Search

45Ca kinetics and calcium balance studies allow for the simultaneous determination of calcium movement in the intestines, kidneys and bones. Since the flow of minerals in each of these organs depends on those in other organs, it is important to evaluate calcium movement as a whole throughout the entire body. Morphological methods can be used to evaluate local bone formation and resorption microscopically within defined windows. However, bone remodeling does not proceed equally in every part of the skeleton, and local events tend to be misread as general phenomena. Although variables such as bone formation and resorption obtained in 45Ca kinetics and calcium balance studies tell nothing about the location of these events, and the concept of compartments can be somewhat difficult to understand, this method is still useful for obtaining quite reliable results compared to those obtained by other methods. Our review describes the concept of the compartment model and explains the pertinent methods in comparison with other methods.

We investigated factors affecting net transperitoneal calcium balance (Ca-BL) and the level of parathyroid hormone in relation to stepwise changes in serum calcium, by short PET (peritoneal equibrium test during 240 min: using 2000 ml of 2.5% dextrose dialysate containing 1.75 mmol/L Ca) in uremic patients undergoing stable CAPD. We calculated Ca-BL (mg/effluent/PET) of 244 effluents obtained from 90 patients receiving calcium carbonate as a phosphate binder without vitamin D supplementation. Their serum calcium level corrected with albumin (cSCa), alkaline phosphatase activity (ALP) and intact-PTH level was 9.7 +/- 0.9 mg/dl, 236 +/- 83 mIU/ml and 153.0 +/- 172.4 pg/ml, respectively. We proposed two statistic significant regression lines between Ca-BL and total drainage effluent volume (Ca-BL = 133X - 0.056: r = 0.981, P < 0.001), cSCa (Ca-BL = -12.9X + 123.6: r = 0.941, P < 0.01). Total drainage volume (TDV) and cSCa were two major factors affecting Ca-BL. A TDV level of 2430 ml/240 min-PET or more was required for positive Ca-BL in cases with 9.5-10.0 mg/dl of cSCa, using this linear regression analysis. A cSCa level of 9.6 mg/dl or more was also required for positive Ca-BL in cases with 2400-2600 ml/240min-PET. We also proposed a significant linear regression line between the intact-PTH level and cSCa (i-PTH = -90.5X + 1015.8, r = 0.973, P < 0.01). This line suggest that 200 pg/ml of intact PTH was obtained by 9.0 mg/dl or less of cSCa level in 90 CAPD uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal studies using mice model such as vitamin D deficiency and global and conditional VDR knock out(KO)mice have disclosed that the physiological role of vitamin D strongly depends on the calcium balance. Vitamin D stimulates active intestinal calcium transport mechanism, thereby maintains normocalcemia that has priority over skeletal integrity. Besides the biological significance of vitamin D extensively studied, its precise function in non-classical target needs further investigation.

About 99% of total body calcium is present in bone. Therefore, negative calcium balance usually means reduction of bone mass. Negative calcium balance is induced by aging from several mechanisms such as reduced renal production of 1,25-dihydroxyvitamin D[1,25(OH) 2 D], intestinal resistance to 1,25(OH) 2 D and increased renal excretion of calcium. However, it is largely unknown how calcium balance is physiologically maintained.

Vitamin D endocrine system is required for normal calcium and bone homeostasis. Trans-epithelial calcium absorption is initiated with calcium entry into the intestinal epithelial cells from luminal fluid through calcium permeable channels, and those expressions are strongly supported by vitamin D action. On the other hands, dietary treatment, mineral supplementation or restriction, successfully improves intestinal calcium absorption in global vitamin D receptor knock-out (VDR KO) mice, though vitamin D dependent active transport pathway is lacking. Dietary rescue of intestinal calcium absorption provided a positive calcium balance in this mouse model, and suggested that the major role of vitamin D function on calcium homeostasis was considered to be intestinal active absorption. To elucidate the entire process of intestinal calcium absorption, vitamin D independent calcium transport system was characterized into either trans-cellular or para-cellular process.

Japanese Experiment Module "KIBO" is Japan's first manned space facility and will be operated as part of the international space station (ISS) . KIBO operations will be monitored and controlled from Tsukuba Space Center. In Japan, after the KIBO element components are fully assembled and activated aboard the ISS, Japanese astronauts will stay on the ISS for three or more months, and full-scale experiment operations will begin. Bone loss and renal stone are significant medical concerns for long duration human space flight. This paper will summarize the results of bone loss, calcium balance obtained from the American and Russian space programs, and ground-base analog bedrest studies. Current in-flight training program, nutritional recommendations and future countermeasure plans for station astronauts are also described.

Hyperphosphatemia is one of the major complications of hemodialysis patients and plays a key role in the pathogenesis of cardiovascular calcification and secondary hyperparathyroidism. Dietary phosphate restriction and removal of phosphate by dialysis are insufficient to control hyperphosphatemia. Therefore, almost all patients undergoing hemodialysis should take oral phosphate binders. Sevelamer hydrochloride (sevelamer) is a novel phosphate-binding polymer that contains neither aluminum nor calcium, and it is not absorbed from the gastrointestinal tract. In rat models with progressive chronic renal insufficiency, in addition to lowering effects on serum levels of phosphorus, calcium x phosphorus product, and parathyroid hormone, dietary treatment of sevelamer can prevent parathyroid hyperplasia, vascular calcification, high turnover bone lesion, and renal functional deterioration. In clinical studies with hemodialysis patients, sevelamer lowers serum phosphorus and calcium x phosphorus product without any incidence of hypercalcemia. Switching calcium-containing phosphate binders to sevelamer can decrease the percentage of hypoparathyroidism and hyperparathyroidism by negative calcium balance and increased dosage of vitamin D, respectively. Sevelamer also decreases serum low-density lipoprotein cholesterol levels by its bile acid-binding capacity. A long-term clinical study has demonstrated that the progression of coronary and aortic calcification in hemodialysis patients is attenuated by sevelamer. Thus, sevelamer offers the promise of impacting cardiac calcification and thereby reducing morbidity and mortality of hemodialysis patients.

