Search

A dialysate containing a calcium concentration of 1.75 mmol/L has been the standard in CAPD for a long time. This concentration was chosen to achieve a positive calcium balance to suppress hyperparathyroidism. In the measurement of peritoneal calcium mass transfer, conflicting results have been published, with positive and negative calcium balances reported. These differences have been explained by differences in the filtration rate, and a negative correlation between the filtration rate and the peritoneal calcium mass transfer can be found. Whereas nearly all patients in this study had a negative calcium balance using a glucose solution of 3.86%, a wide variation was found for the 1.36% glucose solution. There were several patients who had a positive calcium balance despite a positive filtration rate. The explanation for this finding lay in differences in serum concentrations of calcium, and especially differences in the size of the total exchangeable calcium pool that contains the plasma calcium compartment. A negative correlation between peritoneal calcium balance and the size of the total exchangeable calcium pool could be demonstrated. This finding may explain the differences in the peritoneal calcium flux reported in the literature. As an enlargement of the exchangeable calcium pool correlates with the progression of vascular calcification, therapeutic efforts should be directed toward prevention of an enlargement of this pool.

Objective: Fructus ligustri lucidi (FLL) is a widely used herb in China that is classically included in antiaging formulas for the treatment of age-related symptoms. Our laboratory previously showed that FLL could regulate calcium balance in young ovariectomized (OVX) rats. In the present study, we aimed to determine whether FLL could regulate calcium balance in aged OVX rats and to study the potential mechanisms that mediate its action in vivo. Design: Aged OVX rats were orally administered an ethanol extract of FLL and its vehicle and fed with diets containing different levels of calcium [low calcium diet (LCD), 0.1% Ca; medium calcium diet (MCD), 0.6% Ca; and high calcium diet (HCD), 1.2% Ca] for 12 weeks. Results: Significant reductions in urinary and fecal calcium excretion were found in the FLL-treated animals, resulting in a significant induction of calcium retention in rats fed with the MCD and HCD. FLL treatment significantly increased the serum 1,25-dihydroxyvitamin D 3 level and slightly decreased the serum parathyroid hormone level in OVX rats fed with the MCD and HCD. When OVX rats were challenged by LCD, the inductions of serum parathyroid hormone and 1,25-dihydroxyvitamin D 3 were decreased by FLL administration. FLL treatment significantly up-regulated duodenal vitamin D receptor and calcium transport protein 1 mRNA expression in rats fed with the HCD. FLL treatment reduced the expression of renal vitamin D receptor and 25-hydroxyvitamin D-24-hydroxylase mRNA in OVX rats fed with the LCD and MCD. Conclusions: Twelve weeks of FLL treatment could reduce calcium loss, modulate the parathyroid hormone-vitamin D axis, and increase vitamin D-dependent calcium transport in aged OVX rats, suggesting that FLL might be useful as an alternative medicine for improving calcium balance in postmenopausal women.

Study design A cross-sectional study of 2 groups of patients with scoliosis, and an age-matched control group was conducted. Each of the groups such as patients with adolescent idiopathic scoliosis (AIS) as well as control group were divided additionally into 2 groups: premenarcheal and postmenarcheal girls. Objective The aim of the study was to determine the levels of 25-OH-vitamin D3, calcium and phosphate, parathyroid hormone (PTH), and calcitonin in serum of pre- and postmenarcheal girls with AIS and corresponding groups of scoliosis-free controls. Summary of background data The primary etiology and pathogenesis of AIS remains unknown. It is assumed that vitamin D deficiency and genetic predisposition, for example, polymorphisms of vitamin D receptor, have a great significance. Vitamin D plays a key role in skeletal development and prevents bone atrophy, affects the absorption of calcium, maintains calcium-phosphate homeostasis, and the bone matrix mineralization. Its deficiency can result in a wide variety of skeletal deformities, low bone mass, and then leads to the disappearance of bone. Defects in trabecular bone structure and/or bone mineralization are the main features of scoliosis. Some studies have reported that Vitamin D deficiency is common among patients with AIS. The mechanism of Vitamin D action on scoliosis development is still unclear. Methods Determination of serum 25-OH-D3 levels was performed using high-performance liquid chromatography chromatography; concentrations of calcium and phosphate were measured using colorimetric methods, and concentration of PTH and calcitonin was measured using ELISA system. Results Reduction in the serum levels of 25-OH-D3 and calcitonin in girls with AIS compared with healthy girls was demonstrated. Conclusion The phosphate-calcium balance and PTH level seem to be normal in patients with AIS. The calcitonin level in girls with AIS is 2-fold lower than in healthy subjects. It is possible that the deficiency of vitamin D can be involved in AIS. Level of evidence 4.

Presently submitted and previously available data indicate that the recommended calcium requirement of 800 mg/day is inadequate for a large segment of the population, particularly the elderly. With an intake of 800 mg of calcium/day, calcium balance was only slightly positive, without consideration of dermal losses or other risk factors that may play a role in calcium bioavailability and calcium retention. A calcium intake of 1000-1200 mg/day is preferable, as calcium balance increased significantly when calcium intake was increased from 800 to 1200 mg/day; there was no further improvement in calcium balance on higher calcium intakes, up to 2300 mg/day.

Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes.Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies.There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality.

Introduction: Abnormalities of calcium metabolism independent of changes in intracellular calcium have been described in patients with essential hypertension. These include increased urinary calcium excretion for a given salt intake, a raised parathyroid hormone level, an increase in urinary cyclic AMP, a tendency for a low serum ionized calcium level, a raised 1,25-dihydroxyvitamin D level and an increased intestinal calcium reabsorption. These changes have been seen as a consequence of a primary renal calcium leak Hypothesis: We propose that these changes are secondary to a genetic defect in the ability of the kidney to excrete sodium. On the high salt intake in most Western countries (i.e. approximately 170mmol/day sodium) compensatory mechanisms occur to try to overcome this defect. These compensatory mechanisms are responsible for the rise in blood pressure, but also cause an increase in central blood volume which is the direct cause of the increase in urinary calcium excretion. This causes a slightly negative calcium balance, and the other abnormalities of calcium metabolism can then be seen as a compensatory response to try to restore calcium balance to normal. Discussion: This hypothesis explains the increase in kidney stones in essential hypertension and predicts that hypertensives, in the long term, will be more likely to develop bone demineralization (osteoporosis), as has been demonstrated in some animal models of hypertension. Increases in salt intake will not only cause a further rise in blood pressure, but will also increase urinary calcium excretion and aggravate the other abnormalities. A moderate reduction in salt intake from 170 to 70mmol/day will lower the blood pressure and will tend to correct the abnormalities of calcium metabolism. It should simultaneously reduce the incidence of renal stones and the long-term risk of bone demineralization

Purpose of review Vitamin D is important in maintaining calcium homeostasis, but its role in kidney stone disease and its effect on stone formation are still not clear. Recent findings Kidney stone formers tend to experience enhanced intestinal calcium absorption, increased urinary calcium excretion, and excessive bone mineral loss. Although direct actions of active vitamin D have been implicated in all these processes, the effect of nutritional vitamin D (vitamin D2 or vitamin D3) use on calcium balance among stone formers is still not clear. In addition, the safety of nutritional vitamin D use in the stone forming population is also not established, considering the potential effect of its use on raising urinary calcium. However, most of the observational studies do not support a significant association between higher nutritional vitamin D store and increased risk of stone formation. Short-term nutritional vitamin D repletion in stone formers with vitamin D deficiency also does not appear to increase urinary calcium excretion. Summary The effect of nutritional vitamin D use in stone formers is still not clear. As vitamin D deficiency is highly prevalent among stone formers, future prospective studies are needed to establish the biological effect, as well as the safety and efficacy of nutritional vitamin D therapy in this unique patient population.

Parathyroid hormone (PTH) is a principal regulator of calcium balance in physiological and pathological conditions associated with cardiovascular disorders and plays a major physiological role in bone homeostasis (Figure 1). PTH systemically controls bone remodeling by modulating the bone marrow microenvironment and regulating osteogenic signaling pathways.1 PTH and its related peptide can have both anabolic and catabolic effects. Although intermittent administration of PTH is osteoanabolic and antiosteoporotic via stimulation of bone formation, its continuous administration may cause catabolic osteoporotic changes. Experimental studies showed that intermittent injection of full length PTH (PTH1–84) or its N-terminal fragment (PTH1–34) increases bone formation with normal microarchitecture by coupling bone remodeling1 as well as promoting bone vascular structure and function.2 Clinically, intermittent administration of PTH is an established osteoanabolic therapy that improves quality of life in patients with severe osteoporosis.3 However, potential adverse effects by long-term use of PTH have not been fully elucidated. Figure 1. Parathyroid hormone (PTH) as a novel mediator of bone–vascular–renal interaction. Cardiovascular disorders include but are not limited to valvular and vascular calcification, atherosclerosis (inflammation), and hypertension. See accompanying article on page 1567 The presence of PTH receptors within the cardiovascular system,4 including vasculature (smooth muscle cells, endothelial cells) and heart (cardiomyocytes), suggests that secreted PTH may play a role in the pathophysiology of cardiovascular diseases beyond its role in mineral and bone metabolism (Figure 2). Figure 2. Hypothetical signaling pathways of parathyroid hormone (PTH) receptor in cardiovascular disorders based on previously published reports. cAMP indicates cyclic adenosine monophosphate; C-PTH, carboxyl-terminal PTH; dotted arrows, postulated but unknown pathways; ECs, endothelial cells; ERK, …

