Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw: Is there a diverse relationship of amino- and non-aminobisphosphonates?

Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid

“…4,23 Recent studies have demonstrated that the decrease in geranylgeraniol production by ZA-treated cells significantly reduces cell proliferation and migration, as well as inducing cell apoptosis. 23,24 Conversely, increased cell proliferation rates have been observed for LLLT-treated cells at both energy doses selected for use in this study (0.5 and 3 J/cm 2 ), confirming that this type of therapy, at specific parameter levels, may biomodulate cell functions.…”

“…2 Bisphosphonates are analogues of pyrophosphate that are prescribed for diseases associated with intense bone resorption, such as Paget's disease, multiple myeloma, osteoporosis, bone tumours, and metastasis. [3][4][5] Bisphosphonate-induced osteonecrosis has been characterized as a necrotic bone area in the oral cavity that persists for longer than 8 weeks without a history of head and neck radiotherapy. 3 Previous studies have shown that bisphosphonates decrease the proliferation rate of endothelial cells, interfering with the tissue repair process.…”

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

“…Zoledronic acid is more frequently implicated in ONJ, possibly because of its strong antiresorptive potential [48]. Use of the intravenous route probably results in rapid tissue accumulation [49,50] and is more deleterious than the oral route. It is noteworthy in this respect that no cases of ONJ occurred in a series of 3105 osteoporotic patients treated for 3 years with 5 mg of zoledronic acid once a year, a dose ten-fold lower than that used to treat metastatic bone disease (4 mg monthly) [51].…”

New Experimental Therapies Targetting Breast Cancer Cell

“…Non-nitrogen containing BPs (non N-BPs) act by forming non hydrolysable ATP-analogues and are less effective than nitrogen-containing BPs (N-BPs) in inhibiting bone metastasis (Roger et al, 2003). However, Zoledronate treatment of patients are reported to induce toxic side effect characterised by osteonecrosis of the jaw while non N-BP did not produce this effect (Van den Wingaert, 2006;Diel et al, 2007). N-BPs, such as zoledronate, act on the mevalonate pathway, inhibiting the farnesyl diphosphate synthase (FPP) and thereby depleting the cells of the farnesyl (FPP) or geranylgeranyl (GGPP) diphosphate isoprenoids (Roelofs et al, 2006).…”

“…Indeed, the esterified functions seem to be important for the BPs distribution within the systemic system and less for local injection (subcutaneous tumors) since the two N-BPs studied both inhibit D3H2LN xenograft growth. Of note, N-BPs induced osteonecrosis of treated patients (Diel et al, 2007) …”