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Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.
- Source :
-
Endocrinology [Endocrinology] 2018 Jan 01; Vol. 159 (1), pp. 260-271. - Publication Year :
- 2018
-
Abstract
- Sclerostin antibody (Scl-Ab) restored bone mass and strength in the ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral density (BMD) and decreased skeletal fragility fracture risk have been reported in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen leads to rapid decreases in BMD and an increased risk of fragility fractures. We hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis. We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX) subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these sites increased significantly with Scl-Ab to levels matching those of sham-operated controls and correlated positively with improvements in bone mineral content, demonstrating bone quality maintenance. Dynamic histomorphometry of the tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab significantly increased bone formation on periosteal, endocortical, and trabecular surfaces and significantly decreased bone resorption on endocortical and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and decreasing bone resorption led to restoration of bone mass and strength in androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab as a potential therapeutic agent for osteoporosis in men.<br /> (Copyright © 2018 Endocrine Society.)
- Subjects :
- Absorptiometry, Photon
Animals
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal adverse effects
Bone Density drug effects
Bone Density Conservation Agents administration & dosage
Bone Density Conservation Agents adverse effects
Bone Morphogenetic Proteins metabolism
Bone Resorption prevention & control
Bone and Bones diagnostic imaging
Bone and Bones pathology
Dose-Response Relationship, Drug
Injections, Subcutaneous
Male
Molecular Targeted Therapy
Orchiectomy
Organ Size drug effects
Osteoporosis diagnostic imaging
Osteoporosis pathology
Prostate drug effects
Prostate pathology
Rats, Sprague-Dawley
Seminal Vesicles drug effects
Seminal Vesicles pathology
Shear Strength drug effects
Weight Gain drug effects
X-Ray Microtomography
Antibodies, Monoclonal therapeutic use
Bone Density Conservation Agents therapeutic use
Bone Morphogenetic Proteins immunology
Bone and Bones drug effects
Disease Models, Animal
Genetic Markers immunology
Osteogenesis drug effects
Osteoporosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 159
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 29069393
- Full Text :
- https://doi.org/10.1210/en.2017-00794