J Pediatr Gastroenterol Nutr. 2006 Apr;42(4):419-26
Fractional calcium absorption is increased in girls with Rett syndrome
Motil KJ, Schultz RJ, Abrams S, Ellis KJ, Glaze DG.
USDA/ARS Children's Nutrition Research Center, Houston, TX
Abstract
BACKGROUND: Rett syndrome (RTT), an X-linked neurodevelopmental disorder primarily affecting girls, is characterized in part by osteopenia and increased risk of skeletal fractures. We hypothesized that decreased intestinal calcium (Ca) absorption relative to dietary Ca intake and increased renal Ca excretion might cause these problems in RTT. OBJECTIVE: We measured fractional Ca absorption, urinary Ca loss, dietary Ca intake, and the hormonal factors regulating Ca metabolism to determine whether abnormalities in Ca balance might relate to poor bone mineralization in RTT girls and to evaluate the contribution of these factors to the overall dietary Ca needs of RTT girls. STUDY DESIGN: Ten RTT girls and 10 controls, matched for age, sex, and pubertal status, were given a 3 day constant Ca diet that mimicked their habitual intakes. At the end of each dietary period, girls received single doses of Ca (intravenous) and Ca (oral). Fractional urinary excretion of Ca, Ca, 24 hour urinary Ca, and urinary cortisol excretion were determined. Serum Ca, phosphorous, alkaline phosphatase, vitamin D metabolites, parathyroid hormone (PTH), and osteocalcin were measured in the postabsorptive state. Bone mineral content (BMC) was measured by dual-energy x-ray absorptiometry. RESULTS: Fractional Ca absorption was significantly higher in RTT than in control girls (mean +/- SDp, 52 vs. 33 +/- 13%). Dietary Ca intake (mean +/- SDp, 1,100 vs. 1,446 +/- 440 g/d) and net Ca absorption (mean +/- SDp, 513 vs. 362 +/- 306 mg/d) did not differ significantly between RTT and controls, respectively. Although urinary Ca excretion did not differ between groups, the increased urinary Ca:creatinine ratio (mean +/- SDp, 0.39 vs. 0.23 +/- 0.38) was consistent with clinical hypercalcuria and paralleled the significantly increased urinary cortisol excretion (mean +/- SDp, 3.1 vs. 1.7 +/- 1.1 mg/kg lean body mass per day) in the RTT girls. BMC was significantly lower in RTT than in controls (mean +/- SDp, 527 vs. 860 +/- 275 g). Serum Ca, P, alkaline phosphatase, vitamin D metabolites, PTH, and osteocalcin concentrations did not differ between the groups. CONCLUSION: Fractional Ca absorption showed a compensatory increase in the presence of adequate dietary Ca intakes, mild hypercalcuria, and pronounced bone mineral deficits in RTT girls. Whether supplemental dietary Ca could enhance fractional Ca absorption and improve bone mineralization in RTT girls is unknown.Lay Summary
Osteopenia, or low bone density, is a frequent complication of Rett syndrome. Osteopenia is present in Rett patients despite adequate dietary calcium intake, and is characterized by more profound bone demineralization than that found in children with other neurological disabilities. As a consequence, Rett girls are at increased risk for skeletal fractures. In fact, it is estimated that 25% of Rett girls have fractures at some time in their lives. This study examined osteopenia in Rett girls, in order to provide a rationale for dietary calcium recommendations. Specifically, the authors examined intestinal calcium absorption, urinary calcium loss, and dietary calcium intake, as well as other clinical markers, in 10 Rett girls and 10 non-Rett girls. The key finding was that a defect in calcium absorption does not contribute to osteopenia in Rett syndrome. To the authors' surprise, it was found that the fraction of the available calcium absorbed from the gut was actually greater in Rett girls than in non-Rett girls. However, taken together with the amount of dietary calcium intake, and calcium excretion, the overall total absorption of calcium was the same for both Rett and non-Rett girls. Although the authors did not measure bone turnover, theses findings suggest that the osteopenia is probably a consequence of increased bone resorption, or breakdown, rather than decreased bone formation, with a mechanism remaining unknown. Although providing some new information about calcium and Rett syndrome, whether or not additional dietary calcium could improve bone mineralization in Rett girls remains unknown.