Hypercalciuria is of continuing interest as one of the risk factors for stone disease in children, but the definition, incidence and pathogenesis are controversial. Therefore reference values for the urinary calcium/creatinine (Ca/Cr) ratios were established in 564 healthy children aged 6-17.9 years during the fasting state (09.00 h) and in 236 of them also in the post-absorptive state about 2 h after lunch (14.00-16.00 h). The Ca/Cr ratios in both urine specimens were independent of age and sex, rendering it possible to determine a common normal range and to calculate centiles for Ca excretion in a large sample of healthy children and adolescents. To provide information about the incidence of hypercalciuria the Ca/Cr ratios of 1013 other apparently healthy children aged 6-17.9 years were measured during the post-absorptive state on two consecutive days. In 39 (3.8%) of them, 21 girls, and 18 boys, the Ca excretion was elevated in both urine specimens. Thirty-six of these children, all presenting without renal complaints, underwent further investigations to elucidate the possible mechanisms of the hypercalciuria. On the basis of the Ca/Cr concentration during the fasting state and the calciuric response to a standardised oral Ca tolerance test the children were subclassified into three groups: (1) Absorptive hypercalciuria (AH, n = 12): Increased calciuric response to the Ca load, but normal fasting Ca/Cr; (2) Renal hypercalciuria (RH, n = 8): Increased Ca/Cr after Ca load and during the fasting state; (3) Normal Ca excretion during the fasting state and after the Ca tolerance test, but increased sodium excretion (dietary hypercalciuria, DH, n = 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Recent evidence suggests that the protein osteocalcin is like the bone alkaline phosphatase produced by osteoblasts and circulates in human blood. With the introduction of a radioimmunoassay for serum osteocalcin it was hoped that this test would provide a useful index of altered bone metabolism. Therefore serum osteocalcin was measured in 88 controls and 112 patients with disorders of calcium and phosphate metabolism, isolated elevation of alkaline serum phosphatase in the absence of disease (isolated hyperphosphatasaemia) and children prone to osteopenia. In the controls serum osteocalcin was higher in children less than 15 years (median and range: 11.9, 7.7-15.3 ng/ml) than in adults (3.7, 2.6-5.2 ng/ml) and was highly correlated to alkaline serum phosphatase activity (r = 0.87, n = 88, P less than 0.01). Osteocalcin was elevated in primary hypoparathyroidism, low in untreated hypoparathyroidism but normal in hypoparathyroidism (including pseudohypoparathyroidism) during vitamin D treatment. The bone protein was low-normal and increased to high-normal levels during vitamin D therapy in vitamin D deficiency rickets and familial hypophosphataemic rickets, but remained low in patients with end organ resistance to 1,25-dihydroxyvitamin D. Osteocalcin (and urinary hydroxyproline) were not elevated in isolated hyperphosphatasaemia, indicating that mechanisms other than increased bone turnover may account for the markedly elevated serum alkaline phosphatase activity in these subjects. Osteocalcin was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. It is concluded that the measurement of serum osteocalcin seems to be a reliable index of bone formation provided that the vitamin D status and renal function are normal.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARYThe ratio of maximum rate of renal tubular reabsorption of phosphate to glomerular filtration rate (TmPO4/GFR) was determined in 546 schoolchildren, aged between 6 and 17 -9 years, using the nomogram of Walton Serum and urine samples from 120 of these children, 60 girls and 60 boys, were stored at -200C until analysed in duplicate for AP, iPTH, and CT in serum and for cAMP and total OH-P in urine. These children were divided into 2-yearly age groups 217

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n = 20). The results were compared with subjects with low (hypoparathyroidism, HP n = 29), normal (controls, n = 31) and high (primary hyperparathyroidism, 1 degree HPT, n = 13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1 degree HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1 degree HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r = -0.69, P less than 0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct measurements of parathyroid activity are available in only small numbers of children with vitamin D deficiency rickets (VDR). Therefore serum immunoreactive parathyroid hormone (iPTH) and the urinary cyclic adenosine-3',5'-monophosphate excretion (UcAMP) were measured together with other important indices of calcium metabolism in 24 patients (aged 2-42 months) with VDR before vitamin D treatment. iPTH and UcAMP were significantly elevated in comparison to age-matched controls. In patients there was a highly significant positive correlation between iPTH and UcAMP and a negative relationship between both indices of parathyroid activity to serum phosphate and urine calcium, respectively, indicating that the simple measurement of serum phosphate and/or urine cAMP and Ca provides a reliable tool for the assessment of secondary hyperparathyroidism in VDR. In two patients classified as being in the early stage of VDR the parathyroid activity was not elevated despite hypocalcemia indicating relative hypoparathyroidism. Twelve patients with VDR were followed during vitamin D therapy: Within the first 2 weeks of treatment UcAMP slightly increased and thereafter decreased in most patients, but was still elevated in three patients even after 7 weeks, whereas iPTH became normal within 3 weeks of treatment. This favors the concept that vitamin D deficiency diminishes the activation of renal adenylate cyclase by PTH which is overcome by the highly increased PTH secretion in the advanced stages of rickets. The basal and calcium-stimulated serum calcitonin (CT) levels, determined in some of the patients, were normal, ruling out a significant disturbance of CT secretion in VDR.