The posterior portion of the maxilla has been described as the most difficult part of the mouth for the implant practitioner, and it requires great ability to achieve successful results. Anatomical considerations include reduced bone quantity, especially in patients who have had alveolar resorption in the wake of tooth loss. So, it may be necessary to perform a bone augmentation procedure before placing the implant. However, one disadvantage of using autogenous bone is the unpredictable bone resorption, which might be reduced by the use of bisphosphonates, perhaps locally. Bisphosphonates have been tested for treating osteoporosis and they are in clinical use. These drugs can also be used to reduce peri-implant resorption thereby allowing orthopedic implants to achieve a stronger primary fixation. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover, leading to a net increase in local bone density. Clinically, this idea has been tested in orthopedics but not in dentistry. For dental implants, improved fixation would enable surgeons to push the limits regarding the quality of bone (in a surgical sense) in which implants can be inserted.
S.-J.H.S. Qui, G. Gibson, K. Lundin-Cannon, M. Schaffler. Osteocyte apoptosis After Acute Matrix Injury in Compact Bone. The Orthopaedic Research Society, San Francisco 1997.
Hilding M, Ryd L, Toksvig-Larsen S, Aspenberg P. Clodronate prevents prosthetic migration: a randomized radiostereometric study of 50 total knee patients. Acta Orthop Scand 2000;71:553-557.
Wermelin K, Aspenberg P, Linderbäck P, Tengvall P. Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks. J Biomed Mater Res A. 2008;86:220-7.
M. Yoshinari, Y. Oda, T. Inoue, K. Matsuzaka, M. Shimono. Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium implants. Biomaterials. 2002;14:2879-85.
Peter B, Gauthier O, Laïb S, Bujoli B, Guicheux J, Janvier P, van Lenthe GH, Müller R, Zambelli PY, Bouler JM, Pioletti DP. Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats. J Biomed Mater Res A 2006;76:133-43.
Roshan-Ghias A, Arnoldi J, Procter P, Pioletti DP. In vivo assessment of local effects after application of bone screws delivering bisphosphonates into a compromised cancellous bone site. Clin Biomech. 2011; 26:1039-43.
Stadelmann VA, Gauthier O, Terrier A, Bouler JM, Pioletti DP. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study. Eur Cell Mater. 2008; 31:10-6.
Rogers MJ, Watts DJ, Russell RG (1997) Overview of bisphosphonates. Cancer 80:1652-1660.
Holen I, Coleman RE. Bisphosphonates as treatment of bone metastases. Curr Pharm Des 16: 262-7 2010. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res. 1995; 10:1478-87.
Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ. Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest. 1993; 91:2004-11.
Im GI, Qureshi SA, Kenney J, Rubash HE, Shanbhag AS. Osteoblast proliferation and maturation by bisphosphonates. Biomaterials 2004; 25:4105-15.
Rogers MJ. New insights into the molecular mechanisms of actions of bisphosphonates. Curr Pharm 2003; 9:2643-58.
Fast DK, Felix R, Dowse C, Neuman WF, Fleisch H. The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture. Biochem J. 1978; 15: 97- 107.
Cecchini MG, Felix R, Fleisch H, Cooper PH. Effect of bisphosphonates on proliferation and viability of mouse bone marrow derived macrophages. J Bone Miner Res. 1987; 2:135-42.
Reitsma PH, Teitelbaum SL, Bijvoet OL, Kahn AJ. Differential action of the bisphosphonates (3-amino-1- hydroxypropylidene)-1, 1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl2MDP) on rat macrophage-mediated bone resorption in vitro. J Clin Invest. 1982; 70:927-33.
Cremers SC, Pillai G, Papapoulos SE. Pharmacokinetics/pharmacodynamics of bisphosphonates: use for optimisation of intermittent therapy for osteoporosis. Clin Pharmacokinet. 2005; 44:551-70.
van Beek ER, Löwik CW, Ebetino FH, Papapoulos SE. Binding and antiresorptive properties of heterocyclecontaining bisphosphonate analogs: structure-activity relationships. Bone 1998; 23:437-42.
Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 2007; 11:209-57.
Madrid C, Sanz M. What impact do systemically administrated bisphosphonates have on oral implant therapy? A systematic review. Clin Oral Implants Res. 2009; 20 (4): 87- 95.
Coxon FP, Thompson K, Rogers MJ. Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol. 2006; 6:307-312.
Russell RG. Bisphosphonates: mode of action and pharmacology. Pediatrics. 2007; 119 (2):150-162.
Bayliss L, Mahoney DJ, Monk, P. Normal bone physiology, remodeling and its hormonal regulation. Surgery. 2012; 30(2):47-53.
Walia M, Arora S, Singal B. Oral Bisphosphonates and Dental Implants: A Review and Update. J Impl Adv Clin Dent. 2011; 3(1):83-87.
