TY - JOUR
T1 - High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors
T2 - A mechanism for post-bone marrow transplantation osteopenia
AU - Banfi, Andrea
AU - Podestà, Marina
AU - Fazzuoli, Laura
AU - Sertoli, Mario Roberto
AU - Venturini, Marco
AU - Santini, Gino
AU - Cancedda, Ranieri
AU - Quarto, Rodolfo
PY - 2001/11/1
Y1 - 2001/11/1
N2 - 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.
AB - 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.
KW - Bone metabolism
KW - Colony-forming unit fibroblast (CFU-f)
KW - High-dose chemotherapy
KW - Osteopenia
KW - Peripheral blood progenitor cell (PBPC)
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U2 - 10.1002/1097-0142(20011101)92:9<2419::AID-CNCR1591>3.0.CO;2-K
DO - 10.1002/1097-0142(20011101)92:9<2419::AID-CNCR1591>3.0.CO;2-K
M3 - Article
C2 - 11745299
AN - SCOPUS:0035498539
VL - 92
SP - 2419
EP - 2428
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 9
ER -