24-h Calcium Excretion Research Articles

Parathyroid Hormone Predicts Radial Bone Loss in Healthy Nigerian Adults

Objective: The correlation between bone mineral density (BMD) and bone markers is well studied in postmenopausal women and elderly men. However, related literature on healthy adults is scarce. This study determined the correlation between parathyroid hormone (PTH), BMD of the left distal radius, and other biochemical markers in apparently healthy Nigerian adults. Methods: This research included 80 (28 males/52 females) healthy participants between 22 and 50 years of age (32.10 ± 5.8 years) who met the inclusion criteria. All the participants were recruited by a systematic random sampling. Interview questionnaires were used to supplement clinical data and anthropometric measures. Fasting samples were analyzed for calcium, inorganic phosphorus, 25-hydroxyvitamin D (25[OH]D), PTH, osteocalcin (OC), alkaline phosphatase, and 24-h calcium excretion. The left distal radius BMD was examined using dual-energy X-ray absorptiometry. The data were statistically analyzed, and the significance level was set at <0.05. Results: It was found that PTH was inversely correlated with left distal radius BMD/z-score (P = 0.004). It showed positive and negative trends with serum-adjusted calcium and inorganic phosphorus (P = 0.09 and P = 0.07, respectively). Neither the OC nor 24-h calcium excretion correlated with PTH (P > 0.05). The OC was inversely correlated with BMD (P = 0.003), but not with 24-h urinary calcium excretion (P > 0.05). None of the participants had osteoporosis. Regression analysis showed that PTH and OC predict radial bone density in participants (P < 0.05). Conclusion: Higher PTH levels correlate with lower left distal radius BMD in apparently healthy participants.

The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study

Hypovitaminosis D in the elderly causes falls and fractures as a result of impaired neuromuscular functions and also may be a reason for nonspecific musculosceletal pain. The aim of this study is to investigate the benefits of a single dose per os or parenterally administrated vitamin D on increasing the quality of life and functional mobility and decreasing the pain in the elderly. The community-dwelling elderly subjects over 65 years age were included in the study. The subjects were given 300.000 IU Vitamin D via per os and parenteral route and assessed after 4 weeks. The serum creatinine, calcium, phosphorous, ALT, ALP, 24-h urine calcium excretion, PTH, and vitamin D levels, as well as VAS (visual analog scale) for pain assessment, functional mobility with TUG (timed up and go test) and quality of life with SF-36 before and after the treatment were evaluated. The serum vitamin D levels were measured by the RIA method. The subjects were divided into four groups each consisting of 30 subjects. The 1st group took i.m. vitamin D, the 2nd group took i.m. placebo, the 3rd group took p.o. vitamin D, and the 4th group took p.o. placebo. The mean age of all the participants was 70.1 ± 4.3 years. There was no difference in the age and gender between the groups (P > 0.05). After treatment, the PTH level of first group was decreased (P = 0.0001) and the vitamin D level increased (P = 0.0001) significantly. In the third group, the PTH level of first group was decreased (P = 0.0001) and the vitamin D level increased (P = 0.004) and the 24-h calcium excretion in urine (P = 0.015) increased significantly. When the pain, the functional mobility, and the quality of life were evaluated, in the first group, the TUG (P = 0.0001) and the VAS (P = 0.0001) decreased significantly, whereas the SF-36 subtitles: physical functioning (P = 0.0001), role physical (0.006), bodily pain (P = 0.0001), general health (P = 0.007), social functioning (P = 0.05), and mental health (P = 0.048) increased significantly. In group two, the VAS (P = 0.001) decreased, the role physical (P = 0.009), and role emotional (P = 0.034) increased significantly; In group three, the TUG (P = 0.0001) and the VAS (P = 0.002) decreased, whereas the physical function (P = 0.0001) and role physical (0.001) increased significantly; In group four, the VAS (P = 0.007) decreased significantly. The megadose vitamin D administration increases quality of life, decreases pain, and improves functional mobility via po or im route in the elderly.

Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow‐up study on methods

Familial hypocalciuric hypercalcaemia (FHH) must be differentiated from primary hyperparathyroidism (PHPT) because prognosis and treatment differ. In daily practice this discrimination is often based on the renal calcium excretion or the calcium/creatinine clearance ratio (CCCR). However, the diagnostic performance of these variables is poorly documented. To appraise the power of various simple biochemical variables to differentiate between FHH and PHPT using calcium sensing receptor (CASR) gene analysis and histopathological findings as gold standards. Follow-up approach (direct design). We included 54 FHH patients (17 males and 37 females, aged 18-75 years) with clinically significant mutations in the CASR gene and 97 hypercalcaemic patients with histologically verified PHPT (17 males and 80 females, aged 19-86 years). All PHPT patients became normocalcaemic following successful neck exploration. Based on receiver operating characteristic (ROC) curve analysis, the CCCR was only marginally better, as judged by the area under curve (AUC = 0.923 +/- 0.021 (SE)), than the 24-h calcium/creatinine excretion ratio (AUC = 0.903 +/- 0.027) and the 24-h calcium excretion (AUC = 0.876 +/- 0.029). However, overlap performance analysis disclosed that the CCCR included fewer patients with PHPT together with the FHH patients than the other two variables at different cut-off points. Based on the ROC curve, the optimal cut-off point for diagnosing FHH using CCCR was < 0.0115, which yielded a diagnostic specificity of 0.88 and a sensitivity of 0.80. Overlap analysis revealed that a cut-off point for CCCR at < 0.020 would sample 98% (53/54) of all patients with FHH and include 35% (34/97) of the PHPT patients. Our results support the use of the CCCR as an initial screening test for FHH. We suggest a two-step diagnostic procedure, where the first step is based on the CCCR with a cut-off at < 0.020, and the second step is CASR gene analysis in patients with FHH or PHPT.

Calcium load during administration of calcium carbonate or sevelamer in individuals with normal renal function

Under steady-state conditions urinary calcium (Ca) excretion corresponds to the Ca load in healthy subjects. However, in chronic haemodialysis patients reliable data on Ca load are not available. In these patients Ca-containing phosphate binders are suspected to play a role in the progression of arteriosclerosis via increased but not quantified Ca load. The present study evaluated the effect of calcium carbonate (CC) and sevelamer hydrochloride (SEV), a calcium-free phosphate binder, on serum Ca and urinary Ca excretion in healthy individuals. Twelve healthy male individuals were included in a monocentre, randomized, single-blind, placebo-controlled, three-way crossover phase I study. Concurrently with their meals, participants received 4 x 2 tablets of SEV (800 mg), CC (500 mg) or placebo for 6 days with 1-week washout between the treatment periods. During the study, weekly blood samples were taken and 24-h urine was collected each day for measurement of calcium, magnesium, phosphorus, chloride and iPTH. Mean daily urinary phosphorus excretion was significantly lower in subjects undergoing SEV treatment compared to those taking placebo (P < 0.001). Mean daily total urinary excretion of calcium was significantly higher in CC-treated participants compared to those receiving placebo (P < 0.001). Mean 24-h calcium excretion during the 6 treatment days was 6.60 +/- 2.62 mmol [265 +/- 105 mg] (CC) versus 5.15 +/- 2.16 mmol [206 +/- 87 mg] (SEV) versus 4.95 +/- 1.63 mmol [198 +/- 65 mg] (Placebo). Taking into account nutritional calcium intake estimated from dietary records fractional calcium absorption was 8.7% (CC), 13.3% (placebo) and 14.8% (sevelamer). Intake of calcium carbonate compared to placebo in contrast to sevelamer in healthy individuals was associated with increased total urinary calcium excretion indicating an increased calcium load due to increased intestinal calcium absorption.

Changes in Insulin Sensitivity and Glucose and Bone Metabolism over Time in Patients with Asymptomatic Primary Hyperparathyroidism

