Predictors of impaired bone health in long-term survivors after allogeneic stem cell transplantation

Survival after allogeneic stem cell transplantation (allo-HSCT) has improved, but so have long-term sequelae. We studied risk factors for fractures and impaired bone health in allo-HSCT patients in the Basel HSCT registry from 01/2003 to 12/2014 using cox proportional models adjusted for age, gender and Karnofsky Index. Our primary endpoint was the incidence of fractures. Out of 652 patients, 32 (5.0%) had a new fracture after transplantation (yearly incidence rate of 1.6%, 95% Confidence Interval [95% CI] 1.1-2.3%) and 325 (49.8%) had low bone mineral density (yearly incidence rate of 13.1%, 95% CI 11.6-14.8%), including 36.0% with osteopenia and 13.8% with osteoporosis. We found vitamin D deficiency during follow-up (Hazard Ratio [HR] 1.25, 95% CI 1.11-1.41, p < 0.001), hyperthyroidism before transplantation (HR 4.85, 95% CI 1.05-22.54, p = 0.044), cumulative years of immunosuppressant exposure (HR 1.23, 95% CI 1.07-1.41, p = 0.004 for steroidal and HR 1.09, 95% CI 1.01-1.18, p = 0.025 for non-steroidal drugs) and graft-versus-host disease (acute HR 1.24, 95% CI 1.11-1.40, p < 0.001; chronic HR 2.82, 95% CI 1.12-7.13, p = 0.028) to be significantly associated with fractures. Patients undergoing HSCT are at increased risk of fractures, which is associated with various disease and treatment-specific factors. Early identification of patients at risk may help to improve preventive measures.