Abstract
Osteoporosis and fragility fractures represent serious complications for the solid organ transplant population. The recommended osteoporosis therapy for organ recipients involves supplementation with calcium and vitamin D and bisphosphonate administration. However, these options can prove limited for patients with impaired renal function. An alternative therapy option is offered by denosumab, a monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand. We evaluated 63 patients with osteoporosis (23 males and 40 females, age 56.4 ± 13.1 years) following solid organ transplantation (15 diabetic patients after simultaneous transplantation of the kidney and pancreas, 34 patients after kidney transplantation, and 14 patients with liver grafts). Osteoporosis was diagnosed according to standard DEXA examination using the Lunar Prodigy apparatus. Transplanted patients with impaired renal function were treated for osteoporosis of the lumbar spine (L-spine) and/or proximal femur with calcium and vitamin D supplementation and 60 mg of denosumab every 6 months between the years 2012 and 2017. The mean duration of the therapy was 1.65 ± 0.7 years. After denosumab therapy, L-spine T-scores improved across the whole group, ranging from -2.7 ± 0.09 to -1.8 ± 1.0 (p < 0.001). T-score values for the proximal femur increased from -2.5 ± 0.8 to -2.0 ± 0.7 after the therapy (p < 0.01). We observed only a mild, statistically insignificant improvement in distal forearm T-scores. The mean increase in L-spine bone mineral density (BMD) was 11.5 ± 6.2% in subjects with osteoporosis at this site and 10.4 ± 6.1% in the case of all patients. BMD of the proximal femur increased by 10.4 ± 8.3% in patients with osteoporosis and by 7.5 ± 7.3% in all patients. Denosumab therapy decreased the prevalence of osteoporosis in the L-spine from 75 to 27% (p < 0.001) and proximal femur osteoporosis from 54 to 36% (p < 0.05). Denosumab therapy reduced elevated levels of osteocalcin and beta-crosslaps (βCTX) in comparison with baseline levels (p < 0.001) across the whole group of graft recipients. Denosumab therapy was well-tolerated and improved bone density in our group of solid organ transplant recipients. The indications are that denosumab could be a viable therapeutic option for transplanted patients with osteoporosis, especially in those with renal function impairment or bisphosphonate intolerance.
Highlights
Osteoporosis is among the complications that have become more prevalent with the increased survival of patients after solid organ transplantation (Tx)
The median estimated glomerular filtration rate measured in all patients at the beginning of the therapy [0.55 mL/s/1.73 m2] did not differ from the median CKD-EPI values measured at the end of denosumab administration [0.55 mL/s/1.73 m2]
Osteoporosis therapy of patients with renal impairment was limited to the adjustment of calcium-phosphate metabolism and vitamin D levels, to the management of secondary hyperparathyroidism and to optimizing the maintenance of immunosuppressive therapy
Summary
Osteoporosis is among the complications that have become more prevalent with the increased survival of patients after solid organ transplantation (Tx). The pathogenesis of transplantassociated osteoporosis is multifactorial and involves altered bone metabolism during the pre-transplant period, posttransplant bone loss caused by immunosuppressive therapy and corticosteroids, persistent hyperparathyroidism (in renal graft recipients), and vitamin D deficiency [1]. The common complications of immunosuppressive therapy include the following: infections, malignancies, kidney damage, and skeletal impairment with increased risk of bone fracture [2,3,4]. Further bone loss is associated with persistent hyperparathyroidism, which mainly occurs in kidney graft recipients [10], vitamin D deficiency, rejection episodes, and persistent impairment of graft function [11, 12]. The aim of our study was to provide data on the efficacy of denosumab treatment in subjects after solid organ transplantation and to redress the scarcity of investigative data on its use in these subjects far [14, 15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
