Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength

Summary This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice. We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through t...

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Bibliographic Details
Published in:Osteoporosis international 2016-01, Vol.27 (1), p.283-294
Main Authors: Yao, W., Dai, W., Jiang, L., Lay, E. Y.-A., Zhong, Z., Ritchie, R. O., Li, X., Ke, H., Lane, N. E.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - therapeutic use
Autophagy
Autophagy - drug effects
Autophagy - physiology
Body Weight - drug effects
Bone density
Bone Density - drug effects
Bone Density - physiology
Bone Remodeling - drug effects
Bone Remodeling - physiology
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical - methods
Endocrinology
Femur - physiopathology
Glucocorticoids - administration & dosage
Glucocorticoids - toxicity
Glycoproteins - immunology
Lumbar Vertebrae - physiopathology
Male
Medicine
Medicine & Public Health
Mice, Transgenic
Original Article
Orthopedics
Osteopathic medicine
Osteoporosis - chemically induced
Osteoporosis - physiopathology
Osteoporosis - prevention & control
Rheumatology
Side effects
Steroids
X-Ray Microtomography
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Summary:Summary This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice. We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy. Introduction Glucocorticoids (GCs) inhibit bone formation by altering osteoblast and osteocyte cell activity and lifespan. A monoclonal antibody against sclerostin, Scl-Ab, increased bone mass in both preclinical animal and clinical studies in subjects with low bone mass. The objectives of this study were to determine if treatment with the Scl-Ab could prevent loss of bone mass and strength in a mouse model of GC excess and to elucidate if Scl-Ab modulated bone cell activity through autophagy. Methods We generated reporter mice that globally expressed dsRed fused to LC3, a protein marker for autophagosomes, and evaluated the dose-dependent effects of GCs (0, 0.8, 2.8, and 4 mg/kg/day) and Scl-Ab on autophagic osteoblasts, bone mass, and bone strength. Results GC treatment at 2.8 and 4 mg/kg/day of methylprednisolone significantly lowered trabecular bone volume (Tb-BV/TV) at the lumbar vertebrae and distal femurs, cortical bone mass at the mid-shaft femur (FS), and cortical bone strength compared to placebo (PL). In mice treated with GC and Scl-Ab, Tb-BV/TV increased by 60–125 %, apparent bone strength of the lumbar vertebrae by 30–70 %, FS-BV by 10–18 %, and FS-apparent strength by 13–15 %, as compared to GC vehicle-treated mice. GC treatment at 4 mg/kg/day reduced the number of autophagic osteoblasts by 70 % on the vertebral trabecular bone surface compared to the placebo group (PL, GC 0 mg), and GC + Scl-Ab treatment. Conclusions Treatment with Scl-Ab prevented GC-induced reduction in both trabecular and cortical bone mass and strength and appeared to maintain osteoblast activity through autophagy.
ISSN:0937-941X
1433-2965
DOI:10.1007/s00198-015-3308-6