Vitamin D replacement for cirrhosis-related bone disease

Vitamin D deficiency is common in patients with cirrhosis and is associated with bone density changes. It is generally recommended that patients with cirrhosis and low bone density receive calcium and vitamin D supplementation, despite a lack of evidence for a role of vitamin D in the pathogenesis or treatment of osteoporosis in cirrhotic patients. This Review revisits the controversy surrounding the role of vitamin D in hepatic bone disease and discusses vitamin D therapy in this setting. The osteoporotic fracture rate in patients with chronic liver disease is approximately twice that of age-matched, control individuals. About 66% of patients with moderately severe cirrhosis and 96% of patients awaiting liver transplantation have vitamin D deficiency. Studies have shown a strong correlation between vitamin D deficiency and bone density, particularly in the hip. Previous studies of vitamin D therapy in cirrhosis-related bone disease have had major design flaws. Most reports and guidelines on the treatment of hepatic bone disease have concluded that vitamin D deficiency does not have a significant pathogenetic role in the development of osteoporosis in cirrhosis, and that there is no evidence for a therapeutic effect of vitamin D supplementation. Conversely, it is generally recommended that patients with cirrhosis and low bone density should receive calcium and vitamin D supplementation; yet there is a paucity of reliable data on the optimal doses to use, as well as a lack of clearly demonstrated benefit. We believe that clinical trials of vitamin D therapy in these patients with liver disease are warranted. As low-dose oral supplementation often will not normalize vitamin D levels or suppress parathyroid hormone activity in cirrhotic patients, high-dose, parenteral vitamin D might be preferable, but further long-term studies are required to assess the benefits and safety of this approach. Key Points Vitamin D deficiency is common in patients with cirrhosis, and its severity correlates with the progression of cirrhosis Vitamin D deficiency in cirrhotic patients is strongly correlated with bone density changes, particularly in the hip Some patients with vitamin D deficiency and cirrhosis develop secondary hyperparathyroidism; it is not known whether the presence or absence of hyperparathyroidism correlates with changes in bone density or fracture risk The etiology of vitamin D deficiency in patients with cirrhosis is multifactorial and might include lack of