ATLANTAFor men with advanced or recurrent prostate cancer, 24
months of androgen deprivation accelerates bone loss, and these
changes were significant at sites such as the forearm and hip, David
M. Preston, MD (Maj., Medical Corps, U.S. Army), reported at the 95th
Annual Meeting of the American Urological Association (AUA).
At the same meeting, Yasuyuki Suzuki, MD, Jikei University Hospital,
Tokyo, reported that the initial protection provided by adjuvant
treatment with vitamin D is not sustained over 12 months, but low
doses of estrogen slow bone loss, and use of a statin (HMG-CoA
reductase inhibitor) might reverse it.
Prior to the widespread use of serum PSA testing, patients with
advanced prostate cancer were treated with androgen deprivation based
on symptomatic metastasis or abnormal bone scans, Dr. Preston
told ONI. In the PSA era, androgen deprivation is
initiated earlier, thus exposing patients to the therapy for longer
periods and increasing their risk of significant bone loss. Dr.
Preston is in the Department of Urology, Evans U.S. Army Hospital,
Ft. Carson, Colorado.
Dr. Preston reported data from a prospective study comparing bone
mineral density changes and urine markers of bone degradation in 39
subjects receiving androgen-deprivation therapy and 39 age-matched
controls. Subjects were evaluated every 6 months for 24 months. This
report included data from the 22 androgen-deprivation subjects and 30
control subjects who completed the 2-year study.
The androgen-deprivation group had greater rates of bone
mineral density loss than the control group at every site except the
lumbar spine, Dr. Preston said. In addition, urine markers of
bone degradation were higher in the androgen-deprivation group than
in the controls, although these markers did not change significantly
during the study period within groups. The two groups had similar
exercise habits, daily dietary calcium intake, and body mass indices.
Dr. Preston said that these findings indicate that men receiving
androgen-deprivation therapy are at increased risk of bone-related
complications such as osteoporosis and bone fractures.
He recommended baseline and surveillance bone mineral density
measurements for all prostate cancer patients undergoing androgen
deprivation. Medical therapy to halt or reverse bone loss
should be considered in those patients who demonstrate osteoporosis
by bone mineral density measurement, Dr. Preston said.
Dr. Suzuki reported pilot observations from prostate cancer patients
treated with androgen deprivation who were also given an activated
form of vitamin D3 (alfacalcidol, 1 µg/day, n=35); low-dose
estrogen (diethylstilbestrol, 100 mg/day, n=14); or standard-dose
estrogen (300 to 600 mg/day, n = 11). He also described two patients
who coincidentally had been taking a statinpravastatin
(Pravachol) or simvastatin (Zocor)for 2 years to treat
hyperlipidemia. Bone mineral density changes were compared with data
from historical controls.
Bone density loss in men treated with androgen deprivation was about
5% per year. In those treated with either dose of diethylstilbestrol,
this dropped to nearly zero. In men treated with vitamin D, the loss
dropped to 2.8% (not a significant improvement), and in the two men
who were taking a statin, bone density increased by 1.7%.
Dr. Suzuki told ONI that he was surprised at the statin effect.
This drug is used safely to treat hyperlipidemia. Now I am
using it for patients with prostate carcinoma who are being treated
with androgen deprivation. Next year I hope to be able to report the
true effect of a statin in these patients, he said.