Bone Geometry, Density, and Microarchitecture in the Distal Radius and Tibia in Adults With Marfan Syndrome Assessed by HR-pQCT

Marfan syndrome (MFS) is a hereditary disorder of connective tissue caused by mutations in the fibrillin-1 gene. Studies have shown that patients with MFS have lower bone mass, but little is known about the other constituents of bone strength. We hypothesize that patients with MFS will have larger bone area and compromised cortical microarchitecture compared with non-MFS individuals. A total of 74 adult patients with MFS and 145 age- and sex-matched non-MFS reference individuals were included in this study. High-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and dual-energy X-ray absorptiometry of total hip and the lumbar spine were performed, and bone turnover and sex hormones were measured. Patients with MFS had significantly lower areal bone mineral density (BMD) at the total spine (−13%) and total hip (−7%) when compared with the reference group. Patients with MFS had significantly larger total bone area at both the radius (+27%) and tibia (+34%). Volumetric BMD at both measured sites showed significantly reduced total, trabecular, and cortical volumetric BMD in patients with MFS compared with the reference group. The microarchitectural parameters at the radius and tibia were compromised in patients with MFS with significantly reduced trabecular number and thickness, leading to a higher trabecular separation and significantly reduced cortical thickness and increased cortical porosity compared with the reference group. The differences in bone density, geometry, or microarchitecture were not explained by increased bone turnover markers or circulating levels of sex hormones. We conclude patients with MFS have altered bone geometry, altered bone microstructure, and lower bone mass (lower areal BMD and volumetric BMD at all sites) compared with healthy reference individuals. Future studies should focus on fracture rates and fracture risk in adult and aging patients with MFS.