In vivo bone architecture in pompe disease using high-resolution peripheral computed tomography

Abstract

Pompe disease (lysosomal acid alpha-glucosidase deficiency) in adolescents and adults presents primarily with muscle weakness. Bone weakness is an under-recognized finding in patients with Pompe disease, but there is emerging evidence that loss of muscle function and mobility can lead to loss of mineral content and a higher risk of fracture. In addition to the mineral content, architecture is also important in determining the overall strength of the bone. We present the results of the longest longitudinal duration study to date using a novel application of high-resolution peripheral quantitative computed tomography (HR-pQCT) in four patients with Pompe disease over 4 years of observation during the normal course of their disease management. The subjects varied in treatment status with recombinant human alpha-glucosidase (rhGAA), use of anti-resorptive therapy (such as bisphosphonates), mobility and weight-bearing status, and the use of side-alternating vibration therapy. Our observations were that HR-pQCT can measure trends in mineral density and architecture over a long period of observation and may be an early indicator of the response to interventional therapies. In addition, a combination of decreased loading forces due to decreased mobility likely contributes to the compromise of bone integrity in Pompe disease. These trends can be reversed by applying increased loading forces such as vibration therapy and maintaining weight-bearing and mobility. We conclude that HR-pQCT can serve as a valuable tool to monitor bone health in patients with Pompe disease.