Bone Abstracts

Background: Osteoporosis is a prevalent skeletal disorder associated with increased fracture risk and morbidity, affecting one in three women over the age of 50 and one in five men worldwide¹. While metabolic disease is known to impair bone quality, the extent to which early skeletal deterioration influences systemic metabolism remains unclear. This study examined how bone loss in a model of postmenopausal osteoporosis impacts whole-body metabolic organisation.

Methods: Female SpragueDawley rats underwent ovariectomy (OVX) or sham surgery (n 6/group) and were studied over 8 weeks. Glucose homeostasis was assessed using oral glucose tolerance testing and insulin ELISA. Tissue-level changes were evaluated through organ and adipose tissue weighing, histological analysis of adipocyte morphology, and micro-computed tomography (µCT) to assess trabecular bone architecture. Dynamic [¹⁸F]FDG PET/CT imaging was performed to quantify tissue-specific glucose metabolism. Bone and bone marrow volumes of interest were segmented using Hounsfield Unit thresholds, while metabolic organs were segmented manually. Standardised uptake values were used for network analysis (Graphia).

Results: OVX induced early skeletal deterioration, evidenced by uterine atrophy (P 0.0003), increased body mass, and significant impairment in trabecular bone architecture, including reduced bone volume, trabecular number, connectivity, and mineral density (all P ≤ 0.002), alongside increased trabecular separation (P 0.026). These changes were accompanied by systemic metabolic alterations, including increased gonadal adipose tissue mass (P 0.048), reduced liver and kidney mass (P 0.024), and pronounced adipocyte hypertrophy (P ≤ 0.0001). Notably, these effects occurred in the absence of detectable impairments in glucose tolerance or insulin response. Bone turnover markers (CTX and P1NP) were elevated, indicating increased remodelling. Tissue-specific glucose uptake was altered across key metabolic organs, and network analysis revealed marked reorganisation of systemic metabolic interactions in OVX animals.

Conclusion: Early skeletal deterioration in postmenopausal osteoporosis is associated with significant changes in whole-body metabolic organisation, supporting a role for bone loss in driving systemic metabolic dysregulation during oestrogen deficiency.

Reference: 1. Szen, T., Özışık, L., Çalık Başaran, N. (2019). An overview and management of osteoporosis. European Journal of Rheumatology, 4(1), 4656.