The role of magnesium in the pathogenesis of bone disease in childhood cholestatic liver disease: a preliminary report.
BACKGROUND
Magnesium deficiency may contribute to the metabolic bone disease that complicates chronic cholestatic liver disease. We hypothesized that magnesium deficiency alters vitamin D metabolism by decreasing parathyroid hormone (PTH) response, resulting in decreased serum osteocalcin and decreased bone accretion.


METHODS
Nine subjects, age 3-22 years, with cholestatic liver disease were evaluated with the magnesium retention test. The response of PTH, 1,25(OH)2 vitamin D, and osteocalcin to provocative stimuli and dual x-ray absorptiometry measurement of bone mineral density (BMD) of the lumbar spine were assessed. Thereafter, subjects were treated with oral magnesium supplements.


RESULTS
All nine subjects were magnesium depleted. Repletion with magnesium was successful in seven subjects, and required 4 to 31 (median 14) months with doses of 6 to 34 (median 11) mg/kg/day. Baseline serum PTH was significantly reduced in the cholestatic subjects compared to 15 age-matched controls. Comparison of baseline to repleted provocative testing was performed in six Mg-repleted subjects. Osteocalcin response increased significantly (p = 0.048) with repletion, while PTH response increased (p = 0.061). Lumbar spine BMD increased modestly with repletion (p = 0.093).


CONCLUSIONS
This preliminary report suggests that magnesium depletion is extremely common in children with chronic cholestasis. We speculate that magnesium supplementation may be warranted to forestall the progression of metabolic bone disease in chronic cholestasis.
Heubi
J E
JE
Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Higgins
J V
JV
Argao
E A
EA
Sierra
R I
RI
Specker
B L
BL
D000293:Adolescent; D000328:Adult; D016738:Alagille Syndrome / Q000150:complications; D015519:Bone Density; D001847:Bone Diseases / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000150:complications* / Q000188:drug therapy; D004492:Edetic Acid; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000139:chemically induced; D007223:Infant; D008274:Magnesium / Q000502:physiology / Q000627:therapeutic use; D008275:Magnesium Deficiency / Q000150:complications*; D008297:Male; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism
D010281:Parathyroid Hormone; D015675:Osteocalcin; D004492:Edetic Acid; D008274:Magnesium