Effect of glucocorticoids and calcium intake on bone density and bone, liver and plasma minerals in guinea pigs.

The purpose of this study was to see what effect glucocorticoids would have on bone density and mineral distribution in guinea pigs. Adult female guinea pigs were given prednisolone, a synthetic analogue of cortisol, for up to 24 weeks. Bone density and bone, liver and plasma levels of zinc, copper, iron, manganese, chromium, magnesium and calcium were studied in these animals. In one study, the effect of menopause was simulated by using ovariectomy. In another study, dietary calcium was varied to investigate its effect with glucocorticoids. Animals treated with 1 mg prednisolone/kg body weight showed increased femur density compared with controls, but no changes in tissue mineral concentrations. Animals fed 100 mg prednisolone/kg body weight experienced decreased femur density. Differences in effects were not observed between ovariectomized and intact animals. Bone loss was greatest in animals fed the cereal-based closed-formula diet and least in animals fed the low-calcium diet. Changes in mineral content of femurs observed in animals which lost bone mass were increased iron concentration and decreased magnesium concentration. Total liver stores of zinc and magnesium increased. Liver copper increased in concentration per gram as well as in total content. Liver concentration of manganese decreased. Plasma changes in animals fed the high level of drug were decreased iron and calcium, and increased copper. Hemoglobin and hematocrit increased with increasing drug levels. It is suggested that glucocorticoids have marked effects on mineral metabolism which may be related to the bone loss and that these effects may be modified by dietary changes.     

Side effects of danazol compared with an ethinyloestradiol/norgestrel combination when used for postcoital contraception

A postcoital contraceptive with a lower incidence of nausea and vomiting than oestrogen-progestogen combinations would be a significant advance. During a nine-month period, 101 women were treated at the Margaret Pyke Centre in London with either an oestrogen-progestogen combination or with danazol. A comparison of the side effects of each drug is reported. Those treated with danazol were six times less likely to experience nausea and none vomited. With the exception of breast symptoms, other side effects were five times less common in women receiving danazol. These differences give danazol a clear advantage in terms of patient acceptability. Further experience will enable the efficacy of danazol to be evaluated and so determine whether this drug should become the preferred hormonal postcoital treatment.     

Effects of fluoride and ethane-1-hydroxy-1,1-diphosphonate on bone metabolism in the growing chick.

White Leghorn cockerols were fed a semipurified diet (containing fluoride at 0 to 800 ppm) from the day of hatching. The birds were also injected daily with solutions containing ethane-1-hydroxy-1,1-diphosphonate (EHDP) at concentrations ranging from 5 to 20 mg as phosphorus/kg of body weight or isotonic saline. Changes in bone mineral composition and plasma Ca, Mg and F were determined as well as alterations in bone pyrophosphatase and the amounts of bone cyclic-3',5'-adenosine monophosphate (cAMP). Since dietary fluoride in high amounts is known to stimulate new bone formation, the purpose of the study was to assess whether a potent inhibitor of mineralization, such as EHDP, might alter the response to high dietary fluoride. Although bone fluoride and magnesium were increased in relationship to dietary fluoride, the administration of EHDP had little effect on these changes at low to moderate levels of fluoride. The levels of soluble bone pyrophosphatase were not greatly influenced by changes in dietary fluoride. Administration of EHDP at 20 mg P/kg, however, typically decreased the levels of bone pyrophosphatase. Bone cAMP did not appear to be influenced by either dietary fluoride or EHDP. Using tissue culture techniques, the effects of fluoride on calcium uptake and release from embryonic chick bone were also studied. The presence of 1 mM fluoride in the medium appeared to stimulate calcium uptake and reduced calcium release from chick bone. In general, the results were in keeping with previous suggestions that the major effect of fluoride on bone is the formation of fluoroapatite and subsequent effects this may have on other metabolic alterations.     

