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Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice

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Title: Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice
Authors: Tsuboi, Kanako Browse this author
Hasegawa, Tomoka Browse this author
Yamamoto, Tomomaya Browse this author
Sasaki, Muneteru Browse this author
Hongo, Hiromi Browse this author
Luiz de Freitas, Paulo Henrique Browse this author
Shimizu, Tomohiro Browse this author
Takahata, Masahiko Browse this author →KAKEN DB
Oda, Kimimitsu Browse this author →KAKEN DB
Michigami, Toshimi Browse this author
Li, Minqi Browse this author →KAKEN DB
Kitagawa, Yoshimasa Browse this author →KAKEN DB
Amizuka, Norio Browse this author →KAKEN DB
Keywords: Bisphosphonates
Issue Date: Sep-2016
Publisher: Springer
Journal Title: Histochemistry and cell biology
Volume: 146
Issue: 3
Start Page: 337
End Page: 350
Publisher DOI: 10.1007/s00418-016-1450-7
PMID: 27235014
Abstract: In order to determine whether osteoclastic bone resorption is restarted after withdrawn of bisphosphonates, we conducted histological examinations on murine osteoclasts, osteoblasts and osteocytes after discontinuation of a daily regimen of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.
Rights: The final publication is available at Springer via
Type: article (author version)
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 網塚 憲生

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