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

Laboratory of Human Biochemistry, Children’s Hospital Medical Center and Harvard Medical School Boston, Massachusetts 02115
Laboratory for the Study of Skeletal Disorders and Rehabilitation, Children’s Hospital Medical Center and Harvard Medical School Boston, Massachusetts 02115
The Department of Biological Chemistry, Harvard Medical School Boston, Massachusetts 02115
The Department of Oral Biology, Harvard School of Dental Medicine Boston, Massachusetts 02115
The Department of Medicine and the Orthopaedic Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School Boston, Massachusetts 02115

Address requests for reprints to: Dr. Caren M. Gundberg, Children’s Hospital Medical Center, 300 Longwood Avenue, Boston, Massachusetts 02115.

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 -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 < 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 < 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.

^* Presented in part at the VII International Conference on Calcium Regulating Hormones (1980). This work was supported by NIH Grants AG-00376, AM-26333, AM-18268, and RR-00888 and the Arthritis Foundation.

¹ Osteocalcin has also been called bone Gla protein (BGP) in the literature.

Received June 15, 1982.

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