Verapamil stimulates Ca(++)-uptake and Ca(++)-ATPase in plasma membrane vesicles of guinea pig spermatozoa

Verapamil, a potent calcium channel blocker, was administered orally at three different doses to guinea pigs for both short- (4 weeks) and long-term (12 weeks) effects. The drug treatment stimulated Ca(++)-transport and Ca(++)-activated ATPase in isolated plasma membrane vesicles of guinea pig spermatozoa. Ca(++)-uptake studies exhibited partial to complete restoration of stimulated Ca(++)-transport during recovery period, whereas the CA(++)-activated ATPase system remained stimulated even after 4 and 6 weeks of withdrawal of the drug treatment. The lack of inhibitory effect of verapamil on Ca(++)-uptake ruled out the involvement of calcium channels in spermatozoal calcium uptake in guinea pigs. The stimulatory effect of the drug on CA(++)-uptake, on the other hand, might indicate the possible capability of this lipophilic compound to induce favourable changes in the lipid microenvironment of the membrane, wherein the integral membrane proteins operate.     

Evidence for insulin involvement in arginine- and glucose-induced hypercalciuria in the rat

Urinary calcium excretion is increased after the consumption of protein and carbohydrate by both the human and the rat due to a decreased efficiency in the renal reabsorption of calcium. We have previously shown that the magnitude of the postprandial change in urine calcium in human subjects fed a high protein meal was correlated with the protein-induced changes in serum insulin levels. The present study investigates further the relationship between plasma insulin and urinary calcium excretion. Renal calcium clearance studies were performed in rats infused with the insulin secretagogues glucose or arginine, in the presence and absence of mannoheptulose, a drug which suppresses insulin secretion. The hypercalciuretic effect of arginine was also examined in streptozotocin (SZ) diabetic rats. Arginine and glucose infusion increased urinary calcium excretion by 575 and 225%, respectively, by a mechanism which could be inhibited by mannoheptulose. A linear relationship (r = 0.86) was observed between plasma insulin and urinary calcium excretion. Arginine infusion had no effect on urinary calcium excretion in the SZ diabetic rat, in marked contrast to its effect on normal animals. We conclude that insulin is an important mediator of arginine- and glucose-induced hypercalciuria in the rat.     

Interaction of dietary calcium and protein in bone health in humans

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.     

钙对染铅大鼠骨钙素、甲状旁腺激素及其受体表达的影响

目的:研究钙对铅染毒大鼠骨钙素(OC)、甲状旁腺激素(PTH)及其受体(PTHr1)表达的影响。方法:分别以纯净水和1.0g/L醋酸铅水饲喂Wistar大鼠,其中醋酸铅饲喂大鼠又分为正常饲料、高钙饲料和低钙饲料组。测定大鼠骨钙、骨铅、OC和PTH含量,并采用RT-PCR方法观察OC和PTHr1mRNA的表达。结果:铅处理降低了骨钙和血清OC的含量,抑制了OC mRNA的表达;但同时血清PTH的含量升高,PTHr1的表达增强;而高钙可以拮抗铅的这些作用,低钙则加剧了铅的上述效应。结论:补充膳食钙可减轻铅对大鼠骨骼的毒性作用。     

Calcium transport and Ca(++)-ATPase activity in spermatozoal plasma membrane vesicles of nifedipine-administered guinea pigs.

Spermatozoal plasma membrane vesicles isolated from distal portion of the epididymis and vas deferens were found to contain Ca(++)-activated ATPase and calcium transport activities. Nifedipine was administered at two different doses (1.0 and 2.5 mg/kg b.w./day) and the effect was observed for both short- (4 week) and long-term (12 week) period. The cellular ionic calcium content and Ca(++)-ATPase activity were observed to be enhanced in the drug-treated animals. The recovery studies carried out after 4 and 6 weeks of withdrawal of the drug treatment exhibited partial to complete restoration of observed changes. The stimulatory rather than inhibitory effect of Nifedipine, a specific calcium channel blocker, on calcium uptake may suggest that voltage-sensitive calcium channels may be lacking in guinea pig spermatozoa. The stimulatory effect of the drug is speculated to be either by inhibition of Na(+)-Ca++ antiporter or G-protein activated agonistic effect or probably due to altered physicochemical properties of the drug-treated sperm plasma membranes.     

Stop Dietary Calcium Restriction in Kidney Stone–forming Patients

Epidemiologic studies have demonstrated an increased incidence of kidney stones in individuals with low calcium intake. More recently, a 5-year clinical study found the recurrence of kidney stones was higher in stone-formers on a low dietary calcium treatment. Considering these important new findings, and the known adverse effect on bone mass, dietary calcium restriction should be avoided in kidney stone–forming individuals.     

