Successful New Dental Implant Installation in a Healed Site of Medication-Related Osteonecrosis of the Jaw: A Case Report Open Access

Because to their high long-term survival and success rates, dental implants are considered to be the most preferred treatment to replace missing teeth over removable and fixed partial dentures.¹  However, in patients with bone diseases, including osteoporosis and bone metastasis of cancer, dental implant placement may be limited due to the type of antiresorptive therapy the patient is receiving. The use of antiresorptive medications, such as bisphosphonates (BPs), receptor activator of nuclear factor kappa-B ligand inhibitors, or angiogenesis inhibitors, can be accompanied by an increased risk of developing medication-related osteonecrosis of the jaw (MRONJ), especially when treated intravenously or in combination with glucocorticoids.^2–4  Since intravenous BPs are often administered to manage malignancy-related skeletal morbidities, is recommended to avoid elective dentoalveolar surgery, such as extractions and dental implants, in cancer patients treated with intravenous BPs.^5,6  There has been controversy concerning the risks associated with performing dentoalveolar procedures in patients receiving oral BP therapy.^7,8  Nevertheless, the risk of MRONJ development is very low in patients taking oral BPs,⁶  and it has been reported that implant survival rates are comparable with those of healthy patients.³ 

Despite proper management, the development of MRONJ can be inevitable in some cases. For patients who have developed an advanced stage of MRONJ, surgical removal of the necrotic bone along with the affected tooth or implant must be done, and rehabilitation of the edentulous area should be performed subsequently to restore these patients' function and quality of life. However, oral rehabilitation with dental implants is challenging due to severe bone defect as a sequelae of the surgery and is not recommended because of the high risk of implant failure.⁹ 

There are only a few reported cases in the literature of dental implant–prosthetic rehabilitation of patients with a history of healed MRONJ,^9–11  and universally confirmed protocols regarding the clinical management of patients who have already experienced MRONJ have not been established. The aims of this case report are (1) to present the long-term survival of a dental implant installed in a fully treated MRONJ site of the mandible and (2) to demonstrate the treatment plan that led to successful implant placement in our patient with a history of MRONJ.

An 80 year-old female patient visited the Department of Oral and Maxillofacial Surgery, Seoul St. Mary's Dental Hospital, in March 2011 with chief complaint of pain and ginigval swelling around the implants in the right mandibular molar area.

Dental history revealed that 3 dental implants had been placed in the right mandibular first premolar, second premolar, and first molar area at a private dental clinic about 15 years ago. The implant in the right mandibular second premolar area was removed 6 months before the visit to our hospital. However, the symptoms worsened with necrotic bone exposure and pus discharge. The aggravating factor of her symptom was associated with her medical history of osteoporosis, for which she had been taking an oral BP, alendronate (Fosamax, Merck & Co. Inc., Whitehouse Station, NJ), for 10 years, and she discontinued alendronate and started non-BP therapy using raloxifene (Evista, Alvogen, Seoul, Korea) 2 months prior to her arrival at our dental hospital. Additional medical history included well-controlled hypertension and stable angina pectoris.

Upon clinical examination, necrotic bone exposure and severe alveolar bone loss were observed where the second premolar implant was removed. The patient exhibited tenderness, gingival swelling, and erythema on the buccal aspect of the 2 remaining right mandibular implants. Panoramic radiograph showed an extraction socket of the right mandibular second premolar area with no sign of bony regeneration, and a bone resorption pattern involving the adjacent implants was noticed (Figure 1a). In addition, the initial cone-beam computerized tomography (CBCT) revealed the presence of bone destruction, formation of sequestrum, altered trabecular bone pattern, and involvement of the inferior alveolar nerve (IAN). Based on the definition of MRONJ from the 2014 American Association of Oral and Maxillofacial Surgeons (AAOMS) Position Paper,⁹  the patient was diagnosed with stage 2 MRONJ, and the diseased bone was planned to be removed along with the 2 affected implants.

Before the surgery, oral antibiotics (Augmentin [amoxicillin–clavulanic acid], Ilsung, Seoul, Korea) and nonsteroidal anti-inflammatory drug (NSAID; Soleton tablet [zaltoprofen], CJ CheilJedang, Seoul, Korea) were prescribed for 2 weeks to reduce signs and symptoms of infection secondary to MRONJ. Under general anesthesia, sequestrectomy, saucerization, and removal of the 2 involved implants in the right mandibular premolar and molar area were done (Figure 2). Unfortunately, damage of the IAN was inevitable due to its involvement in the lesion. Histopathological examination of the sequestrum confirmed the diagnosis of MRONJ.

