Medico-legal concern raised by bisphosphonate risk

OESOPHAGEAL cancer is set to be added to the list of risks associated with the long term use of bisphosphonates, according to the findings of a UK study. (1)

Although the research, published in the BMJ, found the absolute risk of oesophageal cancer was low, two Australian experts agree that the findings could have medico-legal implications.

The study by Green and colleagues, which included nearly 3000 oesophageal cancer sufferers, found the risk of oesophageal cancer increased with 10 or more prescriptions for oral bisphosphonates and with prescriptions over about a 5-year period.

The researchers estimated that in Europe and North America, where the incidence of oesophageal cancer at age 60–79 is typically 1 per 1000 population over 5 years, the incidence with 5 years’ use of oral bisphosphonates would roughly double, to 2 per 1000.

Concern about a possible link between bisphosphonates and oesophageal cancer was first raised by a US Food and Drug Administration official in January 2009.

A number of other risks associated with long-term bisphosphonate use have gained public attention in recent years, including osteonecrosis of the jaw, atrial fibrillation, and atypical femur fractures. However the study’s authors stressed the cancer risks remained low.

Australian experts, however, have warned doctors to be cautious — for medico-legal reasons — when prescribing bisphosphonates, especially with regard to the importance of establishing which patients stand to benefit from the treatment in terms of fracture reduction.

In particular, doctors should be wary of prescribing oral bisphosphonates to patients in the absence of DXA (dual energy x-ray absorptiometry) evidence of osteoporosis or spinal fracture, said Professor Richard Prince, an endocrinologist at Sir Charles Gairdner Hospital, Perth, WA.

“…[in which case], then the risk is unacceptable and may place the prescribing practitioner at risk of a law suit for malpractice,” he said.

Professor Chris Nordin, eminent Australian endocrinologist, said it was unlikely the study findings were serious enough to contraindicate the use of bisphosphonates in people who needed them.

However, he said they had opened up a “tremendous can of worms” in terms of their use in those who did not need them.

“Anyone who is given osteoporosis drugs with no osteoporosis could sue the company,” he said. “Any risk is important, if you give people treatment with no good reason.”

The study’s findings contrast with those of another study by Cardwell and colleagues published in JAMA last month that used the same database but found no correlation between bisphosphonate use and cancer.(2)

In an editorial(3) in the same issue of the BMJ as the Green study, US epidemiologist Wysowski said the major difference between the two studies was the length of follow-up: 4.5 years in the JAMA study compared with 7.7 years in the BMJ study.

(1) BMJ 2010; 341: c4444
(2) JAMA 2010; 304: 657-663
(3) BMJ 2010; 341: c4506

Posted 6 September 2010