The effects of bisphosphonates on jaw bone remodeling, tissue properties, and extraction healing

Odontology

Volumn 99, Issue 1, 2011, Pages 8-17

  Allen, Matthew R ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Antiremodeling treatment; Bone turnover; Microdamage; Necrosis; Osteonecrosis of the jaw

Indexed keywords

EID: 79251562891     PISSN: 16181247     EISSN: 16181255     Source Type: Journal    
DOI: 10.1007/s10266-010-0153-0     Document Type: Review

References (74)

1. Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008; 19: 733-759.
2. Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest 1996; 97: 2692-2696.
3. Allen MR, Erickson AM, Wang X, Durr DB, Martin RB, Hazelwood SJ. Morphological assessment of basic multicellular unit resorption parameters in dogs shows additional mechanisms of bisphosphonate effects on bone. Calcif Tissue Int 2010; 86: 67-71.
4. Feher A, Koivunemi A, Koivunemi M, Fuchs RK, Burr DB, Phipps RJ, Reinwald S, Allen MR. Bisphosphonates do not inhibit periosteal bone formation in estrogen deficient animals and allow enhanced bone modeling in response to mechanical loading. Bone 2010; 46: 203-207.
5. Allen MR, Follet H, Khurana M, Sato M, Burr DB. Antiremodeling agents influence osteoblast activity differently in modeling and remodeling sites of canine rib. Calcif Tissue Int 2006; 79: 255-261.
6. Allen MR, Reinwald S, Burr DB. Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment. Calcif Tissue Int 2008; 82: 354-360.
7. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 2000; 15: 613-620.
8. Komatsubara S, Mori S, Mashiba T, Li J, Nonaka K, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Morimatsu H. Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res 2004; 19: 999-1005.
9. Lafage MH, Balena R, Battle MA, Shea M, Seedor JG, Klein H, Hayes WC, Rodan GA. Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A oneyear study. J Clin Invest 1995; 95: 2127-2133.
10. Yoshida Y, Moriya A, Kitamura K, Inazu M, Okimoto N, Okazaki Y, Nakamura T. Responses of trabecular and cortical bone turnover and bone mass and strength to bisphosphonate YH529 in ovariohysterectomized beagles with calcium restriction. J Bone Miner Res 1998; 13: 1011-1022.
11. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Guide S, Wu W, Mangood A, Russell RG, Ebetino FH. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 2006; 38: 617-627.
12. Leu CT, Luegmayr E, Freedman LP, Rodan GA, Reszka AA. Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy. Bone 2006; 38: 628-636.
13. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 2001; 296: 235-242.
14. Dunford JE, Kwaasi AA, Rogers MJ, Barnett BL, Ebetino FH, Russell RG, Oppermann U, Kavanagh KL. Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase. J Med Chem 2008; 51: 2187-2195.
15. Allen MR, Turek JJ, Phipps RJ, Burr DB. Greater magnitude of turnover suppression occurs earlier after treatment initiation with risedronate than alendronate. Bone 2010. doi: 10. 1016/j. bone. 2010. 07. 011.
16. Fuchs RK, Phipps RJ, Burr DB. Recovery of trabecular and cortical bone turnover following discontinuation of risedronate and alendronate therapy in ovariectomized rats. J Bone Miner Res 2008; 23: 1689-1697.
17. Silverman SL, Watts NB, Delmas PD, Lange JL, Lindsay R. Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int 2007; 18: 25-34.
18. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006; 296: 2927-2938.
19. Grey A, Bolland MJ, Wattie D, Horne A, Gamble G, Reid IR. The antiresorptive effects of a single dose of zoledronate persist for two years: a randomized, placebo-controlled trial in osteopenic postmenopausal women. J Clin Endocrinol Metab 2009; 94: 538-544.
20. Gray A, Bolland MJ, Wattie D, et al. Prolonged anti-resorptive activity of zoledronate - a randomized controlled trial. J Bone Miner Res 2010; 25: 2251-2255.
21. Allen MR, Burr DB. Mineralization, microdamage, and matrix: how bisphosphonates influence material properties of bone. BoneKEy 2007; 4: 49-60; http://www. bonekey-ibms. org/cgi/content/abstract/ibmske; 4/2/49.
22. Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 2000; 27: 687-694.