Update recent advancements regarding the effect of high-animal protein intakes on calcium utilization and bone health. Increased potential renal acid load resulting from a high protein (intake above the current Recommended Dietary Allowance of 0.8 g protein/kg body weight) intake has been closely associated with increased urinary calcium excretion. However, recent findings do not support the assumption that bone is lost to provide the extra calcium found in urine. Neither whole body calcium balance is, nor are bone status indicators, negatively affected by the increased acid load. Contrary to the supposed detrimental effect of protein, the majority of epidemiological studies have shown that long-term high-protein intake increases bone mineral density and reduces bone fracture incidence. The beneficial effects of protein such as increasing intestinal calcium absorption and circulating IGF-I whereas lowering serum parathyroid hormone sufficiently offset any negative effects of the acid load of protein on bone health. On the basis of recent findings, consuming protein (including that from meat) higher than current Recommended Dietary Allowance for protein is beneficial to calcium utilization and bone health, especially in the elderly. A high-protein diet with adequate calcium and fruits and vegetables is important for bone health and osteoporosis prevention.

Background and objectives: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01). Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Decreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. The purpose of this review is to summarize the recent published evidence that supports a potential role of the bone, and its link to the kidney and intestine, in the pathogenesis of idiopathic hypercalciuria. The effects of hypercalciuria on bone and the implications for treatment are also reviewed.Evidence suggests that the incidence of a first fracture in kidney stone patients is fourfold higher than the control population. Support for the role of bone in the pathophysiology of hypercalciuria has been corroborated. New studies have detailed the effects of several cytokines - increased number and sensitivity of vitamin D receptors, and increased acid production - upon the bone acting cells. Similarly, recent clinical and experimental studies have suggested that genetic factors confer a predisposition to the formation of renal calcium stones and bone demineralization.Whether hypercalciuria is the result of a primary bone disorder, a consequence of a persisting negative calcium balance or a combination of both still remains to be determined. Nevertheless, bone status must be evaluated and followed up in patients with idiopathic hypercalciuria.

Disturbances of mineral metabolism are associated with significant morbidity and mortality in patients with chronic kidney disease. Unfortunately, some of the treatments for these disturbances also have been found to be associated with morbidity. More recently, there is increasing evidence in the form of prospective, randomized trials that the use of calcium-based phosphate binders contributes to progressive coronary artery and aorta calcification compared with the non-calcium-containing binder sevelamer. Moreover, there is compelling biologic plausibility that hyperphosphatemia and excess exogenous calcium administration can accelerate vascular calcification. Unfortunately, there is no bedside test that can determine whether there is a dose of calcium salts (either as maintenance or as cumulative dose) that can be administered safely, and, unfortunately, the serum calcium concentration does not reflect calcium balance. Therefore, calcium-based phosphate binders should be avoided in many, if not most, patients who are undergoing dialysis.

Bone loss occurs early after orthotopic liver transplantation (OLT) in all liver transplant recipients and leads to postoperative fractures, especially in cholestatic patients with the lowest bone mass. Little is known about the underlying changes in bone metabolism after OLT or about the etiology of these changes. Histomorphometric analysis of bone biopsies, a method that allows assessment of bone volume, resorption, and formation, has shown improved bone metabolism at 4 months after OLT. It has further suggested that accelerated posttransplant bone loss occurs in the first 1-2 months after OLT, probably by an additional insult to bone formation. This study attempts to correlate the histomorphometric bone changes in paired bone biopsies (OLT and 4 months after OLT) of 33 patients undergoing OLT for chronic cholestatic liver disease with the many clinical and biochemical changes in these patients over the same period. Cumulative steroid dosage early after OLT is shown to be important, presumably by decreasing bone formation rates. The actual effect of calcineurin inhibitors on this early phase of bone loss is less clear, although posttransplant histomorphometric findings suggest that tacrolimus-treated patients have an earlier recovery of bone metabolism and trabecular structure compared with cyclosporine patients. Other factors important in the recovery of bone metabolism after the early phase of bone loss are recovery of liver and gonadal function and better calcium balance.

