PDF: Biomarkers to predict the onset of biphosphonate-related osteonecrosis of the jaw: A systematic review

Bisphosphonates (BPs) are analogues of pyrophosphate which have potent inhibitory effects on bone resorption. These bone targeted-therapies are widely used for osteoporosis and different types of cancers. BPs have been proven to reduce the risk of skeletal-related events (SREs), delay the onset of SREs and ease bone-related pain.

There are two main classes of BPs from a chemical standpoint: non-nitrogen containing bisphosphonates (i.e. etidronate and clodronate) and nitrogen containing bisphosphonates (nBPs); this last group is subdivided into the alkyl-amino bisphosphonates (i.e. pamidronate, alendronate and ibandronate) and the heterocyclic nitrogen containing bisphosphonates (i.e. risendronate and zolendronate).

Non-nitrogen containing bisphosphonates are metabolised in the cells to an adenosine triphosphate derivative that impairs osteoclast function and induces osteoclastic apoptosis. 

In the case of nBPs, the bone-targeting pharmacokinetic properties of these drugs cause selective inhibition of farnesyl diphosphatase synthase and a reduction in the production of prenylated forms of guanosine thiphosphate biding proteins (GTPases) causing an inhibition of osteoclast activity and generating an increase in bone turnover and bone mineral density (BMD).

The present review suggests that no useful markers are currently available to evaluate BRONJ risk. 

Nevertheless, the present paper indicates that a paradigm shift from bone turnover biomarkers to angiogenesis and endocrine markers could shed light on this search.

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