Are Solid Organ Transplant Patients the New Unsuspecting Osteonecrosis Victims?

Abstract

Purpose Bone disease is common in organ transplant recipients. Immunosuppressive regimens with glucocorticoids have shown to improve patient and graft survival rates following transplantation. As survival rates have improved, so has awareness of long-term complications of transplantation. Pre-existing bone disease combined with immunosuppressive agents serve as primary risk factors for osteoporosis and fractures. Recently, supplementation of the traditional medical regimen with bisphosphonates and denosumab has become necessary to counteract the adverse effects of long-term steroid use. Although it does enhance bone mineral density, bisphosphonate therapy has failed to result in a significant decrease in the fracture rate. We propose an individualized approach aimed at managing bone loss and fracture rates in transplant patients. Methods This study, an evidence-based review, aims to provide a better understanding of the risk factors associated with osteoporosis, incorporating the bone effects of glucocorticoids and antiresorptive medications. We first developed several specific research questions, assorted questions by category, devised an approach to identify appropriate sources in the organ transplant literature, and selected a list of possible articles to review. We completed an initial review to limit the set to 55 articles and then conducted a thorough review, including the current guidelines provided by the American College of Rheumatology for management of bone disease, and the American Association of Oral and Maxillofacial Surgeons for prevention and treatment of osteonecrosis of the jaw. Furthermore, we have summarized our findings to synthesize an improved patient-centered protocol to help limit the indiscriminate use of antiresorptive medications, and strategies for appropriate dental management pre- and post-transplantation. Results Bisphosphonates and other antiresorptive medications reduce excessive turnover of bone, resulting in enhanced bone mineral density (BMD). These medications have become part of the typical treatment regimen for patients in the post-transplantation period to counteract the negative effects of high-dose steroids, despite the lack of evidence that preservation in BMD translates to decreased fracture risk. Although the risk of medication-related osteonecrosis of the jaw (MRONJ) is low, the diagnosis and the sequelae can be devastating and difficult to treat in advanced stages. Conclusions The best method of prevention lies in an evidence-based multidisciplinary approach to ensure that the solid organ transplant patients administered these medications do not become the new MRONJ victims. This should include, but not be limited to, evaluation by a dental professional familiar with antiresorptive medications and bisphosphonates and their adverse effects on the craniofacial skeletal tissues, minimizing steroid use, adequate supplementation of vitamin D in patients with vitamin D deficiency, and careful targeted use of bisphosphonates and denosumab only in those patients where it is mandatory. Although the prevalence of MRONJ among transplant recipients remains to be studied, it behooves providers to help protect these patients from unnecessary harm.