Insulin resistance negatively affects bone quality not quantity: the relationship between bone and adipose tissue

Araújo, Iana Mizumukai de; Parreiras-e-Silva, L.T.; Carvalho, Adriana Lelis; Elías, Jorge; Salmon, Carlos Ernesto Garrido; Paula, Francisco José Albuquerque de

doi:10.1007/s00198-020-05365-5

Cited by 23 publications

(23 citation statements)

References 45 publications

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“…In our study of a non-diabetic population, we found that women in Q4 of HbA1c had the lowest TBS levels, which was maintained after adjusting for age and BMI. Recently, there have been two studies published that analyzed the relationship between HOMA-IR-and TBS-measured insulin resistance in non-diabetic populations [35,36]; their results were similar to ours. Although their sample populations were both heterogeneous (including both men and women) and pre-and postmenopausal, they also had a small sample.…”

Section: Discussionsupporting

confidence: 87%

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

Campillo-Sánchez

Usategui-Martín

Temiño

et al. 2020

JCM

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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.

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Section: Discussionsupporting

confidence: 87%

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

Campillo-Sánchez

Usategui-Martín

Temiño

et al. 2020

JCM

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“…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).…”

mentioning

confidence: 99%

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

Shieh¹,

Greendale²,

Cauley³

et al. 2022

JCI Insight

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Although there is wide recognition that type 2 diabetes mellitus (DM2) is a risk factor for fractures (1), the effects of insulin resistance (a key pathophysiologic mechanism in DM2) on bone remain uncertain. In vitro, insulin signaling promotes osteoblast differentiation, proliferation, and function (2-4). However, in the in vivo models of insulin resistance, insulin signaling leads to expansion of bone marrow adipose tissue, decreased trabecular bone mineral density (BMD), and decreased cortical thickness (5). 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).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). We define this period as the MT; premenopause (more than 1 year prior to the FMP) precedes the MT, and postmenopause BACKGROUND. The effects of insulin resistance on bone mineral density (BMD) are unclear. METHODS.In Study of Women's Health Across the Nation (SWAN) participants, we used multivariable regression to test average insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR) and rate of change in insulin resistance as predictors of rate of change in lumbar spine (LS) and femoral neck (FN) BMD in 3 stages: premenopause (n = 861), menopause transition (MT) (n = 571), and postmenopause (n = 693). Models controlled for age, average BW, change in BW, cigarette use, race and ethnicity, and study site. RESULTS.The relation between HOMA-IR and BMD decline was biphasic. When average log 2 HOMA-IR was less than 1.5, greater HOMA-IR was associated with slower BMD decline; i.e., each doubling of average HOMA-IR in premenopause was associated with a 0.0032 (P = 0.01, LS) and 0.0041 (P = 0.004, FN) g/cm 2 per year slower BMD loss. When greater than or equal to 1.5, average log 2 HOMA-IR was not associated with BMD change. In women in whom HOMA-IR decreased in premenopause, the association between the HOMA-IR change rate and BMD change rate was positive; i.e, slower HOMA-IR decline was associated with slower BMD loss. In women in whom insulin resistance increased in premenopause, the association was negative; i.e, faster HOMA-IR rise was associated with faster BMD decline. Associations of average HOMA-IR and HOMA-IR change rate with BMD change rate were similar in postmenopause, but weaker during the MT. CONCLUSION.When it decreases, insulin resistance is associated with BMD preservation; when it increases, insulin resistance is associated with BMD loss.

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“…Despite the pathophysiological knowledge of obesity leading to increased central adiposity and low-grade systemic inflammatory processes which, in consequence, have a negative impact on bone metabolism, the impact of VAT and SAT on vertebral fracture risk is still not understood [20,35]. The complexity of the interaction between hormonal regulatory mechanisms accompanying fat accumulations is elucidated by de Araujo et al and de Frauda et al, who described the negative association of insulin resistance and VAT on bone quality and BMD [21,36]. Taken together, the recent literature emphasizes the non-linear interaction paths and feedback loops of energy metabolism and bone mineral homeostasis [21].…”

Section: Discussionmentioning

confidence: 99%

Local Bone Mineral Density, Subcutaneous and Visceral Adipose Tissue Measurements in Routine Multi Detector Computed Tomography—Which Parameter Predicts Incident Vertebral Fractures Best?

et al. 2021

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In this case-control study the value of bone mineral density (BMD) at different vertebral levels, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) to identify patients with incident osteoporotic vertebral fractures in routine multi-detector computed tomography (MDCT) exams was assessed. Material and methods: Seventeen patients who underwent baseline and follow-up routine contrast-enhanced MDCT and had an incident osteoporotic vertebral fracture at follow-up were included. Seventeen age-, sex- and follow-up duration-matched controls were identified. Trabecular BMD (from Th5 to L5) as well as cross-sectional area of SAT and VAT were extracted. Results: BMD performed best to differentiate patients with an incident fracture from controls at the levels of Th5 (area under the curve [AUC] = 0.781, p = 0.014), Th7 (AUC = 0.877, p = 0.001), and Th9 (AUC = 0.818, p = 0.005). Applying multivariate logistic regression BMD at Th7 level remained the only significant predictor of incident vertebral fractures (Th5-L5) with an odds ratio of 1.07 per BMD SD decrease. VAT and SAT did not show significant differences between the fracture and control group (p > 0.05). Conclusion: The local BMD measurement appears to be more suitable than standard mean BMD from L1–L3 for fracture risk assessment.

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Insulin resistance negatively affects bone quality not quantity: the relationship between bone and adipose tissue

Cited by 23 publications

References 45 publications

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

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

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

Local Bone Mineral Density, Subcutaneous and Visceral Adipose Tissue Measurements in Routine Multi Detector Computed Tomography—Which Parameter Predicts Incident Vertebral Fractures Best?

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