Sequential Treatment with Eldecalcitol After PTH Improves Bone Mechanical Properties of Lumbar Spine and Femur in Aged Ovariectomized Rats.

Abstract

Parathyroid hormone (PTH) analogs have a powerful anabolic effect on bone and are used in the treatment of patients with severe osteoporosis. However, there are limitations to how long they can be safely administered. Withdrawal of PTH results in the cancelation of its effects, necessitating subsequent treatment to maintain the bone quantity and quality. This study assessed the effects of Eldecalcitol (ELD), an active vitamin D3 derivative, after PTH in estrogen-deficient osteoporotic rats. Six-month-old female rats were ovariectomized, and PTH administration was started 7 weeks later. After 4 weeks of PTH treatment, the animals were divided into three groups and either continued to receive PTH (PTH-PTH), or were switched to ELD (PTH-ELD) or vehicle (PTH-Veh) for an additional 4 weeks. In the femur, increased BMD by 4 weeks treatment of PTH was significantly reduced in PTH-Veh but not in PTH-PTH and PTH-ELD. The same tendency was observed in the lumbar vertebrae. MicroCT imaging and histomorphometry analysis revealed that the favorable bone structure changes by PTH administration were also maintained in the femurs and tibias of the PTH-PTH and PTH-ELD groups. Increased bone strength by 4-week treatment of PTH in lumber also maintained in PTH-ELD. Furthermore, minimodeling was observed in the PTH-ELD group. These results demonstrate that treatment with ELD sequentially following PTH prevented the bone quantity and strength reduction that accompanies PTH withdrawal in estrogen-deficient rats.

• Authors: Sadaoki Sakai, Hiromi Hongo, Tomomaya Yamamoto, Tomoka Hasegawa, Satoshi Takeda, Hitoshi Saito, Koichi Endo, Kenji Yogo, Norio Amizuka
• Journal: Calcified tissue international (Calcif Tissue Int) Vol. 104 Issue 3 Pg. 251-261 (03 2019) ISSN: 1432-0827 [Electronic] United States
• PMID: 30467731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Density Conservation Agents
• Parathyroid Hormone
• Vitamin D
• eldecalcitol

Topics

• Aging (drug effects, physiology)
• Animals
• Biomechanical Phenomena (drug effects)
• Bone Density (drug effects)
• Bone Density Conservation Agents (administration & dosage, adverse effects)
• Bone and Bones (drug effects, physiology)
• Disease Models, Animal
• Drug Administration Schedule
• Female
• Femur (drug effects)
• Lumbar Vertebrae (drug effects)
• Osteoporosis (drug therapy, metabolism, pathology)
• Ovariectomy
• Parathyroid Hormone (administration & dosage, adverse effects)
• Rats
• Rats, Wistar
• Vitamin D (administration & dosage, adverse effects, analogs & derivatives)