Bone loss is a well-recognized complication of primary biliary cirrhosis (PBC). Although it has been suggested that alendronate might improve bone mineral density (BMD) in PBC, no randomized placebo-controlled trial has been conducted. The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC-associated bone loss. We conducted a doubleblinded, randomized, placebo-controlled trial. Patients with a PBC and BMD t score of less than Ψ1.5 were randomized to receive 70 mg per week of alendronate or placebo over 1 year. BMD of the lumbar spine and proximal femur were measured at entry and at 1 year. Changes from baseline in BMD and biochemical measurements of bone turnover were assessed. Thirty-four patients were enrolled. Seventeen patients were randomized to each arm. After 1 year, a significantly larger improvement (P β«Ψβ¬ .005) in spine BMD was observed in the alendronate group (0.09 Ψ 0.03 g/cm 2 SD from baseline) compared with the placebo group (Ψ0.003 Ψ 0.02 g/cm 2 SD from baseline). A larger improvement (P β«Ψβ¬ .046) was also observed in the femoral BMD of alendronate patients versus placebo. BMD changes were independent of concomitant estrogen therapy. The rate of adverse effects was similar in both groups. In conclusion, in patients with PBC-related bone loss, alendronate significantly improves BMD compared with placebo. Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety.
(HEPATOLOGY 2005;42:762-771.) P rimary biliary cirrhosis (PBC) is often associated with decreased bone mass and consequent development of osteoporosis. [1][2][3][4][5] The rate of bone loss in patients with PBC is approximately twice that of matched controls. 3 Approximately 20% to 35% of patients with PBC have significant bone loss by bone mineral density (BMD) measurements. 4,5 The cause of bone loss in PBC is not well understood. Reduced bone formation rates due to decreased osteoblast function have been demonstrated in patients with PBC. 6 Increased bone resorption has also been suggested as a contributing mechanism in PBC-related bone disease, as elevations in serum and urinary markers of bone resorption have been found in these patients. 7,8 No specific therapy for PBC-related bone loss has been definitely established. Ursodeoxycholic acid is of no benefit on the BMD of patients with PBC. 4,9 Similarly, studies involving multiple other agents have failed to show any definitive effect in preventing PBC-related bone loss. These studies have included 25-hydroxy vitamin D, 10 calcitonin, 11 sodium fluoride, 12 and etidronate, 13 among others. Possible benefits of calcitriol 14 and vitamin K 2 15 on the BMD of patients with PBC have been suggested but still require further study. Estrogen replacement therapy has been shown to improve BMD in postmenopausal women with PBC. 16 However, because the Heart and Estrogen/progestin Replacement Study and the Women's Health Initiative trials showed an increased risk of venous Abbreviations: PBC, primary biliary cirrhosis; BMD, bone mineral density; NTx, amino telopeptide of type I collagen of bone matrix.