Association of serum alkaline phosphatase levels with bone mineral density, osteoporosis prevalence, and mortality in US adults with osteoporosis: evidence from NHANES 2005-2018.

Unlabelled: This study examined the association of serum total alkaline phosphatase (T-ALP) with bone mineral density (BMD) and osteoporosis prevalence in the general population, and investigated its association with mortality in individuals with osteoporosis, using data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Elevated serum T-ALP levels were significantly associated with both reduced BMD and an increased risk of osteoporosis in all participants. Moreover, elevated T-ALP levels were linked to higher all-cause mortality among individuals with osteoporosis during this period.

Introduction: The evidence regarding the association between serum T-ALP, BMD and osteoporosis prevalence in general population is incomplete, and limited evidence is available concerning its association with mortality among individuals with osteoporosis. The study investigated the association of serum T-ALP with BMD and osteoporosis prevalence in the general population, and examined its association with mortality in individuals with osteoporosis.

Methods: All participants were adults from the NHANES (2005-2018), and mortality data were obtained from the National Death Index up to December 31, 2019. Firstly, the association of serum T-ALP with BMD and osteoporosis risk was assessed using linear regression model, subgroup analysis, analysis of covariance and weighted logistic regression model, respectively. Secondly, survival analysis including Kaplan-Meier curves, Cox proportional hazards models, and restricted cubic spline regression models were utilized to analyze the relationship between serum T-ALP levels and mortality risk.

Results: The study included 13,724 participants aged 18 to 85 years, and 944 were diagnosed with osteoporosis, among whom 221 died during a median of 133 months follow-up. Totally, elevated serum T-ALP was significantly associated with low BMD in femoral neck and lumbar spine, and the results exhibited consistency across diverse age, genders, races, and BMI subgroups. Moreover, for each 1 SD increase in T-ALP, there was a 0.5% increase in the prevalence of osteoporosis [OR (95%CI): 1.005 (1.005, 1.005), p < 0.001]. Among individuals with osteoporosis, for every 1 SD increase in T-ALP, the all-cause mortality increased by 0.4% [HR (95%CI):1.004 (1.002, 1.006), p < 0.001]. Meanwhile, comparing participants with highest serum T-ALP levels (> 79 IU/L) to those with lowest levels (< 53 IU/L) further raised the prevalence of osteoporosis [OR (95%CI):1.292 (1.021, 1.636), p = 0.033] and all-cause mortality [HR (95% CI):1.232 (1.041, 1.459), p = 0.015].

Conclusions: Based on a representative sample of US adults, elevated serum T-ALP levels were found to be significantly associated with both reduced BMD and an increased risk of osteoporosis across all participants, as well as with a higher all-cause mortality in individuals with osteoporosis.