Vertebral Fractures Occur Regardless of Acromegaly Activity and Are Best Predicted by Proximal Femur Cortical Volumetric Bone Mineral Density

Abstract Introduction: Vertebral fractures (VFs) in patients with acromegaly are not associated with bone mineral density (BMD) decrease. Previous studies showed impaired trabecular bone parameters among acromegaly patients. However, recent studies suggest that cortical bone could also play a role in VF development. Objective: Evaluate the utility of dual energy x-ray absorptiometry (DXA) BMD and bone structural parameters to determine VF risk among acromegaly patients. Patients and Methods: A single-center two years prospective follow up of acromegaly patients regardless of age, gender, disease activity or associated treatments was conducted. Pituitary hormones, glucose metabolism and bone turnover markers in all subjects were assessed. Each subject had L1-4 spine, femoral neck (FN) and total hip (TH) BMD measured using DXA, and TBS measurement performed ± 7 days from blood sampling. 3D Shaper was used to assess proximal femur trabecular and cortical volumetric (v) BMD, cortical surface (s) BMD and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using semi-quantitative approach. Study outcomes were assessed at two time points - baseline and month 24. Results: Seventy subjects (34 M/36F), mean age 55.1 years, including 26 with active disease were studied. After two years a significant decrease in IGF-1 (-30%), osteocalcin (-18%) and TH cortical vBMD (-3%; all p≤0.05) was observed. During follow-up, 13 patients nine of them with controlled disease, developed VF; these patients had greater increase in CTx and decrease in TBS, sBMD, cortical and trabecular vBMD at TH and neck. Multivariate analysis of fracture prediction showed cortical vBMD at TH and neck as best parameters for fracture prediction with AUC 0.766 and 0.774; respectively. TBS was negatively associated with fasting plasma glucose (FPG), HBA1c at each time period. Conclusions: Decrease in cortical vBMD was the most sensitive and specific predictor of incident VF suggesting that cortical bone is involved in fracture development among acromegaly patients. In addition, TBS was strongly negatively associated with glucose metabolism, suggesting glucose intolerance could lead to trabecular bone impairment.