# OSTEOCALCIN SYNTHESIS AND CATABOLISM

> **NIH NIH R01** · YALE UNIVERSITY · 1988 · $108,225

## Abstract

Osteocalcin is the most abundant and thoroughly characterized of
the non-collagenous proteins in bone.  Although it is found
predominantly in bone, nanomolar quantities can be measured in
serum.  Serum osteocalcin is generally regarded as a marker for
bone formation but our studies imply that other factors, in
addition to the rate of its synthesis, may affect osteocalcin
concentrations in blood.  These include:  1) the presence of
immunoreactive fragments of osteocalcin in the circulation, 2)
renal clearance of the protein or its fragments, and 3) the affinity
of protein for hydroxyapatite.  The clinical data cannot be fully
appreciated without an understanding of the factors which
determine osteocalcin's concentration in blood.  In addition, there
is a need for specific non-invasive markers of bone formation and
resorption.  Through these studies, we hope to aid in the
interpretation of clinical data, and develop precise assays for use
in the diagnosis and treatment of metabolic bone disorders.  We
propose to:

I.  Identify fragments of osteocalcin that are produced a) in vitro
using isolated osteoclasts, and b) in vivo using perfused rat
hindlimb.

II.  Study the clearance and catabolism of osteocalcin a) in
perfused isolated liver, and b) in perfused isolated kidney.

III.  Produce monoclonal antibodies to specific regions of the
protein.  These include a) specific fragments that are produced
during bone resorption, b) pro-osteocalcin peptide which is co-
secreted during osteocalcin synthesis, and c) undercarboxylated
osteocalcin which may be synthesized in normal individuals or in
those with metabolic bone disease.

IV.  Develop a useful battery of assays for the evaluation of bone
disorders.  Concentrations of intact osteocalcin, both
carboxylated and under carboxylated,  specific fragments, and
propeptide will be evaluated a) in normal individuals and b) in
patients with metabolic bone diseases in relationship to standard
biochemical and histological parameters.

## Key facts

- **NIH application ID:** 3158559
- **Project number:** 2R01AR038460-03
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** Caren Gundberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $108,225
- **Award type:** 2
- **Project period:** 1986-07-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158559

## Citation

> US National Institutes of Health, RePORTER application 3158559, OSTEOCALCIN SYNTHESIS AND CATABOLISM (2R01AR038460-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158559. Licensed CC0.

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