The results of this study appear in the September 2006 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/livertransplantation.
Osteoporosis and osteopenia, its less severe form, are known complications of cirrhosis, especially in patients with cholestatic liver disease (where bile production stops). However, the underlying mechanism of bone loss in these patients is poorly understood and osteoporosis is often overshadowed by the more pressing health problems seen with liver disease. Early aggressive bone loss occurs in almost all patients following transplant, and although immunosuppression is assumed to play a role in bone loss, risk factors have not been well established to date.
In the largest cohort of patients reported to date that were transplanted at a single center, Maureen M. J. Guichelaar of the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN and her colleagues studied 360 adult patients undergoing liver transplants at the Mayo Clinic between 1985 and 2001. All of the patients were diagnosed either with end-stage primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), where the bile ducts become inflamed and obstructed, causing bile to build up in the liver and damage it. Patients were examined before transplant, at 4 and 12 months following transplant, and every year thereafter. The exam included liver function status, nutritional status, bone marrow density, muscle wasting and complications. All patients were prescribed calcium supplements and vitamin D, if needed. Patients received different immunosuppressive therapies, depending on when the transplant took place.
Only 23 percent of patients had normal bone mass before undergoing a transplant, with a higher prevalence of osteoporosis among those with PBC. Four months after transplant, 51 percent of the patients had osteoporosis, but bone mineral density (BMD) increased for up to 4 years after transplant and remained above pre-transplant levels. The risk factors linked to increased bone loss during the first 4 months after transplant were PSC, younger age at transplant, no inflammatory bowel disease before transplant, smoking, higher pre-transplant bone density, and shorter duration of liver disease before transplant. Bone gain during the first two years after transplantation was greater for patients who were pre-menopausal; had lower pre-transplant and/or 4-month post-transplant bone densities; received lower doses of glucocorticoids; and had higher blood levels of vitamin D.
The authors note that the aggressive bone loss that occurred during the first 4 months did not change over time despite changes in immunosuppressive therapies. "In conclusion," they state, "patients transplanted most recently have improved bone mass before OLT [orthotopic liver transplantation], and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT."
In an accompanying editorial in the same issue, Wolfram Karges and Christian Trautwein of the Department of Internal Medicine at RWTH University Hospital Aachen in Germany note that the study showed that absolute bone mass was higher after liver transplantation than before, approaching BMD values typical of healthy individuals of the same age. "This novel observation is reassuring and rewarding, as it demonstrates that OLT, despite concomitant immunosuppression, is overall suitable to treat cholestatic osteopenia," they state. However it is not enough. "To secure the benefits of OLT on bone mass, and to reduce the risk of fracture after OLT, therapeutic intervention is mandatory," they urge, advocating that patients with progressive liver disease should be treated very early, whether or not they will need a transplant. "Eventually, the prevention of fragility fractures, and not the improvement of bone mineral density, is the ultimate clinical goal for patients with osteoporosis," the conclude, adding that future studies should explore other factors than those described in the present study, namely those that would help reduce the risk of falls and fractures.
David Greenberg | EurekAlert!
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