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Physiologic Fluctuations of Serum Estradiol Levels Influence Biochemical Markers of Bone Resorption in Young Women

Department of Nutrition Science (A.Z., I.S., K.S., P.S.), Department of Clinical Pharmacology (T.S., H.K.B., K.v.B.), and Department of Gynecological Endocrinology (H.v.d.V.), University of Bonn, 53115 Bonn, Germany

Address correspondence and requests for reprints to: Armin Zittermann, Ph.D., Associate Professor, Department of Nutrition Science, University of Bonn, Endenicher Allee 11–13, 53115 Bonn. E-mail: a.zittermann{at}uni-bonn.de

We investigated the effect of physiologic variations in sex hormone levels during the menstrual cycle on biomarkers of bone turnover. Blood and 24-h and fasting urine samples were obtained in nine women (age, 25.1 ± 3.0 yr) with regular menstrual cycles during the early follicular period (t₁), 3 days before ovulation (t₂), 3 days after ovulation (t₃), at the midluteal period (t₄) and again during the early follicular period of the next cycle (t₅). All subjects had a calcium intake covering current dietary recommendations (above 1.000 mg/day, standardized food record).

Serum calcium, phosphorus, calcitriol, 24-h and 2-h fasting urinary calcium, and phosphorus excretion remained constant during the menstrual cycle. Serum 25-hydroxyvitamin D₃ levels decreased slightly from the beginning until the end of the study (P < 0.05), indicating low cutaneous vitamin D synthesis during wintertime.

The serum levels of sex hormones showed typical monthly variations, with the lowest estradiol (E₂) levels at t₁ and t₅. Fasting 2-h pyridinoline (Pyd) concentrations (a marker of bone resorption) fell from t₁ to t₃ and rose again at t₅ (P < 0.01). Similar variations were observed for the resorption marker deoxypyridinoline (Dpd; P < 0.05). The amplitude of the two biomarkers was 32% and 33%, respectively. The serum levels of the carboxyterminal propeptide of type I collagen (a marker of bone formation) showed an inverse cyclic pattern, as compared with the pyridinium cross-links. Low concentrations were observed at t₁; a rise occurred until t₃ and was followed by a decrease until t₅ (P < 0.05). A similar cyclic pattern was observed for serum PTH levels, with the highest concentrations at t₃ (P < 0.05).

Dpd and Pyd values were significantly correlated with serum E₂ levels (r = 0.52; P < 0.0001 and r = 0.50; P < 0.001, respectively). Neither progesterone nor LH nor FSH was correlated with Pyd or Dpd levels.

The data suggest that normal menstrual cycling in young women is associated with monthly fluctuations in bone turnover. This physiological effect of the menstrual cycle is most probably related to variations in serum E₂ concentrations.

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