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. Copyright 2001 American Cancer Society.
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 lymphomapatients 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. Copyright 2001 American Cancer Society.
Authors: L Tauchmanovà; C Selleri; M Esposito; C Di Somma; F Orio; G Bifulco; S Palomba; G Lombardi; B Rotoli; A Colao Journal: Osteoporos Int Date: 2003-09-30 Impact factor: 4.507
Authors: Christopher C Dvorak; Clarisa R Gracia; Jean E Sanders; Edward Y Cheng; K Scott Baker; Michael A Pulsipher; Anna Petryk Journal: Biol Blood Marrow Transplant Date: 2011-10-17 Impact factor: 5.742
Authors: D L Kendler; J J Body; M L Brandi; R Broady; J Cannata-Andia; M J Cannata-Ortiz; A El Maghraoui; G Guglielmi; P Hadji; D D Pierroz; T J de Villiers; R Rizzoli; P R Ebeling Journal: Osteoporos Int Date: 2018-09-03 Impact factor: 4.507
Authors: Kristen R Georgiou; Michaela A Scherer; Tristan J King; Bruce K Foster; Cory J Xian Journal: Int J Exp Pathol Date: 2012-01-05 Impact factor: 1.925
Authors: Min Hee Park; Hee Kyung Jin; Woo-Kie Min; Won Woo Lee; Jeong Eun Lee; Haruhiko Akiyama; Herbert Herzog; Grigori N Enikolopov; Edward H Schuchman; Jae-sung Bae Journal: EMBO J Date: 2015-04-27 Impact factor: 11.598