Vitamin D replacement for cirrhosis-related bone disease.

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.

Zoledronic acid prevents bone loss after liver transplantation: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinically important rapid bone loss occurs within 3 to 6 months after liver transplantation and may be associated with osteoporotic fractures. OBJECTIVE: To determine whether bisphosphonate treatment with zoledronic acid reduces transplant-related bone loss more than placebo in adults having liver transplantation for chronic liver disease. DESIGN: 12-month randomized, double-blind, placebo-controlled trial. SETTING: 2 large liver transplantation centers in Australia. PATIENTS: 62 adults having liver transplantation for chronic liver disease. INTERVENTIONS: Infusions of zoledronic acid, 4 mg (n = 32), or saline (n = 30) were given within 7 days of transplantation and again at months 1, 3, 6, and 9 after transplantation. All patients received supplementation with calcium carbonate, 600 mg/d, and ergocalciferol, 1000 U/d. MEASUREMENTS: The primary outcome was bone mineral density (BMD) measured by dual x-ray absorptiometry before transplantation and 3, 6, and 12 months later. Secondary outcomes included bone turnover markers that were measured before transplantation and 1, 3, 6, 9, and 12 months later. RESULTS: There were statistically significant interactions between treatment effects and time for BMD measurements at the lumbar spine (P = 0.002), femoral neck (P = 0.001), and total hip (P < 0.001). Differences in acute bone loss 3 months after transplantation favored zoledronic acid over placebo. Differences between groups in percentage change from baseline adjusted for baseline weight and serum parathyroid hormone (PTH) level were 4.0% (95% CI, 1.1% to 7.0%) for the lumbar spine, 4.7% (CI, 1.9% to 7.6%) for the femoral neck, and 3.8% (CI, 1.7% to 6.0%) for the total hip. At 12 months after transplantation, the difference in percentage change from baseline between the 2 groups adjusted for baseline weight and serum PTH level was 1.1% (CI, -2.1% to 4.4%) for the lumbar spine, 2.7% (CI, 0.0% to 5.4%) for the femoral neck, and 2.4% (CI, 0.1% to 4.7%) for the total hip. Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo. LIMITATIONS: The trial was not powered to assess fractures, and 10 of 62 (16%) patients were not included in adjusted analyses because of missing weight or serum PTH measurements. CONCLUSION: Treatment with zoledronic acid can prevent bone loss within the first year after liver transplantation.