Elevated Incidence of Fractures in Solid-Organ Transplant Recipients on Glucocorticoid-Sparing Immunosuppressive Regimens

Abstract

This study was conducted to assess the occurrence of fractures in solid-organ transplant recipients. Methods. Medical record review and surveys were performed. Patients received less than 6 months of glucocorticoids. Results. Of 351 transplant patients, 175 patients provided fracture information, with 48 (27.4%) having fractured since transplant (2–6 years). Transplants included 19 kidney/liver (50% male), 47 kidney/pancreas (53% male), 92 liver (65% male), and 17 pancreas transplants (41% male). Age at transplant was 50.8 ± 10.3 years. Fractures were equally seen across both genders and transplant types. Calcium supplementation (n = 94) and bisphosphonate therapy (n = 52) were observed, and an association with a lower risk of fractures was noted for bisphosphonate users (OR = 0.45 95% C.I. 0.24, 0.85). Fracture location included 8 (16.7%) foot, 12 (25.0%) vertebral, 3 (6.3%) hand, 2 (4.2%) humerus, 5 (10.4%) wrist, 10 (20.8%) fractures at other sites, and 7 (14.6%) multiple fractures. The estimated relative risk of fracture was nearly seventeen-times higher in male liver transplant recipients ages 45–64 years compared with the general male population, and comparable to fracture rates on conventional immunosuppressant regimens. Conclusion. We identify a high frequency of fractures in transplant recipients despite limited glucocorticoid use.

Kidney Transplantation with Early Corticosteroid Withdrawal

“…The secondary analyses conducted to date raise concerns about the preconception that ECSW regimens would substantially lower fracture risk. [15][16][17][18] Trials by Woodle et al 17 and Rizzari et al 16 found no difference in fracture rates. However, fractures were a secondary outcome, and spine fractures, among the most common types of post-transplant fractures, 4 were not ascertained.…”

“…However, fractures were a secondary outcome, and spine fractures, among the most common types of post-transplant fractures, 4 were not ascertained. A retrospective study by Edwards et al 18 found that corticosteroid withdrawal did not result in a fracture reduction benefit. However, the corticosteroid withdrawal regimens in the study were not reflective of current ECSW protocols, and the patient population was not reflective of most patients managed with ECSW: patients were managed with up to 6 months of corticosteroids, had type 1 diabetes, and received simultaneous kidneypancreas transplantation.…”

“…10,11 Several trials suggested that they are associated with a stabilization of or an increase in areal BMD at the spine and hip. [12][13][14] However, recent data suggest that management with ECSW may result in only minimal 15 or no [16][17][18] protection against fractures. These studies suggest that our understanding of fracture pathogenesis after transplantation is incomplete, that fracture risk with ECSW may be independent of changes in areal BMD measured at the spine and hip, and that ECSW may be associated with abnormalities in bone quality that are not detected by dual energy x-ray absorptiometry (DXA).…”

Osteoporosis in Organ Transplant Patients

“…However, a small study of kidney transplant recipients detected no difference in bone loss between those who received CsA monotherapy and those who received azathioprine plus prednisolone [45] and a prospective study found that cumulative CsA dose was associated with bone loss in the 2 years following transplant, independent of the effect of steroids [46]. In a study of patients on GC-sparing regimens, less than 6 months of GCs after transplant, 27% sustained a fracture, similar to rates in patients on conventional GC-containing regimens [47].…”

Management of mineral and bone disorders in renal transplant recipients

“…In a large observational study of 77 430 RTRs who were followed for a median of 3.9 years, glucocorticoid withdrawal was associated with a 31 % reduction in fracture risk, and the incidence of fractures was higher in those patients taking glucocorticoids when discharged . In a smaller study of 175 solid organ transplants recipients, those with limited glucocorticoid exposure had similar fracture rates to those on conventional immunosuppressive protocols . Glucocorticoid withdrawal in RTRs has also been associated with improved BMD parameters 1‐year post‐transplantation .…”