Osteoporosis following solid organ transplantation

Damaris Vega & Khashayar Sakhaee† †Author for correspondence University of Texas Southwestern Medical Center, Department of Internal Medicine and, Charles & Jane Pak Center for Mineral Metabolism & Clinical Research, 5323 Harry Hines Boulevard, Dallas, TX 75390-8885, USA Tel.: +1 214 590 7783; Fax: +1 214 590 4091; khashayar.sakhaee@utsouth western.edu ‘Despite the introduction of new immunosuppressive regimens designed for renal allograft recipients ... post-transplantation bone disease remains a major complication in this population.’ Since the introduction of new immunomodulatory agents, the number of organ transplants has increased significantly worldwide. Approximately 28,000 subjects received solid organ transplants in the USA from 2005 to 2006 [101] – approximately double the number of solid organ transplants performed in 1988. Despite the introduction of new immunosuppressive regimens designed for renal allograft recipients, including cyclosporine and tacrolimus, post-transplantation bone disease remains a major complication in this population. It was once thought that the introduction of these new immunomodulatory agents and the limited use of glucocorticoids would ameliorate this complication. However, the sustained loss of bone mineral density and spontaneous bone fractures remain a major cause of morbidity in these subjects [1–5]. The pathophysiologic mechanisms responsible for osteoporosis following organ transplantation are diverse and multifactorial [6]. The most common responsible factors include the underlying conditions leading to transplantation, lifestyle and nutritional changes, hormonal dysregulations, including abnormalities in calcitropic and gonadal hormones, and the skeletal effects of immunomodulatory agents [7–9]. Most commonly, medical immunosuppression has been implicated as the leading catalyst in the development of post-transplantation bone disease [10–13]. However, various renal, hepatic, cardiac and pulmonary diseases also have specific pathophysiologies that may contribute to the outcome of bone disease in this population [14–33]. Careful consideration should be given to the unique clinical picture of each individual patient before and after transplantation. Such a characterization will facilitate optimal management of this diverse group of patients to decrease the incidence of bone fractures and ultimately improve their quality of life. Bone disease is commonly encountered in chronic renal failure patients who experience a continual decline in renal function. Secondary hyperparathyroidism may persist following successful renal transplantation and potentially accentuate the adverse effects of immunosuppressive drugs on the development of bone disease [34]. In addition, the synergistic effect of parathyroid hormone and elevated serum concentrations of phosphatonins, including FGF-23, which has been demonstrated to be elevated after renal transplantation, result in renal phosphorus wasting by reducing renal tubular reabsorption [35–38]. Persistent phosphorus depletion will potentially contribute to defective bone mineralization and progression to osteomalacia and low bone turnover. However, these complications have been largely unnoticed. Therefore, the magnitude of skeletal abnormalities following renal transplantation are much broader than in other solid organ transplantations [39]. These factors may be partly responsible for the continued loss of bone mineral density and increased cumulative risk of new fractures following renal transplantation [3]. Moreover, glucocorticoid treatment, by uncoupling of bone resorption and bone formation, may attenuate the recovery of an impaired bone turnover caused by adynamic bone disease − the most predominant skeletal lesion encountered in patients during dialysis treatment [11,31,40–42].