Use of bisphosphonates is controversial. In a placebocontrolled trial, cyclical etidronate did not significantly improve bone density [327] . Also, a 4-year treatment with clodronate plus calcium/vitamin D did not improve osteopenia in women with PBC in a prospective study [328] . In two controlled trials however, alendronate significantly improved spine and femoral bone mineral density compared with placebo and had greater antiresorptive activity than etidronate [329, 330] .