title: Teriparatide Improves Trabecular Osteoporosis but Simultaneously Promotes Ankylosis of the Spine in the Twy Mouse Model for Diffuse Idiopathic Skeletal Hyperostosis.
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.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hamano
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan. takamasa@med.hokudai.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahata
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hiratsuka
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kameda
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D000844:Ankylosis / Q000139:chemically induced* / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004057:Hyperostosis, Diffuse Idiopathic Skeletal / Q000150:complications / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010024:Osteoporosis / Q000209:etiology / Q000473:pathology*; D013122:Spinal Diseases / Q000139:chemically induced* / Q000473:pathology; D019379:Teriparatide / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide
keywords: Ankylosis of the spine; Diffuse idiopathic skeletal hyperostosis (DISH); Osteoporosis; Spinal hyperostosis; Teriparatide