Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation

A significant proportion of patients will be long-term survivors of bone ma rrow transplantation (BMT) and little is known about their risk of late bon y complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in l ong-term survivors. We performed two analyses. The first was a cross-sectio nal study of 83 consecutive BMT patients (38 F, 45 M), examining the relati onship between BMD and bone turnover, measured immediately prior to transpl antation, and a number of disease and patient variables. The second was a p rospective study of 39 patients (19F, 20 M) followed for a median of 30 mon ths (range 5-64 months) following either allogeneic (allo, n = 29) or autol ogous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal an d femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipie nts than in female allo BMT recipients, respectively (p = 0.12 and p = 0.00 3). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocortico ids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrh oea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and wom en receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared wit h a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD a nd total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, resp ectively, post-allo, compared with an increase (1.5%,p = 0.03) or nonsignif icant decrease (-3.7%,p = NS), respectively, post-auto BMT. Post-allo BMT b one loss correlated best with the cumulative prednisolone dose at the LS an d FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negati vely related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. A vascular necrosis of the femoral head o ccurred in four, and vertebral and rib fractures occurred in one of the all o BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their un derlying illness and/or chemotherapy, particularly in female autograft reci pients, and in allograft recipients secondary to GVHD and its treatment.