Bone Density, Vitamin D Status, and Disordered Bone Remodeling in End-Stage Chronic Liver Disease O. M. Crosbie, 1 R. Freaney, 2 M. J. McKenna, 2 J. E. Hegarty 1 1 Liver Unit, St. Vincent’s Hospital, Dublin, Ireland 2 Metabolism Laboratory, St. Vincent’s Hospital, Dublin, Ireland Received: 11 September 1997 / Accepted: 22 September 1998 Abstract. Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine the relative contribution of increased resorption and decreased formation to hepatic osteodystro- phy by measuring biochemical markers. Twenty-seven pa- tients with advanced CLD (14 female, 13 male) were en- rolled. Bone mineral density (BMD), measured at the lum- bar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed using biochemical markers of bone formation and resorp- tion. Based on WHO criteria, osteoporosis and osteopenia were present in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and hydroxyproline) were increased signifi- cantly in patients with CLD. There was a less marked change in the markers of bone formation (osteocalcin, pro- collagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed to suppress bone resorption, especially in prepa- ration for liver transplantation. Bone biomarkers may be useful alternatives to bone biopsy in evaluating hepatic os- teodystrophy. Key words: Chronic liver disease — Hepatic osteodystro- phy — Bone resorption — Bone formation — Bone mineral density. Osteoporosis is the predominant component of hepatic os- teodystrophy and is present in 20–50% of patients with chronic liver disease (CLD), based on bone mineral density (BMD) measurements [1–3]. Osteomalacia, due to con- comitant vitamin D deficiency and calcium malabsorption, was traditionally considered to be the major bone disorder in patients with CLD, but is found in only a minority of patients [4–7]. Studies of bone histomorphometry have shown a reduction in formation rate at the level of the bone multicellular unit [7–13]; a number of studies have also suggested an increase in resorption [13–15]. The most de- tailed study of bone remodeling at the total tissue level showed an increase in bone turnover with a negative re- modeling balance [12]. New biochemical indices of bone metabolism provide a noninvasive method of investigating the contribution made by bone formation and resorption to hepatic osteodystrophy [16]. Though significant correlations have been documented between serum osteocalcin and the rate of bone formation and between urinary hydroxyproline levels and the rate of bone resorption in patients with CLD [7, 10, 12, 14], few studies provide detailed measurements of biochemical markers of bone turnover in patients with CLD. The aim of this study was to define bone status in a group of patients with end-stage CLD who were admitted to the hospital for liver transplant assessment. Bone mineral density (BMD) and biochemical markers of bone formation and resorption were measured to allow assessment of both the static and dynamic aspects of bone remodeling in order to elucidate the pathogenic mechanisms leading to hepatic osteodystrophy. Bone status was correlated with patient de- mographics and the severity of liver disease in order to identify other indices that might be associated with abnor- malities in bone density and bone remodeling. Materials and Methods Patients Twenty-seven patients with end-stage CLD (13 males and 14 fe- males; age 20–69 years) who were admitted to the liver unit for transplant assessment over a 12-month period were enrolled in the study. Patient demographics and diagnoses are outlined in Table 1. No patient complained of bone pain at the time of inclusion in the study and two had a history of traumatic fractures. Eight of the 14 women were postmenopausal at the time of the study. Six patients were on low-dose corticosteroids (5–15 mg daily) and four were taking vitamin K supplements (10 mg/day). BMD measurements were performed on all patients and a fasting morning serum sample and 2-hour urine collection were taken for estimation of biochemical markers of bone formation and resorption, respec- tively. Ethical approval was granted by the hospital ethics com- mittee and informed consent was obtained from each patient prior to inclusion in the study. Bone Densitometry Bone mineral density was measured by dual energy X-ray absorp- tiometry (DXA) using a Hologic QDR 1000 scanner. Measure- ments were taken at the L1–L4 vertebrae and at the femoral neck. The results were the composites of L1–L4 and the femoral neck, Correspondence to: O. M. Crosbie, The Liver Transplant Unit, Level 9, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK Calcif Tissue Int (1999) 64:295–300 © 1999 Springer-Verlag New York Inc.