Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study

Abstract

Context: The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation.

Objective: The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights.

Design: We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies.

Results: Body mass index (BMI) ranged from 20.1 to 39.2 kg/m(2). Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm(2)/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = -0.50; P < .01) and bone formation rate (r = -0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI.

Conclusions: At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation.

Figure 1.

Regression analysis of VAT by CT on trunk fat by DXA. There is a direct relationship between VAT and trunk fat.

Figure 2.

A, Regression analysis of BV/TV (percentage) on trunk fat by DXA. B, Regression analysis of trabecular surface BFR/BS (square millimeters per millimeter per year) on trunk fat by DXA. There are inverse relationships between trunk fat and both trabecular bone volume fraction and cancellous surface bone formation rate. Because some of the parameters were not normally distributed, the relationships are visually represented in the figure with regression lines, whereas the r and P values presented in the figure are derived from Spearman correlation analyses.

Figure 3.

A, Regression analysis of adipocyte volume/marrow volume on trunk fat by DXA shows a direct relationship. B, Regression analysis of serum IGF-I on VAT by CT shows an inverse relationship. C, Regression analysis of cancellous surface BFR/BS (square millimeters per millimeter per year) on serum IGF-I shows a direct relationship.

Figure 4.

Trabecular bone structure assessed by μCT of transiliac crest bone biopsy samples obtained from representative subjects within each DXA trunk fat tertile. Subjects are chosen to represent the mean BV/TV seen in each tertile.