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Bone Abstracts (2014) 3 PP352 | DOI: 10.1530/boneabs.3.PP352

Osteoporosis: treatment

Abaloparatide (BA058), a novel human PTHrP analog, restores bone mass and strength in the aged osteopenic ovariectomized cynomolgus monkey

Gary Hattersley1, Nancy Doyle2, Aurore Varela2, Robert E Guldberg3 & Susan Y Smith2


1Radius Health, Cambridge, Massachusetts, USA; 2Charles River Laboratories Preclinical Services Montreal, Quebec, Canada; 3School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.

Abaloparatide (ABL) is a novel analog of hPTHrP (1–34) in clinical development for treatment of osteoporosis. This study evaluated the long-term effects of ABL on BMD and bone strength in aged osteopenic, ovariectomized (OVX) monkeys. Four groups of ≥9-year-old female cynomolgus monkeys underwent OVX and one group underwent Sham surgery. After a 9-month bone depletion period, increases in bone markers and decreases in BMD by DXA and pQCT were observed for OVX groups, consistent with estrogen deprivation. Treatment was then initiated with either vehicle (Sham and OVX controls) or ABL at 0.2, 1 or 5 μg/kg for 16 months. Daily administration of ABL resulted in marked bone anabolic effects. Spine and femoral neck BMD was comparable to, or above, pre-surgery levels after 4 months of treatment, with further increases at 12 months, which were sustained at 16 months. Total tibia metaphysis BMD was also increased at all doses, with gains maintained at 16 months. These BMD gains were associated with increases in bone formation markers. As expected for osteopenic animals, decreases in bone mass were associated with decreased bone strength parameters (yield load) for lumbar vertebral cores (−27%) and vertebral body (−20%) in compression. ABL treatment resulted in complete reversal of OVX-induced strength loss at the spine with increased yield load for the vertebral core by +42 and +47% with 1 and 5 μg/kg ABL, and by +21 and +19% with 1 and 5 μg/kg ABL at the vertebral body. At the femoral neck, peak load shear was decreased in OVX controls (−4%), compared to sham, while this loss was reversed with 1 and 5 μg/kg ABL (+6%), compared to OVX controls. In summary, abaloparatide demonstrated the ability to rapidly build high-quality new bone in osteopenic monkeys, with sustained gains over time, and improved bone strength at clinically relevant sites.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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