Pathophysiology of calcium metabolism in children with vitamin D-deficiency rickets.
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 D3 (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)2D) 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)2D was low, normal, or even slightly elevated. Serum calcium level was positively correlated to serum 1,25(OH)2D and to OHP/creatinine ratio, indicating that normocalcemia in untreated rickets (stage 2) is at least partially maintained by 1,25(OH)2D-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)2D 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.


CONCLUSIONS
Circulating 1,25(OH)2D has an important role in the pathophysiology of VDR before and during treatment, mainly by influencing the bone and kidney response to endogenous PTH.
Kruse
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Department of Pediatrics, Medical University of Luebeck, Germany.
D000469:Alkaline Phosphatase / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000008:administration & dosage; D002675:Child, Preschool; D002762:Cholecalciferol / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007223:Infant; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D012279:Rickets / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D002136:Calcium, Dietary; D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; D002762:Cholecalciferol; D003404:Creatinine; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium