Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy.
Serum bone alkaline phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immunoradiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal children (207 males and 156 females, age 0-18 yr) and in 20 GH-deficient children (age 5-13 yr) who showed significant bone growth during GH therapy. We found the following results. 1) There were no significant circadian variations in serum B-ALP levels (coefficients of variation: 2.10-9.66%). 2) In normal children, serum B-ALP levels were high in infants and gradually declined and increased again during puberty. During the pubertal period, the highest serum B-ALP values were observed at midpuberty (stage 3 of breast and pubic hair development and 4-12 mL of testicular volume). 3) Serum B-ALP levels were significantly correlated with levels of the carboxy-terminal propeptide of type 1 procollagen (r = 0.447, P < 0.0001) and osteocalcin (r = 0.433, P < 0.0001). 4) After beginning GH therapy, serum B-ALP levels increased significantly; a 26% increase in serum B-ALP level was observed after 3 months of GH therapy. 5) The ratio between serum B-ALP level after 3 months of GH therapy and before GH therapy was positively correlated with the GH-induced improvement in the height SD score (height SD score after 1 yr of GH therapy minus that before GH therapy) and improvement in the height velocity SD score (height velocity SD score during GH therapy minus before GH therapy) (r = 0.531, P < 0.05 and r = 0.608, P < 0.01, respectively). 6) The increment of SD score in serum B-ALP level after 1 yr of GH treatment was also significantly correlated with that for bone mineral density after 1 yr of GH therapy (r = 0.663, P < 0.005). These results show that B-ALP levels are a useful marker for bone formation because B-ALP levels increased when the growth rate accelerated. Serum B-ALP is a potential predictor of the effectiveness of GH therapy, because the serum level after 3 months of GH therapy reflects the outcome of 1 yr of GH therapy.
Tobiume
H
H
Department of Pediatrics, Okayama University Medical School, Japan.
Kanzaki
S
S
Hida
S
S
Ono
T
T
Moriwake
T
T
Yamauchi
S
S
Tanaka
H
H
Seino
Y
Y
D000293:Adolescent; D000367:Age Factors; D000469:Alkaline Phosphatase / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001827:Body Height; D001842:Bone and Bones / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000097:blood*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012737:Sex Factors
D015415:Biomarkers; D007527:Isoenzymes; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D013006:Growth Hormone; D000469:Alkaline Phosphatase