title: Does methamphetamine affect bone metabolism?
abstract: There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might induce adverse effects, leading to osteoporosis.
authors.affiliation: Department of Medical Toxicology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan. Electronic address: toxicology@med.kawasaki-m.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Katsuyama
authors.affiliation: Department of Natural Sciences, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Medical Toxicology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Okuyama
authors.affiliation: Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Fushimi
authors.affiliation: Division of Legal Medicine, Faculty of Medicine, Tottori University, 86 Nishimachi, Yonago, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Forensic Medicine and Science, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nata
authors.affiliation: Department of Physiology II, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyamoto
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D002118:Calcium / Q000097:blood; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000097:blood; D010758:Phosphorus / Q000097:blood; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D001798:Blood Proteins; D000697:Central Nervous System Stimulants; D007527:Isoenzymes; D015675:Osteocalcin; D010758:Phosphorus; D008694:Methamphetamine; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium
keywords: Bone metabolism; Methamphetamine; Mice; Osteoporosis