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High‐dose chemotherapy shows a dose‐dependent toxicity to bone marrow osteoprogenitors
Author(s) -
Banfi Andrea,
Podestà Marina,
Fazzuoli Laura,
Roberto Sertoli Mario,
Venturini Marco,
Santini Gino,
Cancedda Ranieri,
Quarto Rodolfo
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20011101)92:9<2419::aid-cncr1591>3.0.co;2-k
Subject(s) - medicine , toxicity , bone marrow , chemotherapy , oncology
BACKGROUND Osteoporosis is a sequela of hemopoietic cell transplantation with a complex multifactorial pathogenesis in which the relative role of chemotherapy and irradiation is not completely understood. Therefore, the authors investigated the toxicity of chemotherapy‐only conditioning regimens on bone homeostasis and bone marrow osteoprogenitors, its dose dependency, and the mechanism of chemotherapy‐induced osteopenia. METHODS Fifty‐one patients with high‐grade non‐Hodgkin lymphoma or breast carcinoma who had been treated previously with high‐dose + peripheral blood progenitor cell or conventional chemotherapy or who had not received any treatment (prechemotherapy) were enrolled. The authors measured the bone marrow colony‐forming unit fibroblast (CFU‐f) and long‐term culture‐initiating cell frequency, forearm bone mineral density, serum osteotropic hormones and metabolic markers of bone formation (plasma osteocalcin), and resorption (urinary collagen I C‐crosslinks). RESULTS Both high‐dose chemotherapy regimens caused a 50% reduction in CFU‐f frequency, independently of gonadal function status, whereas conventional chemotherapy and prechemotherapy groups were unaffected. Bone mineral density was measured in 26 non‐Hodgkin lymphoma patients and again only high‐dose chemotherapy caused a 10% loss in cortical bone and 20% in trabecular bone. No endocrine abnormality was found except for the secondary amenorrhea uniformly induced in the high‐dose chemotherapy group. In these patients, plasma osteocalcin unexpectedly failed to increase in response to the menopausal increase in bone resorption rate, showing a selective impairment of the osteoblast compartment to cope with increased functional demand. CONCLUSIONS Chemotherapy without irradiation shows a dose‐dependent toxicity to bone marrow stromal osteoprogenitors and can cause osteopenia by direct damage of the osteoblastic compartment, as a mechanism distinct from and summable to hypogonadism. Cancer 2001;92:2419–28. © 2001 American Cancer Society.