ESPE Abstracts

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has emerged as an increasingly successful option to cure a variety of malignant disorders in children. Children benefit from improved survival; however, HSCT is associated with numerous acute and long-term toxicities. Osteoporosis is a well described, late effect of allogeneic HSCT, associated with corticosteroid treatment and patients exposed to cumulative doses >9000 mg/m2 of prednisone equivalent are more likely be affected. Bisphosphonates are standard treatment of osteoporosis in adults, but their use in children remains off label and is reserved for selected cases.

Case presentation: A 12-year-old boy with myelodysplastic syndrome (MDS-EB) was treated with myeloablative chemotherapy followed by allogeneic HSCT from a matched sibling. The boy had neutrophil engraftment on day +20 and platelet engraftment on day +28. Unfortunately, on day +4, he developed acute graft-vs-host disease of the gut and was started on methylprednisolone 2 mg/kg. The patient was discharged on day +56 on the same dose of methylprednisolone and was supplemented with calcium and vitamin D for prevention of bone loss. He was tapered off glucocorticoid therapy five months post-transplantation. Eight months post-transplantation, the boy developed severe back pain, needing regular pain killers. Radiographs of the spine revealed lumbar and thoracic vertebral compression fractures and dual-energy x-ray absorptiometry (DXA) showed low bone mineral density (BMD) for age and sex, with a lumbar BMD Z-score of -2,3 (osteoporosis). At the age of 13.2 years, he was commenced on bisphosphonate treatment with zoledronate at a dose of 0.025 mg/kg, administered every three months (annual dose 0.1 mg/kg). Five doses of zoledronate were administered over 15 months, with no significant adverse events. Acetaminophen was administered for the first 2 days after infusion to reduce the incidence of acute-phase reaction symptoms and post-infusion hypocalcemia was managed with administration of elemental calcium (2-3 gr/day). On review at 14.1 years, his spine BMD showed considerable improvement (Z-score -0,1) and he had entered puberty with 10 ml testes bilaterally. One year later, at the age of 15.1 years, his spine BMD Z-score was -0,7, and puberty was progressing with 14 ml testes bilaterally. Spine BMD remained normal at the age of 16.5 years. Most importantly, he is no longer in pain.

Conclusion: A high index of suspicion for osteoporosis in patients receiving HSCT is required, to allow prompt treatment with bisphosphonates and improve quality of life, with no skeletal malformations or bone pain.