title: Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats.
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.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Chang-Chin
authors.initials: CC
authors.lastname: Wu
authors.forename: Chen-Chie
authors.initials: CC
authors.lastname: Wang
authors.forename: Dai-Hua
authors.initials: DH
authors.lastname: Lu
authors.forename: Li-Ho
authors.initials: LH
authors.lastname: Hsu
authors.forename: Kai-Chiang
authors.initials: KC
authors.lastname: Yang
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D002130:Calcium Phosphates / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000473:pathology* / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D001843:Bone Cements; D050071:Bone Density Conservation Agents; D002130:Calcium Phosphates; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; C020243:calcium phosphate