Incidence of vertebral fractures in the first three months after orthotopic liver transplantation.

BACKGROUND AND OBJECTIVES: High rates of bone loss and increased fracture incidence have been reported in patients undergoing liver transplantation, mainly within the first post-operative year. The pathogenesis of post-transplantation bone disease has not been clearly established, but the high doses of glucocorticoids used for immunosuppression may contribute. The use of lower doses in recent years has been associated, in some studies, with lower rates of bone loss and decreased fracture incidence. The aim of this prospective study was to establish the incidence of vertebral fractures in the first 3 months in patients undergoing liver transplantation for chronic liver disease and to identify risk factors for fracture in these patients. DESIGN AND METHODS: Thirty-seven adults with end-stage liver disease were studied prospectively prior to and 3 months after liver transplantation. Vertebral fractures were assessed semi-quantitatively from lateral spine X-rays and bone mineral density measured using dual energy X-ray absorptiometry. RESULTS: Prior to transplantation, prevalent vertebral fractures were present in 13 patients (35%). New fractures developed after transplantation in 10 patients (27% of total) and were significantly more common in those with a prevalent vertebral fracture pre-operatively (P<0.02). Osteoporosis, defined as a bone mineral density T score below -2.5, was present in 39% of patients prior to transplantation, but bone mineral density was not helpful in predicting incident fracture, whether measured before or after transplantation. Over the 3-month study period, significant bone loss occurred in the femoral neck (P<0.05) but not the lumbar spine. CONCLUSIONS: Our results demonstrate a high incidence of vertebral fracture in the first 3 months after liver transplantation and indicate that prevalent vertebral fracture is an important risk factor for the subsequent development of fracture in these patients. Prevention of post-transplantation bone disease should focus both on optimizing bone mass prior to transplantation and preventing bone loss in the early post-operative period.

Mechanism of bone loss after liver transplantation: A histomorphometric analysis.

Organ transplantation is associated with increased bone loss and high fracture risk, but the pathophysiological mechanisms responsible have not been established. We have performed a histomorphometric analysis of bone remodeling before and 3 months after liver transplantation in 21 patients (14 male, 7 female) aged 38-68 years with chronic liver disease. Eight-micrometer undecalcified sections of trans-iliac biopsies were assessed using image analysis. 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 microm2/microm/day after transplantation (p < 0.0002) and activation frequency from 0.24 +/- 0.21/year-1 to 0.81 +/- 0. 67/year-1 (p < 0.0001). No significant change was observed in wall width, but there was a trend toward an increase in indices of resorption cavity size. There was a small increase in osteoid seam width postoperatively (p< 0.02) and decrease in mineralization lag time (p < 0.001). No significant changes in indices of cancellous bone structure were observed in the postoperative biopsies. These results demonstrate a highly significant and quantitatively large increase in bone turnover in the first 3 months after liver transplantation. Although no significant disruption of cancellous bone structure was demonstrated during the time course of the study, the observed changes in bone remodeling predispose to trabecular penetration and may thus result in long-term adverse effects on bone strength.

Testosterone concentrations in men on chronic glucocorticosteroid therapy.

To determine whether free (or active) testosterone concentrations are reduced in men receiving glucocorticosteroids for chronic inflammatory diseases, 17 men (mean age 55.5 years) receiving a mean daily dose of 16.3 mg prednisolone, and 13 control patients (mean age 52.2 years) receiving no prednisolone, were studied. Serum testosterone and the testosterone/sex hormone binding globulin (SHBG) ratio were measured. The testosterone/SHBG ratio (a measure of free (active) testosterone) was significantly reduced in patients treated with prednisolone (p = 0.026), thus showing that glucocorticosteroids reduce free testosterone in male patients. This may be an important cause of glucocorticosteroid-induced osteoporosis, and suggests an additional approach to bone prophylaxis and treatment.

Cyclical etidronate increases lumbar spine bone density in patients on long-term glucocorticosteroid therapy.

To determine whether cyclical etidronate modifies bone density in patients on chronic glucocorticosteroid therapy, annual bone density measurements were performed on 55 patients receiving glucocorticosteroids who were randomised to either continuous calcium supplementation or cyclical etidronate plus calcium supplementation in this secondary prevention study. Median L1-L4 lumbar spine bone density decreased by 0.7% in the calcium treated group after one year but increased by 3.1% in the group treated by calcium and etidronate (p = 0.00116). Median L1-L4 bone density decreased by 2.8% from baseline after two years in the calcium treated group but increased by 4.7% from baseline in the group treated by calcium and etidronate (p = 0.04). There were no significant effects of treatment on femoral neck density. Cyclical etidronate and calcium increased lumbar spine bone density in patients established on prednisolone treatment over a two-year period but had no effect on femoral density.

Early increase in plasma parathyroid hormone levels following liver transplantation.

BACKGROUND/AIMS: The pathogenesis of post-transplantation bone loss is poorly understood, although glucocorticoid therapy is believed to play an important role. In the present study we have measured plasma parathyroid hormone concentrations in the first few months after orthotopic liver transplantation, in order to examine the potential contribution of hyperparathyroidism to bone disease. PATIENTS AND METHODS: Twenty-seven patients aged 32-54 years, 12 male, undergoing liver transplantation were studied prospectively before and for 3 months after operation. Plasma parathyroid hormone and serum 25-hydroxyvitamin D concentrations were measured by radioimmunoassay. RESULTS: Plasma parathyroid hormone levels were normal in all but two patients prior to transplantation. There was a highly significant increase in plasma parathyroid hormone concentrations at 1 and 2 months (p < 0.0005 and 0.001, respectively, versus baseline); by 3 months, values were close to those obtained preoperatively. Serum 25-hydroxyvitamin D concentrations showed no significant change over the study period. However, 74% of the patients had subnormal values at baseline. CONCLUSIONS: An early and transient increase in plasma parathyroid hormone after liver transplantation may be responsible for the high rates of bone loss which occur during the first few post-operative months. Prevention of post-transplantation bone disease is most likely to be achieved by peri-operative intervention with an anti-resorptive agent.

Treatment of Paget's disease of bone with single dose intravenous pamidronate.

OBJECTIVES: To assess the efficacy of a single intravenous infusion of pamidronate in Paget's disease of bone. METHODS: Fourteen patients with active Paget's disease (raised serum alkaline phosphatase, bone pain or neurological involvement) were treated with a single intravenous infusion of 105 mg pamidronate. Patients were assessed for biochemical and clinical improvement for up to two years following treatment. A further infusion was given following symptomatic relapse (pain at a known site of pagetic involvement). RESULTS: Serum alkaline phosphatase fell following treatment, with a nadir 5.9 months after treatment. Bone pain was improved in nine of 12 patients after six months. Retreatment of four patients resulted in a similar response. CONCLUSION: Single dose intravenous pamidronate (105 mg) is a convenient and effective treatment for Paget's disease.

Giant cell tumours in mandible and spine: a rare complication of Paget's disease of bone.

The case of a man who was diagnosed as having polyostotic Paget's disease at the age of 52 years is described. He developed a rare neoplastic complication of Paget's disease--a giant cell tumour in his mandible, which was excised. Nine years after the diagnosis of this tumour he developed a new giant cell tumour arising from the L3 vertebral body. He was born in Avellino in Italy, from where five other cases of giant cell tumours arising from Pagetic bone disease have been reported. No family relationship between our patient and the other cases was established. His Paget's disease was particularly aggressive and resistant to treatment with two single high dose infusions of pamidronate almost two years apart.