Bone Calcium Turnover Research Articles

Association of Serum Calcium Levels of Preterm Neonates at Birth with Calcium Intake from Foods and Supplements by Bedridden Women during Pregnancy.

Bone calcium turnover is aggravated in pregnant women recommended to bed rest. In the present cross-sectional study, we aimed to clarify whether preterm neonates would benefit from calcium supplementation during pregnancy. Forty-two mothers (37.5 ± 6.7 years), recommended bed rest at home, and 42 preterm neonates (24-37 weeks gestational age) were enrolled. Neonates' serum calcium was quantified at birth. Mothers' calcium intake from foods and supplements during pregnancy was assessed. Serum 25-OH-D was measured in both mothers and neonates at birth. Results showed that mothers' calcium intake from foods was significantly lower than the recommended daily reference value (p < 0.001), while total calcium intake including supplements was close to the calcium reference value of 1000 mg/day (p = 0.648). Neonates' serum calcium concentration was significantly higher in mothers receiving calcium supplementation during pregnancy compared to mothers who did not (p < 0.001). A significant association between neonates' serum calcium levels and mothers' calcium supplementation was evident, even when adjusted to mothers' age, pre-pregnancy BMI, gestational age, and neonates' birth weight (beta = +0.460, p = 0.025). A statistically significant correlation between neonates' and mothers' serum 25-OH-D levels was found (r = 0.891, p < 0.001). In conclusion, calcium status in preterm neonates, born by bedridden women, could be enhanced after calcium supplementation during gestation.

High Fiber Diets Slow Bone Turnover in Young Men but Have No Effect on Efficiency of Intestinal Calcium Absorption

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Bone calcium turnover during pregnancy and lactation in women with low calcium diets is associated with calcium intake and circulating insulin-like growth factor 1 concentrations

Few data exist on longitudinal changes in bone calcium turnover rates across pregnancy and lactation. Our aim was to characterize calcium kinetic variables and predictors of these changes across pregnancy and early lactation in women with low calcium intakes. Stable calcium isotopes were administered to 10 Brazilian women during early pregnancy (EP; weeks 10-12 of gestation), late pregnancy (LP; weeks 34-36 of gestation), and early lactation (EL; 7-8 wk postpartum). Multicompartmental modeling was used to assess the rates of bone calcium turnover in relation to calcium intakes and circulating concentrations of parathyroid hormone (PTH), insulin-like growth factor 1, and 1,25-dihydroxyvitamin D. Rates of bone calcium deposition increased significantly from EP to LP (P = 0.001) and were significantly associated with serum PTH during LP (P < or = 0.01). Rates of bone calcium resorption were also higher during LP and EL than during EP (P < or = 0.01) and were associated with both PTH (P < or = 0.01) and IGF-1 (P < or = 0.05) during LP but not during EL. Net balance in bone calcium turnover was positively associated with dietary calcium during EP (P < or = 0.01), LP (P < or = 0.01), and EL (P < or = 0.01). The mean (+/-SD) calcium intake was 463 +/- 182 mg/d and, in combination with insulin-like growth factor 1, explained 68-94% of the variability in net bone calcium balance during pregnancy and lactation. Net deficits in bone calcium balance occurred during pregnancy and lactation. Increased dietary calcium intake was associated with improved calcium balance; therefore, greater calcium intakes may minimize bone loss across pregnancy and lactation in women with habitual intakes of <500 mg calcium/d.

Bone calcium turnover, formation, and resorption in bromocriptine- and prolactin-treated lactating rats.

To evaluate the effect of endogenous prolactin (PRL) on bone metabolism, we studied bone calcium turnover by the (45)Ca kinetic method and bone formation and resorption by bone histomorphometry and biochemical markers in 13-wk-old lactating Wistar rats. For 1 wk, the animals received daily administration of 0.9% NaCl (control) intraperitoneally, 6 mg of bromocriptine/ kg of body wt intraperitoneally, or 6 mg of bromocriptine/kg of body wt plus 2.5 mg of ovine PRL/kg of body wt subcutaneously. Bromocriptine, a dopaminergic inhibitor of endogenous PRL secretion, significantly decreased calcium ion deposit rate and calcium resorption rate in femur, tibia, vertebrae 5 and 6, and sternum by 20- 42%. By contrast, calcium resorption rate of the vertebrae and the sternum of the PRL-treated group was higher than that of controls, whereas the tibia and sternum exhibited a greater net loss of calcium. The suppression of bone calcium turnover in the bromocriptine-treated group was further supported by a significant decrease in the urinary deoxypyridinoline, a biochemical index of bone resorption, and the histomorphometric data, which showed changes indicative of suppressed bone resorption and formation. The histomorphometric data from the PRL-treated group were not different from those of the control group with the exception of an increase in the longitudinal growth rate. The results suggested a role of endogenous PRL in the stimulation of bone turnover during lactation.

