Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets.

BACKGROUND: Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolism occurs after the end of puberty without the need for further calcium supplementation. OBJECTIVES: To evaluate the role of vitamin D receptor in intestinal calcium absorption and bone, we investigated intestinal fractional calcium absorption (FCA), bone calcium accretion (Vo+), bone mineral density (BMD), and bone structure parameters in HVDRR patients from infancy into adulthood. PATIENTS AND METHODS: Seventeen HVDRR patients aged 1.5-37 yr were investigated. FCA and Vo+ were determined by stable-calcium isotopes. BMD was determined by dual-energy x-ray absorptiometry and bone structure by high-resolution magnetic resonance imaging. RESULTS: FCA in patients aged 1.5-17 yr was 34.9 ± 11.2% compared with 57.3 ± 2.0% in age-matched controls (P < 0.00004), whereas in patients aged 18-26 yr, it was 82.0 ± 7.8 and 53.6 ± 1.2% in controls (P < 0.001). FCA of patients older than 29 yr was comparable to controls. Patients aged 18-26 yr had higher Vo+ than controls (P < 0.02). Patients under 18 and over 29 yr of age had Vo+ comparable to controls. Femoral-neck BMD Z-score was -2.38 ± 0.3 in patients under 18 yr and 0.28 ± 0.87 in postpubertal patients (P < 0.0001). Bone structure by high-resolution magnetic resonance imaging and bone parameters of HVDRR patients and controls were similar. CONCLUSIONS: Evidence from HVDRR patients reveals that calcium absorption is highly vitamin D dependent during infancy until the end of puberty, after which there is a period of about 10 yr in which mechanisms other than vitamin D-dependent ones are substantially involved in calcium absorption.

Parathyroid hormone-related protein in preterm human milk.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone receptors and cause hypercalcemia. High concentrations of PTHrP are found in human breastmilk of mothers of term-infants. It is not known whether PTHrP is excreted in preterm human milk. This study tested the hypothesis that PTHrP concentrations in milk obtained from mothers of preterm infants are similar to those found in milk from mothers of term infants. METHODS: We collected samples of expressed human milk obtained from 27 mothers of preterm infants (27-34 weeks' gestation) and from 16 mothers of full-term infants. Samples were collected within the first 72 hours postpartum (colostrum) and again at 1 and 2 weeks postpartum. PTHrP concentrations in these samples were measured by two-site immunoradiometric assay. RESULTS: PTHrP concentrations were significantly higher in samples obtained after 1 week postpartum than in samples obtained during the first 72 hours of life in breastmilk obtained from mothers of both term and preterm infants (P < 0.0001). PTHrP concentrations were similar in colostrum and after 1 week in term and preterm milk. PTHrP concentrations after 2 weeks of lactation were significantly higher in samples obtained from mothers of term infants (P < 0.006). CONCLUSION: Human milk expressed by mothers of preterm infants contains amounts of PTHrP similar to those measured in milk expressed by mothers of term infants.

Is there a role for a random measurement of 24-hour urine calcium excretion in the determination of calcium supplementation in osteoporotic postmenopausal women using alendronate?

The article addresses the clinical query whether a casual determination of 24-hour urinary calcium excretion by the end of first-year treatment with alendronate in osteoporotic postmenopausal women correlates with the change in bone mineral density achieved during that year. The study included 2 arms: a prospective arm (n = 31) with women on long-term hormone replacement therapy were followed for 1 year after addition of alendronate (10 mg/daily); a retrospective arm (n = 33) with women using alendronate for 1 year. Bone mineral density and urine deoxypyridinoline were measured at baseline and 1 year, 24-hour urine calcium was obtained at 1 year. All patients used supplemental calcium, but the exact intake values were not determined. The results demonstrated no correlation between the annual increase in both spine and femur bone density and urinary calcium. Assuming that urinary calcium correlates with calcium intake and absorption, a casual measurement of urinary calcium excretion seems irrelevant for the titration of optimal calcium supplementation in this clinical setup.