Associations Between Liver Function, Bone Turnover Biomarkers and Adipokines in Older Patients With Hip Fracture

Abstract

Background: To examine the associations of serum liver markers with parameters of mineral and bone metabolism and their relationship with leptin, adiponectin and resistin in patients with hip fracture (HF). Methods: In 294 older patients (mean age 82.2 ± 7.9 years, 72.1% women) with osteoporotic HF, we measured serum levels of alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, adiponectin, leptin, resistin, 25(OH) vitamin D (25(OH)D), intact parathyroid hormone (PTH), calcium, phosphate, magnesium, osteocalcin (OC), bone-specific alkaline phosphatase (BAP), urinary concentrations of deoxypyridinoline (DPD/Cr) and cross-linked N-telopeptide of type 1 collagen (NTx/Cr) (both corrected for urinary creatinine concentrations), as well as routine blood parameters. Results: In the total cohort, in fully adjusted multivariate linear regression analyses, lower OC was an independent predictor of higher GGT, ALT and bilirubin, whereas higher BAP was positively associated with GGT and ALP; NTx/Cr, hemoglobin (both inversely), adiponectin, coronary artery disease (CAD) and alcohol overuse (all three positively) were also independently associated with GGT activity. However, in malnourished women, OC was not an independent predictor of GGT or ALT and NTx/Cr predicted ALP activity. OC was independently predicted by GGT, ALT (both negatively), ALP, leptin and age (all three positively), BAP by GGT and ALP, OC/BAP ratio by GGT (inversely) and leptin (positively) and both elevated NTx/Cr and DPD/Cr by higher ALP and lower leptin levels. The GGT > 20 U/L indicated increased prevalence of low OC levels (two-fold) and low OC/BAP ratio (2.6-fold) with a positive predictive value above 75%. Conclusions: In older HF patients, bidirectional links exist between liver function (within normal range in the vast majority) and parameters of bone metabolism. Adiponectin is an independent predictor of GGT, whereas leptin is a determinant of OC and bone resorption; these relationships are modulated by nutritional status. GGT > 20 U/L may be used as a marker of impaired bone metabolism. J Endocrinol Metab. 2014;4(5-6):121-135 doi: http://dx.doi.org/10.14740/jem250w