Back to Search
Start Over
Effects of Risedronate in Runx2 Overexpressing Mice, an Animal Model for Evaluation of Treatment Effects on Bone Quality and Fractures
- Source :
- Calcified Tissue International, Calcified Tissue International, Springer Verlag, 2011, 88 (6), pp.464-475. ⟨10.1007/s00223-011-9480-6⟩
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- International audience; Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures.
- Subjects :
- Male
bisphosphonate
[SDV]Life Sciences [q-bio]
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Osteoporosis
Core Binding Factor Alpha 1 Subunit
Bone remodeling
Fractures, Bone
Mice
0302 clinical medicine
Endocrinology
Runx2
Orthopedics and Sports Medicine
Animal model of osteoporosis
Bone mineral
0303 health sciences
Bone Density Conservation Agents
musculoskeletal, neural, and ocular physiology
Etidronic Acid
musculoskeletal system
Up-Regulation
Risedronic acid
Female
Bone Remodeling
Risedronic Acid
medicine.drug
musculoskeletal diseases
medicine.medical_specialty
Mice, Transgenic
030209 endocrinology & metabolism
Bone and Bones
Bone resorption
03 medical and health sciences
Internal medicine
medicine
Animals
030304 developmental biology
Risedronate
business.industry
Cell Biology
Bisphosphonate
medicine.disease
Mice, Inbred C57BL
Osteopenia
Disease Models, Animal
Fracture
business
Subjects
Details
- ISSN :
- 14320827 and 0171967X
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Calcified Tissue International
- Accession number :
- edsair.doi.dedup.....78e2fce7823802d0f7fe5b59207435ab