Patient description: The patient is a 60 year old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is worsening. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions are detected in the head and face. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. His serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). His family history is only significant for hypertension in his mother and DM type 2 in his father. The diagnosis of Paget's Disease of Bone was confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Primary Biliary Cirrhosis Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors History of elevated alkaline phosphatase (ALP) levels for at least 6 months Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (pyruvate dehydrogenase complex-E2 [PDC-E2], 2-oxo-glutaric acid dehydrogenase complex) Liver biopsy consistent with PBC 2. At least 1 of the following qualifying biochemistry values ALP ≥ 1.67x upper limit of normal (ULN) Total bilirubin > ULN but < 2x ULN 3. Age ≥ 18 years 4. Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0. 5. Contraception: Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and for 30 days after the end of treatment (EOT) visit. Effective methods of contraception are considered to be Hormonal (for example, contraceptive pill, patch, intramuscular implant or injection); or Double barrier method, that is, (a) condom (male or female) or (b) diaphragm, with spermicide; or Intrauterine device (IUD); or Vasectomy (partner); or  History or presence of other concomitant liver diseases including Hepatitis C virus (HCV) infection; participants with active hepatitis B (HBV) infection will be excluded, however, participants who have seroconverted (hepatitis B surface antigen [Hbs Ag] and hepatitis B e antigen [Hbe Ag] negative) may be included after consultation with the medical monitor Primary sclerosing cholangitis (PSC) Alcoholic liver disease Definite autoimmune liver disease or overlap hepatitis Nonalcoholic steatohepatitis (NASH) Gilbert's Syndrome (due to interpretability of bilirubin levels) 2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15 Portal hypertension with complications, including: known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds or related therapeutic or prophylactic interventions (for example, beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt [TIPS]), or hepatic encephalopathy Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN