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Commonly used osteoporosis treatment may boost lung immune response

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Bisphosphonates, a common osteoporosis therapy, may help prevent respiratory infections, according to new research.

A popular osteoporosis therapy stimulates immune cells in the lungs, which form one of the first lines of defense against viruses, according to researchers at the Garvan Institute of Medical Research.

In animal studies, bisphosphonate therapy spurred lung macrophages to develop a greater response to an immunological assault.

The findings reported in eLife confirm prior clinical trial findings showing those using bisphosphonates had a decreased risk of pneumonia.

“Bisphosphonates are a safe and effective class of osteoporosis medication that have been the standard-of-care since the 1990s to prevent loss of bone and reduce the risk of fractures,” said senior author Professor Mike Rogers.

“We have found an added potential benefit for this treatment – it can boost the immune function of lung cells, which may protect against respiratory infection and pneumonia. Our evidence warrants further investigation that we hope will lead to improved health outcomes in the older population, who are at higher risk of pneumonia and osteoporosis.”

Boost to immunity

Respiratory infections, such as acute pneumonia, are a leading cause of infection-related death around the world. Due to the fact that our ability to create protective immune responses against infectious diseases diminishes with age, they are increasingly affecting the elderly population.

“Previous clinical trials have suggested that bisphosphonate treatment has a beneficial effect in protecting against pneumonia,” added Dr Marcia Munoz, first author of the paper. “In our research we wanted to understand why that is.”

Using mouse models, the researchers administered a bisphosphonate known as zoledronic acid and monitored how the medicine traveled through the body of the animals.

“It was previously thought that bisphosphonates act only in the bones, but we found that they are taken up by macrophages in the lung, which are ‘first responder’ cells that can recognise, engulf and destroy a pathogen during an immune response,” said Dr Munoz.

The team next assessed the immunological response of their model by exposing them to LPS, a chemical present on the surface of bacteria that is often used to assess response to infection. In comparison to mice that had not received the medication, they discovered that even after a single dose of bisphosphonate, the activity of macrophages in the lungs had increased.

“In the skeleton, bisphosphonates prevent bone loss by blocking an enzyme needed by the specialised cells that break down bone,” added PhD student Emma Fletcher, second author of the paper. “In immune cells in the lung, we found that the treatment blocked the same enzyme, which in this case enhanced the immune response.”

Potential impact for health

“Macrophages are one of the first lines of defence against infection,” said Professor Rogers. “If bisphosphonates are ramping up the ability of these cells to respond when they encounter a viral or bacterial infection, a stronger initial immune response may help clear the infection and lead to a better outcome. This is what we will be investigating next.”

In Australia alone, 3.7 million people over the age of 50 are at high risk of fracture and may benefit from bisphosphonate therapy. However, only about a third of those who should be receiving the medicine based on current clinical criteria are now being treated.

“This leaves a large population of individuals who may receive additional benefits,” Professor Rogers added. “Clinical trials are warranted to determine whether bisphosphonates, aside from preventing bone loss, can provide protection against pneumonia infection in vulnerable individuals, for instance, patients in aged care homes.”

Source: 10.7554/eLife.72430

Image Credit: Getty

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