# OSTEOCALCIN SYNTHESIS AND CATABOLISM

> **NIH NIH R01** · YALE UNIVERSITY · 1993 · $210,659

## Abstract

Serum osteocalcin has been generally regarded as an index of osteoblastic
activity.  There are many studies which use circulating osteocalcin
concentrations in the assessment of bone turnover and for the monitoring
of response to therapy.  However, there are several unanswered questions
which must be resolved before there can be complete confidence in the
information gained from its measurement.

1. What is the nature of the circulating form(s) of osteocalcin?  Studies
suggest that there are several immunoreactive forms of osteocalcin in the
circulation.  This proposal will identify and isolate the circulating
form(s) of osteocalcin by using a series of monoclonal antibodies
produced to various regions of human osteocalcin.  this will be done in:
a) serum from normal adults and children, both males and females, across
all age ranges; b) patients with metabolic bone disease, i.e., 1o and 2o
hyperparathyroidism, hyper- and hypothyroidism, Paget's disease,
osteomalacia and rickets, and osteoporosis; c) during dynamic testing,
and d) from isolated osteoblasts.

2. What are the factors which regulate the concentration of osteocalcin
in the blood?  Studies indicate that serum osteocalcin concentrations can
be regulated by acute changes in extracellular calcium.  these studies
will examine the acute effects of altered calcium homeostasis on
circulating osteocalcin.  This will be done by investigating the effects
of changing mineral concentrations on circulating osteocalcin in intact,
thyroparathyroidectomized, and hindlimb perfused rats?

3. What is the source of circulating osteocalcin?  Animal studies
indicate that serum osteocalcin is derived from new protein synthesis
rather than from release of existing osteocalcin from matrix.  However,
this is inconsistent with acute fluctuations in serum osteocalcin with
changes in CaI.  The proposed studies will identify the source of
circulating osteocalcin in the basal state and under altered conditions.
This will be done by investigating the effects of changing CaI
concentrations on circulating osteocalcin in acutely warfarinized rats.

4. What is the function of osteocalcin in bone?  These studies will
examine the potential role of osteocalcin in calcium homeostasis.  This
will be accomplished by dynamic hormonal and mineral challenges in
chronically warfarinized rats.  These studies will clarify the
interpretation of osteocalcin measurements and to define the role of
osteocalcin in calcium homeostasis.

## Key facts

- **NIH application ID:** 3158560
- **Project number:** 2R01AR038460-08
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** Caren Gundberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $210,659
- **Award type:** 2
- **Project period:** 1986-07-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158560

## Citation

> US National Institutes of Health, RePORTER application 3158560, OSTEOCALCIN SYNTHESIS AND CATABOLISM (2R01AR038460-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158560. Licensed CC0.

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