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Osteoporos Int. 2018 Mar;29(3):685-697. doi: 10.1007/s00198-017-4323-6. Epub 2017 Dec 19.

Abaloparatide, a novel PTH receptor agonist, increased bone mass and strength in ovariectomized cynomolgus monkeys by increasing bone formation without increasing bone resorption.

Author information

1
Charles River Laboratories, Montreal, QC, Canada.
2
School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
3
University of Michigan, Ann Arbor, MI, USA.
4
Phylon Pharma Services, Newbury Park, CA, USA.
5
Radius Health Inc., 950 Winter Street, Waltham, MA, 02451, USA.
6
Radius Health Inc., 950 Winter Street, Waltham, MA, 02451, USA. ghattersley@radiuspharm.com.

Abstract

Abaloparatide, a novel PTH1 receptor agonist, increased bone formation in osteopenic ovariectomized cynomolgus monkeys while increasing cortical and trabecular bone mass. Abaloparatide increased bone strength and maintained or enhanced bone mass-strength relationships, indicating preserved or improved bone quality.

INTRODUCTION:

Abaloparatide is a selective PTH1R activator that is approved for the treatment of postmenopausal osteoporosis. The effects of 16 months of abaloparatide administration on bone formation, resorption, density, and strength were assessed in adult ovariectomized (OVX) cynomolgus monkeys (cynos).

METHODS:

Sixty-five 9-18-year-old female cynos underwent OVX surgery, and 15 similar cynos underwent sham surgery. After a 9-month period without treatments, OVX cynos were allocated to four groups that received 16 months of daily s.c. injections with either vehicle (n = 17) or abaloparatide (0.2, 1, or 5 μg/kg/day; n = 16/dose level), while Sham controls received s.c. vehicle (n = 15). Bone densitometry (DXA, pQCT, micro-CT), qualitative bone histology, serum calcium, bone turnover markers, bone histomorphometry, and bone strength were among the key measures assessed.

RESULTS:

At the end of the 9-month post-surgical bone depletion period, just prior to the treatment phase, the OVX groups exhibited increased bone turnover markers and decreased bone mass compared with sham controls. Abaloparatide administration to OVX cynos led to increased bone formation parameters, including serum P1NP and endocortical bone formation rate. Abaloparatide administration did not influence serum calcium levels, bone resorption markers, cortical porosity, or eroded surfaces. Abaloparatide increased bone mass at the whole body, lumbar spine, tibial diaphysis, femoral neck, and femoral trochanter. Abaloparatide administration was associated with greater lumbar vertebral strength, and had no adverse effects on bone mass-strength relationships for the vertebrae, femoral neck, femoral diaphysis, or humeral cortical beams.

CONCLUSIONS:

Abaloparatide administration was associated with increases in bone formation, bone mass and bone strength, and with maintenance of bone quality in OVX cynos, without increases in serum calcium or bone resorption parameters.

KEYWORDS:

Abaloparatide; Bone quality; Bone strength; Osteoporosis; PTH1R

PMID:
29260289
PMCID:
PMC5834552
DOI:
10.1007/s00198-017-4323-6
[Indexed for MEDLINE]
Free PMC Article

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