Prevalence of vertebral fractures and associated factors in thai diabetic postmenopausal women.

T2DM (Type 2 Diabetes Mellitus) patients with vertebral fractures have a higher mortality rate than non-DM (nondiabetic patients). However, the prevalence of vertebral fractures in the Asian diabetic population is not well established. Moreover, despite an apparent increase in fracture risk in patients with diabetes, Asian countries have provided contradictory data demonstrating that bone mineral density (BMD) varies significantly in T2DM patients. The aim of this study was to examine and compare the prevalence of vertebral fractures and osteoporosis, as well as BMD and the FRAX score, between individuals with and without T2DM and assess the association of these factors with vertebral fractures. Postmenopausal Thai women attending diabetic and health check-up clinics were recruited. BMD at the lumbar spine, total hip, and femoral neck was measured via dual-energy X-ray absorptiometry. A morphometric vertebral fracture (VF) was defined by a lateral thoracolumbar (T-L) X-ray radiograph. The Fracture Risk Assessment Tool (FRAX) was used to calculate the 10-year probabilities of hip and major osteoporotic fracture (MOF), which were calculated on the basis of the Thai FRAX model. A total of 435 participants were recruited, including 145 postmenopausal women with T2DM and 290 non-DM individuals. T2DM patients had a significantly greater BMI (p = 0.006) and BMD at the femoral neck (p = 0.024) and total hip (p = 0.017), but there was no significant difference in the FRAX score, including the 10-year probability of hip fracture or MOF, either with or without BMD, between individuals with and without T2DM. The prevalence of osteoporosis in non-DM women was significantly higher at the femoral neck (OR = 0.56, 95% CI: 0.34 to 0.93, p = 0.029) but comparable at the lumbar spine. Individuals with T2DM had a significantly higher rate of vertebral fractures, particularly those involving two or more levels, than those without T2DM. Diabetes was significantly associated with [Formula: see text]2 VF (OR = 3.83, 95% CI: 1.77 to 8.28, p = 0.001), and the association remained unchanged after controlling for other clinical factors (adjusted OR = 3.72, 95% CI 1.70-8.15; p = 0.001). Our study demonstrated a greater prevalence of multiple ([Formula: see text] two levels) VFs in women with T2DM than in non-DM controls.

In vitro and in vivo effects of zoledronic acid on senescence and senescence-associated secretory phenotype markers.

In addition to reducing fracture risk, zoledronic acid has been found in some studies to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple co-morbidities, the non-skeletal actions of zoledronic acid could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype [SASP]) actions. To test this, we first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronic acid killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronic acid or vehicle for 8 weeks, zoledronic acid significantly reduced circulating SASP factors, including CCL7, IL-1ß, TNFRSF1A, and TGFß1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronic acid demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronic acid, we used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronic acid significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. Collectively, our findings demonstrate that zoledronic acid has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo. These data point to the need for additional studies testing zoledronic acid and/or other bisphosphonate derivatives for senotherapeutic efficacy.

In vitro and in vivo effects of zoledronate on senescence and senescence-associated secretory phenotype markers.

In addition to reducing fracture risk, zoledronate has been found in some studies to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple co-morbidities, the non-skeletal actions of zoledronate could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype [SASP]) actions. To test this, we first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronate killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronate or vehicle for 8 weeks, zoledronate significantly reduced circulating SASP factors, including CCL7, IL-1ß, TNFRSF1A, and TGFß1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronate demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronate, we used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronate significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. Collectively, our findings demonstrate that zoledronate has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo . These data point to the need for additional studies testing zoledronate and/or other bisphosphonate derivatives for senotherapeutic efficacy.

Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus.