Objectives Hip fracture is among the most common causes of acute immobilization in elderly patients leading to increased bone resorption, and elderly patients with hip fracture are at high risk for a subsequent hip fracture. Design In this double-blind, randomized, prospective study, 80 female patients who were immobilized because of a hip fracture were divided into two groups. The etidronate group received oral administration of 200 mg/day etidronate for 2 wks starting 1 day after the surgery. Then, after a 9-wk intermission, etidronate administration was resumed for 2 wks. The placebo group received placebo in a similar manner. Results At baseline, both groups had high serum concentrations of ionized calcium, high urinary deoxypyridinoline (D-Pyr) concentrations, and decreased calcitriol concentrations, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of calcitriol. After treatment, serum calcitriol concentrations increased in the etidronate and placebo groups. The etidronate group had significant decreases in serum ionized calcium and urinary D-Pyr, and the placebo group had higher serum calcium and urinary D-Pyr concentrations. Conclusions Etidronate therapy inhibits bone resorption and improves calcium balance, and such therapy may prevent bone loss and reduce the risk of subsequent hip fracture.

Although participation in vigorous exercise is associated with increased bone mass, recent evidence suggests that loss of calcium in sweat may result in a negative calcium balance and, ultimately, a decrease in bone mass. Anthropometric characteristics, habitual physical activity levels, dietary calcium intake, bone mineral content, and bone turnover markers were measured in 42 male recruits before and after 4 months of firefighter training. During two strenuous mid-training sessions, sweat calcium concentrations were measured; they averaged 1.1 mM. Whole body and total hip bone mineral content increased significantly, as did one marker of bone formation, and were not associated with sweat calcium concentration. This study demonstrates that intense physical training sessions that produce high sweat rates do not have an adverse effect on the bone mineral content of healthy young men.

Two recent studies have reported increased hip fracture rates with long-term proton pump inhibitor (PPI) use raising concerns about adverse effects of this class of drugs on mineral metabolism. One plausible mechanism by which PPIs could affect calcium economy and skeletal homeostasis is by impairing intestinal calcium absorption. In the long term, this could potentially lead to a negative whole body calcium balance, resulting in higher rates of bone loss and a greater risk of fragility fractures.

The long-term clinical effects of the use of a low calcium concentration in the dialysate are largely unknown. For this reason, the influence of low-calcium dialysate on parathyroid hormone (PTH) secretion in hemodialysis patients and its long-term effect on the severity of secondary hyperparathyroidism were studied. In 35 hemodialysis patients, the dialysate calcium concentration was lowered from 1.75 to 1.25 mmol/L. Twelve months later, serum iPTH levels increased significantly from 18.6 to 33.2 pmol/L and so did alkaline phosphatase levels, from 210 to 330 IU/L, without significant changes in serum calcium or phosphorus levels. Hemodialysis with low-calcium dialysate (1.25 mmol/L) induced a net calcium loss in 10 patients, without modifications in ionized serum calcium levels. In addition, mean serum iPTH increased 20% over baseline levels, reaching the maximal level at 30 min after the start of hemodialysis with low-calcium dialysate. In contrast, mean serum iPTH levels drop dramatically at 30 min of hemodialysis with high-calcium dialysate (1.75 mmol/L). It was concluded that low-calcium dialysate worsens secondary hyperparathyroidism in hemodialysis patients, probably by inducing a negative calcium balance and causing repetitive stimulation of PTH secretion in each dialysis. The maintenance of normal serum calcium levels could be due to PTH-induced calcium mobilization from bone.

