# Effects of reproduction and lactation on postmenopausal bone health

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $81,000

## Abstract

Project Summary
 The female skeleton undergoes dramatic physiological alterations as a result of reproduction. While
weaning induces substantial bone recovery, reproduction-induced bone loss is only partially recovered after
weaning. Nevertheless, most epidemiology studies report that history of reproduction and lactation had no
negative, or even a protective effect on fracture risk later in life. This represents a paradox that reproduction
reduces bone mass without increasing risk of future fractures. Thus, the overall objective of this study is to
uncover the mechanisms that explain this paradox. Our preliminary results demonstrated that despite a lower
bone mass, reproductive rats have a distinct bone structural phenotype and a much slower rate of bone loss
than virgin rats when exposed to estrogen deficiency by ovariectomy (OVX). 3 months after OVX, the load
bearing sites, such as vertebral trabecular bone and femoral midshaft, showed no bone loss in reproductive
rats. Our data also indicated that osteocytes can actively modulate material properties of the peri-lacunar bone
matrix during reproduction, which could lead to critical alterations in the micro-mechanical environment of
osteocytes, the presumed mechano-sensors in bone. Indeed, our results suggested that post-reproductive rats
were more sensitive to in vivo tibial loading than virgin rats. In addition, when subjected to OVX later in life, the
size of osteocyte lacunae increased significantly in reproductive rats. Thus, the micro-environmental changes
after reproduction may affect the skeleton's sensitivity to mechanical stimuli and impact bone quality later in life.
These findings from clinical and animal studies provide a strong scientific premise for our novel, central
hypothesis that history of reproduction and lactation causes skeletal adaptation at the structural, material, and
cellular levels, which may protect the skeleton from estrogen deficiency-induced bone loss later in life. To test
this hypothesis and determine the mechanisms behind it, we propose two aims. In Aim 1, we will determine the
influence of reproduction and lactation history on skeletal responses in bone microarchitecture, cellular
activities, and mechano-sensitivity to estrogen deficiency later in life. In Aim 2, we will establish the role of
reproduction history on modulating lacunar and canalicular structure, peri-lacunar bone tissue modulus, and
load-induced fluid flow experienced by osteocytes and their processes in both prior- and post-OVX rats. We
will address an unsolved clinical paradox and elucidate the amazing adaptive mechanisms that protect women
with a history of pregnancy and lactation from postmenopausal osteoporosis. Identifying the phenotypic bone
structure, material properties, and osteocyte microenvironment in virgin and reproductive bone could lead to
novel strategies for osteoporosis prevention, management, and treatment for postmenopausal women by
considering their reproduction histories...

## Key facts

- **NIH application ID:** 10154571
- **Project number:** 3R01AR071718-04S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Xiaowei Sherry Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,000
- **Award type:** 3
- **Project period:** 2020-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154571

## Citation

> US National Institutes of Health, RePORTER application 10154571, Effects of reproduction and lactation on postmenopausal bone health (3R01AR071718-04S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10154571. Licensed CC0.

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