Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19–5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

“…The core findings were a confirmation of prior data, namely a lower TBS in diabetic than non-diabetic controls [40][41][42][43][44][45][46][47][48][49][50] (Table 1). Abbreviations: BMD = bone mineral density, BMI = body mass index, F = female, HbA1c = glycated hemoglobin, M = male, N = number of patients, OR = odds ratio, TBS = trabecular bone score, T2DM = type 2 diabetes mellitus, vs. = versus, y = year.…”

“…Conversely, diabetes status was confirmed to be correlated with higher lumbar BMD (OR = 0.43, 95% CI: 0.21-0.89, p = 0.024), but not with BMD values measured in the other central DXA sites. Moreover, the ratio of subjects with normal DXA was lower in diabetic females group (5%) than controls (12%, p = 0.04) [47].…”

“…Similarly, Dule et al [47] showed that females with T2DM (N = 126 versus 117 nondiabetic, age-matched controls) have impaired bone microstructure as assessed by TBS, although they have normal or increased BMD. T2DM was associated with low TBS according to an adjustment for age, menopausal status, and body mass index (OR = 2.47, 95% CI: 1.19-5.16, p = 0.016).…”

“…We highlighted three studies within our 21-month sample-based analysis that particularly reflected T2DM's lowering effect on TBS and increased BMD [44,47,48]. A cohort study (N = 511) conducted by Haeri et al [44] included both females with T2DM of 80 years and older (N = 433, mean age of 80.6 ± 8.0 years) and males (N = 78, mean age of 82.4 ± 8.3 years).…”

“…With regard to the metabolic components' influence on TBS, we mention two studies: one addressed the issue of fat mass [42] and the other analyzed multiple metabolic components, particularly serum lipids profile [47]. Menopausal females aged between 50 and 75 years with reduced TBS had lower gynoid fat mass and higher android/gynoid fat mass ratio (p = 0.004, and p < 0.0001, respectively) according to one non-interventional, cross-sectional study; 96 females with T2DM (with a median T2DM duration of 15 years) who had normal BMD were included (mean age of 64 years old and an average time since menopause of 16 years).…”