Rickets is a common and paradoxical feature of infantile malignant osteopetrosis and results from the inability of osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. Despite a markedly positive total body calcium balance, rickets arises when the serum calcium x phosphorus product is insufficient to mineralize newly formed chondroid and osteoid. In five children with malignant infantile osteopetrosis, there were clinical, radiographic, biochemical, and histologic findings of rickets. Characteristic biochemical abnormalities included hypocalcemia, hypophosphatemia, and elevated levels of serum acid phosphatase, alkaline phosphatase, c-terminal parathyroid hormone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine ratio was markedly depressed. The serum calcium x phosphorus product was below 30 in all children at the time the rickets was diagnosed, and above 40 by the time the rickets had resolved. Baseline bone density measurements were markedly elevated in all children (> 5 standard deviation above normal) and showed even significant increases (> 7 SD) when the rickets was treated with vitamin D and calcium. The children showed marked clinical improvement, decreased lethargy, increase in mobility and activity, and stimulation of appetite, without any additional adverse hematologic or neurologic effects. The rickets was reversible in all children: in one by HLA-identical sibling bone marrow transplantation and in four by physiologic doses of vitamin D and calcium. The parathyroid and renal responses to hypocalcemia were appropriate, but glucocorticoids, used in treating the hematologic complications of the disease, may have blunted the intestinal response to maximal vitamin D stimulation. This latter blockade can be overcome by increasing dietary calcium. By liberalizing rather than by restricting calcium and phosphorus intake, hypocalcemia can be minimized, phosphorus metabolism can be improved, and rickets can be cured.

Placing a dental implant elicits a time-dependent bone response controlled by wound-healing factors (cytokines, bioelectrical signals), biomechanics (gravitational, functional, and therapeutic loads), and mineral metabolism (hormones, diet, excretion). The osseous response to an implant involves four physiological stages: (1) endosteal and periosteal callus formation; (2) compaction and remodeling of the callus; (3) remodeling (turnover) of the nonvital interface and adjacent bone; and (4) maturation (secondary mineralization) of new bone. Long-term maintenance of a rigid implant interface is related to continual bone remodeling. Common metabolic bone disorders affecting potential implant patients are osteopenia ("osteoporosis"), renal osteodystrophy, osteomalacia, and Paget's disease. The most prevalent problem is a long-term negative calcium balance leading to a compromise in bone strength. Symptomatic osteoporosis (usually wrist, hip, and/or spine fractures) affects 4 to 50 percent of the population depending on age, race, sex, endocrine status, and life-style. Postmenopausal white and Asian females present the greatest risk. The jaws of "osteoporotic" adults are variably affected because of the moderating influence of mechanical function. Management of metabolic bone disorders is an important consideration in diagnosis, treatment planning, and long-term monitoring of dental implants. Bone metabolic counseling, a natural extension of preventative dentistry, is an unexpected benefit readily appreciated by patients and their families.

The mean calcium requirement of normal adults has been estimated from 212 calcium balances on 84 normal subjects and found to be 578 mg. The calcium allowance required to ensure that 95% of normal adults are in calcium balance is about 900 mg. Calcium requirement is relatively higher than that of phosphorus or magnesium because plasma calcium--and therefore urine calcium--is maintained at the expense of the skeleton in the presence of calcium deficiency, whereas plasma phosphate and magnesium--and therefore urine phosphate and magnesium--fall on phosphorus and magnesium deficient diets. Calcium requirement appears to rise at the menopause, and postmenopausal bone loss can be reduced by calcium supplements. In postmenopausal osteoporosis, the severe negative calcium balance can be corrected by giving calcium or calcium and vitamin D, but vitamin D alone is not beneficial. Similarly, bone loss, height loss and further vertebral compression can be reduced by calcium or calcium and vitamin D but not by vitamin D alone.

The pattern of changes in human bone remodeling produced by raloxifene (60 mg/day) was compared to that of estrogen (given as hormone replacement therapy) in 33 early postmenopausal women randomly assigned to raloxifene, estrogen, or no treatment. Remodeling was measured using calcium tracer kinetic methods employed under a constant diet and full metabolic balance conditions. Studies were performed at baseline and, to detect both early and late remodeling changes, at 4 and 31 weeks of treatment. Both raloxifene and estrogen produced a significant positive calcium balance shift at each treatment measurement point: +74 and +60 mg/day at 4 weeks, and +60 and +91 mg/day at 31 weeks for raloxifene and estrogen, respectively. Externally, this balance change was due to a highly significant fall in the urinary calcium level and marginal improvement in calcium absorption efficiency. Internally, bone resorption was significantly reduced at both measurement points: -64 and -60 mg/day at 4 weeks, and -82 and -162 mg/day at 31 weeks for raloxifene and estrogen, respectively. Bone formation was not significantly affected by either agent at 4 weeks; at 31 weeks, formation was reduced by estrogen, but not by raloxifene. Thus, at 4 weeks, the general pattern of remodeling change was identical for the two agents. At 31 weeks, remodeling suppression was greater for estrogen than for raloxifene; however, remodeling balance was the same for the two agents. We conclude that raloxifene and estrogen affect the bone remodeling apparatus similarly, and that raloxifene, therefore, is acting on bone as an estrogen agonist.

