Longitudinal Changes in BMD and Fracture Risk in Orthotopic Liver Transplant Recipients Not Using Bone-Modifying Treatment

Abstract

Osteoporosis is prevalent in end-stage liver disease, but data on long-term changes in bone mineral density (BMD) and related fracture incidence after orthotopic liver transplantation (OLT) are scarce. We evaluated BMD changes up to 5 years in consecutive recipients of a successful OLT at the Leiden University Medical Centre between 2000 and 2011, in whom sequential BMD data were available. Spinal radiographs were available at time of screening and at 6 and 12 months post-OLT and were assessed for vertebral fractures by two independent observers using Genant's semiquantitative method. Patients were excluded from the study when started on bisphosphonates. A total of 201 patients (71% men), median age 53 years (range, 18-70 years) were included in the study. Most common liver pathology was viral (27%) or alcoholic liver disease (25%). All patients received prednisone for at least 6 months after transplantation and the majority received either tacrolimus or cyclosporine for immunosuppression. At time of screening for OLT, osteoporosis and osteopenia were found in 18% and 36% of patients at the lumbar spine (LS), respectively, and in 9% and 42% at the femoral neck (FN), respectively. T-scores declined significantly at both sites 6 months after OLT, but increased thereafter at the LS, reaching pretransplantation values at 2 years and remaining stable thereafter. FN T-scores remained consistently lower than pretransplantation values. The prevalence of vertebral fractures increased from 56% at screening to 71% at 1 year after OLT, with a fracture incidence of 34%. BMD changes did not predict fracture risk. Osteoporosis, osteopenia, and vertebral fractures are prevalent in patients with end-stage liver disease. An overall decline in BMD is observed within the first 6 months after OLT, with subsequent recovery to pretransplantation values at the LS, but not at the FN. Vertebral fracture risk is high after OLT regardless of changes in BMD.

Trabecular bone score in patients with liver transplants after 1 year of risedronate treatment

“…Krol et al . , in 201 patients undergoing LT, observed a higher incidence of vertebral fractures (34%) 1 year after LT. However, in the last study, patients on treatment with bisphosphonates were excluded from the study and radiographs were blindly assessed by two experienced independent observers, which could explain the higher frequency of fractures found.…”

Guidelines for the diagnosis, prevention and management of osteoporosis

“…A large body of evidence is available on the association of some first generation anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone) with low bone mass, as well as with a 2-to 6-fold increased risk of hip fracture in patients with epilepsy, especially when polymedicated (47). The use of cyclosporine in transplanted patients is associated with an increase in clinical fractures that ranges from 10% to 34% in the first year of treatment (48). Long-term use of unfractioned heparin increases fracture risk by 2.5% to 5%, whereas there are no data on low molecular weight heparin.…”

A vitamin D protocol post‐liver transplantation

“…It is well established that compromised liver function will affect an individual's ability to synthesize VD (Arteh, Narra, & Nair, 2010;Autier & Gandini, 2007;Krol et al, 2014), thus causing vitamin D deficiency in patients with liver disease. The targeted population in this Doctor of Nursing Practice (DNP) project are transplanted patients with sub-optimal serum 25(OH)D levels.…”