# Urine cadmium and risk of fracture and bone loss

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $112,219

## Abstract

Diversity Supplement: Urine cadmium and risk of fracture and bone loss
Abstract
We propose to leverage the parent grant, which uses existing samples and data from the two largest prospective
US osteoporosis cohort studies to perform an in depth study of urine cadmium (U-Cd), bone loss, and fractures
that will include long-term follow-up of up to 20 years using: 1) The Osteoporotic Fractures in Men (MrOS)
Study and 2) the Study of Osteoporotic Fractures (SOF). The parent grant uses an efficient case-cohort study
design to investigate the prospective association between U-Cd and incident fractures in 1,321 MrOS men and
1,578 SOF women who will be sex matched with 1500 randomly selected persons from each respective cohort.
Cd, creatinine, osmolality, and cotinine are being analyzed in urine. The parent grant also evaluates the
prospective association between U-Cd and rate of loss of total hip bone mineral density (BMD) in men and
women from the subcohorts, and in incident fracture cases; and will utilize markers of bone metabolism and
structure (PINP, CTX, and HR-pQCT) to provide novel insights into the cellular and structural mechanisms by
which Cd may adversely affect bone.
To this parent project, we are adding two Aims in this Supplement. Aim 1. Evaluate the prospective
association between U-Cd and muscle mass in men and women from the subcohorts, and in fracture cases.
This will be a follow-up to a recent cross-sectional study which reported an association between U-Cd and muscle
loss. Aim 2. Explore whether mixtures of metals and nutrients are associated with fracture in the parent case-
cohort study, and whether these mixtures are associated with bone loss, and muscle loss in the subcohorts.
Shedding insights on risks from mixtures has been a desire of epidemiologists for decades; we will be using
cutting edge statistical learning methods to analyze associations between mixtures and risk of incident fractures,
bone loss, and muscle loss. These methods, including Bayesian kernel machine regression (BKMR) and
weighted quantile sum (WQS) regression, have the advantages over standard regression models containing
interaction terms of avoiding problems associated with multiple testing, interpretation of higher-order interaction
terms, and limited statistical power.
A large fraction of older US men and women have documented Cd exposure. Highly accurate measures of Cd
exposure linked to powerful epidemiological cohorts provide a unique, cost effective approach to this important
public health issue. These studies will transform the field of Cd-musculoskeletal research and have high potential
to impact policy decisions in the US and globally.

## Key facts

- **NIH application ID:** 10612697
- **Project number:** 3R01AR081125-02S1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Jaymie R Meliker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $112,219
- **Award type:** 3
- **Project period:** 2021-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10612697

## Citation

> US National Institutes of Health, RePORTER application 10612697, Urine cadmium and risk of fracture and bone loss (3R01AR081125-02S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10612697. Licensed CC0.

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