Diets that restrict carbohydrate intake but allow unlimited fat and protein, such as the Atkins' diet, are much in vogue today. Whether a low-carbohydrate, high-protein (LCHP) diet increases the risk of bone loss or kidney stone formation was the question asked in this study of 10 healthy individuals ranging in age from 21 to 52 years. Initially they took their usual diet for 2 weeks and then an Atkins'-type induction diet (with severely restricted carbohydrate) for 2 weeks. An Atkins' maintenance diet then was consumed for 4 weeks in the maintenance phase. In the last week, the participants ate constant metabolic meals. Both the induction and maintenance LCHP diets contained nearly twice as much protein and fat as the subjects' usual diets but significantly less carbohydrate. Intakes of calcium, potassium, magnesium, sodium, and chloride did not differ significantly. Both weight loss and increased blood urea nitrogen levels attested to compliance with the diet. None of the 10 dieters developed clinically apparent metabolic acidosis. Serum sodium levels dropped slightly, but there were no changes in levels of potassium, chloride, calcium, or phosphorus. Urinary pH and citrate fell significantly with the induction and maintenance diets. Urinary ammonium, titratable acidity, and net acid excretion rose nearly 2-fold, as did urinary sulfate levels. Urinary calcium and phosphorus levels increased by about 2.25 mmol and 12.5 mmol/day, respectively, during the LCHP diet periods. Urinary magnesium decreased, but uric acid, oxalate, sodium, and potassium excretion did not change measurably levels measured during the baseline diet. The urinary content of undissociated uric acid doubled. Calcium balance decreased during both LCHP diets. Serum alkaline phosphatase decreased, but the bone-specific fraction did not change. Serum osteocalcin was significantly lower when subjects were on the LCHP diets. Urinary levels of deoxypyridinoline and N-telopeptide tended to increase, but not to a significant degree, and serum levels of calcitriol and parathyroid hormone did not change significantly. Endogenous creatinine clearance rose significantly during both LCH diets. This short-term study suggests that intake of a LCHP weight reduction diet, through delivering an exaggerated acid load, may heighten the risk of both kidney stone formation and bone loss. This possibility should be evaluated in a long-term prospective trial.

Fifty years ago Albright contributed the following to understanding osteoporosis: (1) He recognized it as a deficiency of formation, not of mineralization of bone matrix; (2) he observed that 40 of 42 patients with osteoporosis before age 65 were women past menopause or young women postoophorectomy; (3) he concluded that estrogen stimulates osteoblasts (a conclusion later challenged); (4) he demonstrated by metabolic balance studies that estrogen causes a positive calcium balance in postmenopausal osteoporosis; (5) he introduced periodic progesterone to prevent or treat endometrial hyperplasia from prolonged estrogen therapy; and (6) he showed that long-term therapy arrested vertebral damage and height loss in postmenopausal osteoporosis and prevented them if started early. Since Albright's time, more sensitive methods of assessing bone density have replaced conventional roentgenograms. Some large scale trials of estrogen have indicated increased bone density and fewer fractures. Unopposed estrogen increases risk of endometrial cancer and decreases mortality from other cancers, myocardial infarction, stroke, and osteoporosis. Trials of calcitonin, diphosphonates, fluoride, vitamin D, and high calcium intake have not proved more effective than estrogen.

Calcium balances in ten enterally or parenterally hyperalimented trauma victims were compared as protein intake was manipulated from 50.5 +/- 12.8 to 128.0 +/- 17.4 gm/day during an isocaloric metabolic balance study. Calciuresis increased as protein intake increased in all subjects, resulting in an average reduction in daily calcium balance of 195 +/- 65 mg/day (p less than 0.001). There was no difference in fecal calcium in the enterally fed subgroup. Total and "corrected" total serum calcium were lowered, and indirect evidence suggests that ionized calcium was lowered as well. The mechanism of the increase in urinary calcium is not fully elucidated, although it appears to be a direct effect on the kidney rather than an indirect influence of calcium homeostasis. It is suggested that a calorie/nitrogen ratio of about 360 be maintained in enteral and parenteral alimentation of trauma victims. Thus nitrogen balance can be maintained by the increased nonprotein calorie availability, and possible complications of increased calcium mobilization and excretion can be avoided.

