Bone health

Look beyond the usual suspects for ONJ-causing medications


While osteonecrosis of the jaw (ONJ) is usually associated with osteoporosis therapies such as bisphosphonates, a new Australian study has revealed links to other medications such as immunomodulators and anti-angiogenic drugs.

A review of more than 419 reports of medication-related ONJ in the TGA’s adverse reaction database found that most were related to denosumab (221) and bisphosphonates (163) such as zoledronic acid and alendronate.

Some medications without anti-resorptive properties such as glucocorticoids and antineoplastic agents that were taken concurrently with denosumab or bisphosphonates were also linked to ONJ reports.

However there were also 14 reports implicating other agents that directly or indirectly affect bone turnover. These included adalimumab, etanercept, methotrexate, rituximab and lenalidomide.

The study authors, from Melbourne University, noted that several of these drugs were indicated for RA and other auto-immune conditions which may be characterised by high levels of proinflammatory cytokines that lead to increased bone resorption, progressive joint destruction, osteoporosis and increased fracture risk.

RA may be accompanied by other comorbidity risk factors for ONJ, such as osteoporosis, as well as having a direct adverse effect on the jaw, they said.

“All these factors coupled with the use of anti-resorptives, traditional agents or targeted therapies that can cause immunosuppression and affect bone turnover, compound a patient’s risk for medication-related ONJ,” they wrote.

“The results of this analysis of medications that have effects on bone turnover provide possible drugs for consideration for clinicians in the pathogenesis of medication-related ONJ,” they concluded.

And while further research is needed to verify the implicated drugs and their association with ONJ, they said the study “highlights the importance of considering all possible drugs that elevate a patient’s medication-relate ONJ risk.”

The findings are published in the British Journal of Clinical Pharmacology.

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