Bone and Chronic Kidney Disease.

Chronic kidney disease (CKD) induces mineral and bone disorders (CKD-MBD) that affect calcium and phosphate metabolism. This review links pathophysiology, histologic aspects, and radiologic signs. CKD leads to bone lesions, namely renal osteodystrophy, which may combine low or high bone remodeling, impaired mineralization, and bone loss. CKD-MBD also comprises vascular calcifications, which, together with bone disease, lead to a high risk of cardiovascular events and osteoporotic fractures that increase both morbidity and mortality. Osteoporosis assessment is based on screening for classic risk factors and CKD-related factors (disease duration/severity, transplantation history, dialysis vintage). Treatment of mineral disorders may combine serum phosphate lowering drugs, natural vitamin D or its 1-α derivatives, or calcium-sensing receptor agonists. Treatment of osteoporosis is conventional in mild to moderate stages but more complex in severe CKD because evidence about the efficacy and safety of anti-osteoporosis drugs is scant.

Bone Turnover, Mineralization, and Volume Estimated by 18F-Sodium Fluoride PET/CT and Biomarkers in Chronic Kidney Disease: Mineral and Bone Disorder Compared with Bone Biopsy.

INTRODUCTION: Invasive bone biopsy to assess bone metabolism in patients with chronic kidney disease-mineral and bone disorder may be replaced by the noninvasive 18F-NaF PET/CT and biomarkers of bone metabolism. We aimed to compare parameters of bone turnover, mineralization, and volume assessed by bone biopsies with results derived from 18F-NaF PET/CT and biomarkers (bone-specific alkaline phosphatase, osteocalcin, fibroblast growth factor 23, and osteoprotegerin). METHODS: A cross-sectional study included 17 dialysis patients, and results from 18F-NaF PET/CT scans and the biomarkers were directly compared with the results of histomorphometric analyses of tetracycline double-labeled trans-iliac bone biopsies. RESULTS: Bone biopsies showed 40% high, 20% normal, and 40% low bone turnover. No biopsies had generalized abnormal mineralization, and the bone volume/total tissue volume was low in 80% and high in 7%. The pelvic skeletal plasma clearance (Ki) from 18F-NaF PET/CT correlated with bone turnover parameters obtained by bone biopsy (activation frequency: r = 0.82, p < 0.01; bone formation rate/bone surface: r = 0.81, p < 0.01), and Ki defined low turnover with high sensitivity (83%) and specificity (100%). CT-derived radiodensity correlated with bone volume, r = 0.82, p < 0.01. Of the biomarkers, only osteocalcin showed a correlation with turnover assessed by histomorphometry. CONCLUSION: In conclusion, 18F-NaF PET/CT may be applicable for noninvasive assessment of bone turnover and volume in CKD-MBD.

Imaging of Chronic Kidney Disease-Mineral and Bone Disorder.

The characteristic radiological appearances of metabolic bone and soft tissue diseases in chronic renal failure are described and illustrated in the context of advancing understanding of the complex metabolic changes that occur in chronic kidney disease and its management.

Improvement of Mineral and Bone Disorders After Renal Transplantation.

BACKGROUND: Posttransplant mineral and bone diseases are causes of fractures, and their association with cardiovascular events is being studied. METHODS: We analyzed the evolution of biochemical, histological, and imaging parameters pre- and 1 y post-renal transplantation in 69 patients and correlated mineral and bone findings with coronary calcifications. At inclusion and after 12 mo, clinical data and echocardiographic findings were recorded, and laboratory evaluations, radiography of the pelvis and hands, and bone biopsy were performed. Noncontrast cardiac computed tomography was performed during the second evaluation. RESULTS: Serum levels of fibroblast growth factor 23 and sclerostin decreased in all patients, parathyroid hormone levels decreased in 89.8% of patients, bone alkaline phosphatase levels decreased in 68.1% of patients, and alpha-Klotho levels increased in 65.2% of patients. More than half of the patients presented with renal osteodystrophy at both biopsies, but histological findings improved: a significant transition from high to normal or low turnover and no significant differences in volume, mineralization defect, or cortical porosity at the 2 evaluations. Alpha-Klotho, sclerostin, and bone alkaline phosphatase shifts affect bone changes. Neither echocardiographic findings nor vascular calcification scores differed between the 2 points. Both the pretransplant period (dialysis vintage, sclerostin, and low bone volume at baseline) and the maintenance of abnormalities in the posttransplant period (high turnover posttransplant) were the most reliable predictors of the severity of the coronary calcification percentile. CONCLUSIONS: Renal transplantation improved bone and mineral abnormalities. The pretransplant period determines the severity of calcification.

Update on imaging in chronic kidney disease-mineral and bone disorder: promising role of functional imaging.

Disorders of mineral metabolism and bone disease are common complications in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. Bone biopsies, bone scintigraphy, biochemical markers, and plain films have been used to assess bone disorders and bone turnover. Of these, functional imaging is less invasive than bone/marrow sampling, more specific than serum markers and is therefore ideally placed to assess total skeletal metabolism. 18F-sodium fluoride (NaF) PET/CT is an excellent bone-seeking agent superior to conventional bone scan in CKD patients due to its high bone uptake, rapid single-pass extraction, and minimal binding to serum proteins. Due to these properties, 18F-NaF can better assess the skeletal metabolism on primary diagnosis and following treatment in CKD patients. With the increased accessibility of PET scanners, it is likely that PET scanning with bone-specific tracers such as 18F-NaF will be used more regularly for clinical assessment and quantitation of bone kinetics. This article describes the pattern of scintigraphic/functional appearances secondary to musculoskeletal alterations that might occur in patients with CKD.

Bone Histomorphometry and 18F-Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy.

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.

Vascular calcification relationship to vascular biomarkers and bone metabolism in advanced chronic kidney disease.

BACKGROUND: Vascular calcification (VC) and renal osteodystrophy are important complications of advanced chronic kidney disease (CKD). High resolution peripheral quantitative computed tomography (HRpQCT) is able to assess bone microstructure in renal osteodystrophy and lower leg arterial calcification (LLAC) is usually seen as an incidental finding. LLAC can be a useful quantitative assessment of VC in CKD but the relationship between LLAC and vascular biomarkers and bone is unknown. We aimed to assess the relationship between LLAC and biomarkers, bone turnover and microstructure. METHODS: In this cross-sectional study, fasting blood samples were taken from 69 CKD stages 4-5D patients and 68 healthy controls. HRpQCT of distal tibia and radius were performed. 43 CKD patients had trans-iliac bone biopsy after tetracycline labelling. RESULTS: LLAC was more severe in CKD than controls (median [IQR] 1.043 [0.05-16.52] vs 0 [0-0.55] mgHA, p < 0.001). CKD patients with diabetes (28%) had significantly higher LLAC compared to non-diabetic CKD (median [IQR] 24.07 [3.42-61.30] vs 0.23 [0-3.78] mgHA, p < 0.001). LLAC mass in CKD correlated with serum phosphate (rho = 0.29, p < 0.05), calcium x phosphate product (rho = 0.31, p < 0.05), intact parathyroid hormone (rho = 0.38, p < 0.01), intact fibroblast growth factor-23 (iFGF23) (rho = 0.40, p = 0.001), total alkaline phosphatase (rho = 0.41, p < 0.001), bone alkaline phosphatase (rho = 0.29, p < 0.05), osteocalcin (rho = 0.32, p < 0.05), osteoprotegerin (rho = 0.40, p = 0.001) and dephosphorylated-uncarboxylated matrix Gla protein (rho = 0.31, p < 0.05). LLAC in CKD also correlated with worse distal tibia cortical bone mineral density, thickness and porosity. No association was found between LLAC and bone turnover, mineralization or volume on biopsy in CKD. In multivariate analysis, only age, diabetes, iPTH and iFGF23 were independently associated with LLAC in CKD. CONCLUSIONS: High levels of PTH and FGF23, along with older age and the presence of diabetes may all play independent roles in the development of LLAC in advanced CKD.

Bone Mineral Density and Aortic Calcification: Evidence for a Bone-vascular Axis After Kidney Transplantation.

BACKGROUND: Chronic kidney disease mineral and bone disorders (CKD-MBD) and vascular calcification are often seen in kidney transplantation recipients (KTR). This study focused on the bone-vascular axis hypothesis, the pathophysiological mechanisms driving both bone loss and vascular calcification, supported by an association between lower bone mineral density (BMD) and higher risk of vascular calcification. METHODS: KTR referred for a dual-energy X-ray absorptiometry procedure within 6 mo after transplantation were included in a cross-sectional study (2004-2014). Areal BMD was measured at the proximal femur, and abdominal aortic calcification (AAC) was quantified (8-points score) from lateral single-energy images of the lumbar spine. Patients were divided into 3 AAC categories (negative-AAC: AAC 0; low-AAC: AAC 1-3; and high-AAC: AAC 4-8). Multivariable-adjusted multinomial logistic regression models were performed to study the association between BMD and AAC. RESULTS: We included 678 KTR (51 ± 13 y old, 58% males), 366 (54%) had BMD disorders, and 266 (39%) had detectable calcification. High-AAC was observed in 9%, 11%, and 25% of KTR with normal BMD, osteopenia, and osteoporosis, respectively (P < 0.001). Higher BMD (T-score, continuous) was associated with a lower risk of high-AAC (odds ratio 0.61, 95% confidence interval 0.42-0.88; P = 0.008), independent of age, sex, body mass index, estimated glomerular filtration rate, and immunosuppressive therapy. KTR with normal BMD were less likely to have high-AAC (odds ratio 0.24, 95% confidence interval 0.08-0.72; P = 0.01). CONCLUSIONS: BMD disorders are highly prevalent in KTR. The independent inverse association between BMD and AAC may provide evidence to point toward the existence, while highlighting the clinical and epidemiological relevance, of a bone-vascular axis after kidney transplantation.

Impact of physical activity and exercise on bone health in patients with chronic kidney disease: a systematic review of observational and experimental studies.

BACKGROUND: Chronic Kidney Disease (CKD) patients frequently develop life-impairing bone mineral disorders. Despite the reported impact of exercise on bone health, systematic reviews of the evidence are lacking. This review examines the association of both physical activity (PA) and the effects of different exercise interventions with bone outcomes in CKD. METHODS: English-language publications in EBSCO, Web of Science and Scopus were searched up to May 2019, from which observational and experimental studies examining the relation between PA and the effect of regular exercise on bone-imaging or -outcomes in CKD stage 3-5 adults were included. All data were extracted and recorded using a spreadsheet by two review authors. The evidence quality was rated using the Cochrane risk of bias tool and a modified Newcastle-Ottawa scale. RESULTS: Six observational (4 cross-sectional, 2 longitudinal) and seven experimental (2 aerobic-, 5 resistance-exercise trials) studies were included, with an overall sample size of 367 and 215 patients, respectively. Judged risk of bias was low and unclear in most observational and experimental studies, respectively. PA was positively associated with bone mineral density at lumbar spine, femoral neck and total body, but not with bone biomarkers. Resistance exercise seems to improve bone mass at femoral neck and proximal femur, with improved bone formation and inhibited bone resorption observed, despite the inconsistency of results amongst different studies. CONCLUSIONS: There is partial evidence supporting (i) a positive relation of PA and bone outcomes, and (ii) positive effects of resistance exercise on bone health in CKD. Prospective population studies and long-term RCT trials exploring different exercise modalities measuring bone-related parameters as endpoint are currently lacking.

Trabecular bone score may indicate chronic kidney disease-mineral and bone disorder (CKD-MBD) phenotypes in hemodialysis patients: a prospective observational study.

BACKGROUND: In the general population, the trabecular bone score (TBS) represents the bone microarchitecture and predicts fracture risk independent of bone mineral density (BMD). A few studies reported that TBS is significantly reduced in dialysis patients. Chronic kidney disease-mineral and bone disorder (CKD-MBD) are accompanied by increased fracture risk, cardiovascular morbidity, and mortality. We investigated whether TBS is associated with comorbidity related to CKD-MBD or frailty in hemodialysis patients. METHODS: In this prospective observational study, TBS was obtained using the TBS iNsight software program (Med-Imaps) with BMD dual energy x-ray absorptiometry (DXA) images (L1-L4) from prevalent hemodialysis patients. A Tilburg frailty indicator was used to evaluate frailty, and hand grip strength and bio-impedance (InBody) were measured. A patient-generated subjective global assessment (PG-SGA) was used for nutritional assessment. The history of cardiovascular events (CVE) and demographic, clinical, laboratory, and biomarker data were collated. We then followed up patients for the occurrence of CKD-MBD related complications. RESULTS: We enrolled 57 patients in total. The mean age was 56.8 ± 15.9 years (50.9% female). Prevalence of Diabetes mellitus (DM) was 40.4% and CVE was 36.8%. Mean TBS was 1.44 ± 0.10. TBS significantly reduced in the CVE group (1.38 ± 0.08 vs. 1.48 ± 0.10, p <  0.001). Multivariable regression analysis was conducted adjusting for age, sex, dialysis vintage, DM, CVE, albumin, intact parathyroid hormone, fibroblast growth factor 23, handgrip strength, and phosphate binder dose. Age (ß = - 0.030; p = 0.001) and CVE (ß = - 0.055; p = 0.024) were significant predictors of TBS. During the follow up period after TBS measurements (about 20 months), four deaths, seven incident fractures, and six new onset CVE were recorded. Lower TBS was associated with mortality (p = 0.049) or new onset fracture (p = 0.007, by log-rank test). CONCLUSION: Lower TBS was independently associated with increased age and CVE prevalence in hemodialysis patients. Mortality and fracture incidence were significantly higher in patients with lower TBS values. These findings suggest that TBS may indicate a phenotype of frailty and also a CKD-MBD phenotype reciprocal to CVE.

