Relationship between Insulin Resistance (HOMA-IR), Trabecular Bone Score (TBS), and Three-Dimensional Dual-Energy X-ray Absorptiometry (3D-DXA) in Non-Diabetic Postmenopausal Women

Abstract

Background: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments. Methods: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR. Results: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c. Conclusions: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.

Longitudinal associations of insulin resistance with change in bone mineral density in midlife women

“…Unlike our longitudinal study, prior human investigations of the relation between insulin resistance and BMD have been cross-sectional. These studies have generated conflicting results with greater HOMA-IR or serum insulin being related to higher BMD levels (8)(9)(10)(11), lower BMD levels (12)(13)(14)(15)(16), or having no association with BMD levels (17)(18)(19)(20). One potential explanation for these discrepant findings is that, as we found in the current study, the relation between insulin resistance and BMD is nonlinear, but nearly all prior studies (8-11, 13-15, 17-19) tested for only linear associations.…”

“…In states of insulin resistance, osteoblasts may also be resistant to insulin signaling (6, 7). Results from human studies of the relation between insulin resistance and BMD are similarly inconclusive, with studies reporting positive (8-11), negative (12-16), or no association (17)(18)(19)(20). Notably, to our knowledge, all published human investigations on this topic are cross-sectional (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Results from human studies of the relation between insulin resistance and BMD are similarly inconclusive, with studies reporting positive (8-11), negative (12-16), or no association (17)(18)(19)(20). Notably, to our knowledge, all published human investigations on this topic are cross-sectional (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).The objective of this study was, therefore, to examine the longitudinal associations of insulin resistance with BMD in midlife women before, during, and after the menopause transition (MT). BMD decreases rapidly in a 3-year window spanning 1 year before to 2 years after the final menstrual period (FMP).…”

Bone microarchitecture, bone mineral density and bone turnover in association with glycemia and insulin action in women with prior gestational diabetes

“…We found that in the fully adjusted model, women with prediabetes and diabetes had higher odds of having low TBS and, therefore, our findings are in agreement with the existing literature. Furthermore, insulin resistance, expressed as HOMA‐IR, showed negative association with TBS, but positive association with BMD; similar findings have been reported previously 22–24 …”

Triglyceride Glucose–Body Mass Index Is a Reliable Indicator of Bone Mineral Density and Risk of Osteoporotic Fracture in Middle-Aged and Elderly Nondiabetic Chinese Individuals

“…A few studies have examined the relationship between insulin resistance and osteoporosis in nondiabetic patients. Francisco et al [ 21 ] conducted research in nondiabetic postmenopausal women and showed that there is a direct relationship between IR and BMD, but no association between IR and the prevalence of osteoporosis. It is possible that the relationship between IR and bone metabolism varies with sex, race, and bone mass or structure.…”