The prevalence of vitamin D deficiency is 60 % in cirrhotic patients and as high as 96 % at the time of liver transplantation [17]. Despite the high prevalence of vitamin deficiency, osteomalacia (defective bone mineralization with subsequent softening of the bones) is rare but osteoporosis and osteopenia are not uncommon. Low vitamin D has been associated with low bone mineral density, hip fracture, and high bone turnover and contributes to osteoporosis in patients with chronic liver disease. A recent study by Venu et al. showed insufficient vitamin D in 83 % of cirrhotic patients [18]. Osteopenia or osteoporosis was noted in 45 and 18 % of cirrhotic patients, respectively; of those patients with osteoporosis, 100 % had vitamin D deficiency. Etiology of liver disease (including cholestatic etiology versus other) was not predictive of who developed vitamin D deficiency.

Patients with chronic liver disease exhibit many risk factors for low bone density and osteoporosis. Known risk factors include poor nutrition, steroid use, alcohol intake, and hypogonadism [17]. Cirrhotic patients are not the only patients with liver disease at risk for low bone density. One study showed that alcohol intake was inversely related to bone mineral density in men. Additionally, in 76 men who drank 216 g/day or more for 24 years, 30 % had vertebral fractures regardless of stage of fibrosis on histology [19]. Non-cirrhotic patients with hemochromatosis also have high rates of osteoporosis which seem to correlate with the degree of hepatic iron level.

Patients with non-cirrhotic biliary disease have been examined for increased rates of osteopenia and osteoporosis . The incidence of osteoporosis in primary sclerosing cholangitis (PSC) is between 3 and 32 %. It does not appear that treatment with ursodeoxycholic acid improves bone density in this patient population [20]. According to the American Association for the Study of Liver Disease (AASLD) practice guidelines, bone density should be evaluated with any new PSC diagnosis and at subsequent 2–3-year intervals [21]. The AASLD guidelines also recommend calcium and additional vitamin D to promote calcium absorption in patients with proven osteopenia [21]. Patients with end-stage primary biliary cirrhosis (PBC) have significantly greater risk of osteopenia and osteoporosis than do age-matched and sex-matched controls, although this has been subject to controversy. Recent studies show that PBC patients have a fourfold increased risk of osteoporosis [22]. The American Gastroenterological Association (AGA) guidelines suggest that bone mineral density evaluation should be considered in all patients with PBC at diagnosis, whereas other recommendations limit bone mineral density evaluation to patients with bilirubin greater than three times the upper limit of normal [23, 24]. The AASLD recommends baseline and regular screening every 2–3 years using bone mineral density testing [25]. The AASLD also recommends measuring annual vitamin D levels in patients with advanced disease. In PBC patients with osteoporosis, alendronate has been shown in a randomized controlled trial to significantly improve bone density when compared to placebo. Therefore, AASLD recommends alendronate for osteoporosis, but only if the patient has no known varices or reflux [25].

Cirrhotic patients of all etiologies are at an increased risk for osteoporosis. Prevalence of osteoporosis varies in studies but ranges from 12 to 55 % [26, 27]. Rates of osteoporosis increase with worsening hepatic function reflected by a higher Child’s score and do not seem to correlate with degree of cholestasis. AASLD suggests screening densitometry in all cirrhotic patients and all patients undergoing transplant evaluation [28].

Low bone density and osteoporosis are particularly concerning in liver transplant recipients. In the first 3 months following liver transplantation, bone density falls dramatically [29]. This is a time when patients are limited in their mobility and typically receiving high-dose corticosteroids to prevent rejection. Fracture rates of 15–35 % have been reported, with most fractures occurring within the first 2 years of transplantation. A recent study showed that 25 % of patients have new fracture within the first 6 months after liver transplantation. Another study showed that bone density decreases in the first 6 months and remains low in the femoral neck, but improves to exceed pretransplantation density in the lumbar spine by 2 years [29]. The role of calcineurin inhibitors in bone turnover following transplantation remains controversial. However, long-term steroid use increases the risk for decreased bone mineral density.