# Acid-Base Status as a Novel Risk Factor for Fractures

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $761,948

## Abstract

Project Summary/Abstract
 Fractures are a major public health burden with its associated disability, cost, morbidity and mortality. In
recent years, hip fracture rates are higher than expected and the incidence of vertebral fracture appears to be
rising dramatically, especially after age 75 years. A growing body of research suggests that acidosis, even
when subclinical, directly affects bone and can have detrimental effects on bone metabolism and health.
Acidosis can inhibit osteoblast function and bone formation while promoting bone resorption and breakdown,
thus impairing the bone’s ability to repair microdamage that occurs with daily wear and tear and accumulates
with aging, and potentially contributing to higher fracture risk. The Nurses’ Health Studies (NHS) I and II and
the Health Professionals Follow-up Study (HPFS) are ongoing large-scale cohort studies with decades of
follow-up and rich dietary and lifestyle data, and archived biosamples. Integrating metabolomics technology
into population-based studies is emerging as a valuable research tool which could provide novel insights into
cellular processes that affect fracture risk. Therefore, this proposal’s goal is to prospectively study the
association between acid-base status, assessed through dietary acid load, plasma bicarbonate level and
plasma metabolites, and risk of incident fracture. We hypothesize that perturbations in acid-base status
through diet-dependent and independent mechanisms resulting in increased acidosis will be associated with
higher fracture risk. We will prospectively examine the association of dietary acid load with risk of incident hip
and vertebral fracture in NHS I and II and HPFS (Aim 1). We will use a nested case-control study of hip
fracture cases (n=650) and matched controls (n=650) within these three cohorts to study the association
between plasma bicarbonate level (Aim 2), plasma metabolites (Aim 3) and risk of incident hip fracture in
women and men. Archived plasma samples collected pre-hip fracture diagnosis will be measured for
metabolites using state-of-the art, high-throughput liquid or gas chromatography followed by mass
spectrometry (LC/MS/MS and GC/MS) platforms. Using advanced computational and biostatistical methods in
metabolomics and high-dimensional data analyses, we will use a targeted metabolomics approach as well as
an agnostic approach to build distinct metabolite signatures using all of the available plasma metabolite data to
distinguish hip fracture cases from controls. Ultimately, we expect these studies to produce new insights into
the development of fractures that may lead to new approaches to their prevention and treatment.

## Key facts

- **NIH application ID:** 9906852
- **Project number:** 5R01AR075117-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Julie Paik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $761,948
- **Award type:** 5
- **Project period:** 2019-06-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906852

## Citation

> US National Institutes of Health, RePORTER application 9906852, Acid-Base Status as a Novel Risk Factor for Fractures (5R01AR075117-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9906852. Licensed CC0.

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