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Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.

ABSTRACT: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM.This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension.This study was undertaken in 90 centers in 17 countries.Patients were aged 55-80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen.Canagliflozin 100 or 300 mg or placebo were administered once daily.BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 ?-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52.Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: -0.9% and -1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 ?-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol.In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.

SUBMITTER: Bilezikian JP

PROVIDER: S-EPMC4701848 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.

Bilezikian John P JP Watts Nelson B NB Usiskin Keith K Polidori David D Fung Albert A Sullivan Daniel D Rosenthal Norm N

The Journal of clinical endocrinology and metabolism 20151118 1

<h4>Context</h4>Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).<h4>Objective</h4>Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM.<h4>Design</h4>This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension.<h4>Setting</h4>This study was undertaken in 90 centers in ...[more]

PMID: 26580234

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Project description:IntroductionStudies show trabecular bone score (TBS) may provide information regarding bone quality independent of bone mineral density (BMD) in type 2 diabetes (DM2) patients. We analyzed our Southeast Asian severe osteoporotic hip fracture patients to study these differences.MethodsWe conducted a retrospective cross-sectional analysis of subjects admitted to Changi General Hospital, Singapore with severe osteoporotic hip fractures from 2014-2017 who had BMD performed. Electronic records were reviewed and subjects were classified as having diabetes according to the WHO 2019 criteria. DM2 patients were classified according to their HbA1c into well controlled (HbA1c < 7%) and poorly controlled (HbA1c ≥ 7%) DM2.ResultsElderly patients with hip fractures present with average femur neck T scores at the osteoporotic range, however those with DM2 had higher BMD and TBS values compared to non DM2 patients. These differences were statistically significant in elderly women-poorly controlled elderly DM2 women with hip fracture had the highest total hip T-score (-2.57 ± 0.86) vs (-2.76 ± 0.96) in well controlled DM2 and (-3.09 ± 1.01) in non DM2 women with hip fracture, p < 0.001. In contrast, TBS scores were lower in poorly controlled DM2 women with hip fracture compared to well controlled DM2 women with hip fracture (1.22 ± 0.11) vs (1.24 ± 0.09), but these were still significantly higher compared to non DM2 women with hip fracture (1.19 ± 0.10), p < 0.001. In elderly men with hip fractures, univariate analysis showed no statistically significant differences in TBS or hip or LS BMD between those with poorly controlled DM2, well controlled DM2 and non DM2. The differences in TBS and BMD remained significant in all DM2 women with hip fractures even after adjustments for potential confounders. Differences in TBS and BMD in poorly controlled DM2 men with hip fractures only became significant after accounting for potential confounders. However, upon inclusion of LS BMD into the multivariate model these differences were attenuated and remained significant only between elderly women with well controlled DM2 and non DM2 women with hip fractures.ConclusionsElderly patients with DM2 and severe osteoporosis present with hip fractures at a higher BMD and TBS values compared to non DM2 patients. These differences were significant after adjustment for confounders in all DM2 women and poorly controlled DM2 men with hip fractures, TBS differences were attenuated with the inclusion LS BMD. Further studies are needed to ascertain differences in BMD and TBS in older Southeast Asian DM2 patients with variable glycemic control and severe osteoporosis.

Project description:Purpose: The association between bone mineral density (BMD), bone turnover markers, and serum cholesterol in healthy population has already been proved. However, in patients with type 2 diabetes mellitus (T2D), it has not been adequately analyzed. In this study, we investigated the correlation between BMD, bone turnover markers, and serum cholesterol levels in people with T2D. Methods: We enrolled 1,040 men and 735 women with T2D from Zhongshan Hospital between October 2009 and January 2013. Their general condition, history of diseases and medication, serum markers, and BMD data were collected. We used logistic regression analysis to identify the association between serum cholesterol levels and BMD as well as bone turnover markers. Results: In multivariate regression analysis, we observed that in men with T2D, high high-density lipoprotein-cholesterol and total cholesterol levels were significantly associated with low total lumbar, femur neck, and total hip BMD, while low-density lipoprotein-cholesterol level was only inversely associated with total lumbar and femur neck BMD. Total cholesterol and low-density lipoprotein-cholesterol levels were also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and ?-crosslaps. In women with T2D, high-density lipoprotein-cholesterol level was observed to be negatively correlated with total lumbar, femur neck, and total hip BMD, while total cholesterol and low-density lipoprotein-cholesterol levels were only associated with BMD at the total lumbar. Furthermore, total cholesterol was also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and ?-crosslaps; high-density lipoprotein-cholesterol was only related to osteocalcin and parathyroid hormone, while low-density lipoprotein-cholesterol was only related to ?-crosslaps in women. Conclusion: Our study suggests a significantly negative correlation between serum cholesterol levels and BMD in both men and women with T2D. The associations between serum cholesterol levels and bone turnover markers were also observed in T2D patients.

