Researchers have found that a retina that is aging faster than usual can indicate a lower bone density and an increased risk of fractures due to osteoporosis. Published today in PLOS Digital Health, these findings set the basis for a novel diagnostic method for a condition that remains underdiagnosed due to a lack of accessible screening tools.
“Osteoporosis is a common condition that weakens bones and raises the risk of fractures, especially in older adults,” write the study authors, who were led by Ching-Yu Cheng, MD, PhD, professor at the Duke-NUS Medical School and director of the Singapore Epidemiology of Eye Diseases (SEED) program. “However, many individuals are not diagnosed until after a fracture occurs, in part because the standard diagnostic test, dual-energy X-ray absorptiometry (DEXA), is not always readily accessible.”
A DEXA scan uses very low levels of X-ray radiation to measure a patient’s bone density—a major indicator of osteoporosis and fracture risk. However, it is a costly procedure requiring specialized equipment, and therefore typically only recommended for high-risk individuals with suspected fractures on X-rays or patients on long-term steroid therapy. This limits early detection in the broader population, with many people being diagnosed with osteoporosis only after experiencing a fracture.
Worldwide, nearly 20% of the population is affected by osteoporosis. If left untreated, this condition increases the risk of major fractures, which can be life-threatening and represent a large economic burden for healthcare providers. This drives an urgent need for accessible and non-invasive screening methods that can replace traditional DEXA scans.
Cheng’s team investigated whether images from a patient’s retina could help identify those at a higher risk of developing osteoporosis. This idea stemmed from previous research indicating that the retina can reflect the body’s overall biological aging.
The researchers developed a deep learning algorithm, known as RetiAGE, which calculates the probability of a person being older than 65 years based on images from their retina. They then investigated whether there was an association between RetiAGE results and bone mineral density (BMD) scores, as well as osteoporotic and hip fracture risk scores calculated using the fracture assessment tool (FRAX).
Retinal images and DEXA measurements were obtained from 1,965 participants in the PopulatION HEalth and Eye Disease PRofilE in Elderly Singaporeans (PIONEER) study. In this patient population, older RetiAGE scores were linked to lower BMD scores and an increased risk of major osteoporotic and hip fractures.
The ability of RetiAGE to predict the onset of osteoporosis was then evaluated in another 43,938 participants from a prospective UK Biobank cohort with retinal photographs and no osteoporosis at the time of taking these images. Higher RetiAGE scores, indicating accelerated retinal biological aging, were able to predict future osteoporosis onset even when adjusting for common osteoporosis risk factors as well as female-specific risks such as menopause and hormone replacement therapy.
“These findings suggest that retinal biological aging may reflect broader aging processes related to skeletal health,” state the researchers. “Retinal imaging may therefore provide a simple, non-invasive, and accessible way to support opportunistic screening for osteoporosis risk.”
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