Changes in the regulation of calcium metabolism and bone calcium content during growth in the absence of endogenous prolactin and during hyperprolactinemia: A longitudinal study in male and female Wistar rats

Since endogenous prolactin has been shown to enhance food consumption, calcium absorption, and bone calcium turnover in the pregnant rat, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in 3-day balance studies of female Wistar rats from the age of 3 to 11 weeks. The study was divided into two parts. In part I, calcium metabolism in males and females was compared. In part II, 3-week old female rats were divided into 5 groups: (i) control animals receiving 0.9% NaCl; (ii) animals receiving 6 mg bromocriptine/kg/day (- PRLendogroup); (iii) animals receiving 2.5 mg ovine prolactin/kg/day (+PRLexo); (iv) sham-operated animals receiving 0.9% NaCl, and (v) animals with two extra pituitaries implanted under the renal capsule, receiving 0.9% NaCl (AP group). Results showed that rapid growth occurred between 3 and 6 weeks with maximum fractional calcium absorption and calcium retention at 5 weeks of age in both sexes. The data also showed a physiological significance of endogenous prolactin in enhancing calcium absorption and retention in 5 week old rats. In an absence of prolactin, peak calcium absorption was delayed in 7-week old animals, and vertebral calcium content of 11-week old animals was reduced by 18%. Hyperprolactinemia in the AP group was found to enhance fractional calcium absorption and calcium retention at 7, 9, and 11 weeks and increased the femoral calcium content by 16%. It could be concluded that a physiological role of prolactin is the stimulation of calcium absorption and maintainance of bone calcium content during growth and development.Key words: bone calcium content, calcium absorption, calcium balance, hyperprolactinemia, prolactin.

Changes in the regulation of calcium metabolism and bone calcium content during growth in the absence of endogenous prolactin and during hyperprolactinemia: A longitudinal study in male and female Wistar rats

Since endogenous prolactin has been shown to enhance food consumption, calcium absorption, and bone calcium turnover in the pregnant rat, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in 3-day balance studies of female Wistar rats from the age of 3 to 11 weeks. The study was divided into two parts. In part I, calcium metabolism in males and females was compared. In part II, 3-week old female rats were divided into 5 groups: (i) control animals receiving 0.9% NaCl; (ii) animals receiving 6 mg bromocriptine/kg/day (- PRLendo group); (iii) animals receiving 2.5 mg ovine prolactin/kg/day (+PRLexo); (iv) sham-operated animals receiving 0.9% NaCl, and (v) animals with two extra pituitaries implanted under the renal capsule, receiving 0.9% NaCl (AP group). Results showed that rapid growth occurred between 3 and 6 weeks with maximum fractional calcium absorption and calcium retention at 5 weeks of age in both sexes. The data also showed a physiological significance of endogenous prolactin in enhancing calcium absorption and retention in 5 week old rats. In an absence of prolactin, peak calcium absorption was delayed in 7-week old animals, and vertebral calcium content of 11-week old animals was reduced by 18%. Hyperprolactinemia in the AP group was found to enhance fractional calcium absorption and calcium retention at 7, 9, and 11 weeks and increased the femoral calcium content by 16%. It could be concluded that a physiological role of prolactin is the stimulation of calcium absorption and maintainance of bone calcium content during growth and development.

Bone turnover response to changes in calcium intake is altered in girls and adult women in families with histories of osteoporosis.

Heredity and environmental factors contribute to the development of osteoporosis. Because calcium is the major mineral in bone and adolescence is a key period in bone acquisition, we hypothesized that bone turnover would be less responsive to alterations in dietary calcium intake in both girls and adult women from families with histories of osteoporosis. To address this issue, we studied calcium kinetics in the maternal grandmother (age range 56-81 years), mother (age range 32-47 years), and granddaughter (age range 8-15 years) in 10 multigenerational families. In five families, the mother and/or grandmother had osteoporosis (bone mineral density > or = 2 SD below the age-specific mean). To examine both active and passive calcium absorption, families consumed low- (279 +/- 64 mg/day) and high- (1580 +/- 385) calcium diets for 10 days prior to administration of oral (46Ca) and intravenous (42Ca) stable isotopes. Using repeated measures analysis of variance, fractional calcium absorption, true calcium absorption, bone calcium deposition, and the balance in bone calcium turnover were all significantly affected by diet (p < 0.01). Females from nonosteoporotic families had decreased bone calcium resorption with little change in bone calcium deposition during the high-calcium study. In contrast, girls and adult women from osteoporotic families had increased both bone calcium deposition and resorption during the high-calcium period, leading to a less positive balance in bone calcium turnover. A significant interaction between bone status and diet was found for bone calcium resorption (p < 0.05) and approached significance for bone calcium deposition (p < 0.07), effects which were independent of generation. We conclude that girls and women from osteoporotic families have a significantly altered bone turnover response to acute changes in calcium intake.

