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.

Objective: To evaluate the effect of seasonal variations in UV B-exposure on calcium absorption and bone turnover in young women with the overall goal to assess the potential bene®t of a vitamin D supplementation during wintertime. Design: Cross-sectional study. Setting: Area of Bonn, Germany (51 N). Subjects: Thirty-eight women (24.5 AE 0.5 y) studied in winter and 38 females of the same age (24.7 AE 0.4 y) studied in summer. Results: As estimated by a 4 d food record, both groups had similar dietary calcium and phosphorus intakes (b1200 mgad, respectively) covering actual recommendations. Signi®cant reductions in serum concentrations of 25-hydroxyvitamin D (25OHD) and calcitriol, fractional calcium absorption (Fc 220 , measured by means of a stable strontium test), 24 h urinary calcium and 24 h urinary phosphorus excretion were observed during wintertime. 25OHD but not calcitriol was correlated with Fc 220 values and with 24 h urinary phosphorus excretion. Moreover, Fc 220 was related to 24 h urinary calcium excretion. Fasting 2 h-urinary deoxypyridinoline concentrations (biomarker of bone resorption) and serum levels of carboxyterminal propeptide of type I procollagen (biomarker of bone formation) showed no differences between summer and winter. Conclusions: Our data indicate a decrease in intestinal calcium and phosphorus absorption during wintertime, most likely because of a reduction in serum 25OHD levels. Since bone turnover was not affected by the seasonal differences in mineral metabolism, there is no objective for young women with high calcium intake to supplement vitamin D during wintertime.

The effect of physical activity on human calcium (Ca) metabolism is still not completely understood. Thus, we investigated fractional Ca absorption using a stable strontium test (Fc(240)), calciotropic hormones, and renal Ca excretion in 31 young men with a high activity level (GH) and in 26 age-matched sedentary control subjects (GL). Weekly hours spent on physical activity, obtained with a questionnaire were 15.0 +/- 6.6 (GH) and 1.0 +/- 1.4 (GL), respectively. Serum testosterone levels were significantly lower in GH compared with GL (P < 0.005). Dietary Ca intake (4-day food record) was twice as high in GH compared with GL men (P < 0.001). GH had significantly higher serum calcitriol levels and Fc(240) values than GL (P < 0.001 and P < 0.01, respectively). In a stepwise multiple regression analysis including serum levels of 25-hydroxyvitamin D, calcitriol, testosterone, and dietary Ca intake, only calcitriol was significantly correlated with Fc(240) (P = 0. 017). Twenty-four hour renal Ca excretion was only slightly higher in GH compared with GL (P < 0.05). However, additional Ca losses might have occurred through the extensive sweating of GH, as indicated by a difference of 1.7 liter between fluid intake and renal fluid excretion (P < 0.001). In summary, we observed a higher fractional Ca absorption rate in physically active young men compared with sedentary controls which is probably mediated by calcitriol. The low testosterone serum levels of the athletes were obviously not a limiting factor in Ca absorption efficiency. An additional Ca retention might, however, only be obtained if absorbed Ca exceeded total obligatory Ca losses.

Intestinal calcium absorption can be diminished after only three weeks of microgravity. Changes are associated with a severe suppression of circulating calcitriol levels, but are independent of exogenous vitamin D supply and serum PTH levels.

Background: The associations between nitrogen metabolism and bone turnover during bed rest are still not completely understood. Methods: We measured nitrogen balance (nitrogen intake minus urinary nitrogen excretion) and biochemical metabolic markers of calcium and bone turnover in six males before head-down tilt bed rest (baseline), during 2, 10, and 14 weeks of immobilization, and after reambulation. Results: The changes in nitrogen balance were highest between baseline and week 2 (net change, −5.05 ± 1.30 g/day; 3.6 ± 0.6 g/day at baseline vs −1.45 ± 1.3 g/day at week 2; P&lt;0.05). In parallel, serum intact osteocalcin (a marker of bone formation) was already reduced and renal calcium and phosphorus excretions were increased at week 2 (P &lt;0.05). Fasting serum calcium and phosphorus values and renal excretion of N-telopeptide (a bone resorption marker) were enhanced at weeks 10 and 14 (P &lt;0.05–0.001), whereas serum concentrations of parathyroid hormone, calcitriol, and type I collagen propeptide (a marker of bone collagen formation) were decreased at week 14 (P &lt;0.05–0.01). Significant associations were present between changes of serum intact osteocalcin and 24-h calcium excretion (P &lt;0.001), nitrogen balance and 24-h phosphorus excretion (P &lt;0.001), nitrogen balance and renal N-telopeptide excretion (P &lt;0.05), and between serum osteocalcin and nitrogen balance (P &lt;0.025). Conclusions: Bone formation decreases rapidly during immobilization in parallel with a higher renal excretion of intestinally absorbed calcium. These changes appear in association with the onset of a negative nitrogen balance, but decreased bone collagen synthesis and enhanced collagen breakdown occur after a time lag of several weeks.