ADT, bone architecture, and “virtual bone biopsies”

A recent study reported in the Journal of Clinical Endocrinology and Metabolism has been receiving a good deal of media attention, although its immediate clinical importance wouldn’t appear to be particularly high.

Hamilton et al. have used a sophisticated new type of CT scan to assess changes in the bone structure among a cohort of 26 men with non-metastatic prostate cancer during their first year of treatment with ADT.

Their results were as follows:

  • The men had an average age of 70.6 ± 6.8 years.
  • After 12 months of ADT
    • Total volumetric density at the distal radius was reduced by 5.2 ± 5.4 percent.
    • Total volumetric density at the distal tibia was reduced by 4.2 ± 2.7 percent.

The “distal radius” means the lower end of the thinner of the two bones in your arm below the elbow. The “distal tibia” refers to the lower end of the larger and stronger of the two bones in your leg below the knee.

The authors go on to explain that these reductions in bone density are associated with reductions in cortical volumetric bone mineral density (BMD) and trabecular density. They further note that total testosterone levels were independently associated with total and corrected cortical volumetric BMD at the tibia. Estradiol levels were not. 

Cortical bone is the hard, outer shell of the bone, whereas trabecular bone is the softer, “spongy” inner bone structure. Hamilton and her colleagues have explained that the new type of CT scan (high-resolution peripheral quantitative CT) allowed them to take what they have described at “virtual bone biopsies” as a method to carry out this research.

The authors conclude 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.”

From a scientific viewpoint, this study certainly adds to our understanding of bone fragility in men receiving ADT. However, from a clinical viewpoint, the whole objective of ADT is to reduce testosterone levels in order to delay prostate cancer progression, so it is hard to see that this study will actually add a great deal to the way we can treat advanced prostate cancer at the present time. We suspect that the term “virtual bone biopsy” gave the study media attention, although it is not likely that most men on ADT will be receiving this type of CT scan in the near future.

Men receiving long-term ADT are generally advised to receive treatment with bisphosphonates to prevent bone loss. Of course bisphosphonate therapy itself is associated with some risk for side effects, so a careful risk-benefit analysis needs to be carried out for each individual patients to assess the most appropriate form of preventive therapy.

For additional commentary on this paper, see reports on the  MedPage Today and the HealthDay web sites (among others).

2 Responses

  1. As I understand it, as we age we develop more brittle bones as part of the natural process of ageing. If that is so does anyone have any idea what a “normal” rate of microarchitectural decay might be?

    I’m sure it is not of the order demonstrated in this study, but it might be interesting to know.

  2. Terry’s point is well-taken, but I don’t have a ready answer.

    I’m glad this study is getting attention, because it is drawing attention to an issue — accelerated bone density loss due to ADT — that has been known at least since before October 1998 yet is probably still under-appreciated by doctors prescribing ADT and their patients. I’m basing the “1998” statement on the first issue of the PCRI Insights newsletter, which had a one-page piece on bone integrity and prostate cancer, highlighting it way back then as “A Critical Issue in PC Management” and covering the essentials. However, the January 1999 issue of Insights provided great detail and graphics in a six-page article, including mention of a qCT scan. A few years later, the 2002 edition of A Primer on Prostate Cancer presented a detailed review of the merits of the DEXA scan versus the qCT scan, concluding that the qCT scan was superior. As I recall it, the qCT scan is better at assessing trabecular bone, which is more important in assessing bone mineral density (BMD) than cortical bone.

    I became aware of the need for bone density protection early, but my talented urology team was just not comfortable with this as a threat and with their own knowledge. That’s one of the two main reasons they referred me to a medical oncologist to take over my care. (The other reason being that I wanted to add Proscar to the two-drug ADT regimen they had me on, and they were uncomfortable with that.)

    I commenced use of Fosamax on 9/16/200 and was on it continuously until I switched to Boniva a few years ago. My bone density in 2000 was in the osteopenia range, and over the years, the L4 vertebra was well into the osteoporosis range. However, I’m delighted to report that my last DEXA scan averaged out with normal density, and even the L4 vertebra had improved to being well within the osteopenia range. In April, coincident with going off Lupron (and bicalutamide), I ceased taking Boniva. Throughout this period I took calcium and vitamin D3. I was tested periodically for levels of both. For me, bone mineral density was a very important issue an ADT patient from the early days. It’s important to foster awareness of this issue.

    This is a long way of saying that I’m curious whether there is something new in this paper. I’m wondering whether “the new type of CT scan (high-resolution peripheral quantitative CT) is actually a real improvement or different from the qCT that has been available for many years. I suspect it is. Can anyone clarify that? One difference is that my BMD scans look at the lower spine and hip; in contrast, the new scan was used in the paper to look at the arms and legs.

    It is also not clear from the abstract whether the patients took calcium and vitamin D3, as well as other helpful trace elements associated with sound BMD protection, and whether they engaged in regular weight bearing and strength exercise. Those tactics are considered important if not essential in protecting bone mineral density.

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