The study of a physiological significance of prolactin in the regulation of calcium metabolism during pregnancy and lactation in rats

Since a pharmacological dose of prolactin has previously been reported to enhance calcium absorption and bone calcium turnover, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in the balance studies of Wistar rats between days 17 and 20 of first (P1) and fourth (P4) pregnancy and between days 12 and 15 of lactation (L). Each group was divided into 3 subgroups: one subgroup was given 0.9% NaCl (control); one was given 0.3 mg bromocriptine/100 g body weight ip twice daily for 3 days (to suppress prolactin secretion); and one was given bromocriptine and 0.25 mg prolactin/100 g body weight sc daily for 3 days. All three groups received 1 mL/100 g body weight of 1.25 mM calcium gluconate containing 2 mCi (1 Ci = 37 GBq) 45Ca daily for 3 days. Compared with the two pregnant controls, the L group had higher food consumption and higher fecal calcium excretion and lower urinary calcium excretion (% intake). Bromocriptine administration increased total calcium excretion from 59% intake to 84 and 66% intake in P1 and P4, respectively, suggesting that endogenous prolactin decreased total calcium excretion. On the other hand, exogenous prolactin had no effect on the calcium balance of P1 but increased the total calcium excretion in P4 from 57 to 66% intake. In contrast, the calcium balance of lactating rats was not altered by suppression of endogenous prolactin secretion or exogenous prolactin. Considering bone 45Ca content as representing bone Ca turnover, a lower value of bone 45Ca content indicated an accelerated bone Ca turnover. It was found that bromocriptine had no effect in P1 but decreased bone Ca turnover rate in the P4 and L groups, indicating an accelerating effect of endogenous prolactin on bone Ca turnover in the P4 and L groups. Exogenous prolactin, on the other hand, decreased bone Ca turnover rate in every group. Muscle Ca turnover was affected by bromocriptine and exogenous prolactin in the same manner as bone 45Ca contents. Interestingly, the biphasic action of prolactin was demonstrated in both calcium absorption and bone calcium turnover. It could be concluded that during pregnancy and lactation, endogenous prolactin increases food consumption, fractional calcium absorption, and bone calcium turnover, apparently to increase calcium availability for fetal development and milk calcium secretion.Key words: bone turnover, bromocriptine, calcium absorption, calcium excretion, calcium retention, prolactin.

The study of a physiological significance of prolactin in the regulation of calcium metabolism during pregnancy and lactation in rats

Since a pharmacological dose of prolactin has previously been reported to enhance calcium absorption and bone calcium turnover, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in the balance studies of Wistar rats between days 17 and 20 of first (P1) and fourth (P4) pregnancy and between days 12 and 15 of lactation (L). Each group was divided into 3 subgroups: one subgroup was given 0.9% NaCl (control); one was given 0.3 mg bromocriptine/100 g body weight ip twice daily for 3 days (to suppress prolactin secretion); and one was given bromocriptine and 0.25 mg prolactin/100 g body weight sc daily for 3 days. All three groups received 1 mL/100 g body weight of 1.25 mM calcium gluconate containing 2 mCi (1 Ci = 37 GBq) 45Ca daily for 3 days. Compared with the two pregnant controls, the L group had higher food consumption and higher fecal calcium excretion and lower urinary calcium excretion (% intake). Bromocriptine administration increased total calcium excretion from 59% intake to 84 and 66% intake in P1 and P4, respectively, suggesting that endogenous prolactin decreased total calcium excretion. On the other hand, exogenous prolactin had no effect on the calcium balance of P1 but increased the total calcium excretion in P4 from 57 to 66% intake. In contrast, the calcium balance of lactating rats was not altered by suppression of endogenous prolactin secretion or exogenous prolactin. Considering bone 45Ca content as representing bone Ca turnover, a lower value of bone 45Ca content indicated an accelerated bone Ca turnover. It was found that bromocriptine had no effect in P1 but decreased bone Ca turnover rate in the P4 and L groups, indicating an accelerating effect of endogenous prolactin on bone Ca turnover in the P4 and L groups. Exogenous prolactin, on the other hand, decreased bone Ca turnover rate in every group. Muscle Ca turnover was affected by bromocriptine and exogenous prolactin in the same manner as bone 45Ca contents. Interestingly, the biphasic action of prolactin was demonstrated in both calcium absorption and bone calcium turnover. It could be concluded that during pregnancy and lactation, endogenous prolactin increases food consumption, fractional calcium absorption, and bone calcium turnover, apparently to increase calcium availability for fetal development and milk calcium secretion.

