Aromatase Inhibitors: Skeletal Effects and the Role of CYP19 Gene Polymorphisms

A family history of osteoporosis will be noted. Data on the factors that affect estrogen exposure such as age at menarche, average number of periods per year during the reproductive years, number of years of birth control pill use, total number of pregnancies, number of pregnancies to term, months of lactation and age at menopause will be recorded. These data will be collected at baseline. Current medications and other medical problems will be recorded at baseline and during follow-up visits. New medical problems and new medications will be noted on follow-up.

Physical examination will be done at baseline and during follow-up visits. Body mass index calculated as weight (kg) divided by the square of the height (m2) will be obtained every visit. Height will be obtained using a standard stadiometer and weight will be taken using a standard weighing scale.

Dietary calcium and Vitamin D intake will be estimated from a 7-day dietary recall at baseline and adjusted to a daily intake of 1200-1500 mg of calcium per day. Vitamin D intake will also be adjusted to 800 IU per day.

Biochemical Analysis. Routine serum comprehensive metabolic profile (CMP) will be measured by standard autoanalyzer technique, serum 25-hydoxyvitamin D by double-antibody radioimmunoassay (Incstar Corp., Stillwater, Minnesota), and FSH by chemiluminescent assay (Bayer, NY) in those cases when the last menstrual period occurred less than 12 months before the signing of the informed consent. These measurements will be done through the Barnes-Jewish Hospital Laboratory. Serum estradiol will be measured by radioimmunoassay (Diagnostic Systems Laboratories Inc.), and sex hormone binding globulin by double antibody radioimmunoassay (Diagnostic Laboratories Inc). Serum estradiol measurements will be done at the Core Laboratory of the General Clinical Research Center (GCRC) of Washington University School of Medicine while the sex hormone binding globulin assay will be done at Dr. Villareal's laboratory. The inter- and intra-assay coefficients of variation for these assays are all < 10%. In order to improve accuracy of the analysis the biochemical tests (except for 25-OH Vitamin D) will be performed at the end of the study and will be run by the same operator and plate (run in batch).

Bone Mineral Density (BMD) BMD of the total body, lumbar spine and the proximal left femur will be measured by dual energy X-ray absorptiometry (DEXA) using Hologic QDR 4500 (Hologic Inc., Waltham Ma, U.S.A.). Measurements will be done at month 0, 6 and 12 (see Visits and Testing Schedule). To guarantee the necessary flexibility for the patients who can not be seen at the exact date for the follow up a window of 1 month earlier and 2 months of late will be considered. BMD of the lumbar spine will be measured from L1 to L4. The non-dominant hip will be used for studies on the proximal femur. The main regions of interest on the proximal femur will be the total femur, femoral neck and femoral trochanter. The coefficient of variability for these repeated measurements in our institution is1.09% for the lumbar spine and 1.2% for the total femur in our center.