Relative Contribution of Metabolic Syndrome Components in Relation to Obesity and Insulin Resistance in Postmenopausal Osteoporosis

Abstract

Introduction. Osteoporosis (OP) affects 30% of postmenopausal women, often complicated by metabolic syndrome (MetS) with a still controversial role. We aimed to characterize MetS and its components in relation to bone mineral density (BMD), body mass index (BMI), and insulin resistance. Methods. Patients (n = 188) underwent DEXA scans, spine X-rays, and metabolic and hormonal investigations, including bone biomarkers, muscular strength, and physical performance tests, while insulin resistance was evaluated by the Homeostasis Model Assessment (HOMA-IR). Results. Patients with a normal BMD or osteopenia (n = 68) and with OP (n = 120) displayed 51.5% and 30.8% of MetS, but without differences in insulin resistance. When BMD was studied as a function of the cumulative MetS criteria and centiles of BMI, lower levels of BMD were observed beyond an inflection point of 27.2 kg/m² for BMI, allowing for further stratification as lean and overweight/obese (OW/OB) subjects. In contrast with lean individuals (n = 74), in OW/OB patients (n = 46), MetS was associated with HbA1c (p < 0.0037, OR 9.6, 95% CI [1.64-55.6]) and insulin resistance (p < 0.0076, OR 6.7, 95% CI [1.49-30.8]) in the context where BMD values were lower than those predicted from BMI in non-OP subjects. In OP patients with fragility fractures (31% of MetS), glycemia also appeared to be the dominant factor for MetS (p < 0.0005, OR 4.1, 95% CI [1.63-10.39]). Conclusions. These data indicate a detrimental effect of insulin resistance in MetS on OP patients, while the prevalence of the syndrome depends on the proportion of obesity. These findings provide new insights into the pathogenic role of MetS and reveal the need to consider different strata of BMI and insulin resistance when studying postmenopausal OP.

Keywords: HOMA index; insulin resistance; metabolic syndrome; osteoporosis.

Figure 1

Correlation between BMD and HOMA-IR index for insulin resistance as function of cumulative criteria for MetS and degree of obesity. (A) BMD at femoral neck, hip, and lumbar spine as function of cumulative criteria of MetS. (B) Variation in HOMA-IR as function of cumulative criteria of MetS. (C) Variation in BMD at femoral neck as function of centiles of BMI in non-OP, OP, and severe OP with fractures. (D) Variation in HOMA-IR index in patients without any criterion for MetS, 1, 2, and 3 to 5 criteria for MetS.

Figure 2

BMD at different anatomical sites in patients with osteoporosis and MetS compared to predicted values based on BMI. Predicted values of BMD as function of BMI were calculated in linear regression in subjects without osteoporosis (non-OP). Predicted values were then compared with actual values in non-OP and OP with MetS together (Panels (E–H)) with the display of residuals (Panels (A–D)).