A common treatment for prostate cancer known as androgen deprivation therapy (ADT) is linked to bone decay, according to new research from the University of Melbourne in Australia.

Lead author Dr Emma Hamilton and senior author Dr Mathis Grossmann and colleagues carried out the study which was published online in the The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism on 29 September.

Across the world, prostate cancer is the second most common male cancer, with around 600,000 patients in the US being treated for it with ADT, which suppresses or blocks the male hormones that drive the cancer.

Previous studies have already suggested that prostate cancer patients undergoing ADT may experience reduced bone mineral density and greater bone fragility, but what remains uncertain is the structural basis of this change.

In this first study to examine what happens to bone structure in patients undergoing ADT, the researchers used a new technology called “virtual bone biopsy”. They discovered that ADT was linked to structural decay of both cortical (the compact, hard outer shell of bone) and trabecular bone (the spongy interior tissue made of tiny needle-like pieces).

The new technology, which essentially produces a 3D image from scans taken with a high resolution peripheral quantitative computed tomography (HR-pQCT) machine, allowed the researchers to assess the microarchitecture of patients’ bones.

“We found ADT is associated with structural decay of corticol (hard outer shell) and trabecular (spongy inner mesh) bone,” said Hamilton and Grossmann in a statement issued by the Endocrine Society.

“This technology may be a useful test in predicting fractures in patients, but further research is needed in identifying individuals at greatest fracture risk as well as optimal therapeutic strategies,” they added.

For the 12 month study, they followed 26 men of average age 70 years with nonmetastatic prostate cancer as they underwent ADT. At several points during the year, they assessed the patients’ sex hormone levels, markers of bone turnover and bone mineral density, and took “virtual bone biopsies” using the new technology.

The results showed:

  • After 12 months of ADT, there was a total volumetric density reduction of 5.2 ± 5.4% at the distal radius (a bone in the forearm), and 4.2 ± 2.7% at the distal tibia (the shinbone).
  • This was found to be due to a decrease in both cortical volumetric BMD and trabecular density, after adjusting for trabecularization of cortical bone.
  • Trabecular density was reduced due to a reduction in trabecular number (the number of needle-like pieces in a given length of spongy tissue) at both sites.
  • The presence of an independent link between total testosterone (but not estradiol) and volumetric BMD at the tibia.

Estradiol is the female sex hormone estrogen, which is present in men to a lesser extent. A reduction in this hormone has been linked to reduced bone mineral density, but the researchers found no link between reduced bone density and estradiol in this study.

They concluded, therefore that:

“Sex steroid deficiency induced by ADT for prostate cancer results in microarchitectural decay.”

“Bone fragility in these men may be more closely linked to testosterone than estradiol deficiency,” they added.

“Structural Decay of Bone Microarchitecture in Men with Prostate Cancer Treated with Androgen Deprivation Therapy.”
E. J. Hamilton, A. Ghasem-Zadeh, E. Gianatti, D. Lim-Joon, D. Bolton, R. Zebaze, E. Seeman, J. D. Zajac, and M. Grossmann
J Clin Endocrinol Metab published online 29 September 2010.
DOI:10.1210/jc.2010-0902

Sources: The Endocrine Society, Ratoc Systems Engineering: 3D bone morphometry.

Written by: Catharine Paddock, PhD