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Vitamin D replacement for cirrhosis-related bone disease

Abstract

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 sunlight, impaired intestinal absorption and disruption of the enterohepatic cycle

  • Most guidelines recommend calcium and vitamin D supplementation in patients with cirrhosis and low bone density, but there have been no randomized, controlled studies of an adequate scale to assess the effects of such supplementation on bone density or osteoporotic fracture rates

  • Vitamin D deficiency and secondary hyperparathyroidism should be corrected before initiation of bisphosphonate therapy for osteoporosis

  • High-dose, parenteral vitamin D therapy might be beneficial for patients with cirrhosis and vitamin D deficiency; however, further studies are required to assess the potential risks (e.g. hypercalcuria) of this approach

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Figure 1: The relationship between vitamin D levels and liver cirrhosis.
Figure 2: Vitamin D metabolism.
Figure 3: Flow diagram for the assessment and management of vitamin D status in patients with cirrhosis.

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Acknowledgements

The authors thank Associate Professor Rebecca Mason, Department of Physiology, University of Sydney, Australia, for her comments on this paper.

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Correspondence to Bronwyn A Crawford.

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Crawford, B., Labio, E., Strasser, S. et al. Vitamin D replacement for cirrhosis-related bone disease. Nat Rev Gastroenterol Hepatol 3, 689–699 (2006). https://doi.org/10.1038/ncpgasthep0637

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