title: Mineralization disturbances of the developing rat molar induced by mono- and bisphosphonates.
abstract: Morphological changes have been reported previously in the developing dental tissues of the rat molar following administration of mono- or bisphosphonates. However, few studies have been published on the relationship between these and the possible mineralization disturbances. Two monophosphonates, phosphonoformic and phosphonoacetic acids, and two bisphosphonates, dichloromethylene bisphosphonate (Cl2MBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) in a dosage of 10-30 mg P/kg b.w. were injected in 5 day old rats and the induced changes analyzed by microradiographic and histologic examination. A single injection of mono- or bisphosphonates resulted in apparently identical disturbances of the developing enamel associated with subameloblastic cysts. Three different types of cysts were distinguished. In type 1 cysts, enamel hypoplasia near the cusp tip with an outer highly mineralized zone associated with calcified deposits in the cystic lining and inner hypomineralized enamel were discerned. The type 2 cysts were characterized by the formation of a thick enamel layer in the cervical area and deep in the fissures due to the development of internal enamel defects. The type 3 cysts were seen in the cervical area of the mesial or distal sides of the tooth without any remarkable changes in the underlying enamel matrix. Both Cl2MBP and HEBP induced two demarcation lines in the dentin layer. Additionally, HEBP resulted in the formation of niche-like defects of unmineralized dentin which healed by mineral deposition from the periphery. From these results, it can be concluded that mono- and bisphosphonates have similar effects on enamel mineralization and the type of response depends on the stage of enamel matrix secretion while bisphosphonates, in addition, interfere with the dentin mineralization.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Karolinska Institutet, Huddinge, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Fouda
authors.forename: M
authors.initials: M
authors.lastname: Caracatsanis
authors.forename: I A
authors.initials: IA
authors.lastname: Kut
authors.forename: L
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D000539:Alveolar Process / Q000187:drug effects; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology; D003743:Dental Enamel / Q000187:drug effects; D003804:Dentin / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D012968:Etidronic Acid / Q000494:pharmacology; D005260:Female; D017245:Foscarnet; D008297:Male; D008852:Microradiography; D008963:Molar; D009805:Odontogenesis / Q000187:drug effects*; D063065:Organophosphonates / Q000494:pharmacology*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014074:Tooth Calcification / Q000187:drug effects*; D014083:Tooth Germ / Q000187:drug effects*
chemical_list: D004164:Diphosphonates; D063065:Organophosphonates; D004002:Clodronic Acid; D017245:Foscarnet; D012968:Etidronic Acid; D010746:Phosphonoacetic Acid