Bone mineral density and other risk factors for fractures in men on ADT


Clinical guidelines issued by the National Comprehensive Cancer Network recommend that prostate cancer patients being treated with androgen deprivation therapy (ADT) — either alone or in combination with radiation therapy — should be screened for osteoporosis and treatment to prevent deterioration of bone health associated with a decline in bone mineral density. However, there is a perception that all patients who are being treated with ADT should receive drugs like zoledronic acid or denosumab to manage risk of fractures, and that is not actually what is recommended by current guidelines at all.

Patients on ADT can, most certainly, have a significant decline in their bone mineral density within the initial 6 to 12 months after starting on hormone therapy. It is therefore strongly recommended that all men on ADT receive appropriate tests before and during the course of ADT to monitor their bone mineral density. Those patients who exhibit evidence of a significant decline in their bone mineral density are the ones who have an elevated risk for fractures and who therefore do, most certainly, need some form of therapy to manage (and ideally reverse) this decline in bone health.

The Fracture Risk Assessment Tool (FRAX®) is an algorithm developed by the World Health Organization and designed to predict the 10-year risk of either a hip fracture or any other major fracture. The algorithm is carefully structured to take account of many factors that are relevant to risk of fractures (including nationality and race). As an example, here is a link to the FRAX algorithm for Caucasian patients in the USA. This is different to the link to the algorithm for African-Americans in the USA or to the algorithm for men in France. What all men need as part of a bone health evaluation is a DXA bone density test designed to tell them their t score.

A good t score is +1.0 or higher. A t score between +1.0 and –1.0 indicates a normal bone mineral density. If you have a t score between –1.0 and –2.5 you have “thin bones” (osteopenia). If you have a t score of anything less than –2.5 (e.g., –2.7 or –3.1), it suggests that you have osteoporosis (porous bones).

Dhanapal and Reeves recently carried out a retrospective chart review of men being treated with LHRH agonists at their institution. They used the FRAX algorithm to calculate the 10-year fracture risk in a total of 174 patients, and obtained the following results:

  • The average (mean) age of the patients was 65.5 years.
  • 125/174 men (71.8 percent) had AJCC stage II prostate cancer.
  • The average (mean) time on LHRH agonist therapy was 13.8 ± 18.1 months (based on 170/174 men being treated with leuprolide acetate).
  • 99/174 patients (57 percent) had ≥ 2 risk factors for developing osteoporosis.
  • Among these 174 patients
    • The 10-year risk for a major facture increased from 4 percent to 5.6 percent after the initiation of ADT (P ≤ 0.001).
    • The 10-year risk for a hip fracture rose from 1.3 percent to 2.2 percent (P ≤ 0.001).
  • Compliance with national guidelines indicated that
    • Only 9 percent of patients had received DXA testing.
    • Only 5 percent of patients were taking necessary calcium supplements.
    • Only 3 percent of patients were  taking necessary vitamin D supplements.

There are three key learnings here for the prostate cancer community:

  • All patients prescribed ADT for prostate cancer should be receiving baseline and follow-up DXA testing to assess their 10-year risk for major fractures.
  • All patients prescribed ADT for prostate cancer should also be aware of their normal calcium and vitamin D levels and take supplements as appropriate (after discussion with their doctors).
  • Although ADT does significantly increases the risk for fractures among the prostate cancer population, the absolute increase in risk is relatively small (only 1.6 percent for all fractures and only 0.9 percent for hip fractures).

These data suggest that a lot more patients taking ADT need to be aware of their bone health and their risk for fractures (and get appropriate DXA tests). However, the numbers of men who actually require drugs like zoledronic acid  or denosumab to prevent bone fractures may not be anything like as high as some literature might suggest.

4 Responses

  1. Hi Mike.

    My last bone scan (7/28/11) showed no cancer but a unexplained rib fracture. I had a bone density test done on 8/11/11. My last bone density test showed thin bones. So far I have received one Zometa IV back in April. My ribs hurt all the time now.

  2. I think it is important to distinguish men with bone mets vs. those without as denosumab is only approved for those with mets and not yet approved for men with osteoporosis.

  3. Hey Bill … Even for you there is going to come a time when Iron Man training schedules and personal bone density levels may not be 100% compatible!

    :O)

  4. A few items need to be considered:

    a. Is there proof that bisphosphonates limit fractures in men?
    b. Some believe DEXA is too easily fooled by arthritic conditions and QCT should be used.
    c. Very little attention has been given to strontium citrate for bone management. My DEXA values have increased over several years.
    d. The role of exercise while on ADT cannot be ignored.

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