate to T1DM patients who are overweight or obese in respect to maintenance of bone mass remains to be determined through longitudinal studies.

Bone metabolism dysfunction mediated by the increase of proinflammatory cytokines in chronic HIV infection.

Despite the efficacy of antiretroviral therapy (ART) on the control of viral replication, the current challenge is to decrease the chronic inflammatory status and toxicity of the antiretroviral drugs that contribute to increase the risk of metabolic complications. To verify the influence of proinflammatory cytokines on bone metabolism mediated by chronic HIV infection, a cross-sectional study was conducted with 50 HIV-infected adult men treated or not treated with ART. Dual energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analysis were performed of IL-6, TNF-α, osteocalcin, PTH, 25-OH-D, total calcium, albumin, 24 h urinary calcium, and urinary deoxypyridinoline. The participants not treated with ART exhibited higher values of IL-6 and TNF-α than the participants treated with ART for more than 2 years. The TNF-α values were higher in the participants treated with ART for <2 years than in participants treated with ART for more than 2 years (p < 0.05). The increased values of urinary deoxypyridinoline indicated a high reabsorptive activity of bone tissue in all groups, with a significant difference between the participants not treated with ART and the participants treated with ART for <2 years. Through the DXA we found a bone mass reduction in all bone sites in each group. The increase in production of proinflammatory cytokines, most notably in the viremic group, demonstrated the ability to stimulate osteoclast activity and subsequently affect bone mass. The reduction of bone mineral density was observed in all bone sites, principally for the groups receiving antiretroviral treatment.

Relationship Between Adiposity Indices, Lipodystrophy, and Sarcopenia in HIV-Positive Individuals With and Without Lipodystrophy.

Metabolism disorders, as well as body shape abnormalities, have been associated with the introduction of antiretroviral therapy. The objective of this study was to compare the diagnostic ability of adiposity indices and to discuss criteria for the classification of lipodystrophy and sarcopenia (SP) in HIV-positive individuals. Anthropometric measurements were determined in 268 individuals of both genders, also submitted to the dual-energy X-ray absorptiometry exam. The adiposity indices calculated were body mass index, body mass index adjusted for fat mass (BMIfat), body adiposity index, body adiposity Index for the Fels Longitudinal Study sample, and The Clínica Universidad de Navarra body adiposity estimator. The presence of lipodystrophy was evaluated using the fat mass ratio (FMR). SP was classified using the appendicular lean mass/height2 ratio. The subjects were divided into 3 groups: HIV+LIPO+ (n = 41), HIV+LIPO- (n = 65), and control (C, HIV-negative individuals; n = 162). Among the adiposity indices assessed, BMIfat showed the strongest correlation with total body fat (in percent) for men (r = 0.87, p < 0.001) and women (r = 0.92, p < 0.001). The frequency of SP was 44.8% and 41.7% in HIV+LIPO+, 27.8% and 20.7% in HIV+LIPO- and 63.3% and 45.45% in C, for men and women, respectively. The cutoff point suggested for the diagnosis of lipodystrophy according to the FMR was 1.14. The adiposity indices, particularly the BMIfat, have strong correlation with body fat determined by dual-energy X-ray absorptiometry in HIV-positive patients. The implementation of FMR is recommended for more standardized estimates of the frequency of lipodystrophy.

Comprehensive analysis of morbidity and mortality patterns in familial partial lipodystrophy patients: insights from a population study.

Background: There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. Objective: This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. Methods: In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. Results: The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. Conclusion: This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions.

BACKGROUND: Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes. METHODS: Wistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression. RESULTS: The results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-ß1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed. CONCLUSION: Our data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation.

Association between vertebral fragility fractures, muscle strength and physical performance: A cross-sectional study.

