Effect of Exposure to Enzyme Replacement Therapy on Bone Mineral Density in Children With Gaucher Disease

Gaucher disease (GD), caused by variants in the GBA1 gene, is manifested by the accumulation of glucosylceramide within macrophages in visceral organs and bone marrow and can lead to significant bone disease. The aim of this study was to assess longitudinal bone mineral density (BMD) changes in children with GD and the impact of enzyme replacement therapy (ERT). The study included children and adolescents (5-20 years) with GD who had at least two dual-energy x-ray absorptiometry (DXA) scans. These scans, done every 2-3 years with a Hologic Discovery densitometer, were part of regular clinic visits. Whole body less head (WBLH), femoral neck, lumbar spine, and total hip BMD Z scores were adjusted for height-for-age Z score (HAZ). Children were grouped by ERT exposure: untreated, treated throughout, or initiated during follow-up. Low BMD at baseline was more common in children who initiated ERT during follow-up. By study end, BMD status was comparable across all groups. WBLH BMD improved in 52/79, significantly more often than at the femoral neck (18/79), lumbar spine (18/79), or hip (20/79), with no difference between treatment groups. Longitudinal BMD changes were unrelated to sex, GBA1 genotype, follow-up duration, calcium, phosphorus, alkaline phosphatase, or lyso-Gb1 levels. In conclusion, with proper clinical selection, some children with GD can be safely monitored without ERT. Adjustment to HAZ and focusing on the WBLH for clinical decision-making in children with GD is important. Continued monitoring into adulthood is essential to clarify long-term skeletal outcomes and confirm the utility of site-specific monitoring in childhood.