Bone Disease After Liver Transplantation: A Long-Term Prospective Study of Bone Mass Changes, Hormonal Status and Histomorphometric Characteristics

Abstract

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre-transplant risk factors for fractures were age and low bone mass (odd's ratio for osteoporosis, 95% confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass.

Bone disease after transplantation: osteoporosis and fractures risk

“…It has been demonstrated that the bone health before transplantation may be a predictive factor of bone loss and fracture after the liver is transplanted (38). In fact, prospective studies show that the risk of post-transplantation bone loss and fractures were related to age, pre-transplantation BMD and previous vertebral fracture as well as menopause status (39,40). Bone turnover has been reported to be low in many patients with liver failure; however, there is conversion to a high turnover state after liver transplantation that persists afterward.…”

“…The progression of bone loss seen after liver transplantation is similar to that following lung and cardiac transplantation, being more severe in the first 6 months. One bone histomorphometry study showed that bone loss stops around 6 month, followed by a gain of bone mass, mainly at cancellous bone, in the first 2 years after the liver transplantation (39). This increase in BMD is significant higher among premenopausal than perimenopausal and postmenopausal women, probably due the protective estrogen effect to the skeleton (40).…”

Osteoporosis after liver transplantation

“…[6][7][8][9][10][11][12][13][14][15] Most of these fractures occurred in the spine; however, since in some of these studies spinal X-rays were not routinely performed, the true number of vertebral fractures is likely to have been underestimated. In some studies, however, lower fracture rates have been reported.…”

“…7,8,15,17,[20][21][22][23][24][25] Bone loss affects the spine and the proximal femur, some studies suggesting greater bone loss at the latter site. 17,18,26 The majority of studies indicate that there is at least some recovery of bone mineral density after the first year or so of transplantation, although this finding has not been universal.…”

The safety and outcome of joint replacement surgery in liver transplant recipients

“…In the first 6 months after OLT, bone mineral density (BMD) significantly declines, and this decline often is accelerated by immunosuppressive medications, corticosteroids, and immobility. [3][4][5][6] After 6 months, BMD increases rapidly and, by 12 months, approaches pre-OLT values. 6 However, some patients continue to lose BMD greater than 24 months after OLT and are at risk for osteoporotic fractures.…”