title: Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice.
abstract: In order to determine whether osteoclastic bone resorption is restarted after withdrawn of bisphosphonates, we conducted histological examinations on murine osteoclasts, osteoblasts and osteocytes after discontinuation of a daily regimen of alendronate (ALN) with a dosage of 1 mg/kg/day for 10 days. After drug discontinuation, metaphyseal trabecular number and bone volume remained unaltered for the first 4 days. Osteoclast number did not increase, while the number of apoptotic osteoclasts was elevated. On the other hand, tissue non-specific alkaline phosphatase-immunoreactive area was markedly reduced after ALN discontinuation. In addition, osteocytes showed an atrophic profile with empty lacunar areas during and after ALN treatment. Interestingly, as early as 36 h after a single ALN injection, osteocytes show signs of atrophy despite the presence of active osteoblasts. Structured illumination microscopy system showed shortening of osteocytic cytoplasmic processes after drug cessation, suggesting a possible morphological and functional disconnection between osteocytes and osteoblasts. Taken together, it appears that osteoclastic bone resorption is not resumed after ALN discontinuation; also, osteoblasts and osteocytes hardly seem to recover once they are inactivated and atrophied by ALN. In summary, it seems that one must pay more attention to the responses of osteoblasts and osteocytes, rather focusing on the resuming of osteoclastic bone resorption after the ALN discontinuation.
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 Kita-ku, Sapporo, 060-8586, Japan.|Department of Oral Diagnosis and Medicine, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 Kita-ku, Sapporo, 060-8586, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 Kita-ku, Sapporo, 060-8586, Japan.
authors.forename: Tomomaya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Unit of Translational Medicine, Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 Kita-ku, Sapporo, 060-8586, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hongo
authors.affiliation: Department of Dentistry, Federal University of Sergipe, Lagarto, Brazil.
authors.forename: Paulo Henrique Luiz
authors.initials: PH
authors.lastname: de Freitas
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahata
authors.affiliation: Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Bone and Mineral, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Michigami
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, The School of Stomatology, Shandong University, Jinan, China.
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Oral Diagnosis and Medicine, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 Kita-ku, Sapporo, 060-8586, Japan. amizuka@den.hokudai.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
mesh_terms: D019386:Alendronate / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007279:Injections, Subcutaneous; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D010011:Osteocytes / Q000187:drug effects* / Q000473:pathology
chemical_list: D004164:Diphosphonates; D019386:Alendronate
keywords: Bisphosphonates; Discontinuation; Osteoblast; Osteocyte