The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still not completely clarified. Nevertheless, risk factors have been described.
Implants and the placement of implants are known to contribute to BRONJ risk. The development of bone exposure has been reported after insertion of implants, especially in patients taking intravenous bisphosphonates and as linked to existing implants, probably associated with peri-implantitis.1,2,3
Consequently, several authors and societies have labeled bisphosphonate therapy as a limiting or excluding factor for implant placement. In summary, the decision whether or not to insert implants is difficult and is based on the individual risk profile of the patient. This profile is defined by several factors, such as bisphosphonate potency, administration route, duration of application, underlying disease, and co-medication (eg, anti-angiogenetic drugs or chemotherapeutic agents, such as cyclophosphamide, erythropoietin, and steroids). Local factors include local anatomy and concomitant oral disease. In general, low-risk patients suffer from osteoporosis and are mostly treated orally. Patients who are treated intravenously because of secondary osteoporosis have a moderate risk, and patients with malignant diseases have a high BRONJ risk.4
There is no evidence of an increased risk concerning implant surgery in osteoporotic patients.5–8 Nevertheless, implant therapy in patients with low or moderate risk must be cautiously indicated and offer considerable advantage over non-implant–supported prosthetic treatment options. The majority of recommendations regarding invasive dental procedures state that elective surgery, such as dental implantology, is contraindicated in the group of high-risk patient.9–13
The guidelines of the German Society of Orofacial Surgery (DGMKG) specify a current BRONJ as an absolute contraindication. Furthermore, DGMKG guidelines estimate implant placement in cases of already healed BRONJ at least as critical.4 Grötz et al judge patients who have already had BRONJ as highly at risk and advise against implant insertion.7 This statement relies on empirical data; scientific evidence is lacking so far.
A case of successful dental implant treatment after complete healing of a BRONJ in the neighboring region is described as follows. The patient received bisphosphonates intravenously for osteoporosis therapy.
In March 2011, a 64-year-old female patient presented 3 months after left-side wisdom tooth and second molar extraction with empty painful sockets, exposed bone in the third molar region, and hyperplasia of the regional oral mucosa (Figure 1). Because of osteoporosis, the patient had been treated with ibandronate (Bonviva, Roche, UK) 3 mg intravenously every 3 months (overall 6 infusions), daily Colecalciferol (vitamin D3), and calcium carbonate (Kombi-Kalz, MedaPharma, Austria) from February 2009. The last infusion of ibandronate had been administered in December 2010. Answering the patient's wish, the treating physician suspended bisphosphonate therapy immediately after BRONJ diagnosis. There was no additional medication.
Conventional radiological examination demonstrated persistent sockets with no signs of bony regeneration. Scintigraphy displayed increased tracer uptake in the delayed phase, corresponding to concomitant inflammation in the BRONJ region. Bone biomarkers showed normal β-cross laps (CTX 0.22 ng/ml) but decreased vitamin D3 (23.8 ng/ml). The preoperatively performed computerized tomography scan revealed empty sockets, a small sequester, and changes of the trabecular pattern (Figure 2). BRONJ treatment consisted of initial conservative local treatment to fight acute inflammation and surgical revision of the affected jawbone under local anesthesia. The surgical procedure took place in May 2011 (Figure 3). Basically, it consisted of removal of necrotic parts of the jawbone and subsequent dense wound closure as described by Rugani et al.13
Histological examination of a collected biopsy confirmed the diagnosis of superinfected BRONJ. Persistent soft tissue coverage without any apparent necrotic bone could be achieved. The 9-month follow-up confirmed a stable soft tissue situation (Figure 4). A cone-beam computerized tomography (CBCT) scan showed regeneration of the alveolar bone in the left lower third molar region and did not reveal any local pathological findings. For oral rehabilitation, implant placement was scheduled. The patient was specifically informed about BRONJ risk and had to sign a written informed consent.
In February 2012, two implants were placed to replace the first (#19) and second left lower molar (#18). Prior to surgery, digital planning had been performed (Figure 5). Implant site preparation was consistent with the standard protocol for submerged implants. After local flap elevation pilot drilling was performed, implant positions were marked using a prefabricated splint that indicated the ideal prosthetic position. After a 2-mm pilot drill, the hole was extended gradually using the Xive drill system (Dentsply IH GmbH, Germany). The crestal drill was inserted to maximum depth to reduce resistance during implantation. Two Xive implants (Dentsply) were inserted (#19: diameter: 4.5 mm, length: 11 mm; #18: diameter: 5.5 mm, length: 9.5 mm) (Figure 6a and b). Irrigation was extensively used. No grafting procedure was indicated. Wound closure was followed by single-knot sutures (Figure 7). The sutures were removed after one week. No complications occurred during the postoperative healing period.
After an osseointegration phase of 4 months, implants were exposed and healing abutments were inserted. Clinically, both implants showed good stability and stable crestal bony conditions: Periotest – value: #19: −6; #18: −7 (Medizintechnik Gulden, Modautal, Germany). Prosthodontic rehabilitation followed shortly thereafter. Two single implant crowns were supplied. Sixteenth months after implant surgery and 10 months after restoration, the peri-implant region remained inconspicuous (Figure 8a and b).
In the illustrated case, implant placement was successful in a site adjacent to a region with actual history of healed BRONJ. To our knowledge, there is no similar case published so far.
Insertion of implants in patients with healed BRONJ is judged to be risky4 or not even recommended.7 In general, noninvasive procedures should be preferred for prosthetic rehabilitation. Nevertheless, if mucosal-supported conventional dentures are used, the risk of pressure marks and ulcers, as well as resulting jaw necrosis, is evident. Consequently, implant-supported prosthetic therapy should be considered a reasonable alternative. Actually, BRONJ risk could be increased sevenfold by dentoalveolar surgery,14,15 but several authors have published protocols demonstrating that surgical treatment is comparatively safe if certain rules are obeyed4,16–20 (Table). In summary, the basic principles for dentoalveolar surgery in bisphosphonate patients are infection prophylaxis and minimal invasiveness. Prior to surgery, the microbial burden should be reduced by antiseptic rinses and, if necessary, antibiotics or antimycotics. Prophylactic perioperative antibiotic therapy should be started at least 1 day before surgery and continued for 10–14 days. Flaps should be limited as far as possible, and unnecessary periosteal denudation should be avoided.
These prevention protocols can be consulted for implant surgery. To avoid overheating, insertion torque should not excess 50 Ncm, as the increased compressive stress can lead to impaired angiogenesis and hypoxia.21 Rinsing should be extensive, and submerged placement is advisable. In case of postoperative inflammatory signs of the wound, local disinfectant rinsing should be started immediately. Sutures should be removed not before 10–14 days. If provisional mucosa-supported removable dentures have to be used, special attention should be paid to avoid pressure marks.
In general, implant placement in routine cases is not more invasive, for example, than surgical extractions or apical surgery. This is also mentioned in surgical protocols concerning perioperative antibiotics.22,23 Accordingly, the risk of osteonecrosis can be assessed as being likewise in simple implant surgery. From that standpoint, the risk of recurrent pressure marks caused by removable dentures should be weighed in each individual case against the risks that must be considered in implant surgery. From today's point of view, more invasive implant surgery (such as tissue augmentations) should strictly be avoided.
Following the described regime, implant placement usually seems to proceed uneventfully, even in patients who are treated with bisphosphonates. This is especially true for orally administered bisphosphonates.6 In a 2006 controlled study, Jeffcoat et al referred to an equal implant loss rate in 25 patients with osteoporosis treated with bisphosphonates.24 Fugazzotto et al similarly reported no case of BRONJ after implant therapy in 61 patients with oral bisphosphonate therapy,17 and Grant et al likewise did not find any case of BRONJ and a comparable implant success rate in a collective of 115 patients with implants and oral bisphosphonate therapy.25 Nevertheless, even if reports implicate that implant placement in patients with oral bisphosphonate therapy is associated with minor risk, co-medication and other contributing risk factors may increase the risk of osteonecrosis and must be considered.5
Patients who have already experienced BRONJ are estimated to be high-risk cases.7 Therefore, implant therapy is not recommended to date. In this case, we decided on implant therapy because healing after BRONJ surgery was uneventful and CBCT findings even suggested bone remodeling. The report indicates that after successful surgical BRONJ therapy in an intravenously treated osteoporosis patient, implant placement can be conducted without any resulting osseous complications. In short, implant surgery should be cautiously indicated in selected cases, considering individual risks and benefits.
The reported case illustrates that dental implant therapy can be part of individual treatment planning in patients with a history of a healed BRONJ. Further studies are needed to confirm this conclusion.
Source of support for this study has been the Medical University of Graz, Austria.