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

Published Web Location

https://link.springer.com/article/10.1007%2Fs00198-015-3308-6
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Abstract

Unlabelled

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.

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