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Teriparatide Improves Trabecular Osteoporosis but Simultaneously Promotes Ankylosis of the Spine in the Twy Mouse Model for Diffuse Idiopathic Skeletal Hyperostosis

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Abstract

Diffuse idiopathic skeletal hyperostosis (DISH) is a common skeletal disorder in the elderly, which can develop into periosteal hyperostosis and paradoxically into immobilization-associated trabecular osteoporosis. The bone anabolic agent, teriparatide (TPD), seems to be a rational treatment for the immobilization-associated osteoporosis. However, it can lead to development of hyperostosis lesions in DISH patients. Here, we demonstrate TPD effectively treats trabecular osteoporosis while simultaneously promoting ankylosis of the spine in DISH model tiptoe-walking Yoshimura (twy) mice, compared with the ICR mice. Eighteen male twy mice were divided into three groups, and ICR mice were used as a normal control. Subcutaneous injections of TPD or phosphate-buffered saline (PBS) were performed according to three dosing regimens; 40 µg/kg once daily (TPD × 1 group), 40 µg/kg three times daily (TPD × 3 group), and PBS (control; Ctl group). Treatment was commenced at the age of 7 weeks and continued for 5 weeks. Micro-computed tomography (µCT) and histological analysis were performed. Longitudinal µCT study revealed that trabecular bone volume in both the vertebral body and distal femur decreased with time in the Ctl group, but increased dramatically in the TPD × 3 group. The twy mice developed ankylosis of the spine, the progression of which was accelerated with TPD therapy. We also confirmed that TPD therapy promoted ossification of spinal ligaments. Histomorphometrical study revealed that TPD treatment increased bone formation at the vertebrae enthesis region and in the trabecular bone. TPD therapy effectively treats trabecular osteoporosis, but potentially promotes ankylosis of the spine in patients with DISH.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Hiroki Hamano, Masahiko Takahata, Masahiro Ota, Shigeto Hiratsuka, Tomohiro Shimizu, Yusuke Kameda & Norimasa Iwasaki

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  1. Hiroki Hamano
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  2. Masahiko Takahata
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Correspondence to Masahiko Takahata.

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Hiroki Hamano, Masahiko Takahata, Masahiro Ota, Shigeto Hiratsuka, Tomohiro Shimizu, Yusuke Kameda, and Norimasa Iwasaki declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The Ethics Review Committee for Animal Experimentation of Hokkaido University approved the experimental protocol.

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223_2015_68_MOESM1_ESM.pptx

Histology of ectopic calcification at the posterior atlantoaxial membrane (×200). (a–c) Bright field images of the ectopic calcification with Villanueva staining. There were no cells inside the ectopic calcification but there were fibroblast- or osteoblast-like cells and chondrocyte-like cells around the ectopic calcification. (d–f) Fluorescent field imaging of the ectopic calcification. The ectopic calcification lesions were not labelled with calcein and tetracycline. Black and white dotted lines indicate outer border of ectopic calcification (PPTX 1325 kb)

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Hamano, H., Takahata, M., Ota, M. et al. Teriparatide Improves Trabecular Osteoporosis but Simultaneously Promotes Ankylosis of the Spine in the Twy Mouse Model for Diffuse Idiopathic Skeletal Hyperostosis. Calcif Tissue Int 98, 140–148 (2016). https://doi.org/10.1007/s00223-015-0068-4

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  • DOI: https://doi.org/10.1007/s00223-015-0068-4

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