Risk of Fractures Associated with Primary Biliary Cholangitis Does Not Decrease with Bisphosphonate Therapy

A series of analyses presented at The Liver Meeting 2025, in Washington, D.C., showed that primary biliary cholangitis (PBC) increases the risk of bone fractures in women older than 65 years, independently of the postmenopausal status, and revealed that this risk is not mitigated by guideline-directed therapy for osteoporosis. 
Patients with PBC have an elevated risk of osteoporosis and bone fractures, which increases with progression of the diseases. While postmenopausal status is a known risk factor for osteopenia and osteoporosis, PBC may add another layer to the risk stratification in aging women living with this condition. 

In an ongoing, multicenter study, vulnerability to fractures was compared among nearly 300 women aged over 65 years with PBC and a similar number of postmenopausal women without PBC who were treated at the Cleveland Clinic hospitals in Ohio and Florida. Participants had an average age of 77 years and were matched by age to the women in the control group. The rates of osteopenia and osteoporosis were similar among the groups, as was the use of osteoporosis-related medications, documented in approximately one-third of participants in each group. Baseline vitamin D levels and vitamin supplementation were also comparable among the groups. A vast majority of the patients who had fractures (83%) were being treated with ursodeoxycholic acid (UDCA) at the time when the fractures occurred.   

The results showed that women with PBC had a higher risk of fractures than the postmenopausal women without PBC. Moreover, fractures tended to occur earlier after the age of 65 years in women with PBC than in their counterparts in the control group. The long-term cumulative incidence of fractures was also higher in the group with PBC. 

“The elevated risk of fractures among women with PBC was dependent on the disease itself and not dependent on any of the other factors that we modeled,” said lead author Leandro Sierra, MD, an internal medicine resident at the Cleveland Clinic Main Campus, in Cleveland, Ohio. “These patients were actually being treated for either osteoporosis or osteopenia in both cohorts, and when we compared, it did not make a difference in [women with] PBC. What [we observed] is that the treatments that are prescribed for osteoporosis do not work that well in PBC or do not [decrease] the fracture risk as compared to the control group.”

A second analysis from the same retrospective study showed that, while bisphosphonate therapy reduced the 10-year risk for fractures in postmenopausal women without PBC, the risk continued to increase over time in women with PBC who received similar, guideline-recommended therapies. 

“There is a new movement to figure out the bone-related outcomes in PBC, especially after the approval of seladelpar,” Sierra added. “There is a question of whether [seladelpar] increases the risk of fractures or whether [the risk] is related to the disease itself, which is actually not well managed.” Sierra and colleagues are planning a prospective study enrolling roughly the same number of patients, which could offer additional insight into the effects of PBC on bone metabolism in this vulnerable population.