In the sixth edition of the recommended dietary allowance (RDA) for Japanese-dietary reference intakes by the Ministry of Health, Labour and Welfare, Japan, RDA and tolerable upper limit (UL) for vitamin D and calcium were set. RDA and UL for calcium were set on the basis of the calcium balance study and the factorial method. In contrast, plasma 25-hydroxyvitamin D level in subjects as a maker reflecting vitamin D nutrition status was first used for setting the RDA and UL in this edition.

Loss of bone mineral content has been recognized as one of the chronic complications of type 2 diabetes mellitus, although its mechanism is not fully documented. A negative calcium balance due to both enhanced urinary calcium excretion and decreased intestinal calcium absorption has been occurred because of alteration of vitamin D metabolism and/or decreased parathyroid function. From the view point of bone cell metabolism, osteoblastic bone formation is suppressed by alternation of vitamin D metabolism, hypoparathyroidism, chronic hyperglycemia and insufficient insulin action. On the other hand, osteoclastic bone resorption is rather enhanced. The functional bone uncoupling system between osteoblast and osteoclast in type 2 diabetes mellitus could result in loss of bone density.

The bone mineral density of middle-aged and elderly people is determined by the peak bone mass obtained in the adolescent period and the bone loss in the later stage of life. The rapid bone loss observed in the postmenopausal women is largely explained by estrogen deficiency. On the other hand, aging-dependent decrease of bone mass commonly seen in women and men may be attributed to the change in calcium metabolism. In Japan, the calcium intake would be less than the amount sufficient to keep positive calcium balance and to maintain bone mass.

Total parathyroidectomy and autotransplantation to treat secondary hyperparathyroidism (SHP) have been often performed on adult patients with a favorable result, but have rarely been reported in the pediatric literature. We performed the above operations on a 4-year-7-month girl who was treated by continuous ambulatory peritoneal dialysis (CAPD). The postoperative levels of serum calcium remained low in spite of oral calcium and Vitamin D3 medication, and intravenous calcium administration. But an administration of calcium into CAPF fluid has been maintained the normal level of serum calcium. A calcium balance study conducted for 3 days starting the 24th postoperative day showed 391 mg/day of calcium absorption. The girl obtained a relief from the bone pain approximately 2 weeks after the operation and was able to run easily one and a half month after the operation. Total parathyroidectomy and autotransplantation were considered to be an effective treatment for severe symptoms of osteodystrophy in infantile patients with chronic renal failure.

Although serum calcium concentration remains constant during ageing, the plasma concentration of calcium regulating hormones has been known to show dramatic change with ageing. The plasma concentration of parathyroid hormone increases with ageing, whereas plasma concentrations of calcitonin and active vitamin D metabolite decrease with ageing. The age-related change in plasma concentrations of calcium regulating hormones might be a major cause of the age-related bone loss by stimulating bone resorption and thereby releasing calcium from bone. On the other hand, the incidence of soft tissue calcification is known to increase with ageing. In order to further study the relationship between these age-related phenomena, we studied the relationship between radial bone mineral density (BMC) and aortic pulse wave velocity (PWV) which is considered to be a clinical index for the magnitude of aortic calcification. Multi-variate analysis showed the significant relationship (p less than 0.05) between BMC and PWV, suggesting that the decrease in bone mass might be an independent risk factor for the development of aortic calcification. Low calcium intake is an important factor for the development of age-related bone loss. The recommended dietary allowance (RDA) of calcium intake for the Japanese is considered to be 600 mg/day. In order to reevaluate RDA of calcium for the elderly Japanese women, a calcium balance study was performed in 13 subjects; six with osteoporosis (age: 75 +/- 2) and seven without osteoporosis (age: 72 +/- 2). Calcium balance in the individual subject was evaluated by measuring the intake of calcium (food) and output (feces and urine) every 2 days.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dietary protein load on the incidence of nephrolithiasis was studied in rats and men. Three groups of adult male Wister rats were fed with a standard protein diet, a high protein diet, or a low protein diet for 4 weeks. In the high protein group, calcium excretion was significantly increased and citrate excretion was remarkably decreased. This group also exhibited low grade metabolic acidosis due to catabolism of excess amino acids, and increases in urinary cyclic AMP excretion and bone resorption. These findings indicate that protein-induced hypercalciuria is due to low grade metabolic acidosis, which directly affects renal handling of calcium. Long-term calcium loss in the urine may lead to negative calcium balance and hyperfunction of the parathyroid gland may induce bone resorption. The influence of 40 g animal protein load on urinary risk factors of calcium stone formation was investigated in 23 healthy males and 26 patients with nephrolithiasis. All subjects were given control diets each day containing 60 g protein for a week and during the next week each received an additional 40 g animal protein. In the controls, added dietary protein resulted in decreased urinary citrate and increased urinary uric acid, with no change in urinary calcium or cyclic AMP excretion. In contrast, the patients showed increased urinary calcium and cyclic AMP as well as decreased urinary citrate. Further examination of the patients revealed that the significant increases of calcium and cyclic AMP excretion occurred only in hypercalciuric patients, who seemed to be classified into renal hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)