Morpho-Functional Condition of the Mandibular Bones of Labora-tory White Rats at 1- and 3-Months of Exposure to Bisphosphonates in Doses that Cause Osteonecrotic Changes
Keywords:mandible, bisphosphonates, osteonecrosis, geometric morphometry
It is known that medications of the bisphosphonate group can cause severe complications such as osteonecrosis of the jaws. However, the effects of these compounds in doses that cause osteonecrotic lesions on the growth and shaping of the mandibular bones remain unstudied.The aim of the investigation was to study the morphofunctional condition (size and shape) of the mandibular bones on the background of taking bisphosphonate compounds in doses that cause osteonecrotic lesions. The research was performed on 60 white outbred rats that were exposed to the studied remedies. The objects of the study were mandibular bones. They were scanned, digitized and 22 landmarks were determined. The analysis of the form component (geometric morphometry) was carried out with the programs TPSDig and MorphoJ. Digital data characterizing linear dimensions were analyzed due to the program Statistica 10,0 using one-way analysis, two-way analysis and multivariate analysis of variance (ANOVA, MANOVA) and Newman-Keuls post-hoc test. It was revealed that in the early stages of exposure, the studied bisphosphonate compounds have a significant effect on osteostimulation, despite the «acute phase reaction» that takes place during the first two weeks of use. At the later dates of the study, the substances cause growth inhibition and disorder of shaping processes because of the pharmacological properties of the studied substances, blocking bone resorption and a wide range of possible toxic reactions of the urinary, digestive, and cardiovascular systems.
2. Favus M.D. Bisphosphonates for osteoporosis. N. Engl. J. Med, 2010, 363, pp 2027–2035. https://doi.org/10.1056/NEJMct1004903
3. Spevak E.M., Tsymbal А.N. Bisfosfonatnye osteonekrozy chelyustej: sovremennoe sostoyanie problemy [Вisphosphonate-related osteonecrosis of the jaw: current state of the problem]. Kazanskij meditsinskij zhurnal, 2017, 98(1) s 91-95. (In Russian) https://doi.org/10.17750/KMJ2017-91
4. Semen O. Mostovoy, Viktor F. Shul’gin, Elena M. Maksimova, Igor A. Nauhatsky et al. Mineralizing process and morphological structure of the femoral bone in rats under influence of aminophosphonates. J Exp Integr Med, 2014, 4(2), pp 81–84. http://doi.org/ 10.5455 / jeim.260214.br.019
5. Mostovoj S.O., SHul`gin V.F., Peshkov M.V., Patomorfologicheskoe issledovanie pobochnykh ehffektov vozdejstviya aminobisfosfonatov na nizhnechelyustnye kosti laboratornykh belykh krys [Pathomorphological study of the side effects of aminobisphosphonates on the mandibular bone of white laboratory rats]. Klinicheskaya i ehksperimental'naya morfologiya, 2017, 21(1), s 41-46 (In Russian)
6. Mostovoj S. O., Pikalyuk V. S., SHul'gin V.F., Peshkov M. V. Patomorfologicheskie izmeneniya nizhnikh chelyustej laboratornykh belykh krys pod vozdejstviem analoga, fosforosoderzhashhego autopatogenichnogo veshhestva [Pathomorphological changes in mandibles of laboratory white rats under the influence of phosporus-containing analogue of autopathogenic substance]. Krymskij zhurnal ehksperimental`noj i klinicheskoj meditsiny, 2017, 7(2), s 91-98. (In Russian)
7. Vrublevskij А.G. Narkomanii i toksikomanii: Klinicheskie formy narkomanij toksikomanij Lektsii po narkologii [pod. red. N.N. Ivantsa] [Addiction and substance abuse: clinical forms of substance abuse addictions. In: Ivantca NN (ed) Lectures on Drug Abuse]. M.: Meditsina, 2000, s 241. (In Russian)
8. Rybolovlev YU.R. Rybolovlev R.S. Dozirovanie veshhestv dlya mlekopitayushhikh po konstante biologicheskoj aktivnosti [Dosing of substances to mammals in the constant biological activity]. Doklady АN SSSR, 1979, 247(6), s 1513-1516. (In Russian).
9. European convention for the protection of vertebrate animals used for experimental and other scientific purpose: Council of Europe 18.03.1986. Strasbourg; 1986, pp 52.
10. Rohlf F.J. tpsDig. N.Y. State Univ. at Stony Brook. Version 1.23. 2001b. [Electronic resource]. Mode of access: http://life.bio.sunysb.edu/morph.
11. Kendall M., Stuart A. The advanced theory of statistics // Charles griffin & company limited London.1976, 3, pp 400-437.
12. Anderson P.S.L., Renaud S., Rayfield E.J. Adaptive plasticity in the mouse mandible // BMC Evolutionary Biology, 2014, 14, pp 85–93. https://doi.org/10.1186/1471-2148-14-85