Association between serum α-Klotho levels and mortality in US adults with osteoporosis

Klotho, a protein known for its significant involvement in the aging process and age-related diseases, has been demonstrated to be inextricably linked to osteoporosis. Nevertheless, the relationship between serum Klotho levels and mortality risk among individuals with osteoporosis has not been definitively established. Therefore, the purpose of the current research is to examine the potential relationship between serum Klotho levels and mortality risk in individuals aged 40 and above with osteoporosis.

The current study included adults aged 40 years and older diagnosed with osteoporosis from the National Health and Nutrition Examination Survey. Osteoporosis diagnosis was based on a history of osteoporosis or bone mineral density. Moreover, Cox proportional hazards regression, Kaplan-Meier (KM) curves, and restricted cubic spline (RCS) curves were utilized to assess the relationship between Klotho levels and mortality risk. In addition, subgroup analysis was performed using stratification and interaction analysis for all covariates.

A total of 1004 participants (median age: 65 years) with a median follow-up of 9.33 years were included in the final analysis. This study found that serum Klotho levels established a U-shaped relationship with the risk of all-cause mortality in individuals with osteoporosis, with a nadir of Klotho levels was approximately 900 pg/mL, in which lower (< 850 pg/mL) or higher (> 950 pg/mL) Klotho levels were significantly associated with an increased risk of all-cause mortality. Moreover, the results of subgroup analysis indicated that the associations between Klotho levels and mortality risk were modified by several factors, especially a history of hypertension. Specifically, Klotho levels established an L-shaped relationship with the risk of all-cause mortality among participants with a history of hypertension, while a positive and linear relationship with the risk of all-cause mortality among those without a history of hypertension.

For individuals with osteoporosis, it is necessary to be alert to cases with high or low Klotho levels, which may potentially indicate an increased mortality risk.