“Booby-Trap” – Dental implants at bay

Bisphosphonates are used widely in the management of bone diseases including osteoporosis, Paget’s disease and hypercalcemia related to malignancy. Bisphosphonates inhibit osteoclast mediated bone resorption, and therefore contribute to an increase in bone mineral density. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These added features have made bisphosphonates useful in the management of bone metastases. Several clinical trials have shown that bisphosphonates reduce skeletal tumor burden in patients with multiple myeloma, breast cancer and prostate cancer, leading to an increase in the use of bisphosphonates in the management of metastatic disease.

Incidents of osteonecrosis of the jaw have been reported in people using bisphosphonates and undergoing invasive dental treatment procedures, including tooth extractions, dental implants, and surgical and nonsurgical periodontal treatment. However, the rate of occurrence of this complication, and the factors that predispose to its occurrence are not well understood. A true cause-and-effect relationship between osteonecrosis of the jaw and bisphosphonate use has not yet been established.

There is also an incomplete understanding of how bisphosphonate therapy may affect tissue healing and the success rate of dental implants. The risk for bisphosphonate-induced osteonecrosis may be influenced by the route of administration of the drug, the potency and the duration of use. Jaw osteonecrosis appears more associated with the intravenous use of bisphosphonates. A review showed that 94% of the published cases of osteonecrosis had been treated with intravenous, nitrogen-containing bisphosphonates. Furthermore, a retrospective study found that 10% of patients treated with intravenous bisphosphonates developed osteonecrosis. On the other hand, the risk for osteonecrosis seems low in users of oral bisphosphonates. Although most of the complications following oral and intravenous bisphosphonates appear to be triggered by dental surgery or dental trauma, some cases may develop osteonecrosis without a history of preceding dental procedure.

Bisphosphonate-mediated inhibition of osteoclast function seems to decrease bone resorption and inhibit normal bone remodeling. Bone resorption and remodeling play an essential role in maintaining normal bone homeostasis. As osteoclasis occurs, cytokines and growth factors are released into surrounding matrix essential for modulating new bone development. Bisphosphonates may alter bone homeostasis and there by the ability of bone to heal after minor insults is compromised. The bone may also become secondarily infected and sequestrate, leading to a lesion that appears clinically similar to osteoradionecrosis. Pathogenesis of the osteonecrotic process is most consistent with localised vascular insufficiency. This is believed to be important in reducing tumor burden by depriving tumor cells of adequate nutrients and blood supply. However, if osteoclastic function is too severely impaired, osteocytes are not replaced and the capillary network in the bone is not maintained, resulting in avascular bone necrosis.

Presently, there is no effective treatment for the condition. Surgical intervention tends to expose further bone and locating viable bone margins is problematic. Covering exposed bone with tissue flaps is ineffective because of development of fistulae around the flaps. As osteonecrosis and its complications can result in significant chronic pain, dysfunction and disfigurement which are difficult to treat, the aim should be prevention.

There are conflicting reports regarding dental implants. Experimental studies show a positive effect of bisphosphonates on the bone around implants in experimental animals and humans. Failure of osteointegration in a patient on bisphosphonate therapy has been reported. Current advice is that placement of implants may be avoided if the patient has serious bone disease and are on potent doses of the drug. Osteoporotic patients on lower doses need a full informed consent before proceeding with treatment. Patients on bisphosphonate therapy with existing implants should be regularly monitored. Increased bone density around the implant may occur. If bone pain or loss of integrity occurs the superstructure should be removed and the implant left submerged. Bone surgery must be avoided as the bone is exceedingly dense and avascular necrosis may occur.

Dental treatment seems to be a precipitating event in development of most cases of bisphosphonates-related osteochemonecrosis. It is therefore imperative that patients receiving necessary treatment have their dental status assessed prior to bisphosphonate therapy. This includes control of dental caries and periodontal disease, avoiding dental implant placement, using soft liners on dentures, and to recommend an alternative to tooth extractions for patients with history of receiving bisphosphonate therapy. This is because withdrawal of bisphosphonate therapy before major dental procedures does not appear to hasten recovery of osteonecrosis due to their persistence in bone. In established cases, the primary goals are palliation and control of osteomyelitis. Progression of disease can usually be controlled with antibiotics, periodic surgical debridement of sequestrating bone and wound irrigation. However, these have proven consistently ineffective. Surgical treatment should only be reserved for symptomatic patients. It is important to make health care professionals and patients aware of the potential risk of bisphosphonate treatment. Once the therapy has commenced, regular dental monitoring of oral health and a preventive approach should be adopted. Patients should be educated regarding good oral hygiene practices and to report having come across any symptoms. There should be a greater collaboration between oral health providers, physicians and surgeons alike to minimize the complications of this therapy, thereby keeping patient morbidity at check. The goal of this approach should be, like elsewhere, to harness the intrinsic reparative drive to the judicious pharmacokinetic intervention aimed at avoiding treatment related health risks.