Predictors of fracture in treated Gaucher disease patients

Abstract

Listen

Translate article

Skeletal complications, particularly fracture, can be one of the most debilitating consequences of Gaucher disease (GD). Understanding the risk factors for fracture and the relationship to timing of initiation of treatment is important for successful evaluation and management of patients. The International Collaborative Gaucher Group (ICGG) Gaucher Registry is a multinational, observational study (sponsored by Genzyme, a Sanofi company, Cambridge, MA) that captures clinical outcomes in both treated and untreated GD patients. Descriptive statistics and an adjusted logistic regression model were used to evaluate demographics and risk factors in patients enrolled in the ICGG Registry with GD type 1who had experienced a fracture. A total of 4047 patients with GD type 1 in the ICGG Registry who had received imiglucerase had sufficient bone and splenectomy data for analyses. Of these, 46% were male, the median age of diagnosis was 15 years of age, and 336 patients (8%) had experienced a fracture during treatment. Splenectomized patients were nearly twice as likely to have a fracture compared to those who were not (OR 1.930; p = b0.0001). The presence of bone pain or bone crisis (acute pain requiring immobilization, narcotics, and accompanied by periosteal elevation, elevated WBC count, fever and/or debilitation of N3 days) was a predictor of fracture, even if reported considerably prior to the fracture itself. Patients with bone pain were 2.5 times more likely to have a fracture (OR 2.683; p = b0.0001); those with bone crises were nearly twice as likely (OR 1.739; p = b0.0004). Additionally, early treatment decreased fracture risk. Patients who did not begin treatment until after the age of 25 were 30% (OR 1.373; p = 0.0132) more likely to have a fracture. The 3711 patients who did not have a fracture were diagnosed (median age: 14 years) and treated (median age: 27 years) younger than the 336 with a fracture who were diagnosed (median age: 17.5 years) and treated (median age: 37 years) later. Understanding risk factors, symptoms, and treatment patterns is important to avoid potential fractures. Splenectomy, bone pain, and bone crisis substantially elevate risk of fractures in patients on therapy, and should be considered early warning signs. Younger age at treatment initiation lowers the risk of fracture, suggesting that developing bone pathologymay be interrupted when early treatment is provided.