Urinaryγ-Carboxyglutamic Acid and Serum Osteocalcin as Bone Markers: Studies in Osteoporosis and Paget’s Disease*

Abstract

Osteocalcin is a major bone matrix protein with high affinity for hydroxyapatite. This property is conferred by several residues of the calcium-binding amino acid gamma-carboxyglutamate (Gla), which requires vitamin K for its biosynthesis. Because this protein may play a role in the local control of calcium deposition or removal in mineralized tissue, we measured circulating osteocalcin levels and urinary excretion of its breakdown product, Gla, in patients with osteoporosis and Paget's disease. Studies were conducted either on a metabolic ward or in ambulatory patients. Diagnoses were established by clinical and laboratory findings, and were confirmed by histological examination in 19 of 26 patients with osteoporosis. Mean urinary Gla excretion was increased (P less than 0.001) in patients with osteoporosis by 50% above the normal mean; serum osteocalcin, however, was not significantly different from normal. In Paget's disease patients, this pattern was reversed; serum osteocalcin levels were increased 3-fold (P less than 0.001), while urinary Gla excretion was consistently normal, regardless of the extent or activity of the disease. These data demonstrate that measurements of urinary Gla and serum osteocalcin may provide important insights into the metabolic derangements in these and other bone disorders.

Regulation of Human Osteocalcin Promoter in Hormone-independent Human Prostate Cancer Cells

“…It is known as a potent angiogenic stimulus and a strong mitogen for the stimulation of both prostate cancer and osteoblast growth (42). It has been confirmed that basic fibroblast growth factor can induce hOC promoter activity independent of vitamin D 3 and retinoid activation (43). Furthermore, bone growth factors such as bone morphogenetic protein induce the expression of Runx2 in cells where it is not normally expressed (44).…”

“…Upon addition of vitamin D 3 , all the AI prostate cancer cell lines (DU145 and PC3) and MG63 showed an elevated level of hOC mRNA. However, the androgen-dependent/sensitive nontumorigenic prostate cancer cell LNCaP did not have any hOC expression in either the presence or absence of vitamin D 3 .…”

“…1B) in all the cell lines tested. Thus the promoter is tissue-specific and regulated by vitamin D 3 . In this study, PC3 (which has the highest basal hOC promoter activity) was the target cell line for investigating basal hOC promoter regulation in prostate cancer cells and LNCaP was used as the negative control cell line.…”

“…OC is synthesized, secreted, and deposited by mature osteoblasts at the time of bone mineralization. It serves as a phenotypic marker for mature osteoblasts (3). Despite its well characterized specificity of expression in transgenic mouse (4), the precise function of OC in bone remodeling remains unclear.…”

Bone Remodeling: Biochemical Markers or Bone Biopsy?

“…Biochemical markers of bone resorption (C-terminal cross-linking telopeptide of type I collagen [CTx] and N-terminal cross-linking telopeptide of type I collagen [NTx]) increase during the menopause and remain elevated in postmenopausal women until the ninth decade of life. (15) In patients with postmenopausal osteoporosis and vertebral fractures, the mean level of serum osteocalcin has been reported to be either normal (11,15,16) or slightly elevated (17,18) but always with a wide spectrum of individual values. That heterogeneity can explain the differences according to the population studied.…”