Parenteral calcitonin, tested in one controlled trial for 6 months, was ineffective in halting bone loss in patients with PBC [321] , whereas hormone replacement therapy was demonstrated to improve vertebral bone density in PBC [319, 322, 323] . In large clinical trials, however, hormone replacement therapy was associated with serious side effects, including the risks of breast cancer, coronary artery disease, and thromboembolism, limiting its use for the prevention of fractures in osteoporosis [324] [325] [326] .