The patient was prescribed the same antibiotics and NSAID for 7 days postoperatively and antimicrobial mouth rinse (0.12% chlorhexidine gluconate) for 1 month. Maintaining good oral hygiene was emphasized. At the 1-month postoperative follow-up, adequate mucosal healing with absence of necrotic bone was achieved, and a 10-month postoperative CBCT showed no sign of recurrence in the right mandibular premolar and molar region (Figure 3). After satisfactory soft and hard tissue healing was confirmed, we recommmended removable partial denture to restore the edentulous mandibular area. However, the patient strongly desired treatment with dental implants again. The patient was warned about the risk of MRONJ recurrence and implant failure and asked to sign a written informed consent.

At 11 months postoperatively, 3 implants (Osstem, Seoul, Korea) with fixture sizes of 4 × 15 mm, 4 × 15 mm, and 5 × 10 mm were installed in the right mandibular first premolar, second premolar, and second molar area, respectively (Figure 4). The implant site was prepared using the standard protocol for submerged implants. Since there was large crater defect and the patient had permanent hypoesthesia from previous implant removal and sequestrectomy (Figure 3), long implants were installed with simultaneous bone graft using a combination of autogenous bone and xenograft (Bio-Oss, Geistlich, Wolhusen, Switzerland) on the buccal and mesial side of the implant placed in the right mandibular second premolar area. Guided bone regeneration material was used to cover the grafted site with expanded polytetrafluoroethylene membrane (Gore-Tex, W.L. Gore and Associates, Inc, Flagstaff, Ariz), which was removed after 6 weeks. Tension-free, primary wound closure was achieved, and the same postoperative regimen as the previous MRONJ surgery was prescribed. No complications occurred during the postoperative healing period. Close follow-up every 1 month was done during the osseointegration phase of 4 months, after which the implants were exposed for connection of the healing abutments. After confirming acceptable implant stability (implant stability quotient >70) with resonance frequency analysis instrument (Osstell, Integration Diagnostics Ltd, Goteborgsvagen, Sweden) and healthy peri-implant soft tissue condition, an implant-supported provisional prosthesis was fabricated and used for 4 months to evaluate the surrounding soft tissue and peri-implant bone. The peri-implant tissue remained stable, and the final implant-supported fixed prosthesis was delivered.

By the 7-year follow-up (Figure 5), no sign of MRONJ recurrence or complications associated with the implant fixture and prosthesis were observed. The patient showed good compliance with oral hygiene, and the clinical outcome was favorable with minimal marginal bone loss around the implants. Therefore, dental implantation was successful in the same region of the mandible with history of failed implants due to MRONJ.

Osteoporotic or cancer patients with bone-related morbidities being treated with antiresorptive medications are at risk of dental implant failure. For patients with osteoporosis, the major concern regarding implant placement is the likelihood that the disease alters bone quality, formation, or healing to a degree that successful osseointegration is questionable or impossible.¹²  Bone histology of patients with osteoporosis shows decreased mechanical strength, changes in trabecular pattern, reduced mineral content, increased crystallinity, and higher carbonate-to-phosphate ratios.¹³  In addition to the implant surgery itself, the risk on MRONJ increases with presence of a suprastructure,²  which is especially true when the patient has poor oral hygiene, and peri-implantitis of the existing implants may precipitate the severity of the disease.¹⁴  This suggests that bacterial colonization may trigger the progression of MRONJ; thus, antibiotic prophylaxis is highly recommended in patients taking antiresorptive drugs.⁴  Based on this judgment, we have prescribed preoperative antibiotics to reduce the risk of MRONJ.

Despite postsurgical complications in patients taking antiresorptives, recent literature has suggested that administration of oral BPs itself do not influence short-term implant survival rates,^15,16  and the implant survival rates are similar to those in healthy patients.^17,18  However, there are conflicting results on the rate of peri-implant marginal bone loss in osteoporosis patients. According to a recent study comparing marginal bone loss around implants in the elderly population, the rate of peri-implant marginal bone loss does not increase in osteoporosis patients with reduced bone mineral density (BMD),¹⁹  but this observation is in need of long-term follow-up. If an adequate level of oral hygiene is maintained, marginal bone loss is most likely comparable with that perceived in healthy individuals.³ 

Favorable outcomes after implant treatment in patients who have underwent oral BP therapy following appropriate guidelines have been reported.^3,15,16  There have been only a few reports until now, and a long-term follow-up after prosthetic rehabilitation has not been reported. In this case report, we performed long-term follow-up of a patient who had new implants installed in the same site diagnosed with stage 2 MRONJ. According to the AAOMS Position Paper revised in 2014, patients categorized under stage 2 MRONJ are recommended symptomatic treatment using antibiotics and oral antibacterial mouth rinse and infection control via superficial debridement to remove necrotic tissues.⁶  However, in this patient, early intervention was carried out with an extensive surgical procedure under general anesthesia after only 2 months of drug holiday, even though the patient had a long-term history of BP use. According to Kim et al,²⁰  there was no significant association between relapse after surgery and duration of BP use or discontinuation of BP before surgery. In addition, more extensive surgical treatment led to a better prognosis and a reduced risk of recurrence requiring reoperation. This may be due to the type of anesthesia used at the time of surgery, since general anesthesia allows surgeons to more extensively eliminate diseased tissues.²⁰ 

