Evaluation of serum osteocalcin as an index of altered bone metabolism

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<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<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. Although serum osteocalcin and alkaline phosphatase were generally correlated there were examples of dissociation between both indices. In some circumstances (e.g. rickets) serum osteocalcin may severe as a useful index of an effective therapy.Abbreviations AP alkaline phosphatase activity - Gla gammacarboxy-glutamic acid - 1,25 (OH)₂D₃ 1,25-dihydroxyvitamin - D₃ calcitriol - PTH parathyroid hormone - HP hypoparathyroidism - PHP pseudohypoparathyroidism - I^oHPT primary hyperparathyroidism - VDR vitamin D deficiency rickets - VDDR II vitamin D dependency rickets type II - FHL familial hypophosphataemic rickets - IH isolated hyperphosphatasaemia in the absence of disease     

Renal Fanconi syndrome: first sign of partial respiratory chain complex IV deficiency

A 2-year-old boy who developed hypophosphatemic rickets without signs of muscular weakness or neurological disturbances is presented. Biochemical findings included hypophosphatemia, metabolic acidosis, hypouricemia, hyperphosphaturia, severe glucosuria, generalized hyperaminoaciduria, hypercalciuria, proteinuria with elevated excretion of IgG, transferrin, albumin and high levels of α-1-microglobulin. Urine concentration capacity and creatinine clearance were normal. Lactaturia without elevated levels of plasma lactate and a high urinary excretion of β-hydroxybutyrate were suggestive for mitochondriopathy. Partial deficiency of cytochrome c oxidase (complex IV of the respiratory chain) was found in skeletal muscle. A renal biopsy specimen demonstrated enlarged mitochondria with abnormal arborization and disorientation of the cristae in the proximal tubular cells. Reduced activity of mitochondrial cytochrome c oxidase in tubular cells could be demonstrated by ultracytochemistry. In conclusion, rickets due to the renal Fanconi syndrome can be the first clinical sign of mitochondrial cytopathies without extrarenal symptoms. Elevated excretion of lactate and ketone bodies in urine may serve as a diagnostic marker. Received: 6 October 1998 / Revised: 17 August 1999 / Accepted: 18 August 1999     

Brown tumour as a complication of secondary hyperparathyroidism in severe long-lasting vitamin D deficiency rickets

Brown tumour is a localised form of fibrous-cystic osteitis associated with primary or secondary hyperparathyroidism. Despite the fact that secondary hyperparathyroidism occurs in vitamin D deficiency rickets, no cases of rickets with brown tumour have so far been described. We present a 2.9-year-old girl who had brown tumour of the mandible due to severe vitamin D deficiency rickets. Treatment with vitamin D₃ corrected the hyperparathyroidism rapidly which was followed by gradual regression in tumour size. Conclusion Brown tumour can develop in severe, long-standing vitamin D deficiency rickets and responds to vitamin D treatment. Received: 10 March 1999 and in revised forms: 20 June 1999 and 27 June 1999 / Accepted: 27 July 1999     

Bone sodium exchange

Sodium exchange in chick bone has been studied on control, rachitic and rachitic treated with vitamin D₃ animals. The rachitic bone, which shows increased water content, has similar bone exchange than that of their age control group. Vitamin D₃ treatment of rachitic chicks was followed by a decrease in bone water content and increase in bone sodium exchange.

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Zusammenfassung Der Natriumaustausch in Kükenknochen wurde bei Kontroll-und rachitischen Tieren sowie bei rachitischen, mit Vitamin D₃ behandelten Tieren untersucht. Der rachitische Knochen, der einen erhöhten Wassergehalt aufweist, hat einen ähnlichen Natriumaustausch wie der Knochen gleichaltriger Kontrolltiere. Die Behandlung von rachitischen Küken mit Vitamin D₃ bewirkte eine Abnahme des Wassergehaltes im Knochen und eine Zunahme des Natriumaustausches.

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Résumé Les échanges du sodium au niveau d'os de poulet ont été étudiés chez des animaux témoins, rachitiques et reachitiques traités par vitamine D₃. L'os reachitique présente une augmentation du contenu en eau, avec des échanges en sodium osseux identiques à ceux des témoins, de mêne âge. L'administration de vitamine D₃ à des poulets rachitiques est suivie par une décroissance du contenu de l'os en eau et par une augmentation des échanges du sodium osseux.

