# Development and Validation of a Novel and HIV-Relevant Prediction Model for Fracture

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $702,912

## Abstract

ABSTRACT
Fragility fractures (fractures) among persons with HIV (PWH) account for $99 million in excess costs each year
in the United States. Our prior research has shown a significantly higher annual rate of fractures among PWH
– most of whom are middle-aged – compared with uninfected individuals (2.0% vs 1.4%). Such fractures are
associated with increased rates of hospitalization and nursing home admissions, long-term physical disability,
social isolation, and death. Because middle-age is a time when people are most economically and socially
productive, fractures at this time of life set the stage for economic hardship and poorer health outcomes as
these individuals grow older. Highly effective methods exist for preventing fragility fractures, reducing rates by
25%-50%. However, there are no risk prediction models that reliably identify PWH at greatest risk.
The Fracture Risk Assessment Tool (FRAX) is the most widely used model for predicting fractures in the
general population. It incorporates demographics (age, sex, race) and key risk factors (body mass index,
previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary
osteoporosis, and hazardous alcohol use). For settings where dual-energy x-ray absorptiometry is available,
sensitivity of FRAX can be improved by adding bone mineral density (BMD) to the algorithm. However, our
prior studies suggest that FRAX underperforms among PWH, exhibiting poor discrimination (C statistic 0.59)
and sensitivity (0.06). We believe this is because FRAX does not account for risk factors that are important to
PWH. For example, FRAX does not account for falls, hepatitis C and B viruses, substance use disorder,
multimorbidity, polypharmacy, use of other medications associated with fractures, or physiologic frailty – all of
which have been associated with fractures among PWH. Finally, FRAX does not account for antiretroviral
therapy (ART) use. Individual ART as well as ART classes have been independently associated with fracture.
Leveraging an outstanding team of collaborators and research platforms, we will develop, validate and
disseminate a Fracture Risk Assessment Calculator based on FRAX but that incorporates HIV-relevant risk
factors (FRAC-HIV) to calculate the probability of a fracture among PWH in the next year. We have extensive
experience working with the Veterans Aging Cohort Study (VACS), the largest cohort of PWH in North
America, which will serve as our development cohort. To assess generalizability, we will externally validate the
model using electronic health record data from Yale New Haven Healthcare System and Boston Medical
Center. Our final aim sets the stage for the implementation of this predictive model via the development of a
web-based fracture risk prediction calculator, which will be directly informed by insights from providers who
care for PWH. FRAC-HIV will reconceptualize and facilitate clinical decision-making for fracture prevention in...

## Key facts

- **NIH application ID:** 10380905
- **Project number:** 5R01AR078715-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Evelyn Hsieh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $702,912
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380905

## Citation

> US National Institutes of Health, RePORTER application 10380905, Development and Validation of a Novel and HIV-Relevant Prediction Model for Fracture (5R01AR078715-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380905. Licensed CC0.

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