Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse |
| |
| Affiliation: | 1. Dept. of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States;2. Dept. of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA, United States;3. UCB Pharma, Slough, UK;1. Department of Biochemistry, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;2. Center for Diabetes Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;3. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;4. Center for Public Health Genomics, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;5. Department of Biostatistical Sciences, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;6. Department of Pathology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;7. Division of Public Health Sciences, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;8. Department of Internal Medicine-Section on Nephrology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA;9. Department of Radiology, Vanderbilt University School of Medicine, 2525 West End Ave, Suite 300-B, Nashville, TN 37203, USA;10. Department of Biostatistics, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA;11. Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA;12. Department of Medicine, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL, 35294, USA;1. Department of Clinical Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway and Oslo University;2. Laval University, Quebec City, Canada;3. CHU de Québec (CHUL) Research Centre, Quebec City, Canada;1. Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium;2. Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, 3000 Leuven, Belgium;3. Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium;4. Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Department of Oncology, KU Leuven, 3000 Leuven, Belgium;1. Dept. of Clinical Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway;2. Dept. of Rheumatology, Laval University and CHU de Québec (CHUL) Research Centre, Quebec City, Canada |
| |
| Abstract: | Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2 days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25 mg/kg were made twice per week for 5 weeks from the time of HLS. μCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS + OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin-neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
