Romosozumab Improves Bone Mass and Strength While Maintaining Bone Quality in Ovariectomized Cynomolgus Monkeys
| Autor: | Nacera Mellal, Rogely W. Boyce, Kathrin Locher, Steven K. Boyd, Melanie Felx, Jacquelin Jolette, Nancy Doyle, Michael S. Ominsky, Sabina Buntich, Aurore Varela, Susan Y. Smith, Ian Pyrah |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism Osteoporosis Romosozumab 030209 endocrinology & metabolism Metaphysis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lumbar Internal medicine Medicine Orthopedics and Sports Medicine Bone mineral business.industry Biomechanics Anatomy medicine.disease 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Ovariectomized rat Sclerostin business |
| Zdroj: | Journal of Bone and Mineral Research. 32:788-801 |
| ISSN: | 0884-0431 |
| Popis: | Romosozumab (Romo), a humanized sclerostin antibody, is a bone-forming agent under development for treatment of osteoporosis. To examine the effects of Romo on bone quality, mature cynomolgus monkeys (cynos) were treated 4 months post- ovariectomy (OVX) with vehicle, 3 mg/kg, or 30 mg/kg Romo for 12 months, or with 30 mg/kg Romo for 6 months followed by vehicle for 6 months (30/0). Serum bone formation markers were increased by Romo during the first 6 months, corresponding to increased cancellous, endocortical, and periosteal bone formation in rib and iliac biopsies at months 3 and 6. Dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) was increased by 14% to 26% at the lumbar spine and proximal femur at month 12, corresponding to significant increases in bone strength at 3 and 30 mg/kg in lumbar vertebral bodies and cancellous cores, and at 30 mg/kg in the femur diaphysis and neck. Bone mass remained positively correlated with strength at these sites, with no changes in calculated material properties at cortical sites. These bone-quality measures were also maintained in the 30/0 group, despite a gradual loss of accrued bone mass. Normal bone mineralization was confirmed by histomorphometry and ash analyses. At the radial diaphysis, a transient, reversible 2% reduction in cortical BMD was observed with Romo at month 6, despite relative improvements in bone mineral content (BMC). High-resolution pQCT confirmed this decline in cortical BMD at the radial diaphysis and metaphysis in a second set of OVX cynos administered 3 mg/kg Romo for 6 months. Radial diaphyseal strength was maintained and metaphyseal strength improved with Romo as estimated by finite element modeling. Decreased radial cortical BMD was a consequence of increased intracortical remodeling, with no increase in cortical porosity. Romo resulted in marked improvements in bone mass, architecture, and bone strength, while maintaining bone quality in OVX cynos, supporting its bone efficacy and safety profile. © 2016 American Society for Bone and Mineral Research. |
| Databáze: | OpenAIRE |
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