# Pregnancy and lactation associated osteoporosis: Bone microstructure and metabolism, genotypic characteristics, natural history and biomarkers of disease severity

> **NIH FDA R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $387,210

## Abstract

Pregnancy and lactation associated osteoporosis (PLO) is a severe early presentation of osteoporosis in which
young women experience low trauma or spontaneous fractures, most commonly vertebral fractures, during late
pregnancy or lactation. Information on characteristics and management is derived only from case reports and
small series4-25. Before therapies for PLO can be developed, it is necessary to address several key gaps in our
knowledge about this disorder. Currently, there is little information available on the natural history of and risk
factors for PLO, the pathophysiological mechanisms of this acute fracturing syndrome, any biomarkers of
severity, and risk of fracture with subsequent pregnancies. In our studies of the pathogenesis (AR49896)26-31
and treatment (FD003902; FD005114)32,33 of premenopausal idiopathic osteoporosis (IOP), only 10 of 66
women had PLO34. Premenopausal IOP is a rare orphan disease with an estimated prevalence <200,000 in
the US. Our data indicate that PLO represents a small subset (~15%) of premenopausal IOP, and should also
be considered a rare orphan disease. We detected several important differences between women with PLO
and those with IOP unrelated to pregnancy or lactation; those with PLO had more fractures, more vertebral
fractures, more profound cortical bone deficits, and lower bone remodeling than those with IOP34. These data
lead us to hypothesize that the pathophysiology of PLO is distinct from other forms of IOP and may
involve persistent deficits in bone formation and structure, hypotheses with important implications for
the development of effective therapies. The goals of this study are to define the natural history of PLO and
its phenotype, including clinical features, hormonal characteristics, skeletal structure and remodeling, and
predictors of disease severity. We will also investigate potential genetic etiologies of PLO. We will recruit
premenopausal women who experience osteoporotic fracture(s), associated with no trauma or low trauma,
during or within 6 months of pregnancy or lactation. We will categorize participants according to time of
evaluation relative to time of presentation: Recent PLO subjects evaluated <6 months of their initial fracture(s)
and Distant PLO subjects evaluated >6 months after their initial fracture(s). Inclusion of both groups will allow
us to compare patients who are at different stages of disease evolution. In Aim 1, we will conduct an online
survey to obtain information on clinical characteristics and natural history of PLO, capitalizing on our long-term
relationship with a large (>135 women), international Facebook PLO support group. In Aims 2 and 3, we will
recruit 50 women with PLO, the largest cohort to date. Participants will undergo detailed phenotyping at
Columbia University in terms of historical, biochemical, imaging and transiliac biopsy characteristics, and
genotyping by whole exome sequencing. All indices will be investigated as potential biomarkers of...

## Key facts

- **NIH application ID:** 10001348
- **Project number:** 5R01FD006007-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** ADI COHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $387,210
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001348

## Citation

> US National Institutes of Health, RePORTER application 10001348, Pregnancy and lactation associated osteoporosis: Bone microstructure and metabolism, genotypic characteristics, natural history and biomarkers of disease severity (5R01FD006007-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001348. Licensed CC0.

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