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

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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.

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TBS (trabecular bone score) and diabetes-related fracture risk.

William D Leslie, Berengère Aubry-Rozier, Olivier Lamy … (2013)

Type 2 diabetes is associated with increased fracture risk but paradoxically greater bone mineral density (BMD). Trabecular bone score (TBS) is derived from the texture of the spine dual x-ray absorptiometry (DXA) image and is related to bone microarchitecture and fracture risk, providing information independent of BMD.

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Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo.

S. Lin, Andrew G Nicholson, D Naot … (2002)

Fat mass is an important determinant of bone density, but the mechanism of this relationship is uncertain. Leptin, as a circulating peptide of adipocyte origin, is a potential contributor to this relationship. Recently it was shown that intracerebroventricular administration of leptin is associated with bone loss, suggesting that obesity should be associated with low bone mass, the opposite of what is actually found. Since leptin originates in the periphery, an examination of its direct effects on bone is necessary to address this major discrepancy. Leptin (>10(-11) m) increased proliferation of isolated fetal rat osteoblasts comparably with IGF-I, and these cells expressed the signalling form of the leptin receptor. In mouse bone marrow cultures, leptin (>or=10(-11) m) inhibited osteoclastogenesis, but it had no effect on bone resorption in two assays of mature osteoclasts. Systemic administration of leptin to adult male mice (20 injections of 43 micro g/day over 4 weeks) reduced bone fragility (increased work to fracture by 27% and displacement to fracture by 21%, P<0.001). Changes in tibial histomorphometry were not statistically significant apart from an increase in growth plate thickness in animals receiving leptin. Leptin stimulated proliferation of isolated chondrocytes, and these cells also expressed the signalling form of the leptin receptor. It is concluded that the direct bone effects of leptin tend to reduce bone fragility and could contribute to the high bone mass and low fracture rates of obesity. When administered systemically, the direct actions of leptin outweigh its centrally mediated effects on bone, the latter possibly being mediated by leptin's regulation of insulin sensitivity.

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Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass.

Michael McClung, Javier San Martín, Paul D Miller … (2015)

Antiresorptive agents for the treatment of osteoporosis suppress bone remodeling and reestablish bone turnover at a lower rate to reduce bone loss. Recombinant teriparatide (human parathyroid hormone 1-34) stimulates bone formation, increases bone mass, and improves bone microarchitecture. We contrasted the effects of once-daily doses of 20 mug of teriparatide and 10 mg of alendronate sodium on bone mineral density (BMD) and markers of bone turnover. Markers of bone turnover and areal BMD were assessed in 203 postmenopausal women with osteoporosis in an 18-month randomized parallel double-blind study; volumetric BMD was measured in a subset of women. Teriparatide significantly increased markers of bone turnover that peaked at 6 months (serum procollagen type I N-terminal propeptide, 218%, and urinary N-telopeptide corrected for creatinine, 58%; P<.001); alendronate significantly decreased the markers at 6 months (-67% and -72%, respectively; P<.001). At 18 months, areal and volumetric spine BMDs were significantly higher with teriparatide than with alendronate (10.3% vs 5.5% [P<.001] and 19.0% vs 3.8% [P<.01], respectively). Areal femoral neck BMD was significantly higher than baseline in the teriparatide and alendronate groups (3.9% and 3.5%, respectively). There were no significant differences in trabecular femoral neck BMD between the teriparatide and alendronate groups (4.9% and 2.2%, respectively). Cortical volumetric femoral neck BMD was significantly different between the teriparatide and alendronate groups (-1.2% and 7.7%, respectively; P = .05). Two distinct options for the management of osteoporosis lead to increases in BMD by opposite mechanisms of action on bone remodeling.

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Journal

Journal ID (nlm-ta): J Clin Med

Journal ID (iso-abbrev): J Clin Med

Journal ID (publisher-id): jcm

Title: Journal of Clinical Medicine

Publisher: MDPI

ISSN (Electronic): 2077-0383

Publication date (Electronic): 03 June 2020

Publication date Collection: June 2020

Volume: 9

Issue: 6

Electronic Location Identifier: 1732

Affiliations

[1 ]Gynaecology Department, Hospital Clínico Universitario Valladolid, 47003 Valladolid, Spain; fdacampillo@ 123456gmail.com

[2 ]IOBA, University of Valladolid, 47011 Valladolid, Spain

[3 ]Department Medicine, University of Valladolid, 47005 Valladolid, Spain; angelatemi@ 123456hotmail.com (Á.R.-d.T.); mruizm65@ 123456gmail.com (M.R.-M.); dueton@ 123456gmail.com (A.D.-L.)

[4 ]Hospital Nuestra Señora de Sonsoles, 05004 Avila, Spain; jgdayla@ 123456hotmail.com

[5 ]Biology Department, University of Valladolid, 47005 Valladolid, Spain; josefg@ 123456med.uva.es

[6 ]Department of Medicine, University of Valladolid Service of Clinical Toxicology, Río Hortega University Hospital, 47012 Valladolid, Spain

[7 ]Department of Internal Medicine, Department of Medicine, University of Valladolid, Río Hortega University Hospital, 47012 Valladolid, Spain

Author notes

[* ]Correspondence: rusategui@ 123456gmail.com (R.U.-M.); uvacastrv@ 123456gmail.com (J.L.P.-C.); Tel./Fax: +34-98-342-3184 (R.U.-M. & J.L.P.-C.)

[†]

These authors contributed equally to this work.

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Ricardo Usategui-Martín https://orcid.org/0000-0001-7699-4388

Article

Publisher ID: jcm-09-01732

DOI: 10.3390/jcm9061732

PMC ID: 7355807

PubMed ID: 32503328

SO-VID: 7a08a3e0-66c7-4df6-9f96-6d294dfdadfe

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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

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Most cited references 31

TBS (trabecular bone score) and diabetes-related fracture risk.

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo.

Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass.

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