# COLLAGEN SYNTHESIS IN FAMILIAL OSTEOPOROSIS

> **NIH NIH R01** · ST. VINCENT HOSPITAL (WORCESTER, MA) · 1987 · $107,637

## Abstract

Our hypothesis is that in certain individuals and kindreds, adult-onset
osteoporosis primarily results from an inherited disorder of Type I
collagen synthesis.  Previous studies have suggested the existence of
defective synthesis of Type I collagen in postmenopausal osteoporosis.
Twin studies indicate that heredity as well as environmental factors play a
role in determining skeletal mass.  Mother/daughter association and
familial clustering of osteoporosis are not at all uncommon.  Based on our
past observation that pedigree of osteogenesis imperfecta exhibit great
heterogenity in the severity of osteopenia, we believe it is appropriate to
explore the relationship of heredity and collagen synthesis in osteoporotic
subjects whose pedigree reveals a family history of postmenopausal
osteoporosis and other mild connective tissue abnormalities.  Ten
osteoporotic peri- and postmenopausal probands whose relatives also have
stigmata of a connective tissue lesion will be studied.  Adult familial
osteoporosis is thus defined as the familial occurrence of fractures during
mid-or late adult life, short stature, scoliolis and/or hyperectensible
joints.  Following identification of the proband, we will measure Types I
and III collagen synthesis by dermal fibroblasts, the ratios of alpha
chains for these collagen types and the levels of mRNA for Type I and III
collagens.  Once a potential abnormality in Type I collagen is identified
in the proband, then other family members will be studied both
biochemically and clinically to determine if the putative marker segregates
with clinical stigmata in the family.   Linkage polymorphisms for the
alpha-2 chain of Type I collagen will be sought within affected kindreds.
The clinical features of familial osteoporosis will be defined by the
measurement of vertebral bone mineral content by computer tomographic scan
(QCT).  The metabolic activity of bone will be assessed by
histomorphometric analysis of iliac crest biopsies, determination of serum
osteocalcin and osteonectin levels, urinary Gla protein excretion and the
urinary excretion of hydroxyproline.  By selecting the appropriate probands
and family controls this study may define an important subset of the
osteoporotic population, whose disease can be defined by distinct
biochemical and clinical criteria.  Analysis of the hereditary nature and
putative gene defect of this subgroup will form the basis for the
investigation of molecular lesions affecting skeletal tissues in other
osteoporotic women.

## Key facts

- **NIH application ID:** 3158520
- **Project number:** 5R01AR038370-03
- **Recipient organization:** ST. VINCENT HOSPITAL (WORCESTER, MA)
- **Principal Investigator:** JAY Robert SHAPIRO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $107,637
- **Award type:** 5
- **Project period:** 1986-07-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158520

## Citation

> US National Institutes of Health, RePORTER application 3158520, COLLAGEN SYNTHESIS IN FAMILIAL OSTEOPOROSIS (5R01AR038370-03). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158520. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*