Bisphosphonate-Related Osteonecrosis of the Jaw Around Dental Implants

Bisphosphonate is the collective name for compounds in which the backbone of pyrophosphoric acid, a P-O-P structure, is converted to chemically stable P-C-P, and this structure shows the affinity of bisphosphonate for bone hydroxyapatite in the body (Fleisch et al. 2002). Administered bisphosphonate preparations (BPs) transfer to and deposit in bone, exhibiting a bone resorption-inhibitory effect. The chemical structure of the side chain bound to the carbon atom of P-C-P markedly influences bisphosphonate activity, and, particularly, side chains containing nitrogen molecules not only markedly increase the affinity for HA but also bone resorption-inhibitory activity (Migliorati et al. 2005). Because of this potent bone resorption-inhibitory effect, BPs are the first-choice treatment for osteoporosis worldwide (Russell et al. 2007), and their efficacy for malignant tumorassociated hypercalcemia (Body et al.1999), ostealgia complicating bone metastasis of solid tumors (Hortobagyi et al. 1998), and multiple myeloma accompanied by bone destruction (Berenson et al. 1996) has been shown. Adverse effects of BPs were previously considered to be relatively mild, such as digestive symptoms induced by oral preparations and fever induced by injections (Berenson et al. 1996), but the association of BPs with osteonecrosis of the jaw has been frequently described since Marx (2003) initially reported it (Ruggiero et al. 2004; Marx et al. 2005; Khosla et al. 2007) Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is clinically diagnosed when the following 3 conditions are met: 1) current or previous treatment with BPs, 2) persistent exposure of necrotized bone in the maxillofacial region for 8 weeks or longer, 3) no past medical history of radiotherapy for the jaw bone (AAOMS 2007; Ruggiero et al. 2009). BPs inducing BRONJ mostly contain nitrogen (NBPs). BRONJ frequently develops in patients under NBP treatment upon dental treatment, such as tooth extraction, implant placement, and surgical periodontal treatment accompanied by bone invasion, and inflammatory diseases, such as periodontal disease and abscess (Ruggieri et al. 2009; Vahtsevanos et al. 2009; Yoneda et al. 2010). BRONJ shows poor responses to the standard treatment for common osteomyelitis of the jaw, such as curettage/resection of necrotized tissue and antimicrobial drugs, and its intractability is the most serious problem.