BOSTON, MA—Injections of denosumab every 6 months prevent osteoporosis in patients with primary biliary cholangitis and autoimmune hepatitis, with minimal adverse effects, study results presented at The Liver Meeting® 2016 have found.
Osteoporosis often results in pathological fractures, adversely affecting activities of daily living. For that reason, “denosumab is a promising option for improving long-term quality of life in patients with autoimmune liver diseases,” noted Kenichi Ikejima, MD, PhD, of the department of gastroenterology at Juntendo University Graduate School of Medicine, in Tokyo, Japan.
Among patients with primary biliary cholangitis, impaired bile secretion results in malabsorption of vitamin D, while steroid-induced osteoporosis is often observed in autoimmune hepatitis.
Dr. Ikejima and colleagues evaluated the efficacy of denosumab, a human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL), in patients with biopsy-proven primary biliary cholangitis (n=13) and autoimmune hepatitis (n=7) who showed overt osteoporosis by dual-energy X-ray absorptiometry (DEXA).
The primary biliary cholangitis group included 10 naive cases (9 females) and 3 cases (all females) pretreated with bisphosphonates; average age was 67.6 ± 9.5 years and disease duration ranged from 26 to 293 months. The autoimmune hepatitis group was all female and included 5 treatment-naive and 2 bisphosphonate-pretreated patients; average age was 62.5 ± 10.5 years and disease duration ranged from 8 to 332 months.
All patients received repeated injections of denosumab 60μg in 6-month intervals and eldecalcitol, a daily oral vitamin D analog, for 12 months.
“Serum bone resorption markers and DEXA were monitored before and every 6 months during the treatment period,” the study authors noted.
“Denosumab improves bone density in primary biliary cholangitis patients,” the team reported. “DEXA T-scores of lumbar spine were significantly improved following 12-months treatment with denosumab [P<0.001]. Serum levels of bone-type alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were also improved significantly.”
Autoimmune hepatitis group T-scores improved from -2.66 ± 0.44 to -2.33 ± 0.51 (P<0.001). Denosumab was also associated with improved bone density in steroid-treated autoimmune hepatitis patients (P<0.01), and serum levels of bone metabolic markers in steroid-treated autoimmune hepatitis (P<0.01).
During the treatment period, one patient had a fractured humerus at 11 months, and another showed latent hypocalcemia. “It was not severe—it was asymptomatic,” said Dr Ikejima. “We just added some calcium supplements.”