Osteoporosis in the adult solid organ transplant population: underlying mechanisms and available treatment options

Abstract

The prevention and treatment of osteoporosis is an increasingly important topic in the solid organ transplant (SOT) population. Compared to the general population, these patients are at an elevated risk of developing osteoporosis due to progressive disease, lifelong immunosuppressant therapy, and malnutrition. As patients live longer after transplant, chronic disease management is increasingly more important. Supplementation with calcium and vitamin D is often necessary in the SOT population due to a high incidence of vitamin D deficiency. Bisphosphonate therapy is most commonly used for prevention and treatment of osteoporosis, but therapy can be limited by renal dysfunction which is common in transplant recipients. Alternative agents such as teriparatide and calcitonin have not been shown to provide a significant impact on the rate of fractures in this population. Additionally, denosumab may be a promising treatment option due to its novel mechanism of action, and is currently being studied in renal transplant patients. Timely initiation of supplementation and treatment, and minimizing glucocorticoid exposure prior to and after transplantation will aid in the prevention and proper management of osteoporosis in these patients.

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

“…Immunosuppressive treatments for cGVHD have been shown to contribute to the development of osteoporosis (6, 13-17); however, it would also be of interest to determine whether control of cGVHD can prevent osteoporosis or improve recovery in affected sites. In addition, further study is needed to improve our understanding of the differential pathogeneses of osteoporosis at separate sites and how these events and subsequent recoveries are influenced by various events over the course of the post-transplant period.…”

“…Contributing factors include myeloablative conditioning, secondary hypogonadism, abnormal metabolism of calcium and vitamin D, reduced mobility, and use of immunosuppressive medications such as glucocorticoids and calcineurin inhibitors (6, 11-14). These last two drug classes are associated with altered metabolism and absorption of calcium, phosphate, and vitamin D, and trabecular bone loss at the spine and femoral neck (6, 13-17). In addition, hyponatremia, an emerging contributor to osteoporosis, has been reported after allo-HSCT (18-20).…”

Acute hypocalcaemia following denosumab in heart and lung transplant patients with osteoporosis

“…As denosumab suppresses bone resorption it may be necessary to maintain serum calcium values in patients with CKD stages 3 and 4 by using oral calcium supplements and maintaining adequate 25‐hydroxvitamin D levels or by using calcitriol or its analogs. A recent review of osteoporosis management in the transplant population recommended that, due to the high prevalence of vitamin D insufficiency, all transplant patients should maintain serum 25‐hydroxyvitamin D levels >75 mmol/L . However, given that the conversion of 25‐hydroxyvitamin D to its active form is progressively impaired from creatinine clearance less than 70 mL/min, calcitriol may be a more effective supportive therapy than cholecalciferol in denosumab‐treated patients with more severely impaired kidney function .…”

“…A recent review of osteoporosis management in the transplant population recommended that, due to the high prevalence of vitamin D insufficiency, all transplant patients should maintain serum 25-hydroxyvitamin D levels >75 mmol/L. 31 However, given that the conversion of 25-hydroxyvitamin D to its active form is progressively impaired from creatinine clearance less than 70 mL/min, calcitriol may be a more effective supportive therapy than cholecalciferol in denosumab-treated patients with more severely impaired kidney function. 32 Calcitriol may act by improving glucocorticoid induced decreases in intestinal calcium absorption, so limiting the resultant secondary hyperparathyroidism.…”

Transplantationsosteoporose

“…Unabhängig von den bereits vorbestehenden Vorschädigungen des Knochens durch die terminale Organschädigung kommt es nach der Transplantation (TX) zu weiteren negativen Effekten auf den Knochen (12).…”