# Quantifying the Impact of Frailty on Osteoporosis and Fractures in Veterans with Rheumatoid Arthritis

> **NIH VA IK2** · VA PUGET SOUND HEALTHCARE SYSTEM · 2024 · —

## Abstract

Background. Two million osteoporotic fractures occur each year in the United States, resulting in more than
400,000 hospital admissions and over $20 billion spent annually on osteoporosis care. Osteoporotic fractures
cause loss of independence and excess mortality, and persons with rheumatoid arthritis (RA) are twice as likely
to sustain an osteoporotic fracture than the general population. Frailty occurs prematurely in RA and the
underlying pathophysiologic mechanisms are not well studied. Furthermore, Veterans are three times as likely
to be frail and have excess mortality after osteoporotic hip fracture compared to the general population,
underscoring the importance of studying the relationship between frailty, bone mineral density (BMD) and
osteoporotic fractures in Veterans Affairs (VA)-based RA cohorts. Inflammation plays an important role in the
pathogenesis of both frailty and osteoporosis, making RA, a disease of chronic inflammation, an ideal disease
state in which to study these processes. While associations between inflammatory biomarkers, frailty and
osteoporosis have been identified in the general population (most notably interleukin-6 (IL-6), Interleukin-1 (IL-
1β) and tumor necrosis factor alpha (TNFa)), the association between these inflammatory markers and frailty in
RA has not been comprehensively studied. With the aging US population and >10 million Veterans over the age
of 60, it is imperative to improve the management of frailty and osteoporosis especially in high-risk groups, such
as those with RA. Scientific Gap. This proposal addresses two scientific gaps in the high-risk Veteran RA
population: 1) the impact of frailty on BMD loss and osteoporotic fractures and 2) the impact of inflammatory
biomarkers on frailty. Specific Aims. Aim 1 will use a local clinical Veteran RA Cohort to determine if frailty is
independently associated with BMD and longitudinal BMD loss. Frailty will be measured by three unique frailty
indices: (1) a well-established frailty index (Fried Physical Frailty Phenotype), (2) a quick patient-reported scale
(FRAIL scale), and (3) a VA electronic health record-based frailty index (VA-FI). Hypotheses: 1a. Pre-frail and
frail Veterans will have lower baseline total hip BMD than robust Veterans when controlling for traditional
osteoporosis risk factors. 1b. Veterans with worsening frailty will have larger declines in total hip BMD at follow-
up compared to those whose frailty status improves or is unchanged. Aim 2 will use a national RA registry (VARA)
of over 3,000 Veteran enrollees to determine if frailty is a predictor of declines in BMD and incident osteoporotic
fractures. Frailty will be assed using the VA-FI which will be calculated at baseline and at two-year intervals.
Hypotheses: 2a. Worsening frailty is an independent predictor of total hip BMD loss. 2b. Worsening frailty is an
independent predictor of incident osteoporotic fractures. Aim 3 will utilize both cohorts to determine if IL-6, IL-1β
and...

## Key facts

- **NIH application ID:** 10919768
- **Project number:** 5IK2CX002351-03
- **Recipient organization:** VA PUGET SOUND HEALTHCARE SYSTEM
- **Principal Investigator:** Katherine D Wysham
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919768

## Citation

> US National Institutes of Health, RePORTER application 10919768, Quantifying the Impact of Frailty on Osteoporosis and Fractures in Veterans with Rheumatoid Arthritis (5IK2CX002351-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10919768. Licensed CC0.

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