Alendronate Improves Bone Mineral Density in Primary Biliary Cirrhosis: A Randomized Placebo-Controlled Trial * #

Abstract

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 ؊1.5 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 ‫؍‬ .005) in spine BMD was observed in the alendronate group (0.09 ؎ 0.03 g/cm 2 SD from baseline) compared with the placebo group (؊0.003 ؎ 0.02 g/cm 2 SD from baseline). A larger improvement (P ‫؍‬ .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.

Cholestasis and metabolic bone disease – a clinical review

“…As mentioned earlier, only limited data on bisphosphonate therapy in chronic liver disease were published. Alendronate improves bone mineral density in patients with primary biliary cirrhosis [31,32].…”

Bone disorders in chronic liver disease

“…In a further 12-month placebo-controlled study of osteopenic PBC patients, alendronate was associated with improvements in both spinal and femoral BMD, but the study was not powered to show an effect on fracture rates. 36 There are no studies of the safety or efficacy of bisphosphonates in cirrhosis, but anecdotally bisphosphonates appear to be well tolerated once weekly, although it would be reasonable to exercise caution in using the drug in patients with recent esophageal banding/sclerotherapy.…”

Alcoholic liver disease and changes in bone mineral density

“…Their results suggest that in PBC, treatment for two years with cyclical etidronate prevents BMD loss (92), and that alendronate can significantly increase BMD in the lumbar and femoral areas, with an efficacy superior to that of cyclical etidronate (93). Favourable results have recently been published for patients with PBC treated with weekly doses of 70 mg of alendronate, which appears to be better tolerated than daily dosage regimens (94). There are also studies available on the use of bisphosphonates in viral CLD, in which cyclical etidronate reduced the incidence of fractures in postmenopausal women with chronic viral hepatitis after an 8-year follow-up period (95).…”