title: Effect of granulocyte colony-stimulating factor on bone metabolism during peripheral blood stem cell mobilization.
abstract: Granulocyte colony-stimulating factor (G-CSF) has been shown to affect the biochemical markers of bone metabolism, including serum bone alkaline phosphatase (BALP), serum osteocalcin, and urine deoxypyridinoline. To determine the association between bone resorption and formation and the G-CSF-induced mobilization of peripheral blood stem cells (PBSC), we examined these markers during mobilization in 19 healthy donors. The average (+/- SEM) serum BALP level before treatment was 81.6 +/- 17.0 IU/dL, and the level increased significantly to 117.7 +/- 15.8 IU/dL on day 5 of G-CSF administration (P < .0001). The urine deoxypyridinoline level before treatment was 12.3 +/- 2.4 nmol/mmol creatinine, and this level also increased significantly to 19.4 +/- 3.0 nmol/mmol creatinine on day 5 of G-CSF administration (P < .0001). In contrast, the average level of serum osteocalcin significantly decreased from 8.07 +/- 2.88 ng/mL to 1.53 +/- 0.18 ng/mL on day 5 (P = .0353). During G-CSF administration, we also studied the serum levels of various cytokines (IL-1beta, osteoclastogenesis inhibitory factor [OCIF], IL-6, tumor necrosis factor alpha, transforming growth factor beta, interferon-gamma, macrophage colony-stimulating factor) related to bone metabolism. Only the kinetics of OCIF were significantly affected. The serum level of OCIF increased immediately after the start of G-CSF administration and remained high during G-CSF administration. These results demonstrate that high-dose G-CSF affects bone metabolism and that OCIF may play a role in bone metabolism. Consistent with the notion that G-CSF affects bone metabolism, a significant correlation was observed between CD34+ cell yield and the increase in urine deoxypyridinoline but not for the changes in serum BALP and osteocalcin levels. This result suggests that bone resorption is either directly or indirectly related to the mobilization of PBSC by G-CSF.
authors.affiliation: Department of Pediatrics, University of Tokushima School of Medicine, Tokushima, Japan. twatanab@clin.med.tokushima-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroko
authors.initials: H
authors.lastname: Suzuya
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Onishi
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Kanai
authors.forename: Michiya
authors.initials: M
authors.lastname: Kaneko
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakagawa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawano
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuroda
authors.forename: James E
authors.initials: JE
authors.lastname: Talmadge
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D015675:Osteocalcin / Q000097:blood; D036102:Peripheral Blood Stem Cell Transplantation
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D016207:Cytokines; D015675:Osteocalcin; D016179:Granulocyte Colony-Stimulating Factor; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase