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Zometa: Once Yearly Dosage Found Effective
In Combating Osteoporosis In Men On ADT Without Bone Metastases
(November 2006)
Once again prostate
cancer management parallels developments in breast cancer treatment, but
again with a slight lag. Immediately following the female menopause, bone
mineral density in women rapidly decreases as the level of bone-building
estrogen drops. The bisphosphonate, Zometa, is effective in reversing this
loss of bone density. The minimal effective dosage to counteract this fall
was the subject of a Feb 28, 2002 report in the NEJM which somewhat
surprisingly found that a single 4 mg dose of Zometa administered
annually in cancer-free women resulted in an increase in spine
bone mineral density (BMD) of 4.3% - 5.1%, and at the femoral neck of 3.1%
- 3.5%, as compared a placebo.
Multiple studies of
prostate cancer patients with bone metastases have
established a consensus that the standard of care for these men is 4 mg
Zometa administered every 3 weeks. This regimen has repeatedly resulted in
a significant reduction of additional "skeletal events", e.g. mainly
fractures, as compared to men not receiving the drug. And this regimen has
largely been adopted by inference for asymptomatic men with positive bone
scans. The open question has been whether to, and how to, use a
bisphosphonate in men with no indication of bone metastases
in whom the use of ADT predictably leads to an approximately 5% loss of
bone mineral density in the first year of treatment. This loss can be even
greater in men who already have low BMD (T score > 2.5), or are at
increased risk for low BMD, e.g. due to high alcohol or tobacco usage, low
body weight, corticosteroid therapy, or significant co-morbidities. For
these men a pre-ADT bone density study (DEXA) is appropriate.
The answer to the
question "whether to use and how frequently to dose" zoledronic acid (Zometa)
in the large population of asymptomatic men receiving ADT is suggested in
Abstract 4515, ASCO 2006: "Annual Zoledronic Acid to Prevent Gonadotropin-Releasing
Hormone Agoinst-Induced Bone Loss in Men with Prostate Cancer: A
Randomized Placebo-Controlled Trial". Forty-four men with non-metastatic
prostate cancer were treated with one dose of 5 mg Zometa or
placebo. Pretreatment DEXA studies of the lumbar spine and hips were done,
and follow-up testing took place at one year. Results: Mean BMD of the
postanterior lumbar spine increased by 4.0% + 0.9%
with zoledronic acid and decreased by 3.1% +
0.9% with placebo. In the hips the difference was -0.7% + 0.6% for
Zometa, vs - 1.9% + 0.7%, placebo. Their conclusion: "An annual
zoledronic acid dose may be a convenient, effective prophylactic treatment
for bone loss in hypogonadal men". Measurement of N-telopeptides indicated
a confirmatory decrease of bone turnover in the treatment group.
Bottom Line:
A single annual dose of 5 mg Zometa can not only reverse the approximately
5% first-year bone loss from ADT in men without bone metastases, but can
increase bone density in the lumbar spine by 4%.
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