High FGF23 Levels Double Fall Risk in Older Adults

Pam Harrison

November 01, 2018

SAN DIEGO — Elevated levels of circulating fibroblast growth factor 23 (FGF23), a hormone derived from bone that regulates phosphorous and active vitamin D, doubles the risk for falls in older adults, new research shows.

"Falls lead to significant morbidity, such as bone fracture and head trauma, and injuries resulting from falls can lead to mortality," said Anna Jovanovich, MD, from the University of Colorado in Aurora.

"We noted a significant association between FGF23 levels and falls," she reported here at Kidney Week 2018.

And even though that association "was independent of frailty and gait speed, FGF23 could still be a marker for frailty in this population," she told Medscape Medical News.

For their analysis, Jovanovich and her colleagues assessed 2488 patients with an estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m². The elevated levels of FGF23 seen in patients with chronic kidney disease (CKD) are associated with the progression of kidney disease and mortality.

It is well known that frailty increases the risk for falls in older adults and patients with end-stage renal disease. In older adults without CKD, FGF23 levels are associated with frailty.

So the researchers hypothesized that elevated levels of intact FGF23 would be associated with an increased risk for falls in patients with CKD.

All the study participants had been enrolled in the SPRINT trial (NCT01206062) in which intensive targets for systolic blood pressure — below 120 mm Hg — were compared with standard targets — below 140 mm Hg — in older adults with hypertension but without diabetes.

SPRINT was stopped early because the risks for cardiovascular events and mortality were significantly lower with the intensive target than with standard target.

Mean age of the study participants was 73 years, and 40% were women. Mean eGFR was 49 mL/min per 1.73 m² and median intact FGF23 level was 66 pg/mL. Serum calcium and phosphorous levels were in the normal range.

A fragility index used in SPRINT was derived from a 36-item score and included metrics of cognitive function, laboratory values, blood pressure, and self-reported measures of depression, well-being, and comorbidity.

A frailty index of less than 0.1 meant the patient was fit. Only 11% of the cohort met the threshold for fitness, 52% was considered less fit, and 36% was considered frail, Jovanovich reported.

Median time to the first fall was 39 months.

The researchers examined the association between intact FGF23 levels and falls in a variety of models, each adjusted for different risk factors.

But regardless of the model used, "a higher iFGF23 was significantly associated with an increased hazard of falls," Jovanovich said.

The risk for falls was two times greater when intact FGF23 level was in the highest quartile than when it was in the lowest quartile.

And every doubling of intact FGF23 levels increased the risk for falls by a factor of nearly two. This effect was seen regardless of which target group the participants had been randomized to in SPRINT.

In a separate analysis of 1192 patients 75 years and older, the team documented gait speed. Mean age of the study cohort was 81 years and 12% of the cohort was fit, 52% was less fit, and 36% was frail.

In this older cohort, mean gait speed was 6 seconds and median time to the first fall was 23 months.

When gait was incorporated into the models used in the previous analysis, the risk for falls was again nearly two times higher when levels of intact FGF23 were in the highest quartile than when they were in the lowest quartile.

And the hazard ratio for each doubling of intact FGF23 level was 1.82.

These findings indicate a significant association between elevated levels of intact FGF23 and increased risk for falls in SPRINT participants with CKD. And that association was independent of the frailty index and gait speed.

FGF23 levels are not routinely measured outside of a research setting and are not ready for use in daily practice, Jovanovich noted, stressing that further investigation is needed.

These results suggest that FGF23 is an important biomarker for frailty and falls in patients with CKD, said session cochair Tanya Johns, MD, from the Albert Einstein College of Medicine in the Bronx, New York.

But she said she agrees with Jovanovich that the finding "needs to be validated with additional studies."

Kidney Week 2018: American Society of Nephrology Annual Meeting: Abstract TH-OR021. Presented October 25, 2018.

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