Prostate Cancer: No Bones About It
Prostate Cancer: No Bones About It
Abstract & commentary
Synopsis: Do hormone-naive men with prostate cancer have low bone mineral density? Greater underlying bone loss was suggested by quantitative CT than by dual-energy X-ray absorptiometry. Suggestions for management are given.
Source: Smith M, et al. Cancer. 2001;91:2238-2245.
What happens to the bones of osteoporotic prostate cancer patients when treated with bone-depleting androgen-deprivation therapy? Therapy-related loss of bone mineral density (BMD) is not an issue normally addressed in the therapy of prostate cancer, yet all oncologists are familiar with the ravaging effects of bone metastases on patients with prostate cancer. Therefore, Smith and colleagues enrolled 41 men with locally advanced, lymph-node-positive, or recurrent prostate cancer to determine their baseline BMD. Patients with positive bone scans were specifically excluded to avoid interference with BMD calculations. In addition, patients with any medical risk factors for osteoporosis were also excluded.
BMD was evaluated by 2 methods: quantitative computed tomography (QCT) of the lumbar spine, and dual-energy x-ray absorptiometry (DXA) of the hip, lateral-lumbar spine and posterior-anterior (PA) lumbar spine. According to the QCT results, 95% of the patients had diminished BMD. Two-thirds of these patients had a T score < -2.5 consistent with osteoporosis, and one-third had a T score > -2.5 but < -1.0 consistent with osteopenia. The DXA results, on the other hand, revealed that only 14 of the men had a T score < -1.0 at 1 or more of the 3 skeletal sites, with only 2 of these patient’s scores < -2.5.
COMMENT by Kenneth W. Kotz, MD
T scores, expressed in "standard deviation units," are determined by taking the difference between the calculated BMD and the BMD of a 30 year old (same gender and race) and dividing by the standard deviation of the mean. A patient with a BMD that is normal (ie, the same as the mean) would have a score of 0, with positive and negative scores representing above and below normal results, respectively. Z scores are formulated the same way as T scores but the calculated BMD is compared with an age-specific standard rather than the peak young adult standard. The average Z score in this study (as determined by QCT) was -0.7, suggesting at most a minimal decrease compared with age-matched controls. As a general rule, T scores of -1 to -2 and below -2 are associated with a doubling and quadrupling, respectively, of the risk of a fracture.
The title of this study is "Low Bone Mineral Density in Hormone-Naive Men with Prostate Carcinoma." This would appear to be the case when looking at the QCT results as presented in this study when compared with young adult males (mean T score -2.8 ± 1.1). However, when compared with age-matched controls, the mean Z score for QCT was only -0.7 ± 0.9 suggesting that these patients are not much different than age-matched controls. The results as determined by DXA were discordant with the QCT results. In fact, the DXA results of the T and Z scores of the PA lumbar spine were greater than 0.
It is not surprising that the DXA and QCT results were discordant as each modality is limited by the standard database it uses for comparisons as well as inherent differences in technique. QCT provides 3-dimensional BMD based on a direct measurement of mass per volume, compared with DXA results that are calculated from the mass per area scanned. QCT can differentiate between cortical and trabecular bone and can also occasionally visualize unsuspected lesions. However, DXA has superior precision and excellent accuracy. The DXA scan is also associated with significantly less radiation exposure for the patient (10-100 times less than even a CXR), is less expensive, and scans can be performed in several minutes. DXA of the lateral spine (not the PA spine), as performed in this study, is generally not used anymore as it is not really clinically useful and cannot be calculated in overweight individuals, as occurred in 15 of the 41 patients on this study. Therefore, the oncologist looking for underlying osteopenia would most likely order the readily available DXA of the PA spine and/or hip.
Others have also evaluated the BMD of prostate cancer patients. Daniell and associates found that prostate cancer patients had lower femoral neck BMD compared with controls, and that this density decreased by 2.4% and 7.6%, respectively, during years 1 and 2 of medical or surgical castration, followed by additional loss of about 2% per year up to 8 years later.1 Wei and colleagues also found that pre-existing osteopenia and osteoporosis were common in prostate cancer patients.2 Their cross-sectional study also noted significant loss of bone in patients who were on androgen deprivation therapy for more than a year compared with patients on the same therapy for less than a year. Interestingly, they used a regression analysis to estimate that it takes 48 months of androgen deprivation therapy to cause osteopenia in a patient with normal baseline measurements.2
Whereas hypogonadism due to medical or surgical castration clearly leads to loss of BMD, the effects of antiandrogens are less defined. Antiandrogens may suppress osteoblastic production of IL-6, a hormone that promotes bone resorption.3 On the other hand, antiandrogens also inhibit the contribution that adrenal androgens make to the maintenance of bone mass through their effect on the androgen receptor.3
A real concern is whether the complications of bone metastases are worse when progressive bone loss from androgen depletion is not addressed. Unfortunately, it is not known whether treating a low BMD in patients ready to start androgen ablation will lead to any clinical benefit. For example, there are no data demonstrating fewer metastatic lesions or diminished complications (pain, fractures, etc) in prostate cancer patients. Nevertheless, one approach would be to obtain a baseline DXA scan and start patients at greater risk (such as a T score less than -2) on calcium 500 mg/d (assuming diet also contains at least 500 mg), vitamin D 400 IU/d (often found in a multivitamin), and a bisphosphonate (either alendronate or risendronate). Those at lower risk could receive calcium and vitamin D with a follow-up DXA scan. Relevantly, the study by Smith et al revealed that 17% of the patients had hypovitaminosis D and 59% of the patients had dietary calcium intakes below the recommended daily allowance.
References
1. Daniell H, et al. J Urol. 2000;163:181-186.
2. Wei J, et al. Urology. 1999;54:607-611.
3. Pfeilschifter, et al. J Clin Oncol. 2000;18:1570-1593.
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