Kidney Disease and Bone: Changing the Way We Look at Skeletal Health.

PURPOSE OF REVIEW: Kidney disease imparts profound skeletal changes, and unlike many other skeletal diseases, cortical bone is predominantly impacted. Significant advances in medical imaging have led to our ability to now obtain high-resolution three-dimensional views of cortical bone. This paper overviews recent work focused on cortical bone imaging, specifically cortical porosity, in kidney disease. RECENT FINDINGS: Although a number of clinical papers have used high-resolution imaging to assess cortical bone porosity, the most impactful work involves longitudinal study designs that have assessed cortical porosity changes over time. These latter studies demonstrate dramatic increases in cortical porosity in untreated individuals and a lack of clear efficacy in reversing porosity with treatment (although data are limited). Those papers providing longitudinal assessment, both clinical and pre-clinical, reveal powerful data about cortical porosity and provide a foundation upon which future studies can build.

Digital radiography as an alternative method in the evaluation of bone density in uremic rats / Radiografia digital como método alternativo na avaliação da densidade óssea em ratos urêmicos

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.

Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients.

BACKGROUND: The diagnosis of renal osteodystrophy is challenging. Bone biopsy is the gold standard, but it is invasive and limited to one site of the skeleton. The ability of biomarkers to estimate the underlying bone pathology is limited. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging technique that allows assessment of regional bone turnover at clinically relevant sites. The hypothesis of this study was, that 18F-NaF PET correlates with bone histomorphometry in dialysis patients and could act as a noninvasive diagnostic tool in this patient group. METHODS: This was a cross-sectional diagnostic test study. 26 dialysis patients with biochemical abnormalities indicating mineral and bone disorder were included. All the participants underwent a 18F-NaF PET scan and a bone biopsy. Fluoride activity in the PET scan was measured in the lumbar spine and at the anterior iliac crest. Dynamic and static histomorphometric parameters of the bone biopsy were assessed. As histomorphometric markers for bone turnover we used bone formation rate per bone surface (BFR/BS) and activation frequency per year (Ac.f). RESULTS: There was a statistically significant correlation between fluoride activity in the 18F-NaF PET scan and histomorphometric parameters such as bone formation rate, activation frequency and osteoclast and osteoblast surfaces and mineralized surfaces. 18F-NaF PET's sensitivity to recognize low turnover in respect to non-low turnover was 76% and specificity 78%. Because of the small number of patients with high turnover, we were unable to demonstrate significant predictive value in this group. CONCLUSIONS: A clear correlation between histomorphometric parameters and fluoride activity in the 18F-NaF PET scan was established. 18F-NaF PET may possibly be a noninvasive diagnostic tool in dialysis patients with low turnover bone disease, but further research is needed.

Digital radiography as an alternative method in the evaluation of bone density in uremic rats.

INTRODUCTION: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. METHODS: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. RESULTS: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). CONCLUSION: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

Changes in Bone Histomorphometry after Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Over the past decade, the management of CKD-mineral and bone disorder has changed substantially, altering the pattern of bone disease in CKD. We aimed to evaluate the natural history of kidney bone disease in contemporary kidney transplant recipients and patients on dialysis. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Sixty one patients on dialysis who were 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 at 2 years after kidney transplantation or 2 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: A total of 37 out 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% at 2 years after kidney transplantation, whereas the proportion of those with low bone turnover increased from 26% to 52%. Of 19 participants remaining on dialysis after 2 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 specimens.