title: Doses effects of zoledronic acid on mineral apatite and collagen quality of newly-formed bone in the rat's calvaria defect.
abstract: Due to their inhibitory effects on resorption, bisphosphonates are widely used in the treatment of diseases associated to an extensive bone loss. Yet, little is known about bisphosphonates effects on newly-formed bone quality. In the present study, adult male Sprague-Dawley rats (n=80) with a bone defect calvaria area were used and short-term effects of zoledronic acid (ZA) were studied on the healing bone area. Three ZA treatments were tested by using either: 1°) a low single dose (120μgZA/kg, n=10; equivalent to human osteoporosis treatment), 2°) a low fractionated doses (20μgZA/kg daily for 6days either a total of 120μg/kg, n=15), and 3°) a high fractionated doses, (100μgZA/kg weekly for 6weeks, n=15; equivalent to 6months of human bone metastasis treatment). For each treatment, a control "vehicle" treatment was performed (with an identical number of rats). After ZA administration, the intrinsic bone material properties were evaluated by quantitative backscattered electron imaging (qBEI) and Raman microspectroscopy. Neither single nor fractionated low ZA doses modify the intrinsic bone material properties of the newly-formed bone compared to their respective control animals. On the opposite, the high ZA treatment resulted in a significant decrease of the crystallinity (-25%, P< 0.05) and of the hydroxyproline-to-proline ratio (-30%, P<0.05) in newly-formed bones. Moreover, with the high ZA treatment, the crystallinity was positively correlated with the hydroxyproline-to-proline ratio (ρ=0.78, P<0.0001). The present data highlight new properties for ZA on bone formation in a craniofacial defect model. As such, ZA at high doses disrupted the apatite crystal organization. In addition, we report here for the first time that high ZA doses decreased the hydroxyproline-to-proline ratio suggesting that ZA may affect the early collagen organization during the bone healing.
authors.affiliation: Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Faculté de Chirurgie Dentaire, Place de Verdun, F-59000 Lille, France; Service d'Odontologie, Centre Abel Caumartin, CHRU de Lille, F-59000 Lille, France. Electronic address: cecile.olejnik-2@univ-lille2.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Olejnik
authors.affiliation: Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Faculté de Chirurgie Dentaire, Place de Verdun, F-59000 Lille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Falgayrac
authors.affiliation: Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Faculté de Chirurgie Dentaire, Place de Verdun, F-59000 Lille, France.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: During
authors.affiliation: Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Service de Rhumatologie, Hôpital Roger Salengro, CHRU de Lille, F-59000 Lille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Cortet
authors.affiliation: Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Faculté de Chirurgie Dentaire, Place de Verdun, F-59000 Lille, France; Service d'Odontologie, Centre Abel Caumartin, CHRU de Lille, F-59000 Lille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Penel
mesh_terms: D000818:Animals; D001031:Apatites / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects*; D000077211:Zoledronic Acid
chemical_list: D001031:Apatites; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D003094:Collagen
keywords: Bisphosphonate; Bone quality; Collagen; Mineral; Raman microspectroscopy; Rat