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Romosozumab Improves Bone Mass and Strength While Maintaining Bone Quality in Ovariectomized Cynomolgus Monkeys. 2017

Michael S Ominsky, and Steven K Boyd, and Aurore Varela, and Jacquelin Jolette, and Melanie Felx, and Nancy Doyle, and Nacera Mellal, and Susan Y Smith, and Kathrin Locher, and Sabina Buntich, and Ian Pyrah, and Rogely W Boyce
Discovery Research, Amgen Inc., Thousand Oaks, CA, USA.

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.

UI MeSH Term Description Entries
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D010052 Ovariectomy The surgical removal of one or both ovaries. Castration, Female,Oophorectomy,Bilateral Ovariectomy,Bilateral Ovariectomies,Castrations, Female,Female Castration,Female Castrations,Oophorectomies,Ovariectomies,Ovariectomies, Bilateral,Ovariectomy, Bilateral
D011884 Radius The outer shorter of the two bones of the FOREARM, lying parallel to the ULNA and partially revolving around it. Radial Tuberosity,Radial Tuberosities,Tuberosities, Radial,Tuberosity, Radial
D005260 Female Females
D005272 Femur Neck The constricted portion of the thigh bone between the femur head and the trochanters. Femoral Neck,Neck, Femoral,Neck, Femur
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D015502 Absorptiometry, Photon A noninvasive method for assessing BODY COMPOSITION. It is based on the differential absorption of X-RAYS (or GAMMA RAYS) by different tissues such as bone, fat and other soft tissues. The source of (X-ray or gamma-ray) photon beam is generated either from radioisotopes such as GADOLINIUM 153, IODINE 125, or Americanium 241 which emit GAMMA RAYS in the appropriate range; or from an X-ray tube which produces X-RAYS in the desired range. It is primarily used for quantitating BONE MINERAL CONTENT, especially for the diagnosis of OSTEOPOROSIS, and also in measuring BONE MINERALIZATION. Absorptiometry, X-Ray,Dual-Photon Absorptiometry,Photodensitometry, X-Ray,Photon Absorptiometry,Single-Photon Absorptiometry,X-Ray Absorptiometry,Absorptiometry, Dual X-Ray,Absorptiometry, Dual-Energy Radiographic,Absorptiometry, Dual-Energy X-Ray,DEXA Scan,DPX Absorptiometry,DXA Scan,Densitometry, X-Ray,Densitometry, Xray,Dual X-Ray Absorptiometry,Dual-Energy Radiographic Absorptiometry,Dual-Energy X-Ray Absorptiometry,Dual-Energy X-Ray Absorptiometry Scan,Radiographic Absorptiometry, Dual-Energy,X-Ray Absorptiometry, Dual-Energy,X-Ray Photodensitometry,Absorptiometries, DPX,Absorptiometry, DPX,Absorptiometry, Dual Energy Radiographic,Absorptiometry, Dual Energy X Ray,Absorptiometry, Dual X Ray,Absorptiometry, Dual-Photon,Absorptiometry, Single-Photon,Absorptiometry, X Ray,DEXA Scans,DXA Scans,Densitometry, X Ray,Dual Energy Radiographic Absorptiometry,Dual Energy X Ray Absorptiometry,Dual Energy X Ray Absorptiometry Scan,Dual Photon Absorptiometry,Dual X Ray Absorptiometry,Photodensitometry, X Ray,Radiographic Absorptiometry, Dual Energy,Scan, DEXA,Scan, DXA,Scans, DEXA,Scans, DXA,Single Photon Absorptiometry,X Ray Absorptiometry,X Ray Absorptiometry, Dual Energy,X Ray Photodensitometry,X-Ray Absorptiometry, Dual,X-Ray Densitometry,Xray Densitometry
D015519 Bone Density The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS. Bone Mineral Content,Bone Mineral Density,Bone Densities,Bone Mineral Contents,Bone Mineral Densities,Density, Bone,Density, Bone Mineral
D018483 Diaphyses The shaft of long bones. Diaphysis

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