Insulin-like growth factor-1 increases bone calcium accumulation only during rapid growth in female rats

Calcium retention varies with developmental state, which may be partially under the control of insulin-like growth factor 1 (IGF-1). IGF-1 levels can be manipulated through dietary and therapeutic interventions. We investigated the relationship between IGF-1 endogenous production and calcium utilization and bone accretion during growth as well as the effects of IGF-1 treatment on calcium utilization during rapid and slowed growth in intact female Sprague-Dawley rats. In 33 rats killed at 11 time points (n = 3 each) from age 4 to 24 wk, femoral and vertebral bone mass were paralleled by plasma IGF-1 up to 9 wk. Fractional calcium absorption was maximal at 9 wk, reduced by one-half at 12 wk, and there was no further change at 20 wk. From this study, we selected 2 stages of growth, rapid and slow, for a subsequent intervention study. A 4-wk intervention was initiated at 6 or 8 wk when rats (n = 15/group) received either continuous rhIGF-1/IGF binding protein 3 (IGFBP3) infusion (0.3 mg/d) or vehicle (control) by osmotic mini-pumps. In rapidly growing IGF-1/IGFBP3-treated rats compared to controls, but not in slowly growing treated compared to control rats, IGF-1 treatment increased (P < 0.05) calcium absorption (35 vs. 21%), bone calcium balance (0.55 vs. 0.3 mmol/d), and femoral calcium content (31 vs. 24% of dry weight). Exogenous IGF-1/IGFBP3 treatment increased calcium accretion during rapid growth, but rats past rapid growth were no longer as sensitive to this dose of IGF-1/IGFBP3. Thus, interventions designed to improve bone mass through increased IGF-1 will have the greatest impact during rapid growth.     

Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men

INTRODUCTION: Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism in experimental animals and cells in culture, but there are limited human data available. OBJECTIVE: To investigate the effect of CLA supplementation on biomarkers of calcium and bone metabolism in healthy adult males. DESIGN: The study consisted of a double-blind, placebo-controlled trial in which 60 healthy adult males (aged 39-64 y) were randomly assigned to receive daily either 3.0 g CLA isomer blend (50:50% cis-9,trans-11:trans-10,cis-12 isomers) or a palm/bean oil blend (placebo) for 8 weeks. Urine and blood samples were collected at weeks 0 and 8 and were analysed for biomarkers of calcium and bone metabolism. RESULTS: Supplementation with CLA or placebo for 8 weeks had no significant effects on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline), or on serum or urinary calcium levels. Baseline levels of these biochemical parameters were similar in both groups of subjects. While the placebo had no effect, CLA supplementation resulted in a three-fold increase (P<0.00001) in cis-9,trans-11 CLA isomer in total plasma lipids. CONCLUSION: Under the conditions tested in this double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism. Further investigation of the effects of CLA on calcium and bone metabolism in other gender- and age-groups is warranted.     

Effect of cadmium administration on intestinal calcium absorption and vitamin D-dependent calcium-binding protein

The effects of cadmium on intestinal calcium absorption and calcium-binding protein (CaBP) were investigated in chicks by means of the in situ ligated duodenal loop technique. Dietary cadmium, administered in the feed or by gastric intubation, resulted in significant declines in intestinal calcium absorption and mucosal calcium-binding protein concentrations. Cadmium chloride injected directly into the ligated loop of naive chicks also diminished calcium absorption and CaBP concentrations in an apparently dose-response related fashion. No adverse effects of cadmium administration on either the 25- or 1α-hydroxylation reactions of vitamin D were observed. While the general effect of cadmium administration was a reduction in intestinal calcium absorption, plasma calcium levels were consistently elevated in Cd-treated chicks, with the exception of those also maintained on diets low in Ca. The results indicate that cadmium toxicity exerts at least two effects on Ca metabolism, one at the intestinal level and another at the level of the bone, kidney, or both.     

