Increased Marrow Adiposity in Premenopausal Women with Idiopathic Osteoporosis

Context: We have previously reported that premenopausal women with idiopathic osteoporosis based on fractures (IOP) or idiopathic low bone mineral density (ILBMD) exhibit markedly reduced bone mass, profoundly abnormal trabecular microstructure, and significant deficits in trabecular bone stiffness. Bone remodeling was heterogeneous. Those with low bone turnover had evidence of osteoblast dysfunction and the most marked deficits in microstructure and stiffness. Objective: Because osteoblasts and marrow adipocytes derive from a common mesenchymal precursor and excess marrow fat has been implicated in the pathogenesis of bone fragility in anorexia nervosa, glucocorticoid excess, and thiazolidinedione exposure, we hypothesized that marrow adiposity would be higher in affected women and inversely related to bone mass, microarchitecture, bone formation rate, and osteoblast number. Design: We analyzed tetracycline-labeled transiliac biopsy specimens in 64 premenopausal women with IOP or ILBMD and 40 controls by three-dimensional micro-computed tomography and two-dimensional quantitative histomorphometry to assess marrow adipocyte number, perimeter, and area. Results: IOP and ILBMD subjects did not differ with regard to any adipocyte parameter, and thus results were combined. Subjects had substantially higher adipocyte number (by 22%), size (by 24%), and volume (by 26%) than controls (P < 0.0001 for all). Results remained significant after adjusting for age, body mass index, and bone volume. Controls demonstrated expected direct associations between marrow adiposity and age and inverse relationships between marrow adiposity and bone formation, volume, and microstructure measures. No such relationships were observed in the subjects. Conclusions: Higher marrow adiposity and the absence of expected relationships between marrow adiposity and bone microstructure and remodeling in women with IOP or ILBMD suggest that the relationships between fat and bone are abnormal; excess marrow fat may not arise from a switch from the osteoblast to the adipocyte lineage in this disorder. Whether excess marrow fat contributes to the pathogenesis of this disorder remains unclear. (J Clin Endocrinol Metab 97: 2782-2791, 2012)