We describe a case of a patient with a 6-year history of alendronate therapy, in which BRONJ developed around her dental implants. In this patient, the dental implants achieved successful osseointegration, and BRONJ occurred after the second surgery. Several factors could have played a role in the development of BRONJ in this patient. Glucocorticoid therapy is associated with an increased risk of BRONJ. This may be a result of multiple factors including inhibition of osteoblast function and increased osteoblast and osteocyte apoptosis. Other effects of glucocorticoids that may contribute to an increased risk of BRONJ include increased bone resorption, immunosuppression, impaired wound healing, and increased risk of local infection . Patient-related local risk factors include dentoalveolar surgery (e.g., tooth extraction) and pre-existing inflammatory dental disease, such as periodontal disease or periapical pathology . Although BPs tend to accumulate in sites of active bone remodeling, such as the jaws, the surgical trauma to the alveolar bone during implant surgery could have further stimulated the postoperative accumulation of the drug in the implant site. The localized interference of BPs on bone turnover may have influenced the peri-implant bone resistance to oral bacteria in the long term, thus increasing the risk of peri-implantitis. Once infection of the implanted bone site is established, BPs further accumulate because of the increased bone turnover; the onsite activation of bisphosphonates will hamper the healing capacity of bone, leading to bone necrosis and sequestration .
Nevertheless, the role of the dental implant procedure as a BRONJ pathogenetic factor [12–15] is still unclear. Recently, an increasing number of peri-implant BRONJs have been described [5–9]. Peri-implant BRONJ has been classified into two types: implant surgery-triggered BRONJ, when it develops within 6 months after implant surgery, suggesting that the surgical process may be a contributing factor; and non-implant surgery-triggered BRONJ, if it develops 6 months or more after implant surgery, or when BP administration started after implant placement and osteointegration . Most authors do not consider the surgical procedure of implantation as a trigger factor for MRONJ [7, 8, 14, 16–20].
It is therefore important that all patients treated with oral BPs must be given a full explanation of the potential risks of implant failure and BRONJ development in the short and long term. Because the potential role of infection in implant failure and BRONJ occurrence is still debated, great attention should be paid to the long-term oral hygiene and plaque control of implant-prosthetic restorations in patients taking oral BPs.
BPs and other antiresorptives such as denosumab increase apoptosis and inhibit osteoclast differentiation and function, all leading to decreased bone resorption and remodeling . Teriparatide may counteract these mechanisms by stimulating bone remodeling. It has been shown to stimulate the activity and viability of osteoblasts from the alveolar bone of chronic bisphosphonate users , while indirectly increasing the metabolic activity and number of osteoclasts by affecting osteoblast function . An increased number of remodeling units and increased bone formation within each unit may promote healing and the removal of damaged bone. Thus, teriparatide may offer therapeutic promise for localized bone defects of the jaw in patients with BRONJ [3, 23–25].
While it has been suggested recently that assertive surgical removal of the sequestrum appears to be effective [26–29], it can sometimes be difficult to distinguish living bone from necrotic bone. Recently, resection of BRONJ-affected tissue produced healing in patients taking oral bisphosphonates more successfully than conservative management . However, bone resection because of surgical treatment may lead to significant oral disability.
Activation of living bone turnover by teriparatide therapy causes progression of the separation of the sequestrum. As a result, teriparatide therapy promotes sequestrum separation followed by normal mucosal coverage of the exposed bone. After 5 months of teriparatide therapy in our patient, sequestrum separation had progressed and thus a sequestrectomy was performed under general anesthesia. After the wound in the affected area had healed, our patient did not report any problems pertaining to her ability to ingest food, despite the presence of the bone defect in the mandible. We treated the patient with teriparatide for 2 years. CT monitoring of the mandible would assist in determining whether teriparatide can allow complete recovery of the bone defect in the mandible in cases of ONJ induced by bisphosphonates.