Bone metabolism and bone mineral density in childhood hypophosphatasia

Childhood hypophosphatasia (HP) is an inborn error of bone metabolism, char acterized by a reduced tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Bone mineral density (BMD) in childhood HP has not been reported so far. We measured BMD, in addition to markers of bone metabolism, in 6 b oys with childhood HP (age 2-13 years) and in 10 parents and one sibling, e ach carrying the autosomal-recessive trait. BMD, measured by peripheral qua ntitative computed tomography (pQCT) and by dual-energy X-ray absorptiometr y (DXA), was expressed as standard deviation from the normal mean (Z scores ) and compared with bone mineralization by standard X-rays of the same loca tions, HP was confirmed by low TNSALP and its elevated substrates. In patie nts, BMD of the total body or spine, measured by DXA, was in the lower norm al range. Total BMD of the distal metaphyses of the radius, measured by pQC T, was normal (Z score: mean +1.5). However, trabecular BMD of both radius (Z score: mean +4) and femur was grossly elevated. In parallel, X-rays show ed reduced transradiancy of the radial and femoral metaphyses in all patien ts. In parents of patients with HP, BMD was in the lower normal range. Only one father had a decreased lumbar BMD, The discrepancy in BMD between cort ical and trabecular bone of the metaphyses in patients was not present in t heir relatives. TNSALP levels in all first degree relatives were just below or in the lower normal range. The markers of bone turnover hydroxyproline and free deoxypyridinoline in urine were normal in patients and relatives. Hypermineralization/sclerosis of trabecular bone might serve as a compensat ion for a mechanically incompetent bony structure due to an impaired minera lization of cartilage caused by the genetic deficiency of alkaline phosphat ase. (C) 1999 by Elsevier Science Inc. All rights reserved.