A three-hour measurement to evaluate bone calcium turnover

It is well established that short-term clearance of an intravenous calcium load in vivo reflects bone uptake. Using results from isotope-dilution experiments with 42Ca, a 3-h test has been developed to measure a quantity, γ, related to bone accretion. This test is proposed as a useful, clinically applicable measure of bone status. For early times, t, after a bolus of 42Ca, plasma tracer dilution was well approximated by t −γ, where γ is related to the fractional rate of loss of tracer, q, from blood into bone ((1/ q)( dq/dt) = −γ/ t). Gamma was evaluated from kinetic measurements on 91 normal female children, adolescents, and adult women in the age range 4–50 years. For t ⩽ 3 h, all clearance curves were well fit by a power function. Gamma was found to vary from 0.244 ± 0.031 for adult premenopausal women (N = 22) to 0.392 ± 0.056 for prepubertal children (N = 29). Using the Spearman rank-order correlation test, γ was correlated with bone accretion measured from classic calcium kinetic studies with a correlation coefficient of 0.721, significant at p < 0.005. In those cases in which accretion and resorption remain tightly linked, γ also provides information on the state of calcium loss from bone. Gamma was evaluated in 14 subjects with bone disease characterised by increased resorption (osteoporosis, Paget's disease) and in 27 subjects with decreased accretion (osteogenesis imperfecta, types I, III, IV; steroid-treated juvenile dermatomyositis). All subjects with Paget's disease and with osteoporosis showed increased γ, consistent with high bone turnover. The osteoporotic patients furthermore exhibited γ increasing monotonically by approximately 1% per year after age 55. The osteogenesis imperfecta patients consistently showed either normal or decreased γ, depending upon the severity of the disease. The steroid-treated dermatomyositis patients had consistently decreased γ, in concordance with previous studies demonstrating decreased accretion in disease states requiring steroid medication.

A three-hour measurement to evaluate bone calcium turnover.

It is well established that short-term clearance of an intravenous calcium load in vivo reflects bone uptake. Using results from isotope-dilution experiments with 42Ca, a 3-h test has been developed to measure a quantity, gamma, related to bone accretion. This test is proposed as a useful, clinically applicable measure of bone status. For early times, t, after a bolus of 42Ca, plasma tracer dilution was well approximated by t-gamma, where gamma is related to the fractional rate of loss of tracer, q, from blood into bone (1/q)(dq/dt) = -gamma/t). Gamma was evaluated from kinetic measurements on 91 normal female children, adolescents, and adult women in the age range 4-50 years. For t < or = 3 h, all clearance curves were well fit by a power function. Gamma was found to vary from 0.244 +/- 0.031 for adult premenopausal women (N = 22) to 0.392 +/- 0.056 for prepubertal children (N = 29). Using the Spearman rank-order correlation test, gamma was correlated with bone accretion measured from classic calcium kinetic studies with a correlation coefficient of 0.721, significant at p < 0.005. In those cases in which accretion and resorption remain tightly linked, gamma also provides information on the state of calcium loss from bone. Gamma was evaluated in 14 subjects with bone disease characterised by increased resorption (osteoporosis, Paget's disease) and in 27 subjects with decreased accretion (osteogenesis imperfecta, types I, III, IV; steroid-treated juvenile dermatomyositis). All subjects with Paget's disease and with osteoporosis showed increased gamma, consistent with high bone turnover. The osteoporotic patients furthermore exhibited gamma increasing monotonically by approximately 1% per year after age 55.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid hormone effects on calcium metabolism in the rat are impaired by 5-ethyl-5′-(1-methylpropyl)-2-thiobarbiturate (inaktin)

The mechanism by which inaktin, a thiobarbiturate, promotes a moderate drop in serum calcium has been investigated. The effect was cancelled in hypocalcemic parathyroidectomized rats. On the other hand inaktin antagonized the serum calcium raising effects of parathyroid extract in these animals. In rats wit intact parathyroid glands inaktin caused a two-fold increase in urinary calcium excretion and a marked decrease in body and bone calcium turnover (measured with 45Ca). These results support the view that inaktin impairs the parathyroid hormone effects on calcium metabolism.

