Androgen deprivation fracture risk

EXPERTS have disagreed on the risks and benefits of androgen deprivation therapy, after US researchers called for the increased use of bisphosphonates to prevent bone loss in men being treated for prostate cancer.

The Canadian research, published in JAMA, found that bisphosphonate prescription rates for men who were being treated with androgen deprivation therapy (ADT) were low, even for those at increased risk of fractures. (1)

Professor Mathis Grossmann, associate professor of endocrinology at the University of Melbourne and Austin Health, told MJA InSight that this low prescription rate of bisphosphonate highlighted “a fairly alarming treatment gap” that applied to Australian practice.

“ADT causes an accelerated rate of bone loss, and patients can lose up to 10% of their bone density in the first year of treatment alone, which increases their risk of fracture. It’s a significant side effect.”

Professor Grossmann said there had been some encouraging research on the use of bisphosphonates, which included a study published in Urology that found the drugs were associated with a 70% reduction in hip fracture rate among men receiving ADT. (2)

In Australia, wider prescription of bisphosphonates was limited by the Pharmaceutical Benefit Scheme (PBS), which only subsidised the medication for patients with a bone marrow density T-score of less than –2.5.

However, Professor Grossmann said there was not yet sufficient evidence on the impact of bisphosphonates to justify changing the PBS guidelines to cover all patients.

“Instead we should be optimising [our use of] the existing PBS criteria to make sure that patients who are eligible for bisphosphonate receive it.”

Professor Grossmann contributed to the development of standardised management guidelines aimed at mitigating bone loss in men undergoing ADT. These included smoking cessation, weight-bearing physical exercise, increasing calcium and vitamin D levels, and regular assessment of bone density. (3)

He also emphasised the need to address what he saw as the “overuse” of ADT. “For example, ADT is being given to men who are already at risk of osteoporosis. And because therapy further decreases bone density, ADT can do more harm than good in some patients.”

However, Professor Paul de Souza, medical oncologist at Liverpool Hospital and foundation professor of medical oncology at the University of Western Sydney, argued that the adverse side effects of ADT were “a minor facet of managing men with metastatic prostate cancer”.

He said bisphosphonate prescribing “needs to be put into context, because it doesn’t prolong the life of patients, whereas [ADT] does”.

“In my experience, about 95% of prostate cancer patients benefit from ADT, because it extends their life, improves their function, allows them to work and contribute to society.”

Loss of bone density in patients was “a small price to pay for being able to control prostate cancer”, Professor de Souza said.

The JAMA research assessed the rates of bisphosphonate prescriptions in 35 487 Canadian men aged 66 years or older, who were diagnosed with prostate cancer during 1995‒2012 and received ADT.

The authors wrote that the low levels of bisphosphonate prescriptions for these men highlighted “limited awareness among clinicians regarding optimal bone health management”.

They said although the ideal rate of bisphosphonate use in men taking ADT was unknown, it was reasonable that most men with a history of osteoporosis or fracture “should be taking a bisphosphonate or other effective bone medication”.

Dr Handoo Rhee, research fellow in the department of urology at Brisbane’s Princess Alexandra Hospital, told MJA InSight the research highlighted the broader issue of managing the adverse effects linked to ADT, which was included in a recent literature review he coauthored. (4)

“Along with osteoporosis, our study found that ADT was associated with a number of other adverse side effects, including depression, hot flushes, high cholesterol and cardiovascular disease, sexual dysfunction, lethargy, musculoskeletal problems and diabetes”, he said.

Considering the risks, Dr Rhee believed it was important that patients taking ADT had their treatment managed and monitored by a multidisciplinary team in order to minimise the wide range of potential side effects.

Professor de Souza agreed that such an approach was beneficial, saying this was already being put into practice in the form of “virtual and physical team meetings between radiologists, oncologists and urologists where patient progress and treatment is discussed”.
 

1. JAMA 2014; 312: 2285-2286
2. Urology 2013; 81: 1010-1017
3. MJA 2011; 194: 301-306
4. BJUI 2014; Online 18 October

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