title: Healthy children with frequent fractures: how much evaluation is needed?
abstract: OBJECTIVE
  We performed a case-control study to determine whether occult bone disease is associated with a history of frequent fractures in children.
  
  
  METHODS
  Healthy children with > or = 2 incidences of low-energy fractures were recruited (n = 68). Children with no history of fractures served as control subjects (n = 57). Food logs, activity surveys, physical examinations, laboratory tests, and dual-energy radiographic absorptiometry were used.
  
  
  RESULTS
  Bone mineral density z scores were significantly reduced in case subjects, compared with control subjects. Three case subjects (4.3%) and 1 control subject (1.8%) had bone mineral density z scores below the expected range. Of those 4 subjects, 2 had dairy avoidance and 2 had delayed puberty. An additional case subject had evidence of vitamin D deficiency. A significant number of subjects (20% of case subjects and 23% of control subjects) had idiopathic hypercalcuria, based on 24-hour urine collections. Among the case subjects, bone mineral density z scores were significantly lower for those with idiopathic hypercalcuria. Among the control subjects, the presence of idiopathic hypercalcuria did not affect bone mineral density. The case subjects with idiopathic hypercalcuria accounted for virtually all of the differences in bone mineral density between the case and control groups. Analysis of parathyroid hormone and 1,25-dihydroxy-vitamin D levels showed that children with frequent fractures and hypercalcuria had renal hypercalcuria, whereas children with no fractures and hypercalcuria had absorptive hypercalcuria.
  
  
  CONCLUSIONS
  We identified a significant association between a history of frequent fractures and hypercalcuria in children. We propose that the appropriate screening evaluation for children who present with a history of frequent fractures consists of a dietary history targeted at calcium and vitamin D intakes, a physical examination to assess for pubertal delay, and urinary calcium concentration/creatinine ratio determination to assess for hypercalcuria. Children with abnormalities in this screening should undergo dual-energy radiographic absorptiometry and appropriate evaluation.
authors.affiliation: Division of Pediatric Endocrinology, Nemours Children's Clinic-Jacksonville, Jacksonville, FL 32207, USA. rolney@nemours.org
authors.forename: Robert C
authors.initials: RC
authors.lastname: Olney
authors.forename: John M
authors.initials: JM
authors.lastname: Mazur
authors.forename: Leah M
authors.initials: LM
authors.lastname: Pike
authors.forename: Melanie K
authors.initials: MK
authors.lastname: Froyen
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ramirez-Garnica
authors.forename: Eric A
authors.initials: EA
authors.lastname: Loveless
authors.forename: David M
authors.initials: DM
authors.lastname: Mandel
authors.forename: G Alan
authors.initials: GA
authors.lastname: Hahn
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Neal
authors.forename: R Jay
authors.initials: RJ
authors.lastname: Cummings
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000150:complications / Q000175:diagnosis*; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D004032:Diet; D015444:Exercise; D005260:Female; D050723:Fractures, Bone / Q000209:etiology*; D006801:Humans; D008297:Male; D014808:Vitamin D Deficiency
chemical_list: D002118:Calcium