Stimulate Parathyroid Hormone Secretion Research Articles

Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors

ObjectivePatients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency. MethodsWe enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed. ResultsAldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism. ConclusionPTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.

Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion

In brief: A specific anion binding site senses moderate changes of inorganic phosphate levels leading to rapid inhibition of CaSR responsiveness and PTH secretion in a murine and human in vitro model system.

Differentiation of Rat Adipose-Derived Stem Cells into Parathyroid-Like Cells.

Background The current treatment for postoperative hypoparathyroidism has shortcomings, such as repeated blood monitoring for dosage adjustment, uncertain long-term efficacy, and the high price of recombinant parathyroid hormone therapy. Adipose-derived stem cells can undergo adipogenic and osteogenic differentiation in vitro and are considered a novel source of parathyroid-like cells, but the idea lacks theoretical basis and feasibility. We aimed at establishing a protocol for differentiating adipose-derived stem cells into parathyroid-like cells for treating hypoparathyroidism. Materials/Methods Adipose-derived stem cells were isolated and purified from the inguinal adipose tissue of Sprague Dawley rats. Adipogenic differentiation and osteogenic differentiation of the cells were identified by oil red O and alizarin red S staining, respectively. The adipose-derived stem cells were stimulated by sonic hedgehog (SHH) and activin A. The differentiation of the adipose-derived stem cells to parathyroid-like cells was confirmed by the detection of parathyroid hormone and the related parathyroid markers. Results Adipose-derived stem cells were successfully isolated and purified from the rat adipocytes. The adipogenic and osteogenic differentiation capabilities of the adipose-derived stem cells were determined. SHH and activin A stimulated parathyroid hormone secretion by the adipose-derived stem cells and significantly increased the expression of calcium-sensing receptor (CaSR), parathyroid hormone, and glial cells missing homolog 2 (GCM2) in the cells in a time- and concentration-dependent manner. Conclusion We successfully differentiated rat adipose-derived stem cells into parathyroid-like cells, which will pave a new route to curing hypoparathyroidism.

Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion

Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). However, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration, the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.

Comparison of 0.46% calcium diets with and without added anions with a 0.7% calcium anionic diet as a means to reduce periparturient hypocalcemia

Most studies demonstrating that diets with low dietary cation-anion difference (DCAD) reduce hypocalcemia in cows add enough anions to the diet to reduce urine pH below 7.0. One objective of these experiments was to determine whether there is any benefit to periparturient plasma Ca concentration if diet anion addition results in a lesser degree of acidification of the cow and urine pH does not go below 7.0. Another method for reducing hypocalcemia involves feeding a prepartal diet that is Ca deficient. This places the cow in negative Ca balance before calving, stimulating parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D secretion before calving and thus promoting Ca homeostasis at calving. As practiced in the field, low-Ca diets are often about 0.5% Ca. Our second objective was to determine whether a 0.46% Ca diet would be sufficiently low in Ca to stimulate PTH secretion before calving. A meta-analysis of the literature suggests that a 0.5% Ca, low-DCAD diet will reduce hypocalcemia better than a 0.7% Ca diet. A third objective was to compare periparturient plasma Ca in cows fed 0.46 or 0.72% Ca diets with similar DCAD. In experiment 1, anions (primarily chloride) or anions plus Ca were added to a 1.4% K basal diet to create the following diets: 0.46% Ca and +167 mEq/kg of DCAD, 0.46% Ca and -13 mEq/kg of DCAD, and 0.72% Ca and -17 mEq/kg of DCAD. In experiment 2, the same amounts of anion were added to a 2.05% K basal diet to create the following diets: 0.46% Ca and +327 mEq/kg of DCAD, 0.46% Ca and +146 mEq/kg of DCAD, and 0.72% Ca and +140 mEq/kg of DCAD. In experiment 1, cows fed the diet with 0.46% Ca and +167 mEq/kg of DCAD had significantly lower plasma Ca concentration after calving than cows fed the 0.46 or 0.72% Ca diets with anions. Periparturient plasma Ca concentrations did not differ in cows fed the low-DCAD diets with 0.46 or 0.72% Ca. Urine pH was reduced from 8.27 in the diet with 0.46% Ca and +167 mEq/kg of DCAD to 7.07 and 7.41 in the 0.46 and 0.72% Ca anion diets, respectively. Precalving plasma PTH and 1,25-dihydroxyvitamin D concentrations were similar in cows fed the 0.46% Ca diets and the 0.72% Ca diets, suggesting that the 0.46% Ca diets were not low enough in Ca to place the cow in negative Ca balance before calving. In experiment 2, adding the anion supplements to a 2.05% K diet did not reduce urine pH below 8.0. Periparturient plasma Ca concentrations did not differ in cows in any group in experiment 2. Precalving diets that are 0.46% Ca fed ad libitum are too high in Ca to stimulate Ca homeostasis before calving. Adding anions to a diet can benefit periparturient cow plasma Ca concentration, but only if it alters acid-base status enough to reduce urine pH below 7.5.

Annals for Educators - 6 June 2017

Annals for Educators - 6 June 2017

Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system.

Interactions between sodium and calcium regulating systems are poorly characterized but clinically important. Parathyroid hormone (PTH) levels are increased shortly after furosemide treatment by an unknown mechanism, and this effect is blunted by the previous administration of a calcimimetic in animal studies. Here, we explored further the possible underlying mechanisms of this observation in a randomized crossover placebo-controlled study performed in 18 human males. Volunteers took either cinacalcet (60 mg) or placebo and received a 20 mg furosemide injection 3 h later. Plasma samples were collected at 15-min intervals and analyzed for intact PTH, calcium, sodium, potassium, magnesium, phosphate, plasma renin activity (PRA), and aldosterone up to 6 h after furosemide injection. Urinary electrolyte excretion was also monitored. Subjects under placebo presented a sharp increase in PTH levels after furosemide injection. In the presence of cinacalcet, PTH levels were suppressed and marginal increase of PTH was observed. No significant changes in electrolytes and urinary excretion were identified that could explain the furosemide-induced increase in PTH levels. PRA and aldosterone were stimulated by furosemide injection but were not affected by previous cinacalcet ingestion. Expression of NKCC1, but not NKCC2, was found in parathyroid tissue. In conclusion, our results indicate that furosemide acutely stimulates PTH secretion in the absence of any detectable electrolyte changes in healthy adults. A possible direct effect of furosemide on parathyroid gland needs further studies.

Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health

Emerging evidence suggests a stimulating effect of parathyroid hormone (PTH) on the renin–angiotensin–aldosterone system (RAAS). In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the RAAS which may explain the increased risk of cardiovascular disease (CVD). In addition to increased PTH levels, low vitamin D levels may also directly increase risk of CVD, as vitamin D, itself, has been shown to inhibit the RAAS. Angiotensin II, aldosterone and cortisol all negatively impact bone health. Hyperaldosteronism is associated with a reversible secondary hyperparathyroidism due to increased renal calcium excretion. Moreover, the angiotensin II receptor is expressed by human parathyroid tissue, and angiotensin may therefore directly stimulates PTH secretion. An increased bone loss is found in patients with hyperaldosteronism. The angiotensin II receptor seems main responsible for the RAAS-initiated bone loss due to a receptor activator of NF-κB ligand-mediated activation of the osteoclasts. Available data suggest a reduced fracture rate and increased bone mineral density in patients treated with angiotensin II receptor blockers, whereas treatment with angiotensin-converting enzyme inhibitors causes the opposite effects. Mineralocorticoid receptor antagonists seem to be beneficial to bone in patients with hyperaldosteronism, but it is unknown whether this also applies to other individuals. Further long-term studies are needed to clarify the effect of RAAS inhibitors on bone health. RAAS inhibitors, are widely prescribed worldwide and beneficial as well as harmful effects may have large impact on bone health in the general population.

Interactions between adrenal-regulatory and calcium-regulatory hormones in human health

To summarize the evidence characterizing the interactions between adrenal-regulating and calcium-regulating hormones, and the relevance of these interactions to human cardiovascular and skeletal health. Human studies support the regulation of parathyroid hormone (PTH) by the renin-angiotensin-aldosterone system (RAAS): angiotensin II may stimulate PTH secretion via an acute and direct mechanism, whereas aldosterone may exert a chronic stimulation of PTH secretion. Studies in primary aldosteronism, congestive heart failure, and chronic kidney disease have identified associations between hyperaldosteronism, hyperparathyroidism, and bone loss, which appear to improve when inhibiting the RAAS. Conversely, elevated PTH and insufficient vitamin D status have been associated with adverse cardiovascular outcomes, which may be mediated by the RAAS. Studies of primary hyperparathyroidism implicate PTH-mediated stimulation of the RAAS, and recent evidence shows that the vitamin D-vitamin D receptor complex may negatively regulate renin expression and RAAS activity. Ongoing human interventional studies are evaluating the influence of RAAS inhibition on PTH and the influence of vitamin D receptor agonists on RAAS activity. Although previously considered independent endocrine systems, emerging evidence supports a complex web of interactions between adrenal-regulating and calcium-regulating hormones, with implications for human cardiovascular and skeletal health.

Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone Secretion

Oral phosphorus supplementation stimulates fibroblast growth factor 23 (FGF23) secretion; however, the underlying mechanism remains unclear. The aim of this study was to investigate the involvement of parathyroid hormone (PTH) in increased plasma FGF23 levels after oral phosphorus supplementation in rats. Rats received single dose of phosphate with concomitant subcutaneous injection of saline or human PTH (1-34) after treatment with cinacalcet or its vehicle. Cinacalcet is a drug that acts as an allosteric activator of the calcium-sensing receptor and reduces PTH secretion. Plasma phosphorus and PTH levels significantly increased 1 h after oral phosphorus administration and returned to basal levels within 3 h, while plasma FGF23 levels did not change up to 2 h post-treatment, but rather significantly increased at 3 h after administration and maintained higher levels for at least 6 h compared with the 0 time point. Plasma PTH and FGF23 levels were significantly lower in the cinacalcet-treated rats than in the vehicle-treated rats. Plasma phosphorus levels were significantly higher in the cinacalcet-treated rats than in the vehicle-treated rats at 2, 3, 4, and 6 h after oral phosphorus administration. Furthermore, rats treated with cinacalcet+human PTH (1-34) showed transiently but significantly higher plasma FGF23 levels at 3 h after oral phosphorus administration compared with cinacalcet-treated rats. These results suggest that oral phosphorus supplementation secondarily increases circulating FGF23 levels at least partially by stimulation of PTH secretion.

Digoxin‐associated decrease in parathyroid hormone (PTH) concentrations in patients with atrial fibrillation

Parathyroid hormone (PTH) secretion is regulated mainly by the calcium sensor receptor. Recently, other components of calcium homoeostasis have been revealed, namely the effect of Klotho on stimulation of PTH secretion by the recruitment of Na-K-ATPase and by its being a cofactor in the inhibitory effect of FGF 23 on PTH secretion. It seems that ouabain, a Na-K-ATPase inhibitor, prevents the increase in PTH secretion in a hypocalcemic environment, as observed in mouse and bovine tissues. We hypothesized that digoxin, which is similar to ouabain in its effect on the sodium pump, might decrease PTH levels in humans. Twenty patients with atrial fibrillation were studied. Ten patients were treated with digoxin and the other ten patients with verapamil. Baseline chemistry parameters were determined and 0·25mg digoxin injected. Plasma PTH concentrations, ionized calcium concentrations and digoxin levels were recorded at 30min, 1h, 2h and 4h postinjection. Baseline blood parameters were similar in both groups. In the control group plasma PTH concentrations increased, whereas in the digoxin group, they decreased. Ionized calcium concentrations did not change over time in either groups. There seemed to be blunting of the circadian rhythm of PTH levels in the morning hours. Although the patients were normocalcemic, plasma PTH concentrations decreased with digoxin treatment. The effect of the sodium pump on PTH secretion might be important in human PTH homoeostasis and might be a potential target for the treatment of disturbances in calcium homoeostasis.

Excessive Decrease in Serum Magnesium After Total Thyroidectomy for Graves’ Disease Is Related to Development of Permanent Hypocalcemia

Transient postoperative hypocalcemia is one of the most common complications after thyroidectomy. Permanent hypocalcemia, however, is rare, but usually requires life-long treatment and follow-up. The risk of permanent hypocalcemia has been shown to be significantly higher in patients with Graves' disease. In the present study we evaluated short-term and long-term changes in serum calcium, phosphate, magnesium, and parathyroid hormone (PTH) levels in order to characterize subjects at risk of postoperative hypoparathyroidism. Forty patients who underwent total thyroidectomy for Graves' disease were included in the study. Calcium, phosphate, magnesium, and PTH were measured before surgery and regularly during the year that followed. Postoperative hypocalcemia was seen in 21/40 (53 %) patients. Undetectable PTH (<0.6 pmol/L) was registered in 11/40 (27 %) patients. All patients with measurable PTH 6-48 h after operation regained normal calcium. Of those with undetectable PTH after 6-48 h, four developed permanent hypocalcemia. We found a significantly lower serum calcium level before operation in patients who developed permanent hypocalcemia compared to those who did not (p < 0.001). We also found a significant correlation between the decrease in serum magnesium from time 0 to 48 h after operation and permanent hypocalcemia (p = 0.015). Serum calcium prior to operation, serum PTH, and degree of decrease in magnesium levels in serum 48 h after operation may predict development of permanent hypocalcemia. Magnesium plays an important role in calcium homeostasis via stimulation of PTH secretion and modulation of PTH receptor sensitivity. Both mechanisms may have played a role for the findings reported in this article.

ATF936, a novel oral calcilytic, increases bone mineral density in rats and transiently releases parathyroid hormone in humans

Parathyroid hormone (PTH), when injected daily as either the intact hormone PTH(1-84) or the active fragment PTH(1-34) (teriparatide), is an efficacious bone anabolic treatment option for osteoporosis patients. Injections lead to rapid and transient spikes in hormone exposure levels, a profile which is a prerequisite to effectively form bone. Oral antagonists of the calcium-sensing receptor (calcilytics) stimulate PTH secretion and represent thus an alternative approach to elevate hormone levels transiently. We report here on ATF936, a novel calcilytic, which triggered rapid, transient spikes in endogenous PTH levels when given orally in single doses of 10 and 30mg/kg to growing rats, and of 1mg/kg to dogs. Eight weeks daily oral application of 30mg/kg of ATF936 to aged female rats induced in the proximal tibia metaphysis increases in bone mineral density, cancellous bone volume and cortical and trabecular thickness as evaluated by computed tomography. In healthy humans, single oral doses of ATF936 produced peak PTH levels in plasma after a median time of 1h and levels returned to normal at 24-h post-dose. The average maximum PTH concentration increase from baseline was 1.9, 3.6, and 6.0-fold at doses of 40, 70, and 140mg. ATF936 was well tolerated. The sharp, transient increase in PTH levels produced by the oral calcilytic ATF936 was comparable to the PTH profile observed after subcutaneous administration of teriparatide. In conclusion, ATF936 might hold potential as an oral bone-forming osteoporosis therapy.

Novel calcium sensing receptor ligands: a patent survey

Introduction: In the parathyroid gland, the calcium sensing receptor responds to small changes in circulating levels of Ca2+, and consequently stimulates or inhibits the secretion of parathyroid hormone (PTH). Thus, ligands potentiating the action of calcium (calcimimetics) lead to decreased PTH secretion and can thus be useful for the treatment of hyperparathyroidism. On the other hand, ligands which antagonize the action of calcium (calcilytics) stimulate PTH secretion, favoring bone tissue regeneration.Areas covered: This review first discusses the rapid development of calcimimetics (only one of which has been approved for the treatment of hyperparathyroidism) followed by that of calcilytics (none of which has as yet been approved for the treatment of osteoporosis). Peer-reviewed articles generated by these patents are also surveyed.Expert opinion: The rapid progress in developing a clinically approved calcimimetic has not been matched by an identical success in finding an orally available calcilytic useful for the treatment of osteoporosis. However, the growing importance of osteoporosis as a debilitating disease is a stimulating factor in discovering such compounds.

Équilibre phosphocalcique : régulation et explorations

Calcium and phosphate play a key role in bone mineralization but have also many other physiological functions. The control of serum phosphate concentration is mandatory to avoid the occurrence of severe metabolic disorders, but is less tightly regulated than serum ionized calcium concentration, which is maintained in a very limited range thanks to parathyroid hormone (PTH) and the active vitamin D metabolite calcitriol. Any change in serum ionized calcium concentration is detected by the calcium sensing receptor (CaSR), a membranous protein located principally in the parathyroid glands and the kidney. A decrease in ionized calcium level inactivates the CaSR, thus stimulating PTH secretion. PTH in turn stimulates the release of calcium and phosphate from bone, renal calcium reabsorption and calcium and phosphate intestinal absorption by inducing renal calcitriol production. Moreover, PTH inhibits phosphate reabsorption in proximal tubular cells, thus contributing towards phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate by inhibiting renal phosphate reabsorption and calcitriol production and may have a great physiological role in phosphate homeostasis. Recently, vitamin D actions independent of calcium and phosphate homeostasis were discovered. Basal exploration of phosphocalcic metabolism abnormalities consists in measurement of serum calcium (ionized calcium if possible), phosphate, 25-hydroxy vitamine D and PTH and of 24 hours urinary calcium excretion as well as renal function. Hence, the understanding of physiopathological mechanisms has been improved by newly identified genetic disorders responsible for phophocalcic homeostasis disturbances.

Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet

The parathyroid-calcium (Ca(2+)-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca(2+) concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca(2+). Increasing the sensitivity of the parathyroid gland to extracellular Ca(2+) by manipulation of the Ca(2+)-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca(2+), accounting for the simultaneous reduction of Ca(2+) and PTH seen in most patients. The Ca(2+)-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9-22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca(2+) concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca(2+) concentration to induce hypercalcaemia and maximally inhibit PTH secretion. Significant decreases in ionized Ca(2+) and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca(2+) and to a leftward shift of the Ca(2+)-PTH curve. Significant differences were present in all segments of the Ca(2+)-PTH curves. The pathological rightward shift of the Ca(2+)-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.

Recent Updates on the Calcium-Sensing Receptor as a Drug Target

Parathyroid hormone (PTH) secreted from parathyroid cells is a key regulator of circulating levels of calcium ion, which is maintained within a narrow physiological range mainly by the action of a cell surface Ca2+-sensing receptor (CaSR) residing on parathyroid cells. The CaSR belongs to the family C of G-protein-coupled receptors (GPCRs), all members of which have a large extra cellular domain called Venus flytrap, akin to bacterial nutrient sensor. Promiscuity of the CaSR is reflected in its binding to several physiologically relevant di- or polyvalent cations that could elicit cellular signaling, yet the ligand specificity remains poor. This problem has been circumvented by the discovery of calcimimetics, the positive allosteric modulators of the CaSR that activate the CaSR on parathyroid cells, immediately suppressing PTH secretion. Out of several small molecules that act as calcimimetics, cinacalcet is the most extensively studied. The discovery of the CaSR and these specific agonists provides important insights into the discovery of new drugs that will be discussed in this review from the perspective of their structure-activity relationship. The calcimimetic compound cinacalcet has obtained regulatory approval for the treatment of hyperparathyroidism and is the first positive allosteric modulator of any GPCR to reach the market. It has other important uses in dialysis patients with end-stage renal disease, in whom it decreases Ca X P product. Pharmaceutically converse to calcimimetics are calcilytic compounds, which antagonize parathyroid CaSR and stimulate PTH secretion. Antagonism of the CaSR has the potential to yield an anabolic therapy for osteoporosis that awaits clinical validation.