Calcium supplementation provides an extended window of opportunity for bone mass accretion after menarche

BACKGROUND: High calcium intakes during adolescence may increase bone acquisition. The magnitude of the effect of dietary calcium supplementation and the timing of its administration to achieve significant effects on bone health are still incompletely defined. OBJECTIVE: The objective of this study was to assess the effect of calcium supplementation on bone mass accretion in postmenarcheal adolescent girls with low calcium intakes. DESIGN: A double-blind, placebo-controlled calcium supplementation study was implemented. One hundred girls with a mean (+/- SD) age of 14 +/- 0.5 y with habitual calcium intakes < 800 mg/d completed a 12-mo protocol. The treatment group received a daily supplement containing 1000 mg elemental calcium. Bone mineral density (BMD) and bone mineral content (BMC) of the total body, lumbar spine, and femoral neck were determined at inclusion, 6 mo, and 12 mo. Also measured were serum concentrations of biochemical markers of bone turnover (osteocalcin and deoxypyridinoline), parathyroid hormone, and vitamin D. RESULTS: The calcium-supplemented group had greater accretion of total-body BMD and lumbar spine BMD but not BMC than did the control group. Calcium supplementation appeared selectively beneficial for girls who were 2 y postmenarcheal. Calcium supplementation significantly decreased bone turnover and decreased serum parathyroid hormone concentrations. CONCLUSION: Calcium supplementation of postmenarcheal girls with low calcium intakes enhances bone mineral acquisition, especially in girls > 2 y past the onset of menarche.     

Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial

BACKGROUND: Short-term studies established that calcium influences bone accretion during growth. Whether long-term supplementation influences bone accretion in young adults is not known. OBJECTIVE: This study evaluated the long-term effects of calcium supplementation on bone accretion among females from childhood to young adulthood. DESIGN: A 4-y randomized clinical trial recruited 354 females in pubertal stage 2 and optionally was extended for an additional 3 y. The mean dietary calcium intake of the participants over 7 y was approximately 830 mg/d; calcium-supplemented persons received an additional approximately 670 mg/d. Primary outcome variables were distal and proximal radius bone mineral density (BMD), total-body BMD (TBBMD), and metacarpal cortical indexes. RESULTS: Multivariate analyses of the primary outcomes indicated that calcium-supplementation effects vary over time. Follow-up univariate analyses indicated that all primary outcomes were significantly larger in the supplemented group than in the placebo group at the year 4 endpoint. However, at the year 7 endpoint, this effect vanished for TBBMD and distal radius BMD. Longitudinal models for TBBMD and proximal radius BMD, according to the time since menarche, showed a highly significant effect of supplementation during the pubertal growth spurt and a diminishing effect thereafter. Post hoc stratifications by compliance-adjusted total calcium intake and by final stature or metacarpal total cross-sectional area showed that calcium effects depend on compliance and body frame. CONCLUSIONS: Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt. By young adulthood, significant effects remained at metacarpals and at the forearm of tall persons, which indicated that the calcium requirement for growth is associated with skeletal size. These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth.     

Drug treatments for mastalgia: 17 years experience in the Cardiff Mastalgia Clinic.

Mastalgia commonly presents to medical practitioners. The majority of patients can be managed by exclusion of cancer and reassurance. In some the severity of pain affects the quality of life and drug treatment should be considered. Since its inception 324 patients with cyclical mastalgia and 90 with non-cyclical mastalgia have received a therapeutic trial of drug treatment in the Cardiff Mastalgia Clinic. Overall 92% of those with cyclical mastalgia and 64% with non-cyclical mastalgia obtained a clinically useful response to therapy. Danazol was the most effective drug, with bromocriptine and evening primrose oil having equivalent efficacy. Many fewer adverse events were complained of by patients treated with evening primrose oil than danazol or bromocriptine.     

Osteoporosis: calcium, fluoride, and aluminum interactions

A gradual loss of bone occurs with age. There are indications in the literature that not only calcium but also fluoride may play an important role in maintaining the bone mass. In view of the high incidence of osteoporosis and its complications, and in view of the fact that fluoride is beneficial for the treatment of osteoporosis, studies have been carried out in this research unit to determine the retention and excretion of fluoride both during a normal dietary intake of fluoride and during fluoride supplementation. Another problem to be examined was to delineate whether certain substances interfere with the intestinal absorption of fluoride and of calcium. One such substance is aluminum contained in commonly used antacids. The use of small amounts of aluminum-containing antacids increased fecal fluoride significantly, thereby decreasing the intestinal absorption of fluoride. In addition, the small doses of aluminum-containing antacids also affected the metabolism of calcium and phosphorus, the primary effect being complexation of phosphorus in the intestine leading to phosphorus depletion. This change in phosphorus metabolism was associated with an increase of the urinary and fecal calcium excretion resulting in a negative calcium balance. The dual effect of aluminum, namely in causing calcium loss and inhibition of the intestinal absorption of fluoride, can result in adverse effects on bone which may contribute to bone loss.     

Osteoporosis: calcium,fluoride, and aluminum interactions.

A gradual loss of bone occurs with age. There are indications in the literature that not only calcium but also fluoride may play an important role in maintaining the bone mass. In view of the high incidence of osteoporosis and its complications, and in view of the fact that fluoride is beneficial for the treatment of osteoporosis, studies have been carried out in this research unit to determine the retention and excretion of fluoride both during a normal dietary intake of fluoride and during fluoride supplementation. Another problem to be examined was to delineate whether certain substances interfere with the intestinal absorption of fluoride and of calcium. One such substance is aluminum contained in commonly used antacids. The use of small amounts of aluminum-containing antacids increased fecal fluoride significantly, thereby decreasing the intestinal absorption of fluoride. In addition, the small doses of aluminum-containing antacids also affected the metabolism of calcium and phosphorus, the primary effect being complexation of phosphorus in the intestine leading to phosphorus depletion. This change in phosphorus metabolism was associated with an increase of the urinary and fecal calcium excretion resulting in a negative calcium balance. The dual effect of aluminum, namely in causing calcium loss and inhibition of the intestinal absorption of fluoride, can result in adverse effects on bone which may contribute to bone loss.     

Effects of dietary aluminum on chicks Gallus gallus domesticus with different dietary intake of calcium and phosphorus

Birds that feed in acidified areas may be exposed to an increased intake of aluminum, while their intake of calcium and phosphorus may simultaneously be low. In particular, juvenile birds foraging in acidified areas may suffer from increased effects of aluminum due to high demands of calcium. Day old chicks were fed six different diets where aluminum was combined with normal and low concentrations of dietary calcium and phosphorus for 14 days. The normal calcium-available phosphorus (Ca-P) level was 1.05%–0.45%, and the low dietary Ca-P level was 0.49%–0.21%. Aluminum was given in dietary levels of 0%, 0.13%, and 0.31%. Aluminum had no effects on growth, mortality, or hematocrit, but induced hypocalcemia.Bones accumulated more aluminum than kidneys. A high dietary concentration of aluminum (0.31%) increased the accumulation of aluminum twofold in bones and threefold in kidneys when the dietary concentration of calcium and phosphorus was halved. Opposed to the predictions, bone mineralisation was stimulated by an intermediate increase in dietary aluminum (0.13%) at both levels of dietary calcium and phosphorus. Bone stiffness was also stimulated at this dietary aluminum concentration, but only at the diet low in calcium and phosphorus. A high dietary aluminum concentration did not have any effect on bone stiffness or calcium concentration. Bone stiffness correlated positively with the calcium concentration in bone, and negatively with the aluminum concentration in bone. The effect of dietary aluminum on bone stiffness is probably caused by an alteration in bone mineralization, rather than by the presence of aluminum in bones.     

Calcium from plant sources is beneficial to lowering the risk of osteoporosis in postmenopausal Korean women

Osteoporosis, which has become a serious public health concern, is influenced by diet, especially calcium intake. Dairy products are a good source of calcium, but plant calcium may also be important in populations that do not consume a large amount of milk. The purpose of the present study was to examine the hypothesis that calcium from vegetable sources is associated with osteoporosis risk and bone mineral density in postmenopausal Korean women with osteoporosis and age-matched controls (N = 144). The results of multivariate-adjusted regression analyses indicated that the intake of calcium, plant calcium, potassium, vitamin A, carotene, vitamin B₁, niacin, vitamin E, vitamin C, and vegetables was associated with significantly reduced risk of osteoporosis after adjusting for age, body mass index, hormone replacement therapy, and energy intake. In addition, intake of vegetables alone, as well as calcium, plant calcium, potassium, and antioxidant vitamins (vitamin C, vitamin E, β-carotene), which are abundant in vegetables, was significantly and positively associated with bone mineral density. However, in this population of low-dairy consumers, intake of calcium from meat and dairy products was not related to risk of osteoporosis and bone mineral density. Our results suggest that high dietary intake of calcium, especially plant calcium, reduces the risk of osteoporosis and increased bone mineral density in postmenopausal Korean women. Vegetables may be an important source of calcium and may also provide vitamins and minerals that exert additional beneficial effects on the bone.