Natural History of Bone Disease following Kidney Transplantation
Authors: Jørgensen Hanne Skou , Behets Geert , Bammens Bert , Claes Kathleen , Meijers Bjorn , Naesens Maarten , Sprangers Ben , Kuypers Dirk R.J. , Cavalier Etienne , D’Haese Patrick , Evenepoel Pieter 
Published: January 2022

Significance Statement
The natural history of bone disease in contemporary kidney transplant recipients is not well characterized. Studies are generally limited by small samples sizes or a narrow focus on bone biopsy, imaging, or biochemistry. This prospective, observational study performed extensive bone phenotyping by histomorphometry, densitometry, and biomarkers before and after kidney transplantation in a sizable cohort. The main findings include decreasing bone turnover after kidney transplantation and, in parallel, decreasing levels of bone biomarkers. Delayed bone mineralization occurring in a subset of patients is associated with the duration and severity of hypophosphatemia. Resolution of hyperparathyroidism and high bone turnover are associated with gain in bone density. Thus, optimal control of mineral metabolism and regulation of skeletal remodeling could improve bone health in kidney transplant recipients.

Background
Knowledge of the effect of kidney transplantation on bone is limited and fragmentary. The aim of this study was to characterize the evolution of bone disease in the first post-transplant year.

Methods
We performed a prospective, observational cohort study in patients referred for kidney transplantation under a steroid-sparing immunosuppressive protocol. Bone phenotyping was done before, or at the time of, kidney transplantation, and repeated at 12 months post-transplant. The phenotyping included bone histomorphometry, bone densitometry by dual-energy x-ray absorptiometry, and biochemical parameters of bone and mineral metabolism.

Results
Paired data were obtained for 97 patients (median age 55 years; 72% male; 21% of patients had diabetes). Bone turnover remained normal or improved in the majority of patients (65%). Bone histomorphometry revealed decreases in bone resorption (eroded perimeter, mean 4.6% pre- to 2.3% post-transplant; P<0.001) and disordered bone formation (fibrosis, 27% pre- versus 2% post-transplant; P<0.001). Whereas bone mineralization was normal in all but one patient pretransplant, delayed mineralization was seen in 15% of patients at 1 year post-transplant. Hypophosphatemia was associated with deterioration in histomorphometric parameters of bone mineralization. Changes in bone mineral density were highly variable, ranging from –18% to +17% per year. Cumulative steroid dose was related to bone loss at the hip, whereas resolution of hyperparathyroidism was related to bone gain at both spine and hip.

Conclusions
Changes in bone turnover, mineralization, and volume post-transplant are related both to steroid exposure and ongoing disturbances of mineral metabolism. Optimal control of mineral metabolism may be key to improving bone quality in kidney transplant recipients.

Clinical Trial registry name and registration number:
Evolution of Bone Histomorphometry and Vascular Calcification Before and After Renal Transplantation, NCT01886950