Associations of Blood Biomarkers of Bone Turnover with Static Histomorphometry Parameters at the Hip in Patients with Chronic Kidney Disease Undergoing Surgery for Hip Fracture

Individuals with chronic kidney disease (CKD) have higher rates of hip fracture and post-fracture mortality. Although they may develop age-related osteoporosis similar to those without CKD, they may also exhibit CKD-related metabolic bone disease (MBD), characterized by low, high, or mixed turnover at similar levels of bone mineral density (BMD). Because BMD does not provide information about turnover status, clinical decision-making is challenging. This study evaluated the associations between circulating bone-turnover biomarkers and static histomorphometry in patients undergoing hip-fracture surgery. In this cross-sectional study, we enrolled adults with and without CKD, defined as estimated glomerular filtration rate (eGFR) [≤]60 ml/min/1.73m{superscript 2} (CKD-EPI 2021), undergoing hip-fracture surgery. Blood samples, bone specimens from the femoral head or greater trochanter, and demographic and clinical data were collected at the time of surgery. Plasma biomarkers included -Klotho, bone alkaline phosphatase (BAP), dickkopf-related protein 1 (DKK-1), fibroblast growth factor 23 (FGF23), tartrate-resistant acid phosphatase 5b (TRAP5b), parathyroid hormone (PTH), and sclerostin. Logistic regression models, adjusted for age, gender, eGFR, and osteoporosis, assessed associations with CKD status. Tertiles of osteoblast surface (Ob.S/BS) and eroded surface (ES/BS) were defined in participants without CKD and applied to the full cohort. Multinomial and multivariable linear regression evaluated associations of biomarkers with these histomorphometry parameters. Among 97 enrolled participants (mean age 80 {+/-} 11 years; 67% female), 68% had CKD. Of 75 with complete biomarker and histomorphometry data, 96% demonstrated low bone turnover. CKD was associated with lower trabecular thickness (Tb.Th) and higher osteoid thickness (O.Th), osteoid volume (OV/BV), and osteoid surface (OS/BS), suggesting thinner, largely unmineralized trabeculae. Higher BAP (222.2% difference per doubling; 95% CI 77.2-485.8) and TRAP5b (319.3%; 95% CI 128.3-669.5) were directly associated with Ob.S/BS and ES/BS, whereas sclerostin was inversely associated with ES/BS (-28.9%; 95% CI -44.8 to -7.1). PTH was not associated with bone-turnover measures. These findings suggest that BAP, TRAP5b, and sclerostin may provide useful adjunct information alongside PTH for assessing bone turnover and guiding therapy in patients with and without CKD.