Bisphosphonates protect from toxic effects of radiation treatment, leukemia

Used in treating fragile bones, bisphosphonates may prevent leukemia – an after-effect of radiation therapy

Bisphosphonates — the drugs used to treat fragile bones– can help patients get rid of the toxic effects of radiation treatment.

Many patients, who exposed radiation as part of their cancer treatment, were later found to be developing a form of blood cancer called leukemia. Use of bisphosphonates could protect them from developing this often deadly form of cancer, Alexandra Miller, a scientist at the Armed Forces Radiobiology Research Institute in Bethesda, Maryland,  US researchers said.

Two compounds in a class of drugs called bisphosphonates delayed and in some cases prevented mice exposed to high doses of radiation from developing leukemia, a common long-term side effect of radiation exposure, the researchers said.

The compounds studied are bisphosphonates known as ethane-1-hydroxy-1, 1-bisphosphonate or EHBP, which Miller said is chemically similar to Procter & Gamble’s osteoporosis drug Didronel or etidronate.

The other was an experimental drug called CAPBP, which is similar to Roche’s Boniva or ibandronate.

Alexandra Miller has been studying ways to protect military personnel and astronauts from radiation exposure.

While presenting the findings at the American Association for Cancer Research in Denver, Colorado, she said bisphosphonates could also help cancer patients treated with radiation who later develop leukemia as a side effect of their treatment.

She picked the drugs because of studies in humans that suggest bisphosphonates may help prevent cancer from spreading to the bone. They also have been shown to remove uranium from the body.

Miller exposed lab mice to radiation strong enough to cause leukemia. The mice were injected with one of the two compounds.

Typically, mice exposed to radiation developed leukemia and died 92 to 110 days later.

“With the drug, the animals were developing leukemia too, but it took much longer, 150 to 170 days,” Miller said .

The total number that actually developed leukemia was significantly lower with both of the drugs. All of the untreated animals developed leukemia after radiation exposure, but only about half did in the treated group.

However, many more studies would be needed before the drugs could be used in humans, but she thinks the compounds show promise as a way of addressing one of the most toxic side effects of radiation exposure.

What are bisphosphonates?

Bisphosphonates are used clinically for the treatment of osteoporosis, osteitis deformans (Paget’s disease of the bone), bone metastasis, multiple myeloma and other conditions of bone fragility.

In osteoporosis and Paget’s, alendronate and risedronate are the most popular first-line drugs.

High-potency intravenous bisphosphonates have shown to modify progression of skeletal metastasis in several forms of cancer, especially breast cancer.

Other bisphosphonates, medronate and oxidronate are mixed with radioactive technetium and are injected for imaging bone and detecting bone disease.

More recently, bisphosphonates have been used to reduce fracture rates in children with osteogenesis imperfecta.

Common bisphosphonates and their brand names

Etidronate (Didronel) 

Clodronate (Bonefos, Loron)

Tiludronate (Skelid)

Pamidronate (APD, Aredia)

Neridronate

Olpadronate

Alendronate (Fosamax)

Ibandronate (Boniva)

Risedronate (Actonel)

Zoledronate (Zometa, Aclasta)