Evaluation of the Efficacy and Tolerability of Alendronate Versus Denosumab in Kidney Transplant Patients With Reduced Bone Mineral Density

Patients with chronic kidney disease (CKD) exhibit a complex form of bone disease defined by KDIGO as "Mineral and Bone Disorder" (CKD-MBD). CKD-MBD generally encompasses two pathological disorders, namely vascular calcification and renal osteodystrophy, which is the bone health impairment associated with chronic kidney disease. Among the complications associated with renal osteodystrophy, hip or vertebral fractures are associated with an increase in morbidity and mortality in patients with end-stage kidney disease.

CKD-MBD is a systemic disease that links disorders of mineral and bone metabolism due to CKD to either one or all of the following: abnormalities of calcium, phosphorus, parathyroid hormone or vitamin D metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Consequently, since bone status in recently transplanted patients reflects several years of CKD-MBD, it would be useful to assess bone status in this population.

The management of bone disease has often been neglected post-transplantation, when the clinical focus is on allograft function and immunological sequelae. However, most renal transplant recipients (RTRs) have pre-existing CKD-MBD, which results in changes to mineral metabolism and reduced bone mineral density (BMD) and quality, which are linked to an increased incidence of fractures and cardiovascular disease. Pre-existing renal osteodystrophy, including adynamic bone disease, is further affected post-transplantation by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable renal allograft function and post-transplantation diabetes mellitus.

Successful renal transplantation corrects many metabolic abnormalities associated with the development of renal osteodystrophy. However, osteopenia and osteoporosis remain prevalent, even in patients with well-functioning grafts. Increasing attention has focused on preventing late complications of transplantation and on patient quality of life by addressing factors affecting long-term morbidity, such as cardiovascular risk, post-transplantation diabetes mellitus, cancer, and bone disease.

The spectrum of bone diseases in kidney transplant recipients includes renal osteodystrophy, osteoporosis, bone fracture, and osteonecrosis. Earlier studies after transplantation indicate that BMD declines by 4%-10% in the first 6 months, with a further decrease of 0.4%-4.5% in lumbar BMD between 6 and 12 months. After 1 year, BMD remains relatively stable with no further decline but at significantly lower levels than healthy controls. This reduction in BMD contributes to an increased risk of fractures.