Bone calcium exchange in primary hyperparathyroidism as measured by 47Calcium kinetics

A 2-compartmental analysis of 47Ca kinetics was carried out in 21 patients with primary hyperparathyroidism (pHPT) and 7 healthy control subjects. The results were compared with serum concentrations of calcium, inorganic phosphorus, alkaline phosphatase, and immunoreactive parathyroid hormone (iPTH). The well known increase in exchangeable calcium was found to be not uniform in its subcompartments and with a marked predominance of the osseous fraction. The most important result was the increase of calcium efflux from osseous into extraosseous exchangeable calcium in agreement with the results of Talmage et al. 28 studying PTH actions on calcium flux rates between blood and bone in rats. The increased calcium efflux in pHPT was the only kinetic parameter correlated with serum iPTH. Neither increased calcium accretion indicating high bone turnover, nor serum calcium concentrations and exchangeable calcium fractions correlated with serum iPTH. These results lead to the following conclusions: radiocalcium kinetics provides valuable parameters of bone calcium turnover (osseous exchangeable calcium, bone-calcium efflux, and calcium accretion). Calcium efflux from exchangeable bone calcium, determined kinetically, might be related to PTH induced calcium transport from bone fluid compartment to extracellular fluids according to the concept of Talmage 1977. 18

Longitudinal study of calcium and bone metabolism in paraplegic patients

A longitudinal study of bone and calcium metabolism in 28 patients with spinal chord lesion shows an enhancement of bone calcium accretion, generalized to the whole skeleton. The bone calcium turnover rate is more increased in the non-paralysed area during the first 2 months.

HUMAN CALCITONIN IN THE TREATMENT OF PAGET'S BONE DISEASE

Human synthetic calcitonin has produced a striking clinical and biochemical remission in each of five patients with Paget's disease treated for four to twelve months. Bone pain was relieved and skin temperature over affected limbs reduced. Elevated total urinary hydroxyproline levels fell to within the normal range and serum-alkaline-phosphatase to normal or near normal values. In two patients in whom quantitative histological studies were carried out, the number of osteoclasts was markedly reduced. The new bone formed during therapy had a normal lamellar structure. As assessed by the 47-calcium kinetic studies, the enhanced rate of bone-calcium turnover fell progressively. Calcium balance became positive or more positive. In each of the three patients studied, plasma-parathyroid-hormone levels were within the normal range after treatment for at least nine months. Two patients in remission relapsed slowly when calcitonin was withheld; they responded fully with further treatment.

Calcium Kinetic Studies in Patients with Malabsorption Syndrome

In a group of 12 patients with steatorrhea secondary to various etiologies, defective calcium absorption and negative calcium balance occurred in all patients with biochemical osteomalacia. Losses of body calcium resulted from obligatory endogenous fecal losses. High endogenous fecal calcium values appeared to be due to increased digestive juice secretions as well as defective reabsorption. Bone calcium turnover in osteomalacia varied from below to well above the normal range in agreement with reported data on bone biopsy studies. Markedly elevated bone calcium accretion rates were found in idiopathic steatorrhea alone and were associated with advanced bone disease.

Vitamin D-Resistant Rickets and High Fecal Endogenous Calcium Output : A Report of Two Cases

Combined balance and radiocalcium kinetic studies were carried out in two children with vitamin D-resistant rickets during vitamin D therapy (50,000 U/day), and again 8 weeks after vitamin withdrawal. These studies showed: 1) high fecal endogenous calcium excretion, which was slightly aggravated by vitamin D withdrawal; 2) apparently normal intestinal calcium absorption, which was not enhanced by vitamin D therapy; and 3) markedly increased bone-calcium turnover rates following vitamin D withdrawal. High fecal endogenous calcium loss and unresponsiveness of gastrointestinal absorption of calcium to vitamin D are suggested as the primary defects in these two cases. In the absence of any demonstrable increase in the net absorption of calcium from the gastrointestinal tract, the diminution of bone turnover and the increased urinary calcium excretion observed during vitamin D therapy are interpreted as direct effects of the vitamin.