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

Merav Bar, Susan M. Ott, E. Michael Lewiecki, Kyriakie Sarafoglou, Joy Y. Wu, Matthew J. Thompson, Jonathan J. Vaux, David R. Dean, Kenneth G. Saag, Shahrukh K. Hashmi, Yoshihiro Inamoto, Bhagirathbhai R. Dholaria, Mohamed A. Kharfan-Dabaja, Arnon Nagler, Cesar Rodriguez, Betty K. Hamilton, Nina Shah, Mary E.D. Flowers, Bipin N. Savani, Paul A. Carpenter

Research output: Contribution to journalArticlepeer-review

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, high-dose 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.

Original languageEnglish (US)
Pages (from-to)1784-1802
Number of pages19
JournalBiology of Blood and Marrow Transplantation
Volume26
Issue number10
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
Conflict of interest statement: E.M.L. discloses research grants from Radius, Amgen, Mereo, and Bindex; income for service on scientific advisory boards or consulting for Amgen, Radius, Alexion, Sandoz, Samsung Bioepis, Sand anifit; service on speakers’ bureaus for Radius, and Alexion; project development for the University of New Mexico; and royalties from UpToDate for sections on DXA, fracture risk assessment, and prevention of osteoporosis. He is a board member of the National Osteoporosis Foundation, International Society for Clinical Densitometry, and Osteoporosis Foundation of New Mexico. K.S. reports research support from the National Institutes of Health National Cancer Institute (R01 CA181024); Office of Orphan Products Development of the Food and Drug Administration (R01FDR0006100); Alexion, Spruce Biosciences, and Neurocrine Biosciences. J.Y.W. reports research funding from Radius Health. K.G.S. reports research support from Radius, Mereo, and Amgen and consulting fees from Roche, Daiichi-Sankyo, and Amgen. S.K.H. discloses honoraria from Pfizer, Novartis, Mallinckrodt, and Janssen and travel grants from Sanofi, Gilead, Merck, and GSK. Y.I. reports honoraria from Astellas Pharma, Novartis, Chugai Pharmaceutical, Sumitomo Dainippon Pharma, MSD KK (a subsidiary of Merck & Co), and Kyowa Kirin and consulting fees from Novartis. M.A.K.D. reports consultancy fees from Pharmacyclics and Daiichi Sankyo. C.R. has served on speakers bureaus and advisory boards for Celgene/BMS and Amgen. N.S. reports research support from Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, and Teneobio and has served on advisory boards for Genentech, GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, and Kite Pharma. P.A.C. reports research support from Pharmacyclics and Incyte. The other authors have no conflicts of interest to disclose.

Funding Information:
Financial disclosure:, Conflict of interest statement: E.M.L. discloses research grants from Radius, Amgen, Mereo, and Bindex; income for service on scientific advisory boards or consulting for Amgen, Radius, Alexion, Sandoz, Samsung Bioepis, Sand anifit; service on speakers? bureaus for Radius, and Alexion; project development for the University of New Mexico; and royalties from UpToDate for sections on DXA, fracture risk assessment, and prevention of osteoporosis. He is a board member of the National Osteoporosis Foundation, International Society for Clinical Densitometry, and Osteoporosis Foundation of New Mexico. K.S. reports research support from the National Institutes of Health National Cancer Institute (R01 CA181024); Office of Orphan Products Development of the Food and Drug Administration (R01FDR0006100); Alexion, Spruce Biosciences, and Neurocrine Biosciences. J.Y.W. reports research funding from Radius Health. K.G.S. reports research support from Radius, Mereo, and Amgen and consulting fees from Roche, Daiichi-Sankyo, and Amgen. S.K.H. discloses honoraria from Pfizer, Novartis, Mallinckrodt, and Janssen and travel grants from Sanofi, Gilead, Merck, and GSK. Y.I. reports honoraria from Astellas Pharma, Novartis, Chugai Pharmaceutical, Sumitomo Dainippon Pharma, MSD KK (a subsidiary of Merck & Co), and Kyowa Kirin and consulting fees from Novartis. M.A.K.D. reports consultancy fees from Pharmacyclics and Daiichi Sankyo. C.R. has served on speakers bureaus and advisory boards for Celgene/BMS and Amgen. N.S. reports research support from Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, and Teneobio and has served on advisory boards for Genentech, GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, and Kite Pharma. P.A.C. reports research support from Pharmacyclics and Incyte. The other authors have no conflicts of interest to disclose. Authorship statement: M.B. S.M.O. E.M.L. K.S. J.Y.W. M.J.T. J.J.V. D.R.D. and P.A.C. wrote the first draft and subsequent revisions of the manuscript. All authors have contributed to writing and critical review of the manuscript. Financial disclosure: See Acknowledgments on page 1796.

Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy

Keywords

  • Avascular necrosis
  • Bone protective agents
  • Hematopoietic cell transplantation
  • Osteoporosis

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