Soluble klotho levels and hip fracture risk in the elderly

The association between circulating soluble klotho (s-klotho) levels and hip fracture risk is uncertain. We assessed this relationship in 4428 older adults followed for a median of 11.8 years, during which 602 hip fractures occurred. In the overall cohort, s-klotho levels were marginally but not significantly associated with hip fracture risk (hazard ratio (HR) per standard deviation increase, 0.92; 95% CI, 0.83-1.01; p = 0.075). In exploratory analyses, participants in the highest 5% of s-klotho levels (> 1615.2 pg/ml) exhibited a substantially lower risk of hip fracture (adjusted HR, 0.48; 95% CI, 0.27-0.85; p = 0.01), suggesting a threshold effect in which only very high s-klotho concentrations are associated with reduced risk. This finding may help explain inconsistencies in prior studies.