Risk for fractures and fracture prevention among prostate cancer patients

An interesting new paper in BJU International has provided us with a somewhat different perspective on which patients with prostate cancer do and do not need preventive therapy (e.g., zoledronic acid/Zometa, dasatinib/Xgeva) to minimize risk for bone fractures.

Jefferies et al. report data from the PHONIC Collaborative in the UK. Their goal was to explore in greater detail the risk for fractures among men in the UK who were diagnosed with prostrate cancer and the impact of treatment with androgen deprivation therapy (ADT) on that risk.

To to this, they use data from the national Hospital Episodes Statistics (HES) database from 2004 through 2008. This database includes all information patients admitted to National Health Service (NHS) and NHS-funded hospital admissions in England.

Here is a summary of what they found:

  • The total number of male hospital admissions for fracture during the study period was 228,852 men (the so-called “background population”).
  • 8,902 patients were identified as having had prostate cancer and an admission to hospital with a fracture in the study time frame.
  • 3,372/8,902 patients (37.8 percent) were clearly being treated with ADT at time of hospital admission.
  • 5,530/8,902 patients (62.2 percent) had no indication that they were receiving ADT at time of admission.
  • The risk of a fracture requiring hospitalization was
    • 0.58 per 100 person years in the background population
    • 1.12 per 100 person years when a man with prostate cancer is treated with ADT
    • 1.41 per 100 person years when a man with prostate cancer is not being treated with ADT
  • The absolute increase in risk of hospitalization with a fracture for a man with prostate cancer on ADT is
    • 0.83 per 100 person years compared to all men hospitalized for fracture
    • 0.29 per 100 person years compared to men with prostate cancer not receiving ADT

The authors conclude that, at least in the UK

there is a small but statistically increased risk of fracture in men who have been treated with ADT. Men with prostate cancer with or without ADT are at an increased risk of fracture compared with the background population.

They go on to recommend that

if bone health is to be taken seriously in men with prostate cancer … all these men should be risk assessed … rather than singling out men with ADT as all men with prostate cancer have an increased risk of fracture …

and that the men with prostate cancer who are being treated with ADT are at slightly greater risk than those not receiving such treatment.

This recommendation appears to correlate well with recent recommendations that not all men receiving ADT need to start preventive therapy for bone loss immediately. It ties the need for preventive therapy much more closely to other factors that are highly relevant to fracture risk (i.e., things like bone density, osteoporesis, and osteopenia).

Tests used around the world to assess fracture risk include the FRAX and the qfracture tests to assess fracture risk and the DXA or DEXA (dual energy x-ray absorptiometry) test to measure bone density in the spine, the hip, or the total body. It seems likely to The “New” Prostate Cancer InfoLink that the appropriate use of such testing among men with prostate cancer who are (say) over 60 years of age or who are starting ADT is probably a lot lower than the cost of treating all those men with drugs like zoledronic acid or dasatinib, and if such testing helps us to ensure that preventive medication is being given only to those patients at meaningful risk for fractures, then that would be a good idea!

3 Responses

  1. Interesting you read this as correlating with the other recent recommendation, Sitemaster. I thought of the same recommendation re. the use of bisphosphonates as I was reading, and wondered if it flew in its face.

    If all men with PCa and especially those on ADT have an elevated risk of fracture, then prophylactic treatment seems justified. Are bisphosphonates considered prophylactic? They make the bone denser, but also more brittle. Do they increase or reduce the risk of fracture?

    Help me think this through and how it applies to using bisphosphonates!

  2. Dear Rick:

    I think you may be missing the point. No one is saying that prophylactic treatment of appropriately selected men is inappropriate. What they are saying is that just being on ADT isn’t the appropriate criterion for prophylaxis.

    The Jefferies paper is specifically saying that the criterion for prophylaxis should be risk for fractures based on clinical evidence of such risk (osteopenia, osteoporesis) whether the patient is being treated with ADT or not.

  3. Sitemaster,

    I argued here in Uppsala that all men who will go on ADT should get baseline BMD measurements. This is a long story that begins with a failure to think through the osteoporosis risk issue. At any rate the result so far is that all men scheduled to go on ADT for more than 6 months, and who satisfy certain risk factors, will get this measurement by DEXA scan. I do not know if this is sufficient, but am glad to have played some small part in the affair. Some advice is now in the latest Prostate Cancer National Guideline in Sweden. I have not yet looked at it but will do so soon.

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