Serge Guillemant

Acute effects of an oral calcium load on markers of bone metabolism during endurance cycling exercise in male athletes.

Although sport and physical activity are generally considered as positive factors for bone metabolism some endurance trainings such as running and bicycling have few or no beneficial or even deleterious effects on bone mineral density. The present study was designed to investigate the acute effect of an intensive endurance cycling exercise on biochemical bone markers. Futrthermore, the effect of the oral intake of 1g calcium load, by drinking high-calcium mineral water, just prior to and during the exercise was checked. Twelve well-trained elite male triathletes aged 23-37 years were explored. The serum concentrations of calcium, phosphate, PTH, bone alkaline phosphatase (BALP) and C-terminal cross-linking telopeptide of type 1 collagen (CTX) were measured before, during and after a 60 min 80% VO2max cycle ergometer exercise. Since cycling exercise was accompanied by a reduction in plasma volume the total amount of biochemical bone markers was calculated. When the exercise was performed without calcium load both serum concentrations and total amount of CTX began to increase progressively 30 min after the start of the exericse and were still significantly elevated, by 45-50%, 2h after the end of the exercise. Ingestion of high-calcium mineral water completely suppressed the CTX reponse. By contrast serum concentrations and total amount of BALP fluctuated and showed no significant difference with or without calcium load. The present study demonstrates that the burst of osteoclastic activity acutely induced by an endurance cycling exercise can be suppressed by the previous intake of a calcium load afforded by drinking high-calcium mineral water.

Androgen metabolism in hirsute patients treated with cyproterone acetate

Cyproterone acetate (CPA) in association with percutaneously administered estradiol has been used for the treatment of 150 hirsute patients for periods ranging from 6 months to 3 years. A spectacular clinical improvement ensued. Plasma testosterone (T) and androstenedione (A) fell from 69.0 +/- 24 to 33.0 +/- 8 and 210 +/- 103 to 119 +/- 25 ng/dl (mean +/- SD) respectively after 3 months of treatment and remained low thereafter. In contrast, T glucuronide (TG) and 3 alpha-androstanediol (Adiol) remained high during the whole course of treatment: 37 +/- 9 and 115 +/- 43 micrograms/24 h respectively. In vitro T 5 alpha-reductase activity (5 alpha-R) in pubic skin decreased from 147 +/- 34 to 79 +/- 17 fmol/mg skin after 1 year of treatment. To elucidate the discrepancy between plasma and urinary androgens levels, T production rate (PR) and metabolic clearance rate (MCR) were measured with the constant infusion technique in 7 patients before and after 6 months of treatment. PR decreased from 988 +/- 205 to 380 +/- 140 micrograms/24 h (mean +/- SD). In contrast MCRT increased from 1275 +/- 200 to 1632 +/- 360 1/24 h; this increase in MCRT explains the striking plasma T concentration fall and the high TG and Adiol excretion relative to the decrease in PR. Antipyrine clearance rate (n = 8) increased from 36.3 +/- 5.2 to 51.5 +/- 7.4 ml/min whereas 6 beta hydroxycortisol remained unchanged. In conclusion, CPA acts through several mechanisms: (1) it lowers the androgen input to the target cells by (a) depressing T production through its antigonadotropic effect and (b) accelerating T metabolic inactivation due to a partial enzymatic inducer effect on the liver; (2) at the target cell level it competes with any remaining T for the receptor binding sites; (3) the decrease in the androgen-dependent skin 5 alpha-R is a consequence of both actions of androgen suppression and androgen receptor blockade; it reinforces the antiandrogenic effect of CPA.

Different acute responses of serum type I collagen telopeptides, CTX, NTX and ICTP, after repeated ingestion of calcium.

