Parathyroid hormone and alkaline phosphatase are associated with fracture risk in non-dialysis-dependent chronic kidney disease

We studied over 45,000 Danish adults with non-dialysis-dependent chronic kidney disease to assess whether parathyroid hormone (PTH) and alkaline phosphatase (ALP) were associated with fracture risk. Elevated PTH (over twice normal) and ALP (above 70 U/L) were linked to higher fracture rates, suggesting these markers may help identify high-risk patients. PURPOSE: Patients with chronic kidney disease (CKD) have an increased risk of bone fracture. We aimed to examine the association between parathyroid hormone (PTH), alkaline phosphatase (ALP), and fracture risk in non-dialysis-dependent CKDG3-5. METHODS: and measured PTH were identified from nationwide healthcare registers between 2010 and 2022. PTH was standardized to the assay-specified upper normal limit (UNL) and stratified as normal, slightly elevated (1.1-2.0 × UNL), high (2.1-4.0 × UNL), and very high (≥ 4.0 × UNL). ALP was stratified as low to low-normal (< 70 U/L), upper-normal (70-105 U/L), slightly elevated (106-125 U/L), and high (> 125 U/L). Rates of major osteoporotic fracture (MOF; hip, vertebra, wrist, and humerus fracture) and any fracture were estimated in multiple Cox regression models adjusted for relevant confounders. RESULTS: Among 45,611 included individuals adjusted rates of MOF were increased in patients with high PTH (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04-1.26, p = 0.005) and very high PTH (HR 1.23, 95% CI 1.04-1.46, p = 0.012), compared to patients with normal PTH. Patients with ALP levels in the upper-normal (HR 1.11, CI 1.02-1.20, p = 0.01), slightly elevated (HR 1.29 CI 1.13-1.47, p < 0.001), and high (HR 1.59, CI 1.39-1.75, p < 0.001) categories showed significantly higher rates of MOF compared to low to low-normal ALP. We found similar HRs of any fracture event stratified by ALP- and PTH levels. CONCLUSION: Our nationwide observational cohort study demonstrates that PTH and ALP were positively associated with fracture risk in non-dialysis-dependent CKDG3-5.