Urinary gamma-glutamyltransferase (GGT) as a potential marker of bone resorption.
We recently identified gamma-glutamyltransferase (GGT) as a novel bone-resorbing factor. The present study was undertaken to determine whether GGT is a marker of bone resorption in two genetic models of hyper- and hypo-function of osteoclasts, as well as in postmenopausal women with accelerated bone resorption, using type I collagen N-telopeptide (NTX) and deoxypyridinoline (DPD) as established biochemical markers. Urinary excretion of GGT, corrected for creatinine, was found to be increased in osteoprotegerin (OPG)-deficient osteoporotic mice as well as in patients with postmenopausal osteoporosis (67-83 years of age); in both cases the urinary level decreased after treatment of patients or mice with alendronate, a selective inhibitor of bone resorption, concomitantly with a reduction in DPD and NTX. Conversely, in osteopetrotic op/op mice, urinary GGT increased in parallel with DPD after induction of osteoclasts with M-CSF injection. Constant infusion of parathyroid hormone (PTH) also increased urinary GGT along with DPD. In a survey of 551 postmenopausal women (50-89 years of age) at their regular health checkup, urinary GGT excretion exhibited a high correlation with DPD (rho = 0.49, p < 0.0001). The calculated sensitivity and specificity for diagnosing elevated bone resorption, as determined by a DPD value higher than 7.6 nM/mM Cr, were 61% and 92%, respectively, when a cut-off value of 40 IU/g Cr was assigned for urinary GGT. Since GGT activity can be measured inexpensively in large numbers in a very short time, the measurement of urinary level may provide a convenient and useful method for mass screening to identify those with increased bone turnover and hence at increased risk for bone fracture.
Asaba
Yutaro
Y
Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology (NCGG), 36-3 Gengo, Obu, Aichi 474-8522, Japan.
Hiramatsu
Kiyoshi
K
Matsui
Yasumoto
Y
Harada
Atsushi
A
Nimura
Yuji
Y
Katagiri
Nobuyoshi
N
Kobayashi
Toshihiro
T
Takewaka
Tsuyoshi
T
Ito
Masako
M
Niida
Shumpei
S
Ikeda
Kyoji
K
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000494:pharmacology; D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001862:Bone Resorption / Q000188:drug therapy / Q000201:enzymology* / Q000652:urine; D024042:Collagen Type I / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000201:enzymology / Q000652:urine; D053244:Osteoprotegerin / Q000172:deficiency / Q000235:genetics; D010455:Peptides / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine*
D000596:Amino Acids; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D053244:Osteoprotegerin; D010455:Peptides; C506031:Tnfrsf11b protein, mouse; C052929:collagen type I trimeric cross-linked peptide; C036020:deoxypyridinoline; D005723:gamma-Glutamyltransferase; D019386:Alendronate