Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats
Journal
Biomedical Materials
Journal Volume
7
Journal Issue
3
Date Issued
2012
Author(s)
Abstract
Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery. ? 2012 IOP Publishing Ltd.
SDGs
Other Subjects
Computerized tomography; Diseases; Microgravity processing; Phosphatases; Rats; Restoration; Toxicity; ALkaline phosphatase; Blood samples; Bone architecture; Bone ash; Bone defect; Bone formation markers; Bone graft substitutes; Bone mineral content; Bone resorption markers; Bone turnover; Bone-fillers; Calcium phosphate cement; Cancellous bone; Clinical signs; Concomitant decrease; Micro CT; Micro-CT scanning; Osteocalcin; Osteopontin; Postmenopausal women; Type I collagen; Bone; alkaline phosphatase; bone cement; calcium phosphate; carboxy terminal telopeptide; osteocalcin; osteopontin; zoledronic acid; bisphosphonic acid derivative; bone cement; bone density conservation agent; calcium phosphate; imidazole derivative; zoledronic acid; animal experiment; animal model; animal tissue; article; blood sampling; bone graft; bone mineral; bone structure; bone turnover; cancellous bone; computer assisted tomography; controlled study; drug delivery system; female; femur; hematology; histology; metaphysis; nonhuman; omentum; ossification; osteolysis; osteoporosis; ovariectomy; postmenopause osteoporosis; rat; animal; human; osteolysis; pathology; postmenopause osteoporosis; treatment outcome; Wistar rat; Rattus; Animals; Bone Cements; Bone Density Conservation Agents; Bone Resorption; Calcium Phosphates; Diphosphonates; Female; Humans; Imidazoles; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Wistar; Treatment Outcome
Type
journal article