Reply.

We thank Dr. Sugiyama for having interest in our work on denosumab therapy for osteoporosis in patients with autoimmune liver diseases.1

Osteodystrophy is a worrisome complication in chronic liver diseases (CLDS), especially in autoimmune liver diseases such as primary biliary cholangitis and autoimmune hepatitis accompanying vitamin D malabsorption and use of corticosteroid. Given that physical activity is closely associated with bone health,2 physical inactivity in CLD is likely to worsen bone metabolism. We think that regular exercise should be recommended in patients receiving denosumab treatment.

Osteoporosis is closely associated with sarcopenia. For example, Hayashi et al. reported that the appendicular skeletal muscle mass index was significantly correlated with bone mineral density of the lumbar spine and femur neck.3 Several studies demonstrated that exercise improved muscle strength and function in CLD patients. In addition, exercise ameliorated VO2 peak, anaerobic threshold, 6‐mintute walk distance, and quality of life in patients with compensated and decompensated cirrhosis.4, 5 Therefore, exercise programs should be incorporated in the management of CLD. However, appropriate type, intensity, and duration of exercise are largely unknown. These factors should be arranged based upon patients’ liver function (compensated or decompensated) and physical condition. The combination of exercise and a specific treatment such as denosumab will be the focus of future trials.