Esterified estrogen therapy in postmenopausal women. Relationships of bonemarker changes and plasma estradiol to BMD changes: A two-year study

Objective: To determine the relationships among bone mineral density change s, bone marker changes, and plasma estrogens in postmenopausal women receiv ing estrogen replacement therapy. Design: A total of 406 postmenopausal women received 1,000 mg calcium and c ontinuous esterified estrogens (0.3 mg, 0.625 mg, or 1.25 mg) or placebo da ily for up to 24 months. Bone mineral density and bone marker measurements were determined at 6-month intervals; plasma estrogens were measured in a s ubset after 12, 18, and 24 months. Results: Esterified estrogens produced significant increases in bone minera l density (lumbar spine, hip) compared with baseline and placebo at 6, 12, is, and 24 months. Bone markers decreased from baseline with all esterified estrogen doses relative to placebo. Bone marker changes at 6 months correl ated negatively with bone mineral density changes at 24 months (correlation coefficient range = -0.122 to -0.439). The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin. Mean plasma estrogen levels increased with esterified estrogen dose, and bone mineral d ensity changes correlated positively with plasma estrogen levels. Positive bone mineral density changes were noted in treatment groups with plasma est radiol levels at and above 25 pg/mL. Conclusions: Esterified estrogens, at doses from 0.3 mg to 1.25 mg/day, uno pposed by progestin, increase bone mineral density of the spine and hip in postmenopausal women. These bone mineral density changes correlated signifi cantly with bone marker changes at 6 months and with plasma estrogens at 12 , 18, or 24 months. Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy.