Bone Density Wanes and Waxes After Liver Transplantation

ROCHESTER, Minn. Sept. 6 -- Despite serious early bone loss after liver transplantation, bone mineral density then increased for up to four years and remained above pre-transplant levels, researchers here reported.

The development of fractures after liver transplantation results from a combination of preexisting low bone mineral density and early post-transplant bone loss, the risk factors for which are poorly defined, said J. Eileen Hay, M.D., of the Mayo Clinic, and colleagues.

In a study of 360 consecutive adult patients undergoing liver transplantation at Mayo from 1985 to 2001, only 23% of the patients had preexisting normal bone mass, they reported in the September issue of Liver Transplantation. All patients had end-stage primary biliary cirrhosis and primary sclerosing cholangitis.

Fortunately, Dr. Hay added, this first postoperative year represents the nadir in bone density and a recovery of bone mass starts to occur after the early months of bone loss.

At four months post-transplant, the rate of osteoporosis and osteopenia increased abruptly (? of mean T score, -0.42 ) to base line in all patient groups with an average 5% bone loss, a high rate rarely seen in other clinical situations, the researchers said. Men and women were equally affected, and the rate of loss during this period did not change with time, despite changes in immunosuppressive regimens, the researchers said.

Risk factors for low spinal bone density are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase, and low serum albumin, the researchers said. Factors that may contribute to early bone loss include high doses of glucocorticosteroids and disturbances of mineral metabolism, they added.

A high rate of spinal bone loss occurred in the first four post-transplant months (annual rate 16%) especially among those who were younger, had primary sclerosing cholangitis, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, were current smokers, and had ongoing cholestasis.

However, even though 51% of the patients had osteoporosis four months after transplant, bone mineral density increased over the next two years, and continued to increase at four and eight years (? of mean T score + 0.22 and + 0.20, respectively).

Factors favoring spinal bone gain from four to 24 months were lower baseline and/or four-month bone density, premenopausal status, lower cumulative doses of glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone.

Bone mass therefore improves most in patients with the lowest pre-transplant bone density who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status, the researchers wrote.

Referring to the 17-year time-span for the study, the researchers noted that patients transplanted more recently have improved bone mass before surgery, and although bone loss still occurs early after transplantation, the improvement in bone density is greater in the years following surgery.

This improvement, the researchers said, may be due in part to better nutritional status, increased body mass index, increased vitamin D, and less cholestasis.

In addition, Dr. Hay said, patients with osteoporosis or osteopenia can be expected to gain bone mass for at least eight years, despite getting older.

In an editorial in the same issue, Wolfram Karges, M.D., and Christian Trautwein, M.D., of RWTH University Hospital Aachen in Germany wrote that the Mayo study yielded a clear picture of the natural history of bone mass in patients with cholestatic disease and liver transplantation.

The cause of rapid bone loss immediately after transplantation is not completely understood, they said, but postop immobility and high-dose glucocorticoid treatment are likely to play a role.

However, this is not the time to relax, they wrote. It has been shown that low bone density and the presence of vertebral factures are strong predictors of post-transplant fragility fractures. Therefore, efforts to optimize and preserve lifetime bone mass should be started very early in all patients whether or not they will need a transplant, they advised.

"Eventually, the prevention of fragility fractures, and not the improvement of bone mineral density, is the ultimate clinical goal for patients with osteoporosis," they wrote. Finally, they added, "it seems prudent to reconsider and optimize other factors that help reduce the risk of falls, fractures, and their detrimental consequences."