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Abaloparatide, a novel PTH receptor agonist, increased bone mass and strength in
ovariectomized cynomolgus monkeys by increasing bone formation without increasing
bone resorption
#MMPMID29260289
Doyle N
; Varela A
; Haile S
; Guldberg R
; Kostenuik PJ
; Ominsky MS
; Smith SY
; Hattersley G
Osteoporos Int
2018[Mar]; 29
(3
): 685-697
PMID29260289
show ga
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 ?g/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.
|Absorptiometry, Photon/methods
[MESH]
|Animals
[MESH]
|Biomarkers/blood
[MESH]
|Bone Density Conservation Agents/pharmacology/*therapeutic use
[MESH]
|Bone Density/drug effects/physiology
[MESH]
|Bone Resorption/physiopathology/*prevention & control
[MESH]
|Female
[MESH]
|Lumbar Vertebrae/physiopathology
[MESH]
|Macaca fascicularis
[MESH]
|Osteogenesis/*drug effects/physiology
[MESH]
|Ovariectomy
[MESH]
|Parathyroid Hormone-Related Protein/pharmacology/*therapeutic use
[MESH]
|Peptide Fragments/blood
[MESH]
|Procollagen/blood
[MESH]
|Receptor, Parathyroid Hormone, Type 1/agonists
[MESH]
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