Project description:RATIONALE:Osteoporosis is common in individuals with chronic obstructive pulmonary disease. Lung-specific factors, including radiographic emphysema, independently associate with low bone mineral density in cross-sectional smoking cohorts. However, factors associated with progressive bone loss in smokers are understudied and largely unknown. OBJECTIVES:To determine the relationship between radiographic emphysema, circulating bone metabolism markers, and pulmonary function and accelerated bone mineral density loss in smokers. METHODS:Two hundred and forty male and female current and former smokers, 40 years of age or older, underwent baseline and 2-year assessments of pulmonary function, computed tomography-assessed emphysema, dual X-ray absorptiometry-measured bone mineral density, and circulating bone metabolism biomarker levels (type I collagen C-telopeptide [CTX], amino-terminal propeptide of type I procollagen [P1NP]). The association of radiographic emphysema, bone metabolism biomarker levels, and pulmonary function with accelerated hip bone mineral density loss, defined by the 75th percentile of annual hip bone mineral density decline, was determined by logistic regression modeling with adjustment for age, sex, inhaled and intermittent steroid use, active smoking, body mass index, and the presence of baseline low hip bone mineral density. RESULTS:Of those participants with accelerated hip bone mineral density loss, 22% had moderate or severe visually assessed emphysema compared with 7.2% of smokers without accelerated bone mineral density decline. Moderate to severe visually assessed emphysema (odds ratio, 2.84; 95% confidence interval, 1.01-7.98 compared with trace/mild or no visually assessed emphysema) and the 75th percentile of CTX levels (odds ratio, 2.38; 95% confidence interval, 1.20-4.72 compared with CTX levels below the 75th percentile), a marker of bone resorption, were associated with accelerated hip bone mineral density decline after adjustment for covariates and the presence of baseline low hip bone mineral density. FEV1% predicted was not associated with accelerated bone mineral density decline after adjustment for covariates. Multivariate modeling showed moderate to severe visually assessed emphysema, and the 75th percentiles of CTX were independently associated with accelerated hip bone mineral density decline after adjustment for covariates. CONCLUSIONS:Emphysema and elevated markers of bone resorption are independently associated with progressive bone mineral density loss in smokers. These clinical markers may guide targeted bone mineral density screening and monitoring in smokers at highest risk.

Project description:BackgroundThe aim of the study were to analyze the lumbar volumetric bone mineral density (BMD), fat distribution and changes of skeletal muscle with quantitative computed tomography (QCT) in postmenopausal women with type 2 diabetes mellitus (T2DM), and to evaluate the relationship between body composition and BMD.MethodsOne hundred seventy-seven postmenopausal women with T2DM and 136 postmenopausal women without diabetes were included in the study and were divided into two groups according to age, 50-65 years age group and over 65 years of age group. The lumbar BMD (L1-L3), visceral fat mass (VFM), visceral fat area (VFA), subcutaneous fat mass (SFM), subcutaneous fat area (SFA), psoas major mass (PMM) and psoas major area (PMA) of each group were compared. Univariable and multivariable linear regression analysis were used to analyze the contribution of each variable to BMD in postmenopausal women with T2DM.ResultsIn women aged 50-65, the patients in the T2DM group had higher body mass index (BMI), VFM, VFA, and SFM (p < 0.05), compared with non-T2DM group. Over 65 years old, the BMI, BMD, VFM, VFA, and SFM was found to be much higher in participants with T2DM than in non-T2DM group (p < 0.05). Compared with women aged in 50-65 years old, those over 65 years old had higher VFA and VFM and lower BMD (p < 0.05), whether in the T2DM group or the non-T2DM group. Age, VFA and VFM were negatively correlated with BMD (r = -0.590, p ≤ 0.001; r = -0.179, p = 0.017; r = -0.155, p = 0.040, respectively). After adjusting for age, VFM and VFA were no longer correlated with BMD. No correlations between fat distribution or psoas major muscle and BMD in postmenopausal women with T2DM were observed.ConclusionsT2DM can affect abdominal fat deposition in postmenopausal women. Postmenopausal elderly women with diabetes have higher BMD than normal elderly women. There was no correlation between fat distribution or psoas major and BMD in postmenopausal women with diabetes mellitus.

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Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.

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Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.

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