Fracture risk is increased in patients with type 2 diabetes mellitus (T2DM). In addition, these patients sustain fractures despite having higher levels of areal bone mineral density, as measured by dual-energy X-ray absorptiometry, than individuals without T2DM. Thus, additional factors such as alterations in bone quality could have important roles in mediating skeletal fragility in patients with T2DM. Although the pathogenesis of increased fracture risk in T2DM is multifactorial, impairments in bone material properties and increases in cortical porosity have emerged as two key skeletal abnormalities that contribute to skeletal fragility in patients with T2DM. In addition, indices of bone formation are uniformly reduced in patients with T2DM, with evidence from mouse studies published over the past few years linking this abnormality to accelerated skeletal ageing, specifically cellular senescence. In this Review, we highlight the latest advances in our understanding of the mechanisms of skeletal fragility in patients with T2DM and suggest potential novel therapeutic approaches to address this problem.

Determinants of Bone Material Strength and Cortical Porosity in Patients with Type 2 Diabetes Mellitus.

CONTEXT: Reduced bone material strength index (BMSi) and increased cortical porosity (CtPo) have emerged as potentially contributing to fracture risk in type 2 diabetes mellitus (T2DM) patients. OBJECTIVE: To determine whether BMSi or CtPo are related to other diabetic complications. DESIGN: Cross-sectional observational study. SETTING: Subjects recruited from a random sample of southeast Minnesota residents. PARTICIPANTS: A total of 171 T2DM patients (mean age, 68.8 years) and 108 age-matched nondiabetic controls (mean age, 67.3 years). MAIN MEASURES: Bone material strength index was measured using microindentation, skin advanced glycation end-products (AGEs) measured using autofluorescence, high-resolution peripheral quantitative computed tomography at the distal radius and tibia, assessment of diabetic microvascular complications including urine microalbuminuria, retinopathy, neuropathy, and vascular disease (ankle brachial index and transcutaneous oxygen tension [TcPO2]). All analyses were adjusted for age, sex, and body mass index. RESULTS: Skin AGEs were negatively correlated with the BMSi in both T2DM (r = -0.30, P < 0.001) and control (r = -0.23, P = 0.020) subjects. In relating diabetic complications to CtPo, we found that T2DM patients with clinically significant peripheral vascular disease (TcPO2 ≤ 40 mm Hg) had higher (+21.0%, P = 0.031) CtPo at the distal tibia as compared to controls; in these subjects, CtPo was negatively correlated with TcPO2 at both the distal tibia (r = -0.39, P = 0.041) and radius (r = -0.41, P = 0.029). CONCLUSIONS: Our findings demonstrate that bone material properties are related to AGE accumulation regardless of diabetes status, while CtPo in T2DM patients is linked to TcPO2, a measure of microvascular blood flow.

Midterm Outcome of Laparoscopic Sleeve Gastrectomy in Asians: a Systematic Review and Meta-analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a commonly performed bariatric surgery. Studies have suggested that LSG can provide effective and sustainable weight loss although most of them were conducted in Western populations. Our aim was to characterize the midterm outcome of LSG in Asians with obesity. METHODS: MEDLINE and EMBASE were searched through August 2019 for studies that reported % total body weight loss (TBWL) and/or % excess weight loss (EWL) at 3 and/or 5 years among adult Asians with obesity who underwent LSG. Data on complications and surgical revision rate were also extracted. The pooled effect size and 95% confidence interval (CI) were calculated using a random effects model. RESULTS: A total of 19 studies involving 6235 patients were included. The pooled mean %EWLs were 72.6% (95% CI 67.2-78.0, I2 = 97%); 67.1% (95% CI 61.7-72.6, I2 = 95%); and 59.1% (95% CI 48.8-69.4, I2 = 94%) at 1, 3, and 5 years, respectively. The pooled mean %TBWLs were 32.1%, 29.0%, and 25.5% at 1, 3, and 5 years, respectively. The pooled rates of revision due to gastroesophageal reflux disease and weight regain were 1.9% and 2.5%, respectively. CONCLUSIONS: Our meta-analysis suggests that LSG is an effective procedure for weight reduction that offers durable response for up to 5 years among Asians with obesity. The longer-term data is needed.