Dental Tribune Asia Pacific Edition

Dental TribuneAsia Pacific Edition | 11/201514 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, and there is evidence for improved implant fixation in an increasing number of applica- tions. In dentistry, however, bis- phosphonates are often regarded negatively, 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. Inseparable: Zirconia and PermaCem 2.0 PermaCem 2.0 is the new generation of self-adhesive luting cement. The special adhesive monomer formula enables superior natural self-adhesion on zirconia. This ensures excellent adhesive strength with zircon ceramics and gives a safe feeling. It is simple to work with the material: Easy excess removal, no dripping, precise ﬂow into all areas – thanks to the Flow-2.0-Formula. www.dmg-dental.com NEW! 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 DTAP1115_14_Aspen 20.11.15 14:35 Seite 1 DTAP1115_14_Aspen 20.11.1514:35 Seite 1

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