Mechanism of bone loss after liver transplantation: A histomorphometric analysis

Organ transplantation is associated with increased bone loss and high fract ure risk, but the pathophysiological mechanisms responsible have not been e stablished. We have performed a histomorphometric analysis of bone remodeli ng before and 3 months after liver transplantation in 21 patients (14 male, 7 female) aged 38-68 years with chronic liver disease. Eight-micrometer un decalcified sections of trans-iliac biopsies were assessed using image anal ysis. Preoperatively, bone turnover was low with a tendency toward reduced wall width and erosion depth. The bone formation rate increased from 0.021 +/- 0.016 (mean +/- SD) to 0.067 +/- 0.055 mu m(2)/mu m/day after transplan tation (p < 0.0002) and activation frequency from 0.24 +/- 0.21/year(-1) to 0.81 +/- 0.671 year(-1) (p < 0.0001). No significant change was observed i n wall width, but there was a trend toward an increase in indices of resorp tion cavity size. There was a small increase in osteoid seam width postoper atively (p < 0.02) and decrease in mineralization lag time (p < 0,001), No significant changes in indices of cancellous bone structure were observed i n the postoperative biopsies. These results demonstrate a highly significan t and quantitatively large increase in bone turnover in the first 3 months after liver transplantation. Although no significant disruption of cancello us bone structure was demonstrated during the time course of the study, the observed changes in bone remodeling predispose to trabecular penetration a nd may thus result in long-term adverse effects on bone strength.