Medicines

‘Remarkable’ findings for bisphosphonates


Bisphosphonates have been found to significantly reduce in-hospital mortality independent of age, sex or comorbid disease burden, in a large retrospective study of critically ill patients.

The findings, published in The Journal of Clinical Endocrinology & Metabolism  have been described as “remarkable” by co-author and Director of Clinical Translation and Advanced Education at the Garvan Institute, Professor John Eisman.

“We think it’s extremely important and there does need to be further research to see whether this is not an association, but an effective treatment,” he told the limbic.

“The findings are quite remarkable, and it means you need to do the randomised control trial and we’re trying to get that happening.”

The retrospective hospital-based analysis included 7830 critically ill patients between 2003 and 2014 who were treated at a tertiary referral hospital ICU. Researchers investigated the relationship between preadmission bisphosphonate use and clinical outcome in critically ill patients.

Professor Eisman said that while bones are the main reservoirs of calcium, they also acted as a “waste dump” for toxic substances.

Critically ill patients – particularly those who are immobile for extended periods – lose bone, and this could also lead to the release of the toxic substances into the body, causing systemic inflammation and further complications.

Bisphosphonates are proven and potent inhibitors of bone resorption, leading to the hypothesis this may extend to preventing release of these toxic substances.

“The idea that bisphosphonates could stop this release is very interesting,” he said.

He conceded that there are inherent weaknesses in any retrospective design, but said the findings in this latest study were clinically and therapeutically relevant enough to warrant significant investment in further research and trials.

“First, bisphosphonates have proven relatively safe treatment profile, and are immediately available for therapeutic trials in critically ill patients,” the authors wrote.

“Second, critically ill patients suffer bone loss, which in itself merits consideration for bisphosphonate treatment.

“Third, survival benefit was more pronounced among patients with greater comorbid disease burden, suggesting added benefits in patients at greatest risk of bone loss.

“Fourth, the serial clinical CT scan results suggested attenuation of bone loss could be implicated in survival benefits. Thus, although bone is seldom considered as directly relevant in critical illness, our findings suggest “bone failure” may be one facet of multi-organ failure, with potentially severe consequences but amenable to therapeutic intervention.”

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