Serum Phosphorus Levels and Fracture Following Renal Transplantation

Jasna Aleksova; Phillip Wong; William R. Mulley; Kay Weng Choy; Robert McLachlan; Peter R. Ebeling; Peter G. Kerr; Frances Milat


Clin Endocrinol. 2017;87(2):141-148. 

In This Article

Abstract and Introduction


Purpose Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders.[1] Low serum phosphorus levels occur post-transplantation; however, its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre.

Methods A retrospective cross-sectional analysis of 146 patients (75 M, 71 F) who had been referred for dual energy X-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression.

Results The mean age of patients was 54 years and mean time post-transplantation 6.7 years. A total of 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining femoral neck (FN) T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, estimated glomerular filtration rate and pre-transplant history of fracture (P=.011 and P=.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use.

Conclusion Fracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.


Kidney transplantation is the gold standard treatment for patients with end stage kidney disease (ESKD), with ensuing improvements in quality of life, reduced morbidity and mortality and reduced financial burden compared with dialysis.[2,3] Although renal transplantation can reverse many of the mineral and bone disturbances seen in ESKD, fractures post-transplant remain a significant complication.[4] Patients with ESKD have an increased risk of fracture compared with the general population; and hip fracture rates postrenal transplantation exceed those on dialysis.[4–6] Advancing age, pre-existing and persisting mineral and bone disorders as a consequence of ESKD, glucocorticoid immunosuppression, degree of graft function and underlying diabetes mellitus are recognized risk factors for fractures post-renal transplantation.[1]

Low bone mineral density (BMD) as measured by dual energy X-ray densitometry (DXA) is an established risk factor for fractures in the general population.[7] BMD declines rapidly in the first 6–12 months following renal transplantation and has been associated with increased fractures.[8] Studies of long-term changes in BMD post-transplantation show conflicting results, with studies demonstrating continued, stabilization or incremental changes in BMD.[9,10] DXA calculates a two dimensional areal BMD of a three dimensional structure, and therefore cannot provide information with respect to bone microarchitecture and bone quality that also contribute to bone strength and fractures.[11] Glucocorticoid immunosuppression, persisting mineral and bone disorders such as hyperparathyroidism and vitamin D deficiency may all compromise bone quality and fragility, and may not be appreciated on DXA imaging.[10,12] The validity of DXA imaging to predict fracture risk in the renal transplant population is not well established. Some studies have shown no significant association between BMD and vertebral fractures,[10] but others have demonstrated its prognostic value for fracture prediction.[13,14]

Although many mineral and bone disorders can persist or arise de novo post-transplantation, the role of phosphorus in post-transplant fractures has not been well evaluated. Hypophosphataemia is common in the early post-transplant period. Renal phosphate wasting occurs due to high levels of the two phosphaturic hormones, fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH).[15] Elevations in these hormones occur with declining renal function in an attempt to counter phosphate retention and maintain serum phosphorus homoeostasis.[16] At 1-year post-transplantation, most patients with good graft function normalize their serum phosphorus levels, with concomitant reduction in FGF-23 and PTH levels.[15] Despite normal serum phosphorus levels, persistent renal tubular phosphorus leak has been reported in patients for up to 10-year post-transplantation.[17,18] However, implications of low phosphorus levels on BMD and fractures in the short and longer term have not been specifically examined.

We, therefore, performed a cross-sectional study of adult renal transplant recipients (RTRs) to investigate the impact of bone-related biochemistry, clinical and DXA parameters on fractures.