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Effects of Once-Weekly Teriparatide Treatment on Trabecular Bone Microdamage Accumulation and Cortical Structure in the Lumbar Vertebrae of Ovariectomized Cynomolgus Monkeys

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Osteoporotic Fracture and Systemic Skeletal Disorders

Abstract

This study examined the effects of weekly teriparatide treatment on trabecular bone microdamage accumulation and cortical structure in the lumbar vertebrae of ovariectomized cynomolgus monkeys. Female monkeys, aged 9 to 15 years, were divided into four groups: (1) SHAM group, (2) OVX group, (3) OVX with 1.2 μg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 μg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double labeled with calcein, and lumbar vertebrae were analyzed for trabecular histomorphometry, microdamage and collagen cross-linking, and cortical histomorphometry and compressive mechanical tests. Following ovariectomy, we found reductions in the trabecular bone mass, anterior cortical shell area and mechanical properties of the vertebrae and increases in microdamage accumulation and the amount of pentosidine. Weekly teriparatide significantly preserved the anterior cortical shell area and the energy absorption capacity in a dose-dependent manner. Also, teriparatide at either dose prevented decreases in trabecular bone mass and increase in microdamage accumulation and improved the balance of collagen cross-links. These findings suggest that weekly teriparatide treatment increases the compressive mechanical strength of the lumbar vertebrae by thickening the anterior cortical shell and decreases trabecular microdamage accumulation by improving the balance of collagen cross-links.

The present invited review was completed and submitted to the publisher on 18-Jun-20. 

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Acknowledgments

This work was funded by Asahi Kasei Pharma Corporation. The authors wish to express their appreciation to Ms. M. Higashihara and Ms. Y. Agawa for preparing undecalcified bone sections.

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Correspondence to Tasuku Mashiba .

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Mashiba, T., Fujihara, R., Yoshitake, S., Iwata, K., Takao-Kawabata, R., Yamamoto, T. (2022). Effects of Once-Weekly Teriparatide Treatment on Trabecular Bone Microdamage Accumulation and Cortical Structure in the Lumbar Vertebrae of Ovariectomized Cynomolgus Monkeys. In: Takahashi, H.E., Burr, D.B., Yamamoto, N. (eds) Osteoporotic Fracture and Systemic Skeletal Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-16-5613-2_23

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  • DOI: https://doi.org/10.1007/978-981-16-5613-2_23

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