DIET, VITAMIN-D AND VERTEBRAL MINERAL DENSITY IN HYPERCALCIURIC CALCIUM STONE FORMERS

To elucidate the pathophysiology of dietary calcium independent hypercalciuria, 42 calcium stone formers (Ca SF) were selected because they had on free diet a calciuria greater than 0.1 mmol/kg/day. For four days they were put on a diet restricted in calcium (Ca RD) by exclusion of the diary products. They collected 24 hour urines on free diet and on day 4 of Ca RD as well as the two-hour fasting urines on the morning of the day 5 and the four-hour urines passed after an oral calcium load of 1 g, for measurement of creatinine, Ca, PO4, urea and total hydroxyprolinuria (THP). On day 5 fasting plasma concentrations of Ca, PO4, intact PTH, Gla protein, calcidiol and calcitriol were measured. The patients were firstly classified into dietary hypercalciuria (DH, 18 patients) and dietary calcium-independent hypercalciuria (IH, 24 patients) on the basis of the disappearance or not of hypercalciuria on Ca RD. Then the patients with IH were subclassified into absorptive hypercalciuria (AH) because of normal fasting calciuria (8 patients) and into fasting hypercalciuria (16 patients). Fasting hypercalciuric patients were subsequently divided according to the PTH levels into renal hypercalciuria (RH, 1 patient) with elevated fasting PTH becoming normal after the Ca load and undetermined hypercalciuria (UH, 15 patients) with normal PTH levels. Furthermore, their vertebral mineral density (VMD) was measured by quantitative computerized tomography which was normal in DH (91 +/- 6% of the normal mean for age and sex) but was decreased in IH to 69 +/- 4%. No difference in VMD was observed between AH and UH. Urinary excretions of urea, phosphate and THP was higher in IH than in DH and comparable in AH and UH. Sodium excretion Ca RD was the same in all groups and subgroups as well as the plasma parameters. Plasma calcitriol was increased in IH and DH comparatively to normal in spite of normal plasma calcidiol. Calciuria increase after oral calcium load, an index of Ca absorption, was higher in IH than in controls and comparable in IH and DH as well as in the three subgroups of IH. From these data and correlation studies in IH it is concluded: (1.) VMD is decreased in Ca stone formers with IH but not in those with DH, making the distinction of these two groups of hypercalciuria patients clinically relevant. (2.) The further distinction within IH of AH, RH and UH is not very justified, since RH is exceptional and VMD and other biochemical parameters (with the exception of those taken for subclassification) are not different between AH and UH. (3.) Since in IH, fasting hydroxyprolinuria and fasting calciuria were greater than in control, whereas plasma PTH concentrations were low to normal (with the exception of the case with RH), and fasting calciuria was correlated to fasting hydroxyprolinuria, it is suggested that a primary bone hyperresorption, and not a primary renal leak of calcium or a primary intestinal hyperabsorption, is the main cause of IH. (4.) IH is associated with higher urea excretion on free and Ca R diets than in controls, suggesting a higher protein intake of no dairy origin. This higher intake may favor bone resorption since fasting calciuria and hydroxyprolinuria are correlated to urea excretion. (5.) In IH, the positive correlations of calcitriol with VMD and calciuria increase after Ca oral load, and the negative one between calcitriol and fasting calciuria, suggest that calcitriol attenuates bone resorption by increasing calcium absorption. (6.) In IH, plasma calcitriol is correlated positively to calcidiol and negatively to plasma phosphate which remains in the normal range. Therefore, increased plasma calcitriol in IH may be explained by a hypersensitivity of 25 (OH) vitamin D1-alpha hydroxylase to PPO4, making its synthesis dependent upon 25 (OH) D. (7.) Exclusion of dairy products might be deleterious for the skeleton in Ca stone formers. Restriction of protein intake of non-dairy origin should rather be advised.