The clinical profile of asymptomatic primary hyperparathyroidism (PHPT) has shifted from a symptomatic disorder toward a more subtle, asymptomatic state. The lack of knowledge about the natural course of asymptomatic PHPT contributes to the controversy regarding the optimal management of these patients. The aim of this study is to evaluate the natural course of calcium and glucose metabolism abnormalities, insulin sensitivity, and bone mineral density (BMD) in subjects with asymptomatic PHPT over 18 months. The study was designed as a prospective observational examination of asymptomatic PHPT patients at baseline and at 6-month intervals for 18 months. Our study examined 61 patients with asymptomatic PHPT and 80 healthy control subjects matched for age, sex, and body mass index. We evaluated calcium metabolism, glucose metabolism by oral glucose tolerance test, insulin sensitivity by homeostasis model assessment index, and BMD by dual-energy x-ray absorptiometry at distal radius, lumbar spine, and femur. Although in asymptomatic PHPT patients, homeostasis model assessment index at baseline was slightly higher than in controls (3.0 +/- 2.2 vs. 2.2 +/- 1.3; P = 0.035), the prevalence of preexisting diabetes mellitus (13.1 vs. 11.3%), undiagnosed impaired fasting glucose (34.4 vs. 30%), impaired glucose tolerance (13.1 vs. 18.8%), and newly diagnosed diabetes mellitus (4.9% vs. 2.5%) was similar. Baseline BMDs (g/cm2) at all three sites were not different between two groups. Six-month interval measurements showed no change in calcium metabolism parameters including serum calcium, phosphorus, 25-hydroxyvitamin D, and 24-h calcium excretion. No significant longitudinal adverse changes were noted in glucose metabolism, insulin sensitivity, or BMD at any site over the 18-month observation period. Our follow-up of patients with asymptomatic PHPT revealed no progression of calcium and glucose metabolism abnormalities, insulin sensitivity, and loss of BMD during the 18-month study period.

Calcium–phosphorus–magnesium homeostasis in pregnant women after renal transplantation

Objective: The aim of the study was the assessment of calcium–phosphorus–magnesium homeostasis in pregnant women after renal transplantation. Methods: The study covered 64 pregnant women in the third trimester of gestation including: 33 women after renal transplantation (the study group) and 31 healthy pregnant women (the control group). Women from both groups were at the similar age: 30.8±4.7 vs. 31.3±5.0 years (NS) and at the same gestational age 34.8±2.4 vs. 35.3±2.6 weeks (NS). The mean body mass index (BMI) in the women from the study group before pregnancy was 21.49±2.81 vs. 22.1±3.02 in the control group (NS), BMI before delivery was 25.43±3.05 vs. 26.0±3.35 (NS), the percentage of the BMI increase during pregnancy was 18.7±7.68 vs. 17.65±7.13 (NS) and BMI increase during gestation was 3.93±1.56 vs. 3.90±1.54, respectively (NS). Arterial blood pressure at the time of blood samples collection for biochemical tests was 151.4±26.8/92.5±16.9 in women from the study group comparing to 115.0±6.0/68.0±7.0 mmHg ( P<0.001) in the patients from the control group. The maximal blood pressure during pregnancy was 169.2±20.7/102.7±14.0 vs. 118.0±7.0/70.0±8.0 mmHg ( P<0.001), respectively. We estimated serum levels of: total Ca, ionized Ca 2+, inorganic phosphorus (P i), Mg, total protein, albumin and blood morphology. Moreover, urine levels of Ca, P i, Mg and protein were assessed. Results: The pregnant women after renal transplantation presented increases in serum concentrations of total Ca (2.54±0.20 vs. 2.16±0.10 mmol/l; P<0.001) and ionized Ca 2+ (1.322±0.104 vs. 1.12±0.07 mmol/l; P<0.001) and the decrease in P i level (1.013±0.211 vs. 1.10±0.16 mmol/l; P<0.05), total protein (59.3±7.0 vs. 65±5 g/l; P<0.001) and albumin (461.6±65.65 vs. 493.2±59 μmol/l; P<0.05). Moreover, in the study group drop in red blood cells count to 3.71±0.56 vs. 4.01±0.35×10 12/l ( P<0.02) in the control group was detected. Despite increased volume of 24-h urine collection in the kidney recipients we observed significantly decreased urine 24-h calcium excretion 2.47±0.92 vs. 6.72±3.49 mmol ( P<0.001) and simultaneous increase in urine Mg excretion 3.422±1.025 vs. 2.18±0.52 mmol/24 h ( P<0.001). There was no difference in urine 24-h P i excretion between the study and the control group. The pregnant renal transplant recipients presented proteinuria of 1.19±1.9 g/24 h. Conclusions: Women after kidney grafting present vital aberrations in calcium–phosphorus–magnesium homeostasis during pregnancy. The most significant changes are associated with calcium metabolism (high increase in serum Ca levels and impairment of renal elimination of calcium). The observed changes may be influenced by the doses of immunosuppressive agents and disturbed renal function.

Nitrogen Metabolism and Bone Metabolism Markers in Healthy Adults during 16 Weeks of Bed Rest

The associations between nitrogen metabolism and bone turnover during bed rest are still not completely understood. We measured nitrogen balance (nitrogen intake minus urinary nitrogen excretion) and biochemical metabolic markers of calcium and bone turnover in six males before head-down tilt bed rest (baseline), during 2, 10, and 14 weeks of immobilization, and after reambulation. The changes in nitrogen balance were highest between baseline and week 2 (net change, -5.05 +/- 1.30 g/day; 3.6 +/- 0.6 g/day at baseline vs -1.45 +/- 1.3 g/day at week 2; P<0.05). In parallel, serum intact osteocalcin (a marker of bone formation) was already reduced and renal calcium and phosphorus excretions were increased at week 2 (P <0.05). Fasting serum calcium and phosphorus values and renal excretion of N-telopeptide (a bone resorption marker) were enhanced at weeks 10 and 14 (P <0.05-0.001), whereas serum concentrations of parathyroid hormone, calcitriol, and type I collagen propeptide (a marker of bone collagen formation) were decreased at week 14 (P <0.05-0.01). Significant associations were present between changes of serum intact osteocalcin and 24-h calcium excretion (P <0.001), nitrogen balance and 24-h phosphorus excretion (P <0.001), nitrogen balance and renal N-telopeptide excretion (P <0.05), and between serum osteocalcin and nitrogen balance (P <0.025). Bone formation decreases rapidly during immobilization in parallel with a higher renal excretion of intestinally absorbed calcium. These changes appear in association with the onset of a negative nitrogen balance, but decreased bone collagen synthesis and enhanced collagen breakdown occur after a time lag of several weeks.

Urinary Calcium Excretion in Healthy School Children

Two hundred and twenty Argentinian primary school children (122 boys, 98 girls, aged 6 – 13 years) were studied to establish reference values of 24-h urinary calcium excretion (UCa) and calcium/creatinine ratio (Ca/Cr) in 24-h urine collections and in first-morning urine samples. Mean UCa excretion was 2.05±1.40 mg/kg per day and the 95th percentile was 4.74 mg/kg per day. UCa excretion was higher in boys than girls (2.33±1.47 and 1.70±1.24 mg/kg per day respectively, P <0.001). Statistically significant differences were found between the 6- to 9-year and the 10- to 13-year age groups (2.37±1.49 vs. 1.73±1.25 mg/kg per day, P <0.001). Mean Ca/Cr ratios in 24-h collections and in first-morning urine samples were 0.129±0.086 and 0.105±0.079 for the group overall (P <0.001). The Ca/Cr ratio in the first-morning urine sample correlated poorly with the 24-h calcium excretion, suggesting that the Ca/Cr ratio in first-morning urine samples cannot replace the 24-h measurement.

The Effect of Diclofenac Sodium on Urinary Concentration of Calcium, Uric Acid and Glycosaminoglycans in Traumatic Paraplegics

Non-steroidal anti-inflammatory drugs (NSAID) have been shown to decrease calcium excretion in the experimental animal, in human volunteers and in calcium stone formers. Paraplegics tend to be hypercalciuric during the first 2 years after their injury and this is said to be a predisposing factor for stone formation in these patients. The effect of the NSAID diclofenac sodium was studied in 12 traumatic paraplegics who had sustained their injury 1 to 6 months previously; 24-h urine samples collected before and 2 weeks and 4 weeks after oral diclofenac sodium 50 mg tds were analysed for calcium, uric acid, glycosaminoglycans (GAGs) and volume. There were no significant changes in urinary volume, uric acid and GAGs excretion. However, urinary calcium concentration and 24-h calcium excretion decreased significantly following 2 weeks' and 4 weeks' treatment with diclofenac sodium.

