Bone metabolism and fracture risk in type 2 diabetes mellitus.
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ABSTRACT:
SUBMITTER: Yamaguchi T
PROVIDER: S-EPMC3727726 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:T2DM is linked to an increase in the fracture rate as compared to the nondiabetic population even with normal or raised bone mineral density (BMD). Hence, bone quality plays an important role in the pathogenesis of skeletal fragility due to T2DM. This study analyzed the changes in the trabecular bone microstructure due to T2DM at various time points in ovariectomized and nonovariectomized rats. Animals were divided into four groups: (I) control (sham), (II) diabetic (sham), (III) ovariectomized, and (IV) ovariectomized with diabetes. The trabecular microarchitecture of the femoral head was characterized using a micro-CT. The differences between the groups were analyzed at 8, 10, and 14 weeks of the onset of T2DM using a two-way analysis of variance and by post hoc multiple comparisons. The diabetic group with and without ovariectomies demonstrated a significant increase in trabecular separation and a decrease in bone volume fraction, trabecular number, and thickness. BMD decreased in ovariectomized diabetic animals at 14 weeks of the onset of T2DM. No significant change was found in connectivity density and degree of anisotropy among groups. The structural model index suggested a change towards a weaker rod-like microstructure in diabetic animals. The data obtained suggested that T2DM affects the trabecular structure within a rat's femoral heads negatively and changes are most significant at a longer duration of T2DM, increasing the risk to hip fractures.
| S-EPMC6878775 | biostudies-literature
Project description:BackgroundRecently, increasing reports showed that the risk of fracture may be correlated with type 2 diabetes mellitus (T2DM). However, their results still remained controversial. Thus we performed a meta-analysis including 11 studies to estimate the risk factor of limb fracture in type 2 diabetes mellitus.Materials and methodsDatabases including PubMed, Embase, Cochrane Library and Web of Science were searched to September, 2017. Risk Ratio (RR) with its 95% confidence intervals (CI) was used to evaluate the association between risk of limb fracture and type 2 diabetes mellitus. Two reviewers assessed the quality of all the included studies and extracted data for analysis independently.ResultsA total of 11 studies including 663,923 participants were included in this meta-analysis. Our analysis results showed that patients with type 2 diabetes mellitus had a significant association with risk of limb fracture (RR 1.18; 95% CI 1.02-1.35), including leg or ankle fracture (RR 1.80; 95% CI 1.13-2.87). Subgroup analysis showed individuals with type 2 diabetes had almost two-fold excessive risk of leg/ankle fracture in women and the pooled RR of leg/ankle fracture was 2.03 (95% CI 1.36-3.05; P = 0.0006).ConclusionsThe results of the present meta-analysis showed that individuals with type 2 diabetes mellitus had higher risk of limb fractures, and this relationship is more pronounced in leg or ankle fracture.
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Project description:Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).The purpose of this study was to describe the effects of canagliflozin on bone fracture risk.This was a randomized phase 3 study in patients with T2DM.Canagliflozin doses of 100 and 300 mg were evaluated in the overall population of patients from 9 placebo- and active-controlled studies (N = 10 194), as well as in separate analyses of a single trial enriched with patients with a prior history/risk of cardiovascular disease (ie, the CANagliflozin cardioVascular Assessment Study [CANVAS]; N = 4327) and a pooled population of 8 non-CANVAS studies (N = 5867).The incidence of adjudicated fracture adverse events (AEs), fall-related AEs, and volume depletion-related AEs was assessed.The incidence of fractures was similar with canagliflozin (1.7%) and noncanagliflozin (1.5%) in the pooled non-CANVAS studies. In CANVAS, a significant increase in fractures was seen with canagliflozin (4.0%) vs placebo (2.6%) that was balanced between the upper and lower limbs. The incidence of fractures was higher with canagliflozin (2.7%) vs noncanagliflozin (1.9%) in the overall population, which was driven by the increase of fractures in CANVAS. The incidence of reported fall-related AEs was low, but significantly higher with canagliflozin in CANVAS, potentially related to volume depletion-related AEs, but not significantly different in the pooled non-CANVAS studies and the overall population.Fracture risk was increased with canagliflozin treatment, driven by CANVAS patients, who were older, with a prior history/risk of cardiovascular disease, and with lower baseline estimated glomerular filtration rate and higher baseline diuretic use. The increase in fractures may be mediated by falls; however, the cause of increased fracture risk with canagliflozin is unknown.