In general, conservative treatment using tooth-mucosa or mucosa-supported removable dentures are favored for the prosthetic rehabilitation of patients who have experienced MRONJ.^7,8  However, the use of a removable prosthesis can cause continuous trauma to the underlying oral mucosa and bone, possibly producing pressure spots or ulcers that may lead to bone exposure with a risk of secondary infection. Also, patients who have undergone surgery due to MRONJ most likely lack vestibular depth, which affects stability and retention of the dentures. Therefore, placing new implants after MRONJ surgery was a rational alternative since the bioavailability of oral BP is much lower compared with intravenously administered BPs and thus less risk of MRONJ recurrence. In this case report, implant placement was successful in the same region with a history of implant removal and healed MRONJ. As the BMD in osteoporosis patients is reduced, the risk of MRONJ recurrence was reported to be the highest immediately after the surgery, and the probability decreased afterwards²⁰ ; a sufficient healing period has been recommended before fabrication of the suprastructure.²¹  Relapse of MRONJ occurred most frequently within the first 9 months, suggesting that time frame to be the critical period.²⁰  Therefore, we waited more than 9 months before implant placement to ensure proper healing of the surgical site and reduce the possibility of recurrence after surgery. In addition, to decrease the risk of MRONJ recurrence, the patient was switched to non-BP therapy using raloxifene (Evista, Alvogen), which is a second-generation selective estrogen receptor modulator used to treat osteoporosis by increasing BMD.

Implant placement in previously treated MRONJ sites is challenging because of the significantly reduced amount of alveolar bone. Therefore, reconstructing the bone defect with sufficient healthy soft tissue is needed for successful implant treatment. Even though staged reconstruction is recommended to reduce the risk of secondary infection,¹³  our patient had adequate soft and hard tissue healing along with good oral hygiene. In addition, because satisfactory primary stabilities of implants were achieved along with well-stabilized graft materials around the implants, we performed bone graft along with implant placement simultaneously.

There is no consensus regarding whether dental implants are preferred in patients taking antiresorptive medications. Hence, a patient's individual risk factors must be carefully considered before making the decision to place implants. Previous studies in the literature have proposed protocols for dental implant surgery in patients taking BPs,^3,9  but these studies focused only on the surgical aspect of implant treatment or did not take into account installation of the implant in the same site where the MRONJ occurred. Therefore, based on our own experience, we describe a treatment plan that led to successful implant placement in a patient with a history of MRONJ (Figure 6). In summary, early and extensive surgical intervention should be considered under general anesthesia for patients with established MRONJ. Then, periodic follow-up for at least 9 months should be conducted to detect the possible recurrence of MRONJ. Before deciding to initiate implant treatment, the patient should have good oral hygiene and adequate soft and hard tissue healing and take non-BP medication to maintain good bone quality. For 1 week before implant placement, the patient should be on antibiotics (amoxicillin and clavulanic acid 325 mg, 3 times a day) and oral antimicrobial mouth rinse (0.12% chlorhexidine gluconate, twice a day) to reduce the risk of infection and recurrence of MRONJ.³  Implant placement should be performed using a 2-stage approach, with minimally invasive technique, and if bone grafting is needed, a staged procedure is recommended when the primary stability of the implants cannot be achieved with stabilization of the graft materials. After implant surgery, the patient should be on the same antibiotic regimen and antimicrobial mouth rinse for 1 week. A longer healing time should be given before fabricating the4 final prosthesis; thus, delayed loading after implant placement is advocated for the long-term success of the implant.

The present case report emphasized the feasibility of new dental implant installation after complete healing of MRONJ and provided new insight regarding the risk of implant placement in patients with a history of MRONJ. Because the patient's quality of life is greatly enhanced from prosthetic rehabilitation through implant therapy, surgical treatment is recommended over conservative treatment when possible. Therefore, a dental implant is indicated in carefully chosen cases of healed MRONJ, taking into account individual risks and benefits, and following appropriate guidelines and precautions in dental implant therapy.

AAOMS

American Association of Oral and Maxillofacial Surgeons

BMD

bone mineral density

BP

bisphosphonate

CBCT

cone-beam computerized tomography

IAN

inferior alveolar nerve

MRONJ

medication-related osteonecrosis of the jaw

NSAID

nonsteroidal anti-inflammatory drug

The authors state that there are no conflicts of interest in connection with this article.