Objective: A post hoc exploratory analysis was conducted to examine correlations between changes in bone density, bone markers, and hot flushes after the treatment of postmenopausal women with bazedoxifene (BZA)/conjugated estrogens (CE).
Methods: In a 2-year phase 3 study, 3,397 postmenopausal women were randomized to BZA 10 mg/CE 0.45 mg, BZA 20 mg/CE 0.45 mg, BZA 40 mg/CE 0.45 mg, BZA 10 mg/CE 0.625 mg, BZA 20 mg/CE 0.625 mg, BZA 40 mg/CE 0.625 mg, raloxifene 60 mg, or placebo. In this analysis, bone density changes at 2 years were compared with baseline levels of the bone markers serum C-telopeptide and osteocalcin. Correlations between changes in bone density and changes in 12-week hot flush composite scores in symptomatic women were also analyzed.
Results: Treatment with BZA 20 mg/CE 0.45 mg or BZA 20 mg/CE 0.625 mg increased lumbar spine bone density more in women with higher bone resorption and formation, categorized by baseline levels of C-telopeptide and osteocalcin (P < 0.001, both BZA/CE doses). With placebo, larger decreases in lumbar spine bone density were seen in the highest tertile of serum C-telopeptide. There was no correlation between changes in total hip bone density and baseline bone markers. There were significant correlations between percent change in hot flush score at week 12 and percent changes in lumbar spine (r = −0.31, P = 0.006) and total hip (r = −0.23, P = 0.044) bone densities at month 24.
Conclusions: With 2-year BZA/CE treatment, women with larger increases in lumbar spine and total hip densities also have higher baseline bone markers. Early reductions in hot flush score (12 wk) are predictive of long-term increases in bone density (24 mo).
From the 1Creighton University Medical Center, Omaha, NE; and 2Pfizer Inc, Collegeville, PA.
Received December 18, 2012; revised and accepted January 30, 2013.
Funding/support: This study was sponsored by Wyeth Research, which was acquired by Pfizer Inc in October 2009. Medical writing assistance for this manuscript was provided by Katie Gersh, PhD, of MedErgy and was funded by Pfizer.
Financial disclosure/conflicts of interest: H.S. and S.M. are full-time employees of Pfizer Inc. A.A.C. was a former employee of Pfizer Inc. J.C.G. has received research study support from Wyeth Research, which was acquired by Pfizer Inc in October 2009, and has been a consultant for 9 years, but not in the last 3 years.
Address correspondence to: John Christopher Gallagher, MD, Endocrinology Division, Creighton University Medical Center, Suite 6712, 601 North 30th Street, Omaha, NE 68131. E-mail: email@example.com