Bone health and vascular calcification relationships in chronic kidney disease

Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca x P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca x P product within K/DOQI guidelines (<4.4 mmol l(-1)). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca x P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.

Acute Effects of 2 Hours of Moderate-Intensity Cycling on Serum Parathyroid Hormone and Calcium

Previous studies have found that serum parathyroid hormone (PTH) increases in response to relatively short (<60 minutes), intense bouts of exercise, possibly as a result of decreases in serum calcium. Whether longer, less intense exercise also stimulates an increase in PTH is not known. The effects of 2 hours of moderate-intensity cycling on serum PTH and calcium were investigated in 20 competitive male cyclists, aged 22-45 years. Serum concentrations of PTH and calcium were measured before and after exercise. Dermal calcium loss was estimated using patch collections and loss of sweat. There were increases in PTH from 40.6 +/- 15.6 to 69.5 +/- 25.5 pg/mL (P < 0.001) and in serum calcium from 9.3 +/- 0.3 to 9.6 +/- 0.5 mg/dL (mean +/- standard deviation, P = 0.001) in response to exercise. Contraction of plasma volume explained the rise in calcium but not PTH. Dermal calcium loss was estimated at 138.0 +/- 71.9 mg for the 2-hour exercise bout. Neither the change in serum calcium nor the dermal calcium loss was significantly related to the increase in PTH. The study demonstrated that prolonged exercise stimulates PTH secretion. The effects of such transient increases in PTH on bone metabolism are not known.

Nutritional needs of premature infants: Current Issues

With the major advances in life-support measures, nutrition has become one the most debated issues in the care of very low birth weight infants. Current nutritional recommendations are based on healthy premature infants and are designed to provide postnatal nutrient retention during the stable-growing period equivalent to the intrauterine gain of a normal fetus. However, this reference is still a matter of debate, especially in the field of protein and mineral requirements. Protein requirements recently have been reevaluated, taking into consideration that (1) fetal lean body mass gain and the contribution of protein gain to lean body mass gain appear as more suitable references than does weight gain; (2) an additional protein supply needs to be provided for early catch-up growth, compensating for the cumulative protein deficit developed during the first weeks of life; (3) an increase in the protein-energy ratio is mandatory to improve the lean body mass accretion and to limit fat mass deposition; (4) the fractional nitrogen absorption rate and protein efficiency vary according to the feeding regimens; and (5) recommended dietary protein allowance needs to be adapted for postconceptional age instead of gestational age or birth weight to integrate the dynamic aspect of growth and protein metabolism. Thus recommended intakes for premature infants 26 to 30 weeks postconceptional age are 3.8 to 4.4 g of protein/kg/d with a protein/energy ratio between 3.0 to 3.3 g/100 kcal, according to their relative postnatal growth restrictions and should decrease progressively up to the time of discharge. After birth, there is a dramatic physiological change in bone metabolism resulting from various factors; abrupt reduction in mineral supply, stimulation of parathyroid hormone secretion, change in hormonal environment, and relative reduction in mechanical stimulation. There is a stimulation of the remodeling process, inducing an increase in endosteal bone resorption and a decrease in physical density. In preterm infants, this process of postnatal bone metabolism adaptation modifies the mineral requirements, with the remodeling stimulation itself providing a part of the mineral requirement necessary for postnatal bone turnover. In extrauterine conditions, the care of premature infants should not necessarily aim to achieve intrauterine calcium accretion rates. Considering long-term appropriate mineralization and the fact that calcium retention between 60 to 90 mg/kg/d suppresses the risk of fracture and clinical symptoms of osteopenia, a mineral intake between 100 to 160 mg/kg/d of highly-absorbed calcium and 60 to 75 mg/kg/d of phosphorus could be recommended.