In their pilot study, Arase et al.(1) assessed the efficacy and safety of treatment with denosumab for three years in postmenopausal osteoporotic women with autoimmune liver diseases such as primary biliary cholangitis and autoimmune hepatitis. Although there is debate, the authors' suggestion that denosumab can be used as a first-line osteoporosis drug(1) is supported by the Endocrine Society's clinical practice guideline for the pharmacological management of osteoporosis in postmenopausal women(2) . Here I would like to point out that physical activity might play a considerable role in both bone health and denosumab treatment in autoimmune liver diseases.

Vitamin K2, also called menaquinone, is an essential lipid-soluble vitamin that plays a critical role in blood clotting and prevention of osteoporosis. It has become a focus of research in recent years and has been widely used in the food and pharmaceutical industries. This review will briefly introduce the functions and applications of vitamin K2 first, after which the biosynthesis pathways and enzymes will be analyzed in-depth to highlight the bottlenecks facing the microbial vitamin K2 production on the industrial scale. Then, various strategies, including strain mutagenesis and genetic modification, different cultivation modes, fermentation and separation processes, will be summarized and discussed. The future prospects and perspectives of microbial menaquinone production will also be discussed finally.

Osteodystrophy is a worrisome complication in chronic liver diseases (CLD), especially in autoimmune liver diseases such as primary biliary cholangitis and autoimmune hepatitis accompanying vitamin D malabsorption and use of corticosteroid. As 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.