Submitted to: Journal of Pediatric Gastroenterology and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/29/2005
Publication Date: 4/1/2006
Citation: Motil, K.J., Schultz, R.J., Abrams, S.A., Ellis, K.J., Glaze, D.G. 2006. Fractional calcium absorption is increased in girls with Rett syndrome. Journal of Pediatric Gastroenterology and Nutrition. 42(4):419-426. Interpretive Summary: Osteopenia, or bone mineral loss, occurs in girls with Rett (RTT) syndrome. The cause of bone mineral loss is unknown, although their poor walking ability and use of seizure medications may play a role. Low bone density is present at an early age despite adequate dietary calcium (Ca). As a consequence of bone mineral loss, RTT girls are at increased risk for skeletal fractures. We wanted to know if factors related to Ca balance resulted in bone mineral loss and if these factors contributed to the overall dietary Ca needs of RTT girls. We studied intestinal Ca absorption, urinary Ca loss, dietary Ca intake, and hormone markers related to bone metabolism using stable isotopes and duel energy x-ray absorptiometry in RTT and unaffected girls. We found that Ca absorption is higher in RTT girls whose diet contained adequate Ca, but who exhibit increased urinary Ca loss and have low bone density. Whether additional dietary Ca improves intestinal Ca absorption and bone mineral retention in RTT girls is unknown.
Technical Abstract: 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 causally related factors may include decreased intestinal Ca absorption relative to dietary Ca intakes and increased renal Ca excretion in these individuals. We measured fractional Ca absorption, urinary Ca losses, dietary Ca intakes, and the hormonal factors that regulate Ca metabolism to determine if abnormalities in Ca balance result in poor bone mineralization in RTT girls and to evaluate the contribution of these factors to the overall dietary Ca needs of RTT girls. Ten RTT girls and 10 controls, matched for age, gender, and pubertal status, were given a 3-day constant Ca diet that mimicked their habitual intakes. At the end of each dietary period, all girls received single bolus doses of 42Ca (intravenous) and 46Ca (oral). Fractional urinary excretion of 42Ca:46Ca and 24-h urinary Ca and cortisol excretion were determined. Serum Ca, P, alkaline phosphatase, vitamin D metabolites, PTH, and osteocalcin were measured in the postabsorptive state. Bone mineral content (BMC) was measured by dual-energy x-ray absorptiometry. Fractional Ca absorption was significantly higher in RTT than in control girls (mean + SDp, 52 vs. 33 + 13 %). Dietary Ca intakes (mean + SDp, 1100 vs. 1446 + 440 g/d) and net Ca absorption (mean + SDp, 513 vs. 362 + 306 mg/d) did not differ significantly between RTT and control girls, respectively. Although urinary Ca excretion did not differ between the 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 control girls (mean + SDp, 527 vs. 860 + 275 g). Serum Ca, P, alkaline phosphatase, vitamin D metabolites, PTH, and osteocalcin concentrations did not differ significantly between both groups of girls. 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 calcium further enhances fractional Ca absorption and improves bone mineralization in RTT girls is unknown.