Effect of calcium pidolate on biochemical and hormonal parameters in involutional osteoporosis

The purpose of this study was to determine the value of calcium pidolate in the treatment of involutional osteoporosis. This compound has been reported to be better absorbed than other calcium salts, to lower the levels of parathyroid hormone (PTH) and to raise those of growth hormone (GH). We accordingly treated one group of 10 women suffering from involutional osteoporosis with the equivalent of 1 g elemental calcium and administered a placebo to a second group of 10 osteoporotic women whose mean age and body surface area were comparable. Basal sequential multiple analysis (SMA-12) was performed in all subjects to determine calcium, phosphorus, alkaline phosphatase (ALP) and total protein levels, the same blood samples being used for the evaluation of mean PTH, GH and osteocalcin (BGP). Urinary 24-h calcium excretion was determined and the calcium/creatinine (Ca/Cr) and hydroxyproline/Cr (HP/Cr) ratios were measured in 12-h fasting urine samples, the results being corrected for glomerular filtrate. The same parameters were measured again following a month of uninterrupted treatment. After 30 days, we observed no differences in either group as regards calcaemia, phosphataemia, ALP, total proteins, PTH, GH, BGP or 24-hour calciuria. The only noteworthy changes seen were significant decreases (P < 0.001) in the Ca/Cr and HP/Cr ratios in the group treated with calcium pidolate. These results show that calcium pidolate at the dose administered inhibits bone resorption but does not affect the levels of PTH, GH, BGP or ALP in the medium term. Our findings indicate that it has no influence on bone formation.

The diagnosis of hypercalciuria in children.

Calcium loading tests were performed in 21 children with hypercalciuria, haematuria and/or nephrolithiasis and 10 control subjects. Comparisons of 24-h calcium excretion before and after loading were evaluated rather than fasting urinary calcium to urinary creatinine ratio. The differences in calcium excretion before and after loading clearly distinguished absorptive from renal hypercalciuria. A difference higher than 0.035 mmol/kg indicated absorptive hypercalciuria in 6 of 21 patients, whereas in the remaining 15 much lower differences indicated renal hypercalciuria. Resorptive hypercalciuria caused by low serum values of 25-hydroxyvitamin D was considered in 6 of the 15 patients with renal hypercalciuria. These patients had low values of phosphate reabsorption (TmP/GFR) and could be clearly separated by high values of calcium reabsorption (TmCa/GFR), in contrast to patients with renal hypercalciuria who had normal values of TmP/GFR and low values of TmCa/GFR. The correct treatment and prevention of nephrolithiasis caused by hypercalciuria in children should be based on accurate diagnosis; this can be achieved by using the calcium loading test described in this report.

Humoral hypercalcemia of malignancy in canine lymphosarcoma.

Studies on the pathogenesis of hypercalcemia in canine lymphosarcoma have led to conflicting results. The biochemical and bone histomorphometric findings in canine lymphosarcoma were examined in 19 hypercalcemic and 17 nonhypercalcemic dogs with lymphosarcoma. Compared to the nonhypercalcemic group, the hypercalcemic dogs demonstrated an increase in fasting and 24-h calcium excretion, an increase in fractional phosphorus excretion, and a significant increase in nephrogenous AMP excretion. Plasma 1,25-dihydroxyvitamin D and immunoreactive PTH levels were equivalent in the two groups. Quantitative bone histomorphometry performed on iliac crest biopsies revealed increased parameters of bone resorption in those hypercalcemic dogs with no evidence of tumor at the biopsy site, without a compensatory increase in bone formation. Acid-urea tumor tissue extracts from eight hypercalcemic and six nonhypercalcemic dogs were examined for adenylate cyclase-stimulating activity (ACSA). All tumors from hypercalcemic dogs contained ACSA, whereas none of the tumors from nonhypercalcemic dogs had ACSA. Further purification of one tumor extract yielded an adenylate cyclase-stimulating protein which appeared to interact specifically with the PTH receptor. We conclude that in some cases, hypercalcemia in canine lymphosarcoma is mediated by a tumor-derived circulating bone-resorbing factor which is distinct from PTH. ACSA detected in tumor tissue appears to be a reliable marker for the syndrome in vivo. The role of this activity in the pathogenesis of the syndrome remains to be determined.