     

The effect of Solanum malacoxylon on rachitic bone lesions in the rat

Summary The plant Solanum malacoxylon (S.M.) is known to cause severe soft tissue calcifications in cattle and sheep and has recently become of special, interest since it exerts biological actions which resemble those of vitamin D. In order to investigate whether S.M. is capable to improve the rachitic bone changes in vitamin d and phosphate deficient rats, a watery extract of 50, 100 and 200 mg S.M. was fed daily to these animals over a period of 10 days. The width of epiphyseal plates was compared after that time with those of rats treated with 0, 0.225, 0.45 and 0.9 IU of vitamin D₃ daily. There was a dose related curative effect of S.M. on the epiphyseal lesions very similar to that of vitamin D₃. The hypercalcemic and hyperphosphatemic effect of S.M. was identical to that of vitamin D₃. The 25-hydroxy-vitamin D serum levels remained almost undetectable, in the S.M. treated rats as well as in the vitamin D₃ treated animals.Supported by the Deutsche Forschungsgemeinschaft.     

Pycnodysostosis with heterozygous beta-thalassemia

A 6-year follow-up of a Greek girl with pycnodysostosis associated with heterozygous beta-thalassemia is reported. Active rickets in infancy was superimposed on pycnodysostosis. In the family the autosomal recessive disease, pycnodysostosis, appeared in two of three siblings in combination with the autosomal dominant disease, thalassemia minor.     

Hypocalcemic Rickets: An Unusual Cause of Dilated Cardiomyopathy

We report a breast-fed infant with clinical evidence of rickets and with dilated cardiomyopathy who responded well to supplemental calcium and vitamin D. We believe that this is the first report of such an association in an American child.     

Children with nutritional rickets referred to hospitals in Copenhagen during a 10-year period

Aim: To describe the prevalence of nutritional rickets among children admitted to three large paediatric departments in the Copenhagen area during a 10 y period. Methods: Retrospective analysis of cases identified from the diagnosis registers fulfilling the diagnostic criteria for nutritional rickets. Results: Forty cases were identified, distributed in two distinct age groups: 0.5-4 y (n = 31) and 9-15 y (n = 9). All cases were immigrants, of whom 95% were born in Denmark. The main symptoms in the younger age group were bowed legs and clumsy walk, and in the peri-pubertal group were painful joints. Two children had generalized convulsions. None of the cases had received vitamin D supplementation. Conclusion: Nutritional rickets is still present among immigrants in Denmark, and it is likely that the prevalence of mild cases is high. Prevention through vitamin D supplementation is important, but requires a dedicated health education effort.     

婴幼儿佝偻病与血铅水平关系的研究

目的:探讨佝偻病的发病及治疗与血铅水平的关系。方法:将资料完整的842例患儿分为佝偻病组、对照组和治疗组,比较其血铅水平。结果:血铅水平与儿童性别有关(P<0.05),与佝偻病发病无关(P>0.05);排铅治疗对佝偻病有一定的治疗效果。结论:环境铅污染可能是儿童佝偻病高发及常规治疗效果不佳的原因之一。     

Evidence for vitamin D-independent active calcium absorption in newborn piglets

Summary The role of 1,25-dihydroxycholecalciferol (calcitriol) for intestinal calcium (Ca²⁺) absorption was studied in newborn (<1 week old) and weaned piglets (>6 weeks old). In both groups, normal piglets and piglets suffering from inherited pseudo vitamin D-deficiency rickets, type I (PVDRI) were used. In this inherited disorder, renal production of calcitriol is absent. Plasma samples were assayed for calcitriol and total Ca, and dissociation constants (K_d) and maximum binding capacities (B_max) of intestinal calcitriol receptors were determined under equilibrium conditions at 4°C. Unidirectional Ca²⁺-flux rates were measured across stripped duodenal mucosae in Ussing chambers in the absence of electrochemical gradients. The plasma calcitriol concentrations of neonatal (26.5±7.1 pg/ml, n=11; ± SEM) and weaned PVDRI piglets (18.8±5.7 pg/ml, n=8)were unphysiologically low and differed significantly from control animals (83.6±14.8 pg/ml, n=8, and 86.9±9.6 pg/ml, n=11, respectively). However, newborn PVDRI piglets had normal plasma Ca levels at least during the first days of life. They became hypocalcemic and developed clinical symptoms of rickets during the following weeks. In newborn PVDRI and control piglets, B_max was significantly lower (84±28 fmol/mg protein and 127±55 fmol/mg protein, n=9, respectively) than in weaned piglets (741±82 fmol/mg protein, n=9, and 778±121 fmol/mg protein, n=8, respectively). Significant net Ca²⁺-fluxes were found in both newborn PVDRI and control piglets (88.8±25.1 nmol · cm^-2 · h^-1, n=6, and 86.5±10.5 nmol · cm⁻² · h⁻¹,n=9, respectively). However, active net Ca²⁺ absorption was completely absent in weaned PVDRI piglets. These results indicate the presence of vitamin D-independent mechanisms for active intestinal Ca²⁺ absorption during early postnatal life in pigs.