Anastrozole osteoporosis with

Anastrozole is a selective nonsteroidal aromatase inhibitor that lowers estrogen levels. The pharmacokinetics of anastrozole demonstrate good absorption, with hepatic metabolism the primary route of elimination and only 10% excreted unchanged by the kidney. The elimination half-life is approximately 50 hours. Anastrozole is used for the adjuvant treatment of postmenopausal women with hormone-positive breast cancer and in breast cancer patients who have had disease progression following tamoxifen. Side effects include hot flashes, arthralgias, osteoporosis/bone fractures, and thrombophlebitis. 

Normal endometrial tissues are devoid of aromatase activity. In patients with endometriosis, evidence suggests that high levels of aromatase are present in endometrial implants. Aromatase is the enzyme that catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively (Fig. 46.3). If an aromatase inhibitor, such as anastrozole (Fig. 46.11), is administered, then estrogen production will be decreased in the endometrial implants. A local state of estrogen deficiency will prevent growth of these implants (84). Unfortunately, one outcome of prolonged aromatase therapy is the development of osteoporosis. As a result, an OC typically is coadministered to provide baseline estrogen concentrations and limit the risk of osteoporosis. 

Tamoxifen (Tam) (Novaldex) is an estrogen receptor antagonist present in breast tissue, with activity linked to its metabolite hydroxytamoxifen (OHTam). In other tissues (endometrium) it behaves as an agonist due to the presence of other coactivators. This SERM is involved in the endocrine therapy commonly used with hormone-dependent breast cancers, although aromatase inhibitors (Anastrozole) are also frequently used for the same female patient group. Tamoxifen is the most common hormonal treatment for breast cancer in men. It also protects against osteoporosis [17]. 

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, with its median follow-up of 68 months, has provided the best evidence to date that an adjuvant ana-strozole regimen is better tolerated (and more effective) than tamoxifen alone, but the problem remains that anastrozole reduces circulating estrogen, and that low estradiol concentrations cause reduced bone mineral density and hence an increased risk of fractures. In a substudy of the ATAC trial, the effects of prolonged long-term aroma-tase inhibitor therapy on bone mineral density have been examined in 197 patients, who took anastrozole 1 mg/day or tamoxifen 20 mg/day as adjuvant therapy for 5 years [45 ]. Anastrozole-treated women had reduced median bone mineral density compared with those who took tamoxifen, but it is striking that no patients with normal bone mineral density at the outset developed osteoporosis at 5 years. The real risks with anastrozole thus seem to be limited to women who have osteopenia at the start of treatment. 

---