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13Dental Tribune United Kingdom Edition | 6+7/2015 TRENDS&APPLICATIONS Most dentists will be familiar with bisphosphonates mainly as a cause of osteonecrosis of the jaw (ONJ). ONJ is a complication of systemic treatment. In contrast, locally ap- plied bisphosphonates have been proven efficacious for improving the fixation of dental implants.Theoret- ical reasoning, experimental data, and small clinical trials suggest that local application of bisphospho- nates is safe and effective in peri- odontology and implant surgery. Bisphosphonates have positive effects on many conditions in bone and few and rare side-effects. Their efficacy in osteoporosis is well known,andthereisevidenceforim- proved implant fixation in an increasing number of applications. In dentistry, however, bisphospho- natesareoftenregardednegatively, owing to the small risk of ONJ. ONJ is indeed a problem. How- ever,thereistheoreticalandclinical evidence to suggest that the risk of ONJ can be avoided by local treat- ment. Local bisphosphonate treat- ment has shown beneficial effects without complications in ran- domised blinded clinical trials in periodontologyanddentalimplant surgery.1 Howcanthisbe?Hereisan explanation: Bisphosphonates either bind to bone mineral or are quickly ex- creted. Normally, they do not enter cells and are therefore not toxic. Only osteoclasts can resorb bone, and when they do so, the dissolved bone material passes through the cell. Therefore, bisphosphonates can reach the intracellular space of osteoclasts. Once inside the osteo- clast, they will inactivate the cell and thus reduce bone resorption. When bone is infected, the bone surrounding the infection will be quicklyresorbed.Theinfectedbone will therefore become surrounded by richly vascularised soft tissue that demarcates the infected area. Thus, a good resorption capability is important for preventing the spread of bony infection. This pro- tection mechanism can be im- paired if resorption is reduced by any potent anti-resorptive, leading tothespreadofinfectionandestab- lished osteomyelitis. In dentistry, this kind of osteomyelitis is called osteonecrosis. Thus, from a patho- physiological perspective, ONJ is a somewhat misleading term. The alreadywell-knownanti-osteoclastic effects of bisphosphonates are suf- ficient to explain ONJ without sup- positions about other, less known, mechanisms.2 Moreover, the the- ory fits with the observation that non-bisphosphonate anti-resorp- tives are associated with ONJ too. When implants are inserted in- to bone, numerous studies have shown that—especially in cancel- lous bone—bisphosphonates re- duce the resorptive response to the trauma without impairing the bone formation response, there- fore having a net anabolic effect. This explains why both local and systemic bisphosphonates have been shown to improve the early fixation of knee and hip replace- ments in randomised blinded clin- ical trials.3 Because bisphosphonates bind strongly to bone, local treatment will stay local. Bisphosphonates applied to a bone surface will stay there more or less forever, and thus not impair the resistance to infec- tion anywhere else. In an animal model of dental implants (at sites compromised by local wounding), the author’s group showed that systemic bisphosphonate treat- ment induced osteomyelitis (ONJ), whereas implants with a bisphos- phonatecoatingimprovedimplant fixation without problems in spite ofthecompromisedinsertionsite.4 Moreover, if an implant site in hu- mans were infected, only the bone about one millimetre away from the implant surface would contain bisphosphonate and could be re- moved if necessary. In a randomised blinded con- trolled trial of dental implants coated with a protein layer loaded with bisphosphonates, improved fixation was demonstrated.5 The resonance frequency was 6.9 ISQ units higher for the coated im- plants compared with the controls (p = 0.0001; Cohen’s d = 1.3). Radi- ographs showed less marginal resorption both at two months (p = 0.012) and at six months (p = 0.012). The patients were fol- lowed for five years without com- plications. To conclude, systemic anti- resorptives may impair protection against osteomyelitis, thereby in- creasing the risk of ONJ in patients with other risk factors. Local bis- phosphonates seem not to confer this risk, and improve implant fix- ation by their net anabolic effect. Local bisphosphonate treatment could become an important tool in dentistry and maxillofacial surgery. Editorial note: A list of references is available from the publisher. Conflict of interest declaration: The author has shares in AddBIO. Y education everywhere and anytime Y live and interactive webinars Y more than 500 archived courses Y a focused discussion forum Y free membership Y no travel costs Y no time away from the practice Y interaction with colleagues and experts across the globe Y a growing database of scientific articles and case reports Y ADA CERP-recognized credit administration ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providersof continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. www.DTStudyClub.com Register for FREE! AD Dr Per Aspenberg is Professor of Orthopaedic Sur- gery at Linköping University in Swe- den with two de- cades of experi- ence in research and clinical trials on the use of bisphosphonates to treat orthopaedic conditions. He can be contacted at per. aspenberg@liu.se. Bisphosphonates:Athreatoranoption? Prof.Per Aspenberg,Sweden DTUK0615_13_Aspen 27.11.15 12:25 Seite 1 DTUK0615_13_Aspen 27.11.1512:25 Seite 1