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Project description:Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.
| S-EPMC4817554 | biostudies-other
Project description:To examine the effect of functional impairments in older women with diabetes mellitus (DM) on incident clinical fractures.Secondary analysis of two large prospective cohort studies.North Carolina Established Populations for Epidemiologic Studies of the Elderly (EPESE) and Women's Health Initiative (WHI) clinical trials.EPESE included 2,704 community-dwelling women aged 65 and older; WHI clinical trials included 68,125 postmenopausal women.Women with DM at baseline were compared with women without in successive Cox proportional hazards models. Functional limitations were determined according to self-reported difficulties with activities of daily living (ADLs) and physical activities.The risk of any clinical fracture during the study period was greater in women with DM, after controlling for age, race and ethnicity, and body mass index, in the EPESE (hazard ratio (HR) = 1.36, 95% confidence interval (CI) = 1.08-1.72) and WHI (HR = 1.29, 95% CI = 1.19-1.39) cohorts. After inclusion of functional limitations, the greater risk of fracture associated with DM decreased in the EPESE (HR = 1.25, 95% CI = 0.98-1.59) and WHI (HR = 1.21, 95% CI = 1.12-1.31) cohorts. In participants with DM, difficulties with moderate physical activities, such as bending or stooping, walking several blocks, and heavy housework, were significantly associated with incident fracture (P < .05).Older women with DM are at greater risk of clinical fractures than those without, independent of bone mineral density. Greater functional impairment in moderate physical activities mediates this greater fracture risk in part, although there remains an unexplained residual DM-associated risk for fracture.
| S-EPMC4729209 | biostudies-other
Project description:Diabetes mellitus (DM) affects hundreds of million people worldwide and the impaired bone healing is an important DM-related complication. Understanding how DM affects the activities of osteoclasts and the underlying mechanisms is crucial to the development of effective approaches for accelerating bone healing in DM condition. To date, however, the influence of DM on osteoclasts remains obscure and controversial. In this study, we established a type 2 DM (T2DM) alveolar bone defect model, which closely simulates the pathogenesis of human T2DM, to explore the diabetic osteoclast activity during bone regeneration. We found that a high glucose concentration diminished the formation of osteoclasts, and the differentiation and function of osteoclasts from T2DM rats were suppressed. The degradation of matrix by osteoclasts was significantly reduced at a high glucose concentration. In vivo experiments further indicated that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of matrix during the alveolar bone regeneration in T2DM rats. Our work clarifies the influence of T2DM on osteoclasts, and provides valuable insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration. STATEMENT OF SIGNIFICANCE: Impaired bone healing is one of the diabetes mellitus (DM)-related complications. Understanding how DM affects osteoclast activity and scaffolding matrix degradation is pivotal to the development of effective approaches for accelerating bone healing in DM condition. Currently, the influences of DM on osteoclast activity and matrix degradation in bone defect areas, however, remain controversial and obscure. Herein, we established a type 2 DM (T2DM) alveolar bone defect model and our results show that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of scaffolding matrix. Our work clarifies the influence of T2DM on osteoclasts and matrix degradation, and provides insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration.
| S-EPMC6326860 | biostudies-literature
Project description:Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells. With addition of exogenous BMP6 in culture, osteogenesis of BMSCs from T1DM donors was restored whereas the treatment of BMP6 seemed not to affect non-T1DM control cells. We also demonstrated that bone mineral density (BMD) was reduced in streptozotocin-induced diabetic mice compared with that in control animals, and intraperitoneal injection of BMP6 mitigated bone loss and increased BMD in diabetic mice. Our results suggest that bone formation in T1DM patients is impaired by reduction of endogenous BMP6, and supplementation of BMP6 enhances osteogenesis of BMSCs to restore BMD in a mouse model of T1DM, which provides insight into the development of clinical treatments for T1DM-assocaited bone loss. Stem Cells Translational Medicine 2019;8:522-534.
