Chronic Kidney Disease Stage 5D (CKD-5D) imparts a 4-fold increase in minimal trauma fracture with a substantial increase in mortality following hip fracture. Bone disease in CKD is complex, characterised by abnormal levels of PTH, calcium, phosphate, ALP, and vitamin D, manifesting as a condition known as CKD-Mineral and Bone Disorder (CKD-MBD). While bisphosphonates (BP) are the gold-standard in the management of osteoporosis, their therapeutic role when end-stage renal function and bone disease co-exist remains unclear. This 15-year retrospective cohort study examines the long-term use of BPs in 148 CKD patients receiving haemodialysis and renal transplant in a tertiary centre in Sydney, Australia. In multivariate regression adjusting for age, baseline BMD and fracture incidence, BPs increased bone density in renal transplant recipients over a mean treatment period of 3.5 years (net annual BMD gain of 0.039 g/cm2, p=0.005). No such benefit was seen in BMD in subjects on haemodialysis and treated with BPs (net annual BMD gain of 0.008 g/cm2, p=0.62). BP therapy did not result in significant changes in biochemical parameters (ALP, PTH, and phosphate) and there was no evidence that BPs resulted in adynamic bone disease in CKD over the 15-yr period. Whilst a significant decline in eGFR in haemodialysis patients on BPs was noted, no such effect was seen in transplant recipients. BPs are generally safe and effective in CKD5, mitigating bone loss in kidney transplant recipients without increasing the risk of adynamic bone disease or transplant failure over the 15-year study period.