BACKGROUND: Few studies have investigated the association between vertebral fragility fractures and lower limb muscle strength and physical performance in women with low bone mass. OBJECTIVES: To explore whether the presence of vertebral fracture is independently associated with poor physical performance and decreased lower limb muscle strength. To understand whether lower limb muscle strength is associated with physical performance in women with vertebral fracture. METHODS: Older women with low bone mass were divided into 2 groups: no vertebral fracture (NF) and presence of vertebral fragility fracture (VFF). Physical performance was evaluated using the Five Times Sit to Stand (5TSS) test, the Timed Up and Go (TUG) test and a 5m walk test (5MWT). Lower limb muscle strength was assessed using an isokinetic dynamometer. RESULTS: We included 94 women with low bone mass (mean age 71.6 [SD 5.7] years, time since menopause 24.4 [7.1] years, mean BMI 27.5 [5.1] kgm-2). VFF was only associated with low peak hip abductor torque (p = 0.001) after adjustments. In the VFF group (n= 47), each 1 Nmkg-1 increase: in knee extensor torque was associated with improved 5MWT (p = 0.005), TUG (p = 0.002) and 5TSS (p = 0.005) performances; in knee flexor torque was associated with improved 5MWT speed (p = 0.003) and TUG time (p = 0.006); in hip abductor torque was associated with improved 5MWT speed (p = 0.003); and in hip extensor torque with improved TUG time (p = 0.046). CONCLUSION: VFF was associated with reduced hip abductor strength in older women. However, the number of vertebral fractures influenced the association. Additionally, lower limb muscle strength was associated with physical performance, regardless of the clinical characteristics of the fractures. Therefore, strength and power training programs for the lower limbs could improve physical performance.

Experimental in vivo acute and chronic biomechanical and histomorphometrical comparison of self-drilling and self-tapping anterior cervical screws.

PURPOSE: Self-drilling screws (SDS) and self-tapping screws (STS) allow for quicker bone insertion and are associated with increased anchorage. This is an experimental in vivo comparison of anterior cervical SDS and STS in the post-insertion acute and chronic phases. METHODS: Thirty C2-C6 vertebrae from six Santa Inês hair sheep were used. Each screw design was randomly assigned to five of each spinal level. Insertion torque was measured using a torque device. Three animals were killed in each phase. Vertebrae were randomly assigned to pullout tests and histomorphometrical bone-screw interface evaluation (percent screw-bone contact and bone density inside and outside the threaded area). Statistical significance was set at P < 0.05. RESULTS: SDS insertion torque was greater than STS (P = 0.0001). SDS pullout strength was significantly greater than STS in the acute and chronic phases (P = 0.0001, 0.0003, respectively). SDS percent screw-bone contact and inside area bone density were significantly greater in both phases. No outside area bone density differences were observed in either phase. CONCLUSIONS: SDS had higher insertion torque and better anchorage than STS in both phases. SDS percent bone-screw contact and inside area bone density were higher in both phases.

Diabetes and bone.

Globally, one in 11 adults has diabetes mellitus of which 90% have type 2 diabetes. The numbers for osteoporosis are no less staggering: 1 in 3 women has a fracture after menopause, and the same is true for 1 in 5 men after the age of 50 years. Aging is associated with several physiological changes that cause insulin resistance and impaired insulin secretion, which in turn lead to hyperglycemia. The negative balance between bone resorption and formation is a natural process that appears after the fourth decade of life and lasts for the following decades, eroding the bone structure and increasing the risk of fractures. Not incidentally, it has been acknowledged that diabetes mellitus, regardless of whether type 1 or 2, is associated with an increased risk of fracture. The nuances that differentiate bone damage in the two main forms of diabetes are part of the intrinsic heterogeneity of diabetes, which is enhanced when associated with a condition as complex as osteoporosis. This narrative review addresses the main parameters related to the increased risk of fractures in individuals with diabetes, and the mutual factors affecting the treatment of diabetes mellitus and osteoporosis.

Bone, fat, and muscle interactions in health and disease.

Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual's development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues.

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO).

Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.

Paricalcitol Improves the Angiopoietin/Tie-2 and VEGF/VEGFR2 Signaling Pathways in Adriamycin-Induced Nephropathy.

