Affiliation:
1. Spinal Cord Damage Research Center James J. Peters Veterans Affairs Medical Center Bronx New York USA
2. Departments of Medicine The Icahn School of Medicine at Mount Sinai New York New York USA
3. Pharmacologic Sciences The Icahn School of Medicine at Mount Sinai New York New York USA
4. Center for Translational Medicine and Pharmacology The Icahn School of Medicine at Mount Sinai New York New York USA
5. Rehabilitation Medicine The Icahn School of Medicine at Mount Sinai New York New York USA
Abstract
AbstractSpinal cord injury (SCI) causes severe and resistant sublesional disuse bone loss. Abaloparatide, a modified parathyroid hormone related peptide, is an FDA approved drug for treatment of severe osteoporosis with potent anabolic activity. The effects of abaloparatide on SCI‐induced bone loss remain undefined. Thus, female mice underwent sham or severe contusion thoracic SCI causing hindlimb paralysis. Mice then received subcutaneous injection of vehicle or 20 μg/kg/day abaloparatide for 35 days. Micro‐computed tomography (micro‐CT) analysis of the distal and midshaft femoral regions of the SCI‐vehicle mice revealed reduced trabecular fractional bone volume (56%), thickness (75%), and cortical thickness (80%) compared to sham‐vehicle controls. Treatment with abaloparatide did not prevent SCI‐induced changes in trabecular or cortical bone. However, histomorphometry evaluation of the SCI‐abaloparatide mice demonstrated that abaloparatide treatment increased osteoblast (241%) and osteoclast (247%) numbers and the mineral apposition rate (131%) compared to SCI‐vehicle animals. In another independent experiment, treatment with 80 μg/kg/day abaloparatide significantly attenuated SCI‐induced loss in cortical bone thickness (93%) when compared to SCI‐vehicle mice (79%) but did not prevent SCI‐induced trabecular bone loss or elevation in cortical porosity. Biochemical analysis of the bone marrow supernatants of the femurs showed that SCI‐abaloparatide animals had 2.3‐fold increase in procollagen type I N‐terminal propeptide, a bone formation marker than SCI‐vehicle animals. SCI groups had 70% higher levels of cross‐linked C‐telopeptide of type I collagen, a bone resorption marker, than sham‐vehicle mice. These findings suggest that abaloparatide protects the cortical bone against the deleterious effects of SCI by promoting bone formation.
Subject
Genetics,Molecular Biology,Biochemistry,Biotechnology
Cited by
1 articles.
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