Bisphosphonates and Osteonecrosis of the Jaw

Abstract

Bisphosphonates are used worldwide as a successful treatment for people with osteoporosis, which is the major underlying cause of fractures in postmenopausal women and older adults. These agents are successful at increasing bone mass and bone trabecular thickness, decreasing the risk of fracture, and decreasing bone pain, enabling individuals to have better quality of life. Bisphosphonates are also used to treat multiple myeloma, bone metastasis, and Paget's disease; however, bisphosphonate treatment may result in negative side effects, including osteonecrosis of the jaw (ONJ). ONJ involves necrotic, exposed bone in the jaw, pain, possible secondary infection, swelling, painful lesions, and various dysesthesias, although less-severe cases may be asymptomatic. First-generation bisphosphonates, which do not contain nitrogen, are metabolized into a nonfunctional, cytotoxic analogue of adenosine triphosphate and cause osteoclast death by starvation. Second-generation bisphosphonates are nitrogen-containing agents; these inhibit osteoclast vesicular trafficking, membrane ruffling, morphology, and cytoskeletal arrangement by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. Physicians treating older adults with osteoporosis and cancer should work together with dental practitioners, pharmacists, and other clinicians to inform individuals receiving bisphosphonates of their possible side effects and to suggest precautionary steps that may minimize the risk of osteonecrosis, particularly of the jaw. These include practicing good oral hygiene; scheduling regular dental examinations and cleanings; and cautioning people who are scheduling treatment for periodontal disease, oral and maxillofacial therapy, endodontics, implant placement, restorative dentistry, and prosthodontics. Recommendations for management of people with ONJ include an oral rinse, such as chlorhexidine, and antibiotics.

Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study

“…17 Recent studies have shown that BPs have side effects, such as MRONJ, atrial fibrillation, provocation of an acute-phase response, and renal failure. 18 MRONJ is one of the most important complications and was first reported in 2003. 1 More recently, MRONJ has been noted more commonly, but its true incidence remains undetermined.…”

Resolution of Localized Chronic Periodontitis Associated with Longstanding Calculus Deposits

“…In this case, a history of treatment with alendronate and concern about the potential risk of ONJ following extraction of tooth 47 had motivated the patient to investigate alternative treatment options. Alendronate has an estimated terminal skeletal half-life of 10.9 years, so its benefits and any side effects are prolonged [50]. While the risk of developing ONJ in patients who have taken relatively low oral doses of antiresorptive agents appears to be low, treatment plans that minimize periosteal and intrabony exposure or disruption are preferred [22].…”

“Bisphosphonates: Possible Modes of Action and Implications for Dental Implant Treatment. A Review of the Literature”

“…Those patients receiving oral bisphosphonates appear to represent a group with a much smaller risk of developing BRONJ, however with increasing numbers of reports of cases of BRONJ in these patients it would appear that dentoalveolar surgery is a specific risk factor [146,[190][191][192][193][194].…”