Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis

H. Ikeda, D. Yoshiga, S. Kokabu, W. Ariyoshi, H. Tsurushima, O. Sakaguchi, J. Tanaka, J. Kaneko, M. Habu, M. Sasaguri, E. Jimi, T. Nishihara, I. Yoshioka, K. Tominaga

Research output: Contribution to journalArticle

Abstract

Osteonecrosis of the jaw is a complication in patients using bisphosphonate agents. In this study, we aimed to investigate the effects and mechanism of teriparatide (TPTD) in a rat model of bisphosphonate-related osteonecrosis (BRON). Osteonecrosis was induced by administration of zoledronic acid (ZOL). Four weeks after ZOL injection, the rats underwent a surgery in which drilling holes were made. These holes were filled with freeze-dried Aggregatibacter actinomycetemcomitans. After the four-weeks period, TPTD or saline (n = 9) was intermittently administered for four weeks. Later, rats were euthanized, and the mandible and femur bones were examined the amount of necrosis and bone regeneration. Serum receptor activator of NF-κB ligand (RANKL), osteocalcin (OC), and C-terminal crosslinking telopeptide of type I collagen (CTX) were also examined. TPTD administration reduced necrotic bone area of the mandibles and femurs in the BRON rat model and induced new bone formation. In addition, TPTD injection increased the number of osteoclasts. The suggested underlying mechanism is the induction of protein levels of RANKL by TPTD. Furthermore, the serum levels of bone metabolism biomarkers (OC and CTX) were upregulated in the TPTD injection group. In conclusion, ZOL has negative effects on osteoclasts. TPTD was found to be effective in eliminating the negative effects of ZOL. TPTD had positive effects in preventing bone resorption and promoting osteogenesis. In addition, TPTD improved osteoclastogenesis, which in turn led to the improvement of BRON.

Original languageEnglish
Pages (from-to)333-341
Number of pages9
JournalJournal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Volume31
Issue number5
DOIs
Publication statusPublished - Sep 2019

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zoledronic acid
Bisphosphonate-Associated Osteonecrosis of the Jaw
Teriparatide
Therapeutic Uses
Osteogenesis
Osteonecrosis
Osteocalcin
Osteoclasts
Mandible
Bone and Bones
Femur
Injections
RANK Ligand
Aggregatibacter actinomycetemcomitans
Bone Regeneration
Diphosphonates

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oral Surgery
  • Pathology and Forensic Medicine
  • Otorhinolaryngology

Cite this

Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis. / Ikeda, H.; Yoshiga, D.; Kokabu, S.; Ariyoshi, W.; Tsurushima, H.; Sakaguchi, O.; Tanaka, J.; Kaneko, J.; Habu, M.; Sasaguri, M.; Jimi, E.; Nishihara, T.; Yoshioka, I.; Tominaga, K.

In: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Vol. 31, No. 5, 09.2019, p. 333-341.

Research output: Contribution to journalArticle

Ikeda, H, Yoshiga, D, Kokabu, S, Ariyoshi, W, Tsurushima, H, Sakaguchi, O, Tanaka, J, Kaneko, J, Habu, M, Sasaguri, M, Jimi, E, Nishihara, T, Yoshioka, I & Tominaga, K 2019, 'Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis', Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, vol. 31, no. 5, pp. 333-341. https://doi.org/10.1016/j.ajoms.2019.03.001
Ikeda, H. ; Yoshiga, D. ; Kokabu, S. ; Ariyoshi, W. ; Tsurushima, H. ; Sakaguchi, O. ; Tanaka, J. ; Kaneko, J. ; Habu, M. ; Sasaguri, M. ; Jimi, E. ; Nishihara, T. ; Yoshioka, I. ; Tominaga, K. / Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis. In: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 2019 ; Vol. 31, No. 5. pp. 333-341.
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AU - Ikeda, H.

AU - Yoshiga, D.

AU - Kokabu, S.

AU - Ariyoshi, W.

AU - Tsurushima, H.

AU - Sakaguchi, O.

AU - Tanaka, J.

AU - Kaneko, J.

AU - Habu, M.

AU - Sasaguri, M.

AU - Jimi, E.

AU - Nishihara, T.

AU - Yoshioka, I.

AU - Tominaga, K.

PY - 2019/9

Y1 - 2019/9

N2 - Osteonecrosis of the jaw is a complication in patients using bisphosphonate agents. In this study, we aimed to investigate the effects and mechanism of teriparatide (TPTD) in a rat model of bisphosphonate-related osteonecrosis (BRON). Osteonecrosis was induced by administration of zoledronic acid (ZOL). Four weeks after ZOL injection, the rats underwent a surgery in which drilling holes were made. These holes were filled with freeze-dried Aggregatibacter actinomycetemcomitans. After the four-weeks period, TPTD or saline (n = 9) was intermittently administered for four weeks. Later, rats were euthanized, and the mandible and femur bones were examined the amount of necrosis and bone regeneration. Serum receptor activator of NF-κB ligand (RANKL), osteocalcin (OC), and C-terminal crosslinking telopeptide of type I collagen (CTX) were also examined. TPTD administration reduced necrotic bone area of the mandibles and femurs in the BRON rat model and induced new bone formation. In addition, TPTD injection increased the number of osteoclasts. The suggested underlying mechanism is the induction of protein levels of RANKL by TPTD. Furthermore, the serum levels of bone metabolism biomarkers (OC and CTX) were upregulated in the TPTD injection group. In conclusion, ZOL has negative effects on osteoclasts. TPTD was found to be effective in eliminating the negative effects of ZOL. TPTD had positive effects in preventing bone resorption and promoting osteogenesis. In addition, TPTD improved osteoclastogenesis, which in turn led to the improvement of BRON.

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