Unexplained high BMD in DXA-scanned patients is generalized throughout the skeleton and characterized by thicker cortical and trabecular bone.

Unexplained high bone mineral density (BMD) is a rare condition and the mechanisms responsible are yet to be described in detail. The aim of the study was to identify patients with unexplained high BMD from a local DXA database and compare their radiological phenotype with an age- and a gender-matched group of population-based controls. We defined high BMD as a DXA Z-score ≥ + 2.5 at the total hip and lumbar spine. We characterized the findings as "unexplained" if no osteodegenerative changes, bone metabolic disease, or arthritis at the hip or lumbar spine was observed. All participants were investigated with high-resolution peripheral quantitative computed tomography (HR-pQCT), QCT, DXA, fasting blood samples, a 24-h urine sample, and questionnaires. The DXA database contained data on 25,118 patients. Initially, 138 (0.55%) potential participants with high BMD were identified, and during the study ten additional cases were identified from new DXA scans. Sixty-seven patients accepted to participate in the study, and among these we identified 15 women and one man with unexplained high BMD. These 15 women had higher BMD throughout the skeleton relative to controls, similar area/volume at the hip and the distal extremities, a higher number of trabeculae, which was thicker than in the controls, and a higher finite element estimated bone strength. The 15 women were heavier and had a higher fat mass then controls. We conclude that patients with unexplained high BMD have a generalized high BMD phenotype throughout their skeleton, which is characterized with a denser microarchitecture.