Bone loss in stem cell transplantation survivors

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

There is growing use of hematopoietic stem cell transplantation for treatment of primary, refractory, and recurrent malignancies. Although this treatment leads to the salvage of many lives, it is not without potential long-term toxicities. Some toxicities—such as those of the skeletal system—may go undetected until advanced stages are reached, when attempts at amelioration may be unsuccessful and significant compromise of function occurs. Such is the case with transplantation-induced osteoporosis, which may predispose bone marrow transplantation (BMT) survivors to earlier onset and more severe osteopenia and osteoporosis than the healthy population.

In this issue of Blood, Schulte and Beelen (page 3635) present a large prospective study of bone mineral density (BMD) deficits and potential risk factors for its development following allogeneic bone marrow transplantation. This study of 280 adults (median age, 38 years; range, 16-59 years) represents one of the few prospective longitudinal studies of BMD in allogeneic BMT patients. Their extensive statistical analyses of risk factors for rapid bone loss revealed a limited number of factors that directly correlate with BMD loss in this patient cohort: steroid dose, total dose of cyclosporine A, loss of body weight (particularly of muscle mass), and baseline BMD parameters. Interestingly, other potential factors such as age at transplantation, sex, primary diagnosis, pretransplantation regimen, and state of HLA match were not found to be significant factors.

The authors demonstrate that posttransplantation BMD loss is greatest in the first year following transplantation for all sites evaluated. Recovery of bone loss over the subsequent 3 to 4 years was notable and site specific, with the least recovery being seen in the femoral neck and Ward triangle. These site-specific differences suggest an increased risk for proximal femoral fractures in this relatively young patient cohort and should underscore the critical need to develop clinical guidelines directed at optimizing BMD recovery in this patient cohort.

Little information is currently available that addresses effective means of improving BMD in BMT survivors. The authors have provided us with insight into the potential utility of antiresorptive therapy in this patient cohort. They describe a subset of 35 patients in whom antiresorptive therapy was initiated as protection for and/or treatment of osteoporotic fracture after BMT. Of the 10 patients with demonstrated osteoporotic fractures, 9 were younger than 50 years (average age, 31.6 years; median, 39.5 years). Thus, this relatively young cohort seems to be at risk for osteoporotic fracture several decades earlier than the healthy population.

This long-term follow-up study by Schulte and Beelen provides needed details of temporal bone loss related to hematopoietic stem cell transplantation. As they indicate, there is a limited protective effect of younger age at the time of transplantation for spine BMD, the propensity for at least partial restitution of bone loss over time, and an increased risk for transplantation-induced osteoporotic fracture in this cohort. Their work should prompt development of large prospective longitudinal studies to refine risk factors for BMD loss and underscores the need for improved technologic assessments for bone quality, morphology, and quantification in long-term BMT survivors.