BACKGROUND N- and C-terminal fragments of type I collagen such as NTX, CTX and ICTP are released into circulation during bone resorption and can be quantified in serum. Their respective sensitivity as indices of osteoclastic activity was compared after a short-term inhibition of resorption induced by repeated drinking of calcium-fortified water. METHODS Serum NTX, CTX and ICTP were measured by specific immunoassays in one group of 15 subjects sampled at 08.00, 11.00, 14.00 and 17.00 (referred to as T0, T3h, T6h and T9h) and having ingested in two experimental periods 660 ml of either low-calcium mineral water or the same low-calcium mineral water fortified with calcium (300 mg/l) at three times (08.00, 11.00 and 14.00). RESULTS Oral intake of calcium-fortified water resulted in progressive decrease in serum CTX (by 38.7% at T3h, 61.0% at T6h and 60.4% at T9h) and NTX (by 19.0% at T3h, 24.1% at T6h and 25.2% at T9h) while serum ICTP concentrations were not significantly affected. Since ingestion of low-calcium water induced a modest but significant decrease in both CTX (-19.4%) and NTX (-10.6%) we compared the two sets of assays with repeated-measures two-factor analysis of variance with interaction. Ingestion of calcium-fortified water vs. low-calcium water resulted in a significant decrease in both serum CTX (time, P<0.0001; treatment, P<0.0001; time-by treatment, P<0.0001) and NTX (time, P<0.0001; treatment, P=0.0001; time-by treatment, P=0.0066). CONCLUSIONS CTX is more sensitive than NTX while ICTP is not sensitive to calcium-induced acute changes in osteoclastic activity. The present results stress the importance of choosing appropriate biochemical bone markers to demonstrate the effects of calcium on bone resorption.

Acute Effects of Oral Calcium Load on Parathyroid Function and on Bone Resorption in Young Men

Aim: The aim of the present study was to check whether a calcium oral load was able to inhibit bone resorption as assessed by urinary excretion of a new bone marker, type 1 collagen cross-linked C-telopeptide (CrossLapsTM), in healthy young male adults. Methods: Twenty healthy young male adults (age 22 ± 2 years) were studied. In one series of assays, an oral calcium load of 1 g of elemental calcium as calcium citrate dissolved in 200 ml of low-calcium water was ingested, while in another series of assays the subjects ingested 200 ml of water alone. Blood samples were collected before and 1, 2, 3 and 4 h after the intake of calcium. Urine was collected at 2-hour intervals, i.e. before and for 4 h after the intake of calcium. Serum ionized calcium, phosphate and intact parathormone (iPTH) were measured at each time point. Urinary calcium, phosphate, creatinine and CrossLaps (as a ratio to creatinine) were measured in each urine sample. Results: Calcium intake was associated with very significant (ANOVA, p < 0.001) increases in serum ionized calcium and decreases in PTH. After calcium intake, measurements of urinary CrossLaps showed a progressive statistically significant (ANOVA, p < 0.001) decrease (–20% at 2 h and –55% at 4 h), whereas after ingestion of water, the changes were modest and not statistically significant. Conclusions: The present results show that bone resorption as assessed by urinary excretion of CrossLaps can be significantly suppressed by the ingestion of a 1-gram calcium load and attest that calcium supplementation has an acute effect on bone metabolism.

Comparison of the suppressive effect of two doses (500 mg vs 1500 mg) of oral calcium on parathyroid hormone secretion and on urinary cyclic AMP

SummaryThe respective effects of the ingestion of two different doses of calcium (500 and 1500 mg) on serum ionized calcium, intact parathyroid hormone (PTH -1-84), and the urinary excretion of 3′,5′-cyclic adenosine monophosphate (cyclic AMP) were evaluated in 15 young male adults. Ionized serum calcium and PTH 1-84 were measured before and 1 hour, 2 hours and 3 hours (P1, P2, and P3) after the oral intake of calcium. Cyclic AMP was measured in 2-hour urine samples collected before and during 4 hours after the ingestion of calcium. Similar increments in serum ionized calcium (ΔCa2+) were observed except at P3 where the ΔCa2+ was significantly (P < 0.02) higher after 1500 mg (0.088 mmol/liter) than after 500 mg of (0.062 mmol/liter). In the same way, the comparison of the PITH 1-84 concentrations showed no statistical difference except at P3 (P < 0.002). When expressed as a percentage of P0, the P1 and P2 PTH 1-84 values were more suppressed after 1500 mg than after 500 mg of calcium (Pl: -69% vs -59%;P < 0.02; P2: -66% vs −50%; P < 0.02). However, the simultaneous cyclic AMP responses (−24% vs −19%) were not significantly different. The results show that the respective maximal effects on PTH secretion and on urinary cyclic AMP of two very different oral doses of calcium are only slightly different.

Early rise in cyclic GMP after 1,25-dihydroxycholecalciferol administration in the chick intestinal mucosa

Abstract cGMP and cAMP levels were measured in the duodenal mucosa of 12-day-old chicks that had been raised from hatching in vitamin D-depleting conditions and at the time of use were moderately hypocalcemic. After administration of a dose (250 ng) of 1,25-dihydroxycholecalciferol, the cGMP levels increased about twofold in 2–3 hr and returned to control levels between 4 and 6 hr. Our data suggest that 1,25-dihydroxycholecalciferol behaves like other steroid hormones which induce an early rise in cGMP in their respective target tissues.