23. Allen MR, Gineyts E, Leeming DJ, Burr DB, Delmas PD. Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. Osteoporos Int 2008; 19: 329-337.
24. Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone 2006; 39: 872-879.
25. Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone 2001; 28: 524-531.
26. Allen MR, Burr DB. Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment. J Bone Miner Res 2007; 22: 1759-1765.
27. Follet H, Li JL, Phipps RJ, Hui S, Condon K, Burr DB. Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. Bone 2007; 40: 1172-1177.
28. Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999; 104: 1363-1374.
29. Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T. Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signalregulated kinase activation. J Biol Chem 2005; 280: 7317-7325.
30. Plotkin LI, Bellido T. Bisphosphonate-induced, hemichannelmediated, anti-apoptosis through the Src/ERK pathway: a gap junction-independent action of connexin43. Cell Commun Adhes 2001; 8: 377-382.
31. Plotkin LI, Lezcano V, Thostenson J, Weinstein RS, Manolagas SC, Bellido T. Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res 2008; 23: 1712-1721.
32. Plotkin LI, Bivi N, Bellido T. A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. Bone 2010; 22: 22.
33. Plotkin LI, Manolagas SC, Bellido T. Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their antiapoptotic effects on osteoblasts/osteocytes with novel analogs. Bone 2006; 39: 443-452.
34. McCauley LK, Li X. Distinguishing features of the oral cavity and its predisposition to osteonecrosis. J Musculoskelet Neuronal Interact 2007; 7: 356-357.
35. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004; 62: 527-534.
36. Ruggiero SL. Bisphosphonate-related osteonecrosis of the jaw (BRONJ): initial discovery and subsequent development. J Oral Maxillofac Surg 2009; 67: 13-18.
37. Allen MR, Burr DB. The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 2009; 67: 61-70.
38. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, van Poznak CH, Watts N, Woo SB, Shane E; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007; 22: 1479-1491.
39. Aghaloo TL, Felsenfeld AL, Tetradis S. Osteonecrosis of the jaw in a patient on denosumab. J Oral Maxillofac Surg 2010; 68: 959-963.
40. Allen MR, Burr DB. Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment. J Oral Maxillofac Surg 2008; 66: 987-994.
41. Allen MR, Kubek DJ, Burr DB. Cancer treatment dosing regimens of zoledronic acid result in near-complete suppression of mandible intracortical bone remodeling in beagle dogs. J Bone Miner Res 2010; 25: 98-105.
42. Huja SS, Fernandez SA, Hill KJ, Li Y. Remodeling dynamics in the alveolar process in skeletally mature dogs. Anat Rec A Discov Mol Cell Evol Biol 2006; 288: 1243-1249.
43. Allen MR, Kubek D, Burr DB, Ruggiero SL, Chu TM. Compromised osseous healing of dental extraction sites in zoledronic acid-treated dogs. Osteoporos Int 2010. doi: 10. 1007/s00198-010-1268-4.
44. Bentolila V, Boyce TM, Fyhrie DP, Drumb R, Skerry TM, Schaffler MB. Intracortical remodeling in adult rat long bones after fatigue loading. Bone 1998; 23: 275-281.
45. Cardoso L, Herman BC, Verborgt O, Laudier D, Majeska RJ, Schaffler MB. Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J Bone Miner Res 2009; 24: 597-605.
46. Li CY, Schaffler MB, Wolde-Semait HT, Hernandez CJ, Jepsen KJ. Genetic background influences cortical bone response to ovariectomy. J Bone Miner Res 2005; 20: 2150-2158.
47. Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res 2000; 15: 60-67.
48. Kubek D, Burr DB, Allen MR. Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible. Orthod Craniofac Res 2010; 13: 214-222.
49. Melsen B. Tissue reaction to orthodontic tooth movement - a new paradigm. Eur J Orthod 2001; 23: 671-681.
50. Huja SS, Fernandez SA, Phillips C, Li Y. Zoledronic acid decreases bone formation without causing osteocyte death in mice. Arch Oral Biol 2009; 54: 851-856.
51. Meta IF, Fernandez SA, Gulati P, Huja SS. Alveolar process anabolic activity in C3H/HeJ and C57BL/6J inbred mice. J Periodontol 2008; 79: 1255-1262.
52. Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D. Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int 2009; 20: 887-894.
53. Engen DW. The effect of alendronate and risedronate on bone microdamage accumulation surrounding the first mandibular molar in dogs. Masters thesis, Indiana University School of Dentistry. Indianapolis; 2002.
54. Hoefert S, Schmitz I, Tannapfel A, Eufinger H. Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and nonsymptomatic osteonecrosis of the jaw based on scanning electron microscopy findings. Clin Oral Investig 2010; 14: 271-284.
55. Lesclous P, Abi Najm S, Carrel JP, Baroukh B, Lombardi T, Willi JP, Rizzoli R, Saffar JL, Samson J. Bisphosphonate-associated osteonecrosis of the jaw: a key role of inflammation? Bone 2009; 45: 843-852.
56. Almazrooa SA, Woo SB. Bisphosphonate and nonbisphosphonateassociated osteonecrosis of the jaw. A review. J Am Dent Assoc 2009; 140: 864-875.
57. Allen M. Studying the role of microcracks in the pathophysiology of BRONJ. Clin Oral Investig 2009; 13: 481-482; author reply 483-4.
58. Burr DB, Stafford T. Validity of the bulk-staining technique to separate artifactual from in vivo bone microdamage. Clin Orthop Relat Res 1990;(260): 305-308.
59. Burr DB, Hooser M. Alterations to the en-bloc basic fuchsin staining protocol for the demonstration of microdamage produced in-vivo. Bone 1995; 17: 431-433.
60. Burr DB, Allen MR. Mandibular necrosis in beagle dogs treated with bisphosphonates. Orthod Craniofac Res 2009; 12: 221-228.
61. Allen MR. Bisphosphonates and osteonecrosis of the jaw: moving from the bedside to the bench. Cells Tissues Organs 2009; 189: 289-294.
62. Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS. Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. J Natl Cancer Inst 2007; 99: 1016-1024.
63. Mavrokokki T, Cheng A, Stein B, Goss A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 2007; 65: 415-423.
64. Amler MH, Johnson PL, Salman I. Histological and histochemical investigation of human alveolar socket healing in undisturbed extraction wounds. J Am Dent Assoc 1960; 61: 32-44.
65. Kingsmill VJ. Post-extraction remodeling of the adult mandible. Crit Rev Oral Biol Med 1999; 10: 384-404.
66. Aguirre JI, Altman MK, Vanegas SM, Franz SE, Bassit AC, Wronski TJ. Effects of alendronate on bone healing after tooth extraction in rats. Oral Dis 2010; 30: 674-685.
67. Kobayashi Y, Hiraga T, Ueda A, Wang L, Matsumoto-Nakano M, Hata K, Yatani H, Yoneda T. Zoledronic acid delays wound healing of the tooth extraction socket, inhibits oral epithelial cell migration, and promotes proliferation and adhesion to hydroxyapatite of oral bacteria, without causing osteonecrosis of the jaw, in mice. J Bone Miner Metab 2010; 28: 165-175.
68. Hikita H, Miyazawa K, Tabuchi M, Kimura M, Goto S. Bisphosphonate administration prior to tooth extraction delays initial healing of the extraction socket in rats. J Bone Miner Metab 2009; 27: 663-672.
69. Sonis ST, Watkins BA, Lyng GD, Lerman MA, Anderson KC. Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonaterelated osteonecrosis in cancer patients. Oral Oncol 2009; 45: 164-172.
70. Gotcher JE, Jee WS. The progress of the periodontal syndrome in the rice rat. II. The effects of a diphosphonate on the periodontium. J Periodontal Res 1981; 16: 441-455.
71. Kikuiri T, Kim I, Yamaza T, Akiyama K, Zhang Q, Li Y, Chen C, Chen W, Wang S, Le AD, Shi S. Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice. J Bone Miner Res 2010; 25: 1668-1679.
72. Senel FC, Duman MK, Muci E, Cankaya M, Pampu AA, Ersoz S, Gunhan O. Jaw bone changes in rats after treatment with zoledronate and pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 2010; 109: 385-391.
73. Biasotto M, Chiandussi S, Zacchigna S, Moimas S, Dore F, Pozzato G, Cavalli F, Zanconati F, Contardo L, Giacca M, Di Lenarda R. A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw. J Oral Pathol Med 2010; 39: 390-396.
74. Hokugo A, Christensen R, Chung E, Sung EC, Felsenfeld AL, Sayre JW, Garrett N, Adams JS, Nishimura I. Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats. J Bone Miner Res 2010; 25: 1337-1349.