Pathophysiology of calcium metabolism in children with vitamin D-deficiency rickets,☆☆,

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Abstract

Objective: To improve understanding of the biochemical events in vitamin D-deficiency rickets (VDR). Methods: We investigated 51 untreated patients, 2 to 36 months of age, during three stages of VDR. Nineteen of these patients were also studied during therapy with 5000 to 10,000 U vitamin D 3 (cholecalciferol) and 0.5 to 1 gm calcium. Together with calcium and inorganic phosphate in serum and urine, we measured (1) parathyroid hormone (PTH) secretion (intact serum PTH) and action on the kidney (urinary adenosine 3',5'-cyclic monophosphate (cAMP)/creatinine ratio; (2) serum alkaline phosphatase level; (3) urinary hydroxyproline/ creatinine ratio; and (4) serum 1,25-dihydroxyvitamin D (1,25[OH] 2 D) level. Results: The untreated patients had secondary hyperparathyroidism (high serum PTH and urinary cAMP/creatinine ratio), low calcium and phosphate concentrations in serum, and increased bone turnover (elevated serum alkaline phosphatase and OHP/creatinine ratio), whereas serum 1,25(OH) 2 D was low, normal, or even slightly elevated. Serum calcium level was positively correlated to serum 1,25(OH) 2 D and to OHP/creatinine ratio, indicating that normocalcemia in untreated rickets (stage 2) is at least partially maintained by 1,25(OH) 2 D- induced calcium mobilization from bone. There was no correlation between serum calcium and serum PTH, or between serum PTH and urinary cAMP/creatinine ratio or serum phosphate, indicating disturbed regulation and action of PTH. During vitamin D treatment, serum 1,25(OH) 2 D values increased to supranormal concentrations in association with the restoration of the physiologic relationship of PTH to serum calcium and phosphate concentrations and urinary cAMP/creatinine ratio. Conclusion: Circulating 1,25(OH) 2 D has an important role in the pathophysiology of VDR before and during treatment, mainly by influencing the bone and kidney response to endogenous PTH. (J P EDIATR 1995;126:736-41)

Section snippets

METHODS

We studied 51 children (33 boys) with VDR, 2 to 36 months of age (median, 16 months). The patients were not selected and attended several pediatric clinics, mainly from the northern part of Germany, from 1989 to 1994. All children had a history of deficient vitamin D intake.

The diagnosis of VDR was based on radiologic signs of rickets and laboratory findings such as elevated AP activity, low 25(OH)D concentration (<12.5 nmol/L; 5 ng/ml), and low or normal Ca and P levels in serum. None of the

Calcium metabolism in different stages of VDR

Table I summarizes the median values and ranges of several biochemical variables in the untreated patients, who were divided into three groups according to the stage of VDR. As previously defined, serum Ca level was low in stages 1 and 3 but normal in stage 2, whereas serum P level was normal in stage 1 but low in stages 2 and 3.

The median value of serum AP activity was elevated in stage 1, with a significant further increase in stage 2 and a decrement thereafter. The index of bone degradation,

DISCUSSION

The present study confirms that vitamin D depletion (low serum 25(OH)D levels), secondary hyperparathyroidism, and high bone turnover are the hallmarks of VDR in children. The serum levels of Ca, P, and 1,25(OH) 2 D are of minor diagnostic relevance; these values may be normal, and 1,25(OH) 2 D may even be increased in VDR. The latter observation confirms investigations in other vitamin D-deficient children 8, 9 and adults. 10, 11 In the face of secondary hyperparathyroidism, hypocalcemia, and

References (21)

  • RJ Walton et al.

    Nomogram for derivation of renal threshold phosphate concentration

    Lancet

    (1975)
  • K Kruse et al.

    Calcium metabolism in Williams-Beuren syndrome

    J P EDIATR

    (1992)
  • D Fraser et al.

    Hyperparathyroidism as the cause of hyperaminoaciduria and phosphaturia in human vitamin D deficiency

    Pediatr Res

    (1967)
  • CD Arnaud

    Parathyroid hormone and its role in the pathophysiology of the common forms of rickets and osteomalacia

  • K Kruse et al.

    Renal threshold phosphate concentration (TmPO 4 /GFR)

    Arch Dis Child

    (1982)
  • K Kruse et al.

    Die Hydroxyprolin-Ausscheidung im Morgen-Urin: ein geeigneter Parameter des Knochen-Umsatzes im Kindesalter

    Monatsschr Kinderheilkd

    (1983)
  • K Kruse et al.

    Urinary adenosine-3'-5'-monophosphate excretion in childhood

    J Clin Endocrinol Metab

    (1981)
  • T Markestad et al.

    Plasma concentrations of vitamin D metabolites before and during treatment of vitamin D deficiency rickets in children

    Acta Paediatr Scand

    (1984)
  • RW Chesney et al.

    Vitamin D metabolite concentrations in vitamin D deficiency: are calcitriol levels normal?

    Am J Dis Child

    (1981)
  • SE Papapoulos et al.

    Metabolites of vitamin D in human vitamin D deficiency: effect of vitamin D 3 or 1,25-dihydroxycholecalciferol

    Lancet

    (1980)
There are more references available in the full text version of this article.

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From the Department of Pediatrics, Medical University of Luebeck, Luebeck, Germany

☆☆

Reprint requests: Klaus Kruse, MD, Klinik fuer Paediatrie der Medizinischen Universitaet zu Luebeck, Kahlhorststrasse 31-35, D-23538 Luebeck, Germany.

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