Gutta R, Louis PJ. Bisphosphonates and osteonecrosis of the jaws: science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:186-193.
Tengvall P, Skoglund B, Askendal A, Aspenberg P. Surface immobilized bisphosphonate improves stainless-steel screw fixation in rats. Biomaterials. 2004; 25:2133-8.
Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Porras AG. Clinical pharmacology of alendronate sodium. Osteoporos Int. 1993;3:13-6.
Daley-Yates PT, Dodwell DJ, Pongchaidecha M, Coleman RE, Howell A. The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases. Calcif Tissue Int 1991; 49:433-5.
Devitt B, McLachlan SA. Use of ibandronate in the prevention of skeletal events in metastatic breast cancer. Ther Clin Risk Manag 2008; 4:453-58.
Bobyn JD, McKenzie K, Karabasz D, Krygier JJ, Tanzer M. Locally delivered bisphosphonate for enhancement of bone formation and implant fixation. J Bone Joint Surg Am 2009; 6:23-31.
Wermelin K, Suska F, Tengvall P, Thomsen P, Aspenberg P. Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats. Bone. 2008; 42:365-71.
Goss A, Bartold M, Sambrook P, Hawker P. The nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in dental implant patients: a South Australian case series. J Oral Maxillofac Surg. 2010; 68: 337-343
Abtahi J, Tengvall P, Aspenberg P. A bisphosphonate-coating improves the fixation. J Dent Res of metal implants in human bone. A randomized trial of dental implants. Bone 2012; 50:1148-1151.
Berardi D, Carlesi T, Rossi F, Calderini M, Volpi R. Potential applications of biphosphonates in dental surgical implants. Int J Immuno pathol Pharmacol 2007; 20:455-465.
Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. American Society for Bone and Mineral Research 2007; 22:1479-91.
American Association of Oral and Maxillofacial Surgeons positionpaper on bisphosphonate-related osteonecrosis of the jaws. Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. Source AAOMS, Rosemont IL 60018, USA 2007; 65:369-76.
Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate - inducedex posed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63: 1567-75
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: 527-34
Barasch A, Cunha-Cruz J, Curro FA, Hujoel P, Sung AH, Vena D, Voinea-Griffin AE. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN 2011; 90:439-44.
Vescovi P, Campisi G, Fusco V, Mergoni G, Manfredi M, et al. Surgerytriggered and non surgery-triggered Bisphosphonaterelated Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study. Oral Oncol 2011; 191-4.
Vescovi P, Merigo E, Meleti M, Manfredi M, Guidotti R. Bisphosphonates-related osteonecrosis of the jaws: a concise review of the literature and a report of a single-centre experience with 151 patients. J Oral Pathol Med 2012; 41:214-221.
Vescovi P, Nammour S. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review. Minerva Stomatol. 2010; 59: 181-203 204-13.
Allen MR. The effects of bisphosphonates on jaw bone remodeling, tissue properties, and extraction healing. Odontology 2011; 99:8-17.
Palaska PK, Cartsos V, Zavras AI. Bisphosphonates and time to osteonecrosis development. Oncologist. 2009;14:1154-66.
Rutkowski JL. Combined use of glucocorticoids and bisphosphonates may increase severity of bisphosphonaterelated osteonecrosis of the jaw. J Oral Implantol 2011; 37:505.
Carlson ER, Basile JD. The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2009; 67:85-95.
Mucke T, Koschinski J, Deppe H, Wagenpfeil S, Pautke C, Mitchell DA, Wolff KD, Holzle F. Outcome of treatment and parameters influencing recurrence in patients with bisphosphonate-related osteonecrosis of the jaws. J Cancer Res Clin Oncol. 2010; 137:907-13.
Seth R, Futran ND, Alam DS, Knott PD. Outcomes of vascularized bone graft reconstruction of the mandible in bisphosphonate-related osteonecrosis of the jaws. Laryngoscope. 2010; 120:2165-71.
Filleul O, Crompot E, Saussez S. Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol. 2010; 136:1117-24.
Ruggiero SL, Fantasia J, Carlson E. Bisphosphonaterelatedosteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102:433-41.
Pazianas M. Osteonecrosis of the jaw and the role of macrophages. J Natl Cancer Inst. 2011;103:232-240.
Reszka AA, Rodan GA. Nitrogen-containing bisphosphonate mechanism of action. Mini Rev Med Chem. 2004; 4:711-719.
Allen MR, Burr DB. Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: what we think we know and what we know that we don't know. Bone 2011; 49:56-65.
Otto S, Schreyer C, Hafner S, Mast G, Ehrenfeld M. Bisphosphonate related osteonecrosis of the jaws - characteristics, risk factors, clinical features, localization and impact on oncological treatment. J Craniomaxillofac Surg. 2012; 40:303-309.