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.