Bone Health Management After Hematopoietic Cell Transplantation: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy

Abstract

Bone health disturbances commonly occur after hematopoietic cell transplantation (HCT) with loss of bone mineral density (BMD) and avascular necrosis (AVN) foremost among them. BMD loss is related to pretransplantation chemotherapy and radiation exposure and immunosuppressive therapy for graft-versus-host-disease (GVHD) and results from deficiencies in growth or gonadal hormones, disturbances in calcium and vitamin D homeostasis, as well as osteoblast and osteoclast dysfunction. Although the pathophysiology of AVN remains unclear, highdose glucocorticoid exposure is the most frequent association. Various societal treatment guidelines for osteoporosis exist, but the focus is mainly on menopausal-associated osteoporosis. HCT survivors comprise a distinct population with unique comorbidities, making general approaches to bone health management inappropriate in some cases. To address a core set of 16 frequently asked questions (FAQs) relevant to bone health in HCT, the American Society of Transplant and Cellular Therapy Committee on Practice Guidelines convened a panel of experts in HCT, adult and pediatric endocrinology, orthopedics, and oral medicine. Owing to a lack of relevant prospective controlled clinical trials that specifically address bone health in HCT, the answers to the FAQs rely on evidence derived from retrospective HCT studies, results extrapolated from prospective studies in non-HCT settings, relevant societal guidelines, and expert panel opinion. Given the heterogenous comorbidities and needs of individual HCT recipients, answers to FAQs in this article should be considered general recommendations, with good medical practice and judgment ultimately dictating care of individual patients. Readers are referred to the Supplementary Material for answers to additional FAQs that did not make the core set.

Successful treatment with lenalidomide for relapsed adult T-cell leukemia/lymphoma after cord blood cell transplantation

“…Most other risk factors described previously to affect BMD were not significant in our study, probably due to the small number of patients 14,14 . Given the high prevalence of low BMD pre-HCT and at day+100 post-HCT, we agree with the recent ASTCT and International Osteoporosis Foundation recommendations to screen all patients undergoing allo-HCT with a DXA scan at pre-HCT or at day+100 if not done pre-HCT 1,7 rather than restricting early screening to only patients with GVHD and steroid use 2 .…”

“…The American Society for Transplantation and Cellular Therapy (ASTCT) expert panel opinion has recently updated their guidance on the management of bone health after hematopoietic cell transplantation (HCT) based on evidence derived from retrospective HCT studies, results extrapolated from prospective studies in non-HCT settings, and societal guidelines 1 . They advise BMD measurement pre-HCT in patients with high-risk factors and at 3-months post-HCT if measurement is not done pre-HCT 1 . As per the previous recommendation, dual-energy X-ray absorptiometry (DXA) was done at 1-year post-transplant and at earlier time points in patients with GVHD and steroid use 2 .…”

“…Although there is an evolving consensus on when to do DXA scans, there is no consensus on the timing for pharmacologic intervention based on T-score/Z-score cutoffs or percentage BMD loss in the younger population (age < 40 years) in the post-HCT setting 3,6 . The ASTCT guidance proposes starting pharmacologic therapy in those < 40years of age receiving prednisone equivalent doses of 7.5 mg/day for 6 months and either exhibiting fragility fractures, Z-score < -3.0, or 10% BMD loss over a year 1 . The Indian population has a lower BMD compared to the Caucasian population 8 .…”

“…Objectives of the study: (1) to study the incidence and risk factors for low BMD (Z-score ! -2, below the expected range for age) in a cohort of young Indian patients pre-and post-HCT and (2) to study if antiresorptive therapy in patients with a Z-score !…”

Vitamin D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review

“…Hormone substitution treat-ment is a common therapy in females, while in males, further analysis on gonadal function is necessary [228]. Some authors suggest avoiding bone-protective treatment during the first 3 months after HCT to avoid collateral effects correlated with polypharmacy [229].…”