Calcium in mineral water can effectively suppress parathyroid function and bone resorption

Abstract The present study was designed to measure the effects, on parathyroid function and bone metabolism, of ingestion of high-calcium mineral water and of a calcium salt bringing the same dose (600 mg) of calcium as a reference. Fifteen healthy young men (mean ± SD age : 23.3 ± 1.2) ingested, during 3 different experimental periods chosen at random, a) high-calcium mineral water (596 mg/L), b) low-calcium mineral water as a control assay, c) one bag of tricalcium phosphate powder containing 600 mg of calcium. Serum concentrations of ionized calcium (iCa), intact parathyroid hormone (iPTH) and of a biochemical marker of bone resorption, type I collagen cross-linked C telopeptide (CTX), were measured before 08.00 and every hour from 09.00 to 17.00. Serum iCa concentrations were significantly ( P P P P = 0.011) than in the control period and a statistically significant difference ( P t test between the effects of high-calcium mineral water and of tricalcium phosphate was observed from 14.00 to 17.00. The same total amount of calcium (# 600 mg) from one liter of high-calcium mineral water, divided into three intakes, at 3 hours intervals, resulted in a more prolonged suppression of serum CTX, than from the ingestion of a calcium salt.

Effect of vitamin D3 administration on serum 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and osteocalcin in vitamin D-deficient elderly people

In elderly institutionalized people, confined to bedroom and receiving no vitamin D supplementation, the frequency of vitamin D deficiency is found very high. Systematic administration of vitamin D has, therefore, been proposed to correct vitamin D deficiency. Within this context, we studied 40 elderly institutionalized subjects (mean age 80.5 + 7.2 yr) with low 25(OH)D3 concentrations (4.4 + 1.8 micrograms/l). Sixteen of them (Group I) had low serum calcium concentrations (less than 2.3 mmol/l) and 24 (Group II) had normal serum calcium concentrations (from 2.3 to 2.6 mmol/l). As hypocalcemia has been shown to regulate 1,25(OH)D3 production independent of PTH in animals and in humans, we compared their respective responses to the administration of vitamin D3. Subjects received a total dose of 15 mg (600,000 IU) of vitamin D3 divided into 3 i.m. injections at one month intervals and were explored before therapy and one and 6 months after the last dose of vitamin D3. The treatment induced a similar marked rise in 25(OH)D3 levels (from 4.1 + 1.7 to 24.4 + 8.7 micrograms/l for group I and from 5.1 + 1.8 to 27.2 + 8.0 micrograms/l for group II) in both groups but increased the 1,25(OH)2D3 concentrations only in group I (from 22.9 + 6.9 to 32.6 + 11.3 ng/l). Meanwhile serum calcium concentrations rose in group I (to low normal range i.e. 2.31 + 0.07 mmol/l) and were unaffected in group II. These results suggest that hypocalcemia is a potent stimulator of renal 1-hydroxylase in elderly people. Furthermore, a transient significant (P less than 0.01) increase in serum osteocalcin (from 10.6 + 4.1 to 14.1 + 5.9 micrograms/l) could be observed in group I which demonstrates for the first time that the osteocalcin response of osteoblasts to stimulation by 1,25(OH)2D3 is retained in very old people.

Elevated cyclic GMP concentrations in rat adrenal cortex after dexamethasone administration

Abstract The levels of cGMP and cAMP were measured in the fasciculata-reticularis zona of the adrenal cortex in both intact and hypophysectomized young adult male rats. After administration of a single dose of dexamethasone to intact rats, cGMP levels were elevated 2–4 fold after 4hr and returned to control level after 8hr. At the same time, cAMP concentrations were moderately lowered. In hypophysectomized rats dexamethasone administration was followed by a similar increase in the cGMP level, the basal cAMP concentrations were not altered by dexamethasone. Our data suggest that dexamethasone might have a direct effect on cGMP concentration in the adrenal cortex of the rat.

Natriuresis and cyclic GMP stimulation by parathyroid hormone 1-34 in man

Synthetic human parathyroid hormone (PTH 1-34) was infused into seven healthy adults and their renal responsiveness examined. Blood and urine were collected at time zero and at 30 and 60 min after the infusion of PTH 1-34 (15µg in 50 ml of glucose solution infused in 10 min). A highly significant and parallel rise in both cyclic GMP and sodium excretion was found. No variation in blood atrial natriuretic factor concentration could be detected thereby suggesting that cyclic GMP is directly stimulated by PTH 1-34 and may play a role in the natriuretic effect of PTH.