Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review

Abstract

Introduction The skeletal anomalies represent a characteristic feature of Gaucher disease type 1 (GD1). We evaluated the impact of an integrated therapy with Enzyme Replacement Therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. Methods From January 1st,2015 to February 28th, 2019, all GD1 patients referring to Federico II University were enrolled and treated with the integrated therapy. The bone turnover markers (BTMs) and bone mineral density (BMD) were evaluated at baseline (T0) and after 24 months (T24). Results We enrolled 25 GD1 patients, all showing 25OHD levels <50 nmol/l (hypovitaminosis D) at T0. The response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis and 7 BMD Z-score ≤ -2. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared to those without bone anomalies. During the 2-years follow-up no new bone anomalies occurred. At T24, the BMD remained stable in the entire study cohort and in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Conclusion In GD1 patients, hypovitaminosis D is prevalent. The response to cholecalciferol treatment is effective but different to healthy subjects and to patients with metabolic bone disorders. The integrated therapy including ERT, cholecalciferol, and bone diet guarantee the bone health.