Six Weeks of Daily Abaloparatide Treatment Increased Vertebral and Femoral Bone Mineral Density, Microarchitecture and Strength in Ovariectomized Osteopenic Rats

Autor: Kyla Gallacher, Julie Downall, Gary Hattersley, Carol A. Nelson, Hila Bahar, Maysoun Shomali
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
musculoskeletal diseases
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Abaloparatide
PTHrP
Ovariectomy
Osteoporosis
PTHR1
030209 endocrinology & metabolism
Bone strength
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Endocrinology
Absorptiometry
Photon
Bone Density
Internal medicine
medicine
Animals
Orthopedics and Sports Medicine
Femur
Original Research
Bone mineral
Lumbar Vertebrae
Bone Density Conservation Agents
business.industry
Parathyroid Hormone-Related Protein
X-Ray Microtomography
Anabolic treatment
medicine.disease
Vertebra
Rats
Bone Diseases
Metabolic
030104 developmental biology
medicine.anatomical_structure
Orthopedic surgery
Ovariectomized rat
Female
business
hormones
hormone substitutes
and hormone antagonists
PTH
Zdroj: Calcified Tissue International
ISSN: 1432-0827
0171-967X
Popis: Abaloparatide is a novel, potent and selective activator of parathyroid hormone receptor 1 (PTHR1) under clinical development for the treatment of osteoporosis. We assessed the effect of 6 weeks of abaloparatide on bone mass, microarchitecture, quality and strength in ovariectomized (OVX) rats. After 8 weeks of post-surgical bone depletion (baseline), OVX rats (n = 20–21/group) received daily subcutaneous vehicle (OVX-Veh) or abaloparatide at 5 or 20 µg/kg. Sham-operated control rats (n = 24) received vehicle. Areal bone mineral density (aBMD) of the lumbar spine (L4), total femur and femur diaphysis was measured at baseline and after 6 weeks of treatment. Femur and vertebral bone architecture and mechanical properties were assessed at the end of the treatment phase. At baseline, OVX-Veh rats exhibited significantly lower aBMD relative to Sham controls. Treatment of OVX rats with abaloparatide at 5 or 20 µg/kg/day increased aBMD dose-dependently in the lumbar spine, total femur and femur diaphysis to levels exceeding OVX-Veh or Sham controls. The abaloparatide 5 and 20 µg/kg groups had improved trabecular microarchitecture relative to OVX vehicle, with trabecular BV/TV exceeding OVX-Veh control values by 57 and 78 % (respectively) at the lumbar spine, and by 145 and 270 % at the distal femur. Femur diaphyseal cortical volume and thickness were significantly greater in the abaloparatide 20 µg/kg group relative to OVX vehicle or Sham controls. Bone strength parameters of the femur diaphysis, femur neck and L4 vertebra were significantly improved in the OVX-ABL groups relative to OVX-Veh controls. Bone mass–strength relationships and estimated intrinsic strength properties suggested maintained or improved bone quality with abaloparatide. These data demonstrate skeletal restoration via abaloparatide treatment of osteopenic OVX rats, in association with improved trabecular microarchitecture, cortical geometry and bone strength at sites that have clinical relevance in patients with osteoporosis.
Databáze: OpenAIRE
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