BERKELEY, CA (UroToday.com) - In an article recently published in the journal Osteoporosis International (April 2013), we explored the effects of starting continuous androgen deprivation therapy (ADT) on the changes in bone mineral density (BMD) in men with non-metastatic prostate cancer. The effects of supplementation with calcium and vitamin D on bone loss in these men were also evaluated.
Prostate cancer is the most common visceral cancer and second leading cause of cancer death among men. Approximately one in every two men with prostate cancer will receive ADT at some point after diagnosis, and the majority will take it for a minimum of 2-3 years.[2, 3] Although it has been shown that ADT can suppress tumour growth, delay progression of metastases, and prolong survival,[4, 5] the concurrent and marked reduction in androgen levels within the body are associated with numerous adverse effects including sexual dysfunction, metabolic side effects, and skeletal complications.
In the context of bone health, androgens such as testosterone and estrogen are vital for maintaining bone mass, extending the activity of bone-building cells (osteoblasts), and promoting the death of those involved in bone resorption (osteoclasts). Based on physiologic grounds, ADT should result in a reduction in BMD, a hypothesis corroborated by the results of our investigation.
Using a matched cohort study design, we measured BMD via dual x-ray absorptiometry (DXA) scans at baseline, and yearly over three years, comparing two groups of patients with prostate cancer, half of whom received ADT. Measurements were performed at the lumbar spine, total hip, and femoral neck. We showed that the loss in BMD was greatest in the first year following ADT initiation and at the lumbar spine. In addition, while calcium supplement use was not shown to significantly affect BMD, the use of vitamin D was associated with an increase in BMD at the lumbar spine in year one and at the hip in year 2.
In isolation, it can be argued that BMD levels and their associated decreases mean little to patients. However, the increased risk of low-trauma fractures, chiefly those at the hip and spine, are of great concern to patients and clinicians due to their excess morbidity and mortality. Given that low BMD levels have a high predictive value for subsequent fracture, clinicians prescribing or monitoring ADT should take heed of this increased risk and take steps to mitigate it.
A simple step available to clinicians is the measurement of baseline BMD (via DXA) before initiating ADT. Unfortunately, we and others have shown that clinicians do not commonly order BMD tests (or prescribe bisphosphonates for that matter) before starting ADT. A baseline BMD test enables clinicians to stratify the risk of future fracture as well as monitor BMD levels over time, allowing them to not only identify patients at high risk of future fracture, but also measure the effectiveness of prescribed treatments.
Historically, vitamin D and calcium have been prescribed to increase bone strength and reduce fracture risk, although their use in men on ADT has been variable. As shown in our study, significant increases in BMD were seen with vitamin D use, and therefore clinicians should implement this safe and simple intervention more widely. In addition, despite the lack of significant findings in regards to calcium use in our study, the effectiveness of calcium supplementation in slowing bone loss has been demonstrated in other patient populations and is recommended in major guidelines for men on ADT.[11, 12] At the same time, given the association of excess calcium with kidney stones and a possible link to cardiovascular disease, it is important to aim for no more than 1 000-1 200 mg of elemental calcium per day from all sources (i.e., both diet and supplements). To get a simple estimate of daily calcium intake, clinicians can recommend websites such as Osteoporosis Canada that feature dietary calcium calculators.[6, 13]
- López, A. M. et al. Fracture risk in patients with prostate cancer on androgen deprivation therapy. Osteoporos Int 16, 707–711 (2005).
- Meng, M. V. et al. Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Urology 60, 7–11; discussion 11–12 (2002).
- Sharifi N, Gulley JL & Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA 294, 238–244 (2005).
- Bolla, M. et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N. Engl. J. Med. 337, 295–300 (1997).
- Shahinian, V. B., Kuo, Y.-F., Freeman, J. L. & Goodwin, J. S. Risk of Fracture after Androgen Deprivation for Prostate Cancer. N. Engl. J. Med. 352, 154–164 (2005).
- Higano, C. S. Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know? Nature Clinical Practice Urology 5, 24–34 (2008).
- Lee, C. E. et al. A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy. Curr Oncol 18, e163–e172 (2011).
- Cauley, J. A., Thompson, D. E., Ensrud, K. C., Scott, J. C. & Black, D. Risk of Mortality Following Clinical Fractures. Osteoporos Int 11, 556–561 (2000).
- Johnell, O. et al. Predictive Value of BMD for Hip and Other Fractures. Journal of Bone and Mineral Research 20, 1185–1194 (2005).
- Alibhai, S. M. H. et al. Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19,079 men. J. Urol. 184, 918–923 (2010).
- Dawson-Hughes, B., Harris, S. S., Krall, E. A. & Dallal, G. E. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N. Engl. J. Med. 337, 670–676 (1997).
- Datta, M. & Schwartz, G. G. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: a critical review. Oncologist 17, 1171–1179 (2012).
- "Calculate My Calcium." Osteoporosis Canada Calcium Calculator. Osteoporosis Canada, n.d. www.osteoporosis.ca/osteoporosis-and-you/nutrition/calculate-my-calcuim/.
Gulamhusein H,a Timilshina N,a and Alibhai SMHa, b, c* as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aDepartment of Medicine, University Health Network
bDepartment of Medicine, University of Toronto
cInstitute of Health Policy, Management and Evaluation, University of Toronto
Corresponding Author: Shabbir M.H. Alibhai, University Health Network, Room EN14-214, 200 Elizabeth Street, Toronto, ON, Canada, M5G 2C4. E-mail: