Miyabara, Yuko

Bone loss and development of atherosclerosis characterized by coronary arterial calcification (CAC) accelerate in women after menopause. This study evaluated the relationship between blood borne markers of bone turnover and development of CAC in newly menopausal women being screened for the Kronos Early Estrogen Prevention Study. Women (n=137) were 52.3±2.3 years of age and were 18.1±9.2 months past their last menses. CAC was measured using 64‐slice computed tomography. Concentrations of osteocalcin, bone alkaline phosphatase (BAP), tartrate‐resident acid phosphatase 5b and osteopontin as bone matrix protein in serum and plasma were evaluated by ELISA. CAC scores ranged from 0 to 327.6 Agatston Unit (AU); 113 women had scores of 0 AU, 20 had CAC scores of 0<50 and 4 had CAC scores >50. Average levels of all of the markers of bone turnover were within a normal range reported in the literature. There was a positive correlation between BAP and osteocalcin. However, levels of these markers did not correlate with age or months past menopause. None of the markers correlated with CAC scores. These results suggest that blood borne markers of bone turnover do not correlate with the presence of CAC in newly menopausal women. Additional work is needed to determine if this relationship would change with increasing age. Supported by the Kronos Longevity Research Institute and Mayo Foundation.

Abstract Context: In women, cortical bone mass decreases significantly at menopause. By contrast, loss of trabecular bone begins in the third decade and accelerates after menopause. Objective: The aim of the study was to investigate the effects of estrogen on cortical and trabecular bone. Design: The Kronos Early Estrogen Prevention Study is a double-blind, randomized, placebo-controlled trial of menopausal hormone treatment (MHT) in women, enrolled within 6–36 months of their final menstrual period. Setting: The study was conducted at the Mayo Clinic, Rochester, Minnesota. Intervention: Subjects were treated with placebo (n = 31), or .45 mg/d conjugated equine estrogens (n = 20), or transdermal 50 μg/d 17β-estradiol (n = 25) with pulsed micronized progesterone. Main Outcome Measures: Cortical and trabecular microarchitecture at the distal radius was assessed by high-resolution peripheral quantitative computed tomography. Results: At the distal radius, cortical volumetric bone mineral density (vBMD) decreased, and cortical porosity increased in the placebo group; MHT prevented these changes. By contrast, MHT did not prevent decreases in trabecular microarchitecture at the radius. However, MHT prevented decreases in trabecular vBMD at the thoracic spine (assessed in a subset of subjects; n = 51). These results indicate that MHT prevents deterioration in radial cortical vBMD and porosity in recently menopausal women. Conclusion: The maintenance of cortical bone in response to estrogen likely has important clinical implications because cortical bone morphology plays an important role in bone strength. However, effects of MHT on trabecular bone at the radius differ from those at the thoracic spine. Underlying mechanisms for these site-specific effects of MHT on cortical vs trabecular bone require further investigation.