Renal endothelial cell (EC) injury and microvascular dysfunction contribute to chronic kidney disease (CKD). In recent years, increasing evidence has suggested that EC undergoes an endothelial-to-mesenchymal transition (EndoMT), which might promote fibrosis. Adriamycin (ADR) induces glomerular endothelial dysfunction, which leads to progressive proteinuria in rodents. The activation of the vitamin D receptor (VDR) plays a crucial role in endothelial function modulation, cell differentiation, and suppression of the expression of fibrotic markers by regulating the production of nitric oxide (NO) by activating the endothelial NO synthase (eNOS) in the kidneys. This study aimed to evaluate the effect of paricalcitol treatment on renal endothelial toxicity in a model of CKD induced by ADR in rats and explore mechanisms involved in EC maintenance by eNOS/NO, angiopoietins (Angs)/endothelium cell-specific receptor tyrosine kinase (Tie-2, also known as TEK) and vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) axis. The results show that paricalcitol attenuated the renal damage ADR-induced with antiproteinuric effects, glomerular and tubular structure, and function protection. Furthermore, activation of the VDR promoted the maintenance of the function and structure of glomerular, cortical, and external medullary endothelial cells by regulating NO production. In addition, it suppressed the expression of the mesenchymal markers in renal tissue through attenuation of (transforming growth factor-beta) TGF-ß1/Smad2/3-dependent and downregulated of Ang-2/Tie-2 axis. It regulated the VEGF/VEGFR2 pathway, which was ADR-deregulated. These effects were associated with lower AT1 expression and VDR recovery to renal tissue after paricalcitol treatment. Our results showed a protective role of paricalcitol in the renal microvasculature that could be used as a target for treating the beginning of CKD.

Official position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry: part I (technical aspects)-general concepts, indications, acquisition, and analysis.

OBJECTIVE: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence. MATERIALS AND METHODS: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans. CONCLUSION: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.

The intravenous glucose tolerance and postprandial glucose tests may present different responses in the evaluation of obese dogs.

The present study compared the intravenous glucose tolerance test (IVGTT) and the glucose postprandial response (GPPR) test for the evaluation of glucose metabolism in obese dogs. A total of ten owned obese dogs (body condition score (BCS) of 9; fat mass, 45.7 (sem 1.51) %) were used. These dogs had their weight reduced by 20 % (BCS, 8; fat mass, 33.5 (SEM 1.92) %; P < 0.001), designated as weight-reduced (WR) group. A control group of ten Beagle dogs was also included (BCS, 4.5; fat mass, 18.3 (SEM 1.38) %; P < 0.01). Glucose tolerance was measured by two methods: IVGTT (infusion of 0.5 g of glucose/kg body weight) and GPPR (consumption of cooked rice to achieve 6 g of starch/kg body weight). When using the IVGTT, the area under the curve (AUC) for glucose and maximum glycaemia were higher for obese dogs compared with controls (P < 0.05), with intermediate results for the WR group (P>0.05). Basal insulin, insulin response peak, insulinogenic index and the AUC for insulin increment from 0 to 15 min and from 60 to 120 min were higher for the obese group (P < 0.05), while the WR group and control dogs showed similar results (P>0.05). When using the GPPR test, the AUC for insulin increment from 0 to 120 min was higher for the obese group compared with the control group (P < 0.05) and intermediate for the WR group (P>0.05). However, the AUC for insulin increment from 120 to 360 min was similar between the obese and WR groups (P>0.05), while it was lower for the control group (P < 0.05). The IVGTT showed that the loss of 20 % body weight resulted in an improvement of glucose control with reduced insulin secretion, and these same WR dogs showed higher insulin secretion with values similar to those of obese dogs when the GPPR test was used.

Repetitive stress fracture: a warning sign of genetic susceptibility to fracture? A case report of a heterozygous variant in SERPINF1.

The occurrence of fractures in young individuals is frequently overlooked by physicians, especially when associated with exercise or trauma. Nevertheless, multiple fractures should always be investigated since underlying conditions can predispose to such events. We describe here the case of a young, healthy woman who sustained multiple fractures in the lower limbs, which were initially considered to be "stress fractures". Further investigation, including a panel of genes associated with osteogenesis imperfecta, revealed that the patient is a heterozygous carrier of a SERPINF1 variant. According to criteria recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, this variant is classified as likely benign (PM2, PP3, PP4, BP1, and BP4). The patient's mother and brother were also asymptomatic carriers of the variant and had sustained previous minor fractures. The patient had normal biochemical profile and bone density. This condition has been rarely described and is not associated with low bone mineral density or altered bone turnover markers. This case highlights the importance of investigating multiple fractures in young patients who are otherwise healthy since these may be a warning sign of rare genetic conditions associated with fragility fractures.

Ex vivo vibro-acoustography characterization of osteoporosis in an experimental mice model.

BACKGROUND: Osteoporosis is a highly prevalent multifactorial osteometabolic disease, classically diagnosed, in vivo, by dual energy X-ray absorptiometry (DXA). This study evaluated osteoporosis, ex vivo, using vibro-acoustography (VA), an elastographic technique based on ultrasound radiation force. METHODS: Three groups of mice femurs were used: (I) control group (CG), (II) osteoporosis group (OG) and (III) treated osteoporosis group (TOG), in which the animals received pamidronate, an antiresorptive drug. Evaluation was performed in an acoustic tank, using two high frequency focused beams produced by a confocal ultrasonic transducer. A hydrophone registered the low frequency acoustic response (AR) of bone samples. We used micro-computed tomography (microCT) as the reference standard and evaluated the correlation between VA and microCT parameters. RESULTS: The spectral analyses of the ARs with estimated area under the curve (AUC) values (mean; st. dev.) were, respectively, 1.29e-07 and 9.32e-08 for the CG, 3.25e-08 and 2.16e-08 for the OG, and 1.50e-07 and 8.37e-08 for the TOG. VA differentiated the experimental groups (P<0.01) and the results were reproducible [interclass correlation coefficient (ICC): 0.43 (95% CI: 0.15-0.71)]. There was also a statistically significant association between VA and microCT connectivity (Conn.) (r=0.80; P<0.01) and connectivity density (Conn. D) (r=0.76; P<0.01). CONCLUSIONS: These results encourage further studies aimed at evaluating the potential use of VA for the diagnosis of osteoporosis as a relatively low-cost and radiation-free alternative to DXA.

Does sensorimotor training influence neuromuscular responses, balance, and quality of life in diabetics without a history of diabetic distal polyneuropathy?

OBJECTIVE: To evaluate the effect of supervised and home sensorimotor training on static postural balance (SPB), quality of life (QL), and neuromuscular responses of Type 2 Diabetics (DM-2). DESIGN: Randomized controlled blind study with DM-2 patients, between 45 and 64 years old, of both sexes, divided into 3 groups: Control Group - CG (n = 27), Home Training Group - HTG (n = 27), and Supervised Training Group - STG (n = 26). The subjects were evaluated before and at the end of 3 months of treatment, with a four-week follow-up. The intervention was held twice a week, for 45 min, divided into three phases: warm-up, sensorimotor training, and cool-down. The primary outcome was SPB, using the force platform. Secondary outcome: questionnaires and clinical measures related to diabetic foot and knee flexor-extensors using isokinetic dynamometry. RESULTS: In the baseline, the characteristics were similar between groups and between times. Tactile and vibratory sensitivity demonstrated the absence of symptoms of peripheral neuropathy in diabetic patients. In the intra-group comparison, there was a significant increase in the classification without symptoms of diabetic distal polyneuropathy in the HTG and STG groups (p < 0.05) and there were no significant effects on other clinical outcomes and QL and SPB, muscle strength, and sense of knee joint position. CONCLUSION: The intervention showed no improvement in SPB, QL, and other clinical outcomes of DM-2 patients. Thus, no differences were found between the groups, considering that the patients did not present clinical characteristics of diabetic distal polyneuropathy.