| S-EPMC6525561 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women. PCOS may have reproductive, metabolic, cardiovascular, and psychological implications. Vitamin D deficit is often encountered in PCOS women and may contribute to the pathophysiology of this disorder. As of the key role of vitamin D in bone and mineral metabolism, and because the vitamin D status appears to be closely linked with the PCOS manifestations including insulin resistance, obesity, ovulatory and menstrual irregularities, oxidative stress and PTH elevation, hypovitaminosis D may directly and indirectly via the different facets of PCOS impair bone health in these women. Although limited data are available on life-long fracture risk in women with PCOS, the importance of preserving bone health in youth and adults to prevent osteoporosis and related fractures is also recognized in PCOS women. Evidence of the association between vitamin D and the clinical hallmarks of PCOS are summarized and discussed. Vitamin D arises as a cornerstone in women with PCOS and contributes to the pathophysiological link between PCOS and bone metabolism.
| S-EPMC7922814 | biostudies-literature
Project description:ImportanceThe reasons for the increased fracture risk in type 2 diabetes (T2D) are not fully understood.ObjectiveTo determine if poorer skeletal characteristics or worse physical function explain the increased fracture risk in T2D.Design, setting, and participantsThis prospective observational study is based on the population-based Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures study cohort of older women, performed in the Gothenburg area between March 2013 and May 2016. Follow-up of incident fracture data was completed in March 2023. Data analysis was performed between June and December 2023.ExposuresData were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using bone densitometry (dual-energy x-ray absorptiometry), and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess bone material strength index (BMSi).Main outcomes and measuresBaseline assessment of bone characteristics and physical function and radiograph verified incident fractures.ResultsOf 3008 women aged 75 to 80 years, 294 women with T2D (mean [SD] age, 77.8 [1.7] years) were compared with 2714 women without diabetes (mean [SD] age, 77.8 [1.6] years). Women with T2D had higher bone mineral density (BMD) at all sites (total hip, 4.4% higher; femoral neck (FN), 4.9% higher; and lumbar spine, 5.2% higher) than women without. At the tibia, women with T2D had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction. There was no difference in BMSi (T2D mean [SD], 78.0 [8.3] vs controls, 78.1 [7.3]). Women with T2D had lower performance on all physical function tests. The study found 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes. During a median (IQR) follow-up of 7.3 (4.4-8.4) years, 1071 incident fractures, 853 major osteoporotic fractures (MOF), and 232 hip fractures occurred. In adjusted (for age, body mass index, clinical risk factors, and FN BMD) Cox regression models, T2D was associated with an increased risk of any fracture (HR, 1.26; 95% CI, 1.04-1.54) and MOF (HR, 1.25; 95% CI, 1.00-1.56).Conclusions and relevanceIn this cohort study of older women, T2D was associated with higher BMD, better bone microarchitecture, and no different BMSi but poorer physical function, suggesting that poor physical function is the main reason for the increased fracture risk in T2D women.
| S-EPMC11304123 | biostudies-literature
Project description:Purpose of reviewIn this narrative review, we have summarized the literature on fracture risk in T1DM and T2DM with a special focus on fracture site, time patterns, glucose-lowering drugs, and micro- and macrovascular complications.Recent findingsT1DM and T2DM were associated with an overall increased fracture risk, with preferent locations at the hip, vertebrae, humerus, and ankle in T1DM and at the hip, vertebrae, and likely humerus, distal forearm, and foot in T2DM. Fracture risk was higher with longer diabetes duration and the presence of micro- and macrovascular complications. In T2DM, fracture risk was higher with use of insulin, sulfonylurea, and thiazolidinediones and lower with metformin use. The increased fracture risk in T1DM and T2DM concerns specific fracture sites, and is higher in subjects with longer diabetes duration, vascular complications, and in T2DM with the use of specific glucose-lowering medication.
| S-EPMC8716348 | biostudies-literature