A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model
| Autor: | Theresa Chen, J. Ruth Wu-Wong, Phimon Atsawasuwan, Maysaa Oubaidin, Yung-wu Chen, Jerry L. Wessale |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Bone mineral
musculoskeletal diseases medicine.medical_specialty Calcitriol Vitamin D analog business.industry Osteoporosis Parathyroid hormone medicine.disease Calcitriol receptor Bone resorption Article Bone remodeling Endocrinology Vitamin D receptor Internal medicine medicine Ovariectomized rat polycyclic compounds Bone mineral density business medicine.drug PTH |
| Zdroj: | Journal of exploratory research in pharmacology |
| ISSN: | 2572-5505 |
| Popis: | Background and objectives VS-105, a novel vitamin D receptor agonist with significantly less hypercalcemic side effects than calcitriol, is a useful tool to investigate whether or not a vitamin D receptor agonist at non-hypercalcemic doses could improve bone mineral density (BMD). Methods VS-105 and calcitriol were evaluated in an ovariectomized (OVX) osteoporosis rat model and in calvariae bone organ culture. Results Treatment of OVX rats by VS-105 (0.1, 0.2 or 0.5 μg/kg, intraperitoneal, 3×/week, for 90 days) significantly improved BMD in the L3 lumbar vertebra in a dose-dependent manner (sham vs. OVX/vehicle: 324 ± 14 vs. 279 ± 10 mg/cm2; VS-105 at 0.1, 0.2 and 0.5 μg/kg: 306 ± 9, 329 ± 12, and 327 ± 10 mg/cm2, respectively) without affecting serum calcium (Ca). Calcitriol at 0.1 μg/kg significantly increased BMD but it also increased serum Ca. VS-105 and calcitriol at the test doses significantly suppressed serum parathyroid hormone and promoted tibia bone growth. With respect to biomarkers of bone remodeling, calcitriol and VS-105 both significantly elevated serum osteocalcin. In the calvariae bone organ culture, net Ca release was significantly less in VS-105-treated groups (vs. calcitriol). Conclusions VS-105 is efficacious in improving BMD in a dose range that does not affect serum Ca in OVX rats; the improvement in BMD by VS-105 is attributable to increased osteoblastic activity and reduced osteoclastic bone resorption. |
| Databáze: | OpenAIRE |
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