Ten patients with symptomatic Paget's disease of bone were treated with mithramycin. Subjective improvement, as demonstrated by complete pain relief and increased activity, was reported by seven patients and partial pain relief was reported by two. Pain persisted in one patient with a co-existing osteogenic sarcoma. No roentgenographic changes were noticed in the involved bones after therapy. Chemically, improvement was demonstrated by reduction of levels of serum alkaline phosphatase and urinary hydroxyproline. Five patients were in positive calcium balance before mithramycin therapy and showed an increase after therapy. Mithramycin administered in the dose of twenty-five micrograms per kilogram of body weight by slow intravenous drip method, once every two to three weeks, was well tolerated and showed suppressive effects on symptomatic Paget's disease of bone, and no hepatic, renal, or myelogenous evidence of toxicity was noticed in the immediate or long-term follow-up in these patients.

The significance of cellular calcium metabolism and systemic calcium balance in sodium chloride sensitivity was studied in 16 patients with essential hypertension and in 13 normotensive subjects. With changes in sodium chloride intake from 3 to 20 g/day, mean blood pressure, lymphocyte [Ca2+]i and the acute hypotensive response to nifedipine were increased in the hypertensive patients, but not in the normotensive subjects. Serum calcium concentration was decreased and urinary calcium excretion was increased in both groups. In the hypertensive patients, elevation of mean blood pressure was positively correlated with the increase in lymphocyte [Ca2+]i and with the enhancement of the hypotensive response to nifedipine, but it was not related to the change in serum or urinary calcium. These results suggest that enhancement of cellular-calcium-dependent vasoconstriction may lead to increased blood pressure following sodium chloride loading in patients with essential hypertension.

Calcium and magnesium metabolism was investigated in 10 hypertensive subjects with primary aldosteronism (seven adenomatous, three idiopathic). Serum levels of total calcium (9.03 +/- 0.2 mg/dl) and ionized calcium (2.06 +/- 0.06 meq/liter) were in the low-normal range, except for two patients who had levels of serum ionized calcium clearly above normal. Furthermore, both serum total (n = 6, p less than 0.01) and ionized calcium levels (n = 3) rose postoperatively in the patients who had an aldosterone-producing tumor removed. Dramatic elevations of parathyroid hormone levels (mean, 645 +/- 109 pgeq/liter; normal, less than 150 to 375 pgeq/liter) were seen in the majority of patients, including those two with frank ionized calcium elevations. Magnesium levels were within normal limits (2.07 +/- 0.07 meq/liter). These results indicate that parathyroid hypersecretion is a common feature of primary aldosteronism and also suggest a physiologic relationship between the activity of the renin-aldosterone system and parathyroid physiology. Sodium-volume expansion and negative calcium balance induced by aldosterone excess may predispose to hyperparathyroidism.

In 167 women, ages 41 +/- 3.5 years, who constituted 80 per cent of nuns of this age group in the Omaha area, body dimensions and radiogrammetric indices were determined in (1) radius; (2) femoral shaft; (3) second metacarpal. Calcium, phosphorus and nitrogen balance were measured and calcium kinetics were calculated following oral and intravenous administration of two radioisotopes of calcium. The bone indices were significantly correlated to each other. The femoral diameter was correlated to all the kinetic variables, the radial to many, and the metacarpal to a few. All bone diameters were correlated to height, but only the femoral diameter to body weight. Femoral shaft diameter increased with time after the menopause, but was not correlated to age. There was no correlation between any bone variable and dietary calcium, absorbed calcium, or calcium balance. High dietary calcium was associated with lower bone resorption. There was no correlation between any bone variable and the urinary excretion of estrogens or 17 ketosteroids or 17 hydroxycorticosteroids. Although different bones of the skleton are qualitatively and quantitatively related, in survey work the femoral shaft should be included as a skeletal marker in addition to the second metacarpal. Femoral expansion occurs in women after the menopause. In normal women, dietary calcium is unrelated to skeletal indices.