Background: Over the past decade, the management of chronic kidney disease-mineral and bone disorder has changed substantially, altering the pattern of bone disease in chronic kidney disease. We aimed to evaluate the natural history of kidney bone disease in contemporary kidney transplant recipients and dialysis patients. Design, settings, participants, and measurement: Sixty-one dialysis patients referred to kidney transplantation participated in this prospective cohort study during November 2009 and December 2010. We performed baseline bone biopsies while the patients were on dialysis and repeated the procedure in 56 patients two years after kidney transplantation or two years after baseline if transplantation was not performed. Measurements of mineral metabolism and bone turnover as well as dual energy X-ray absorptiometry scans were obtained concurrently. Results: 37 of 56 participants received a kidney transplant, of which 27 underwent successful repeat bone biopsy. The proportion of patients with high bone turnover declined from 63% at baseline to 19% two years after kidney transplantation, while the proportion of those with low bone turnover increased from 26% to 52%. Of 19 participants remaining on dialysis after two years, 13 underwent successful repeat biopsy. The proportion of patients remaining on dialysis with high bone turnover decreased from 69% to 31%, and low bone turnover increased from 8% to 38%. Abnormal bone mineralization increased in transplant recipients from 33% to 44%, but decreased in patients remaining on dialysis from 46% to 15%. Trabecular bone volume showed little change after transplantation, but low bone volume increased in patients remaining on dialysis. Bone mineral density did not correlate with histomorphometric findings. Conclusions: Bone turnover decreased over time both in patients remaining on dialysis and in kidney transplant recipients. Bone mineral density and bone biomarkers were not associated with bone metabolism changes detected in bone biopsy.

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a dynamic imaging technique that measures turnover. 18F-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a 18F-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche’s historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1–L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, 18F-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD.

Anecdotal evidence suggests that azithromycin is effective for the treatment of cyclosporine-induced gingival hyperplasia in solid-organ transplant recipients. We present the cases of two heart transplant patients who insidiously developed gingival hyperplasia, likely because of immunosuppression with cyclosporine, which was treated with azithromycin. Evidence supporting the efficacy of azithromycin in the treatment of cyclosporine-induced gingival hyperplasia in solid organ transplant recipients was searched for, identified, and then critically assessed. While no data were found specifically evaluating azithromycin in cardiac transplant patients, there were nine pertinent papers identified that evaluated the clinical question of interest in the renal transplant population [Wahlstrom et al. (1995) The New England Journal of Medicine 332, 753; Boran et al. (1996) Transplantation Proceedings 28, 2316; Gomez et al. (1997) Nephrology Dialysis Transplantation 12, 2694; Ljutic (1997) Dialysis & Transplantation 26, 787; Puig et al. (1997) Transplantation Proceedings 29, 2379; Nash et al. (1998) Transplantation 65, 1611; Nowicki et al. (1998) Annals of Transplantation 3, 25; Wirnsberger et al. (1998) Transplantation Proceedings 30, 2117; Citterio et al. (2001) Transplantation Proceedings 33, 2134]. These studies and case reports are summarized. While more evidence is required to support routine use of azithromycin for the treatment of cyclosporine-induced gingival hyperplasia in cardiac transplant recipients, preliminary published evidence from renal transplant patients is certainly favourable.

Low bone volume and changes in bone quality or microarchitecture may predispose individuals to fragility fractures. As the dominant component of the human skeleton, cortical bone plays a key role in protecting bones from fracture. However, histological investigations of the underlying structural changes, which might predispose to fracture, have been largely limited to the cancellous bone. The aim of this study was to investigate the age-association and regional differences of histomorphometric properties in the femoral neck cortical bone. Undecalcified histological sections of the femoral neck (n = 20, aged 18-82 years, males) were cut (15 μm) and stained using modified Masson-Goldner stain. Complete femoral neck images were scanned, and cortical bone boundaries were defined using our previously established method. Cortical bone histomorphometry was performed with low (×50) and high magnification (×100). Most parameters related to cortical width (Mean Ct.Wi, Inferior Ct.Wi, Superior Ct.Wi) were negatively associated with age both before and after adjustment for height. The inferior cortex was the thickest (P < 0.001) and the superior cortex was the thinnest (P < 0.008) of all cortical regions. Both osteonal size and pores area were negatively associated with age. Osteonal area and number were higher in the antero-inferior area (P < 0.002) and infero-posterior area (P = 0.002) compared to the postero-superior area. The Haversian canal area was higher in the infero-posterior area compared to the postero-superior area (P = 0.002). Moreover, porosity was higher in the antero-superior area (P < 0.002), supero-anterior area (P < 0.002) and supero-posterior area (P < 0.002) compared to the infero-anterior area. Eroded endocortical perimeter (E.Pm/Ec.Pm) correlated positively with superior cortical width. This study describes the changes in cortical bone during ageing in healthy males. Further studies are needed to investigate whether these changes explain the increased susceptibility to femoral neck fractures.