Bone Abstracts

Allogeneic hematopoietic stem cell transplant (AlloHSCT) is an established treatment for benign and malignant hematologic disorders. Five-year cure rates for childhood alloHSCT currently exceeds 60%. Unfortunately, chemotherapy, total body irradiation (TBI), glucocorticoid therapy, immune dysregulation, graft versus host disease, and treatment-related endocrine disorders result in significant late effects, including poor bone health and metabolic derangements. Consequently, medical attention has shifted to prevention and treatment of long-term alloHSCT-related morbidities. AlloHSCT survivors exhibit bone deficits and excess adiposity, related to altered mesenchymal stem cell differentiation into osteoblasts and adipocytes. The location of fat deposition is implicated in adverse cardiovascular and bone outcomes. We recently reported DXA measures of total body fat and lean mass in 55 long-term survivors of childhood alloHSCT. Although body mass index Z-scores did not differ between alloHSCT and a large group of reference participants, alloHSCT recipients demonstrated significant sarcopenic obesity. Furthermore, AlloHSCT survivors had substantial deficits in trabecular volumetric bone mineral density and cortical geometry by peripheral quantitative CT compared with reference participants. On tibia micro-MRI, survivors had lower bone volume fraction and abnormal bone microarchitecture with a greater number of vertebral deformities (P<0.01). These abnormalities were more pronounced in survivors with a history of TBI and growth hormone deficiency. DXA whole body (WB) and leg-lean mass (LM) Z-scores were also significantly lower in alloHSCT compared to reference participants (P<0.001 for both), and the magnitude of LM deficits was more pronounced for leg-LM, compared with WB-LM Z-scores. AlloHSCT survivors had significantly greater WB-fat mass (FM) Z-scores (P<0.001). DXA visceral adipose tissue, subcutaneous adipose tissue, and marrow adipose tissue (measured by MR spectroscopy) were significantly higher in alloHSCT. Muscle density was significantly lower, indicative of greater fat infiltration of muscle (P<0.05 for all). None of these group differences were attenuated after adjustments for greater WB-FM in alloHSCT. Importantly, alloHSCT demonstrated significant insulin resistance independent of physical activity. In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight risks of long-term treatment-related morbidity and mortality in alloHSCT recipients. These findings underline the need for lifelong specialized healthcare to institute appropriate and timely intervention strategies.

Disclosure: The authors declared no competing interests.