Osteoporosis in chronic kidney disease (CKD) grade 4–5D constitutes a profound burden and the treatment gap remains unacceptably wide. People with advanced CKD and osteoporosis should receive comprehensive treatment based on available data, and there is an urgent need to expand the evidence base through inclusion in osteoporosis clinical trials.

Children after kidney transplantation (KTx) are prone to mineral and bone disease (MBD) including growth restriction, bone pain, skeletal deformities, fractures, and vascular calcifications. We present a position paper on the diagnosis and management of post-transplant MBD in this population based on the available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD, Dialysis and Transplantation Working Groups. PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and structured literature searches were conducted for a population of children under 18 years of age who were kidney transplant recipients with a functioning allograft. Patients with a failing allograft (i.e., with an eGFR less than 30 mL/min per 1.73 m2) are not discussed here. Clinical practice points (CPPs) were developed and graded using the American Academy of Pediatrics grading matrix. A Delphi consensus method was followed. We present 46 CPPs for the diagnosis and management of MBD in paediatric KTx, including assessment and management before and after KTx, highlighting the specifics of monitoring post-transplant MBD between 0 and 3 months after KTx, and including the impact of steroid minimization and withdrawal. As there are few high-quality studies in this field, the strength of most statements is weak to moderate and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

Background:Kidney transplant recipients face a high risk of adverse events, including fractures. Reported fracture rates post-transplant vary widely and may have changed over time. The consequences of a fracture, especially subsequent fractures, remain under-investigated. This study examined the risk and prognosis of fractures after kidney transplantation in the current era. Methods:This retrospective cohort study included all adults who received a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide healthcare registries were utilized to identify the study population and provide demographic data, diagnostic and procedural codes, and prescription data. Cumulative incidence (risk) of both first fracture and subsequent fracture was computed, treating death as a competing risk. Crude, and sex- and age-standardized incidence rates were estimated for different time periods. Results:The study included 3977 first kidney transplant recipients, of whom 788 sustained any post-transplant fracture. The 10-year risk of fracture was 21% (95% confidence interval 20-23). Crude incidence rates of any fracture remained unchanged over time, while standardized estimates showed a slight decline. Fractures were primarily located at the peripheral skeleton. Twenty-eight percent of patients with a fracture sustained a subsequent fracture, with the highest incidence at 6-12 months following the first event. Conclusions:Kidney transplant recipients remain at high fracture risk, with unchanged fracture rates over the past 20 years. The imminent fracture risk following a first fracture is high and largely unaddressed. Although formal guidelines have yet to be established, this knowledge should urge clinicians to perform risk assessment and consider intervention following a post-transplant fracture.

Skeletal fragility has long been overlooked by the nephrology community despite patients with chronic kidney disease (CKD) facing double the risk of hip fracture compared with the general population. Consequently, the term CKD-associated osteoporosis was recently coined to increase awareness. In this context, vertebral fractures are even less studied. Vertebral fractures predict increased fracture risk, and especially in advanced CKD, show a strong association with aortic and iliac vascular calcifications and cardiovascular events such as myocardial infarction. The scope of the present consensus paper is to comprehensively discuss the management of skeletal fragility in CKD patients, from diagnosis to treatment, with a particular focus on vertebral fractures in CKD G4-G5D.

Osteoporosis and chronic kidney disease (CKD)–metabolic bone disease (MBD) (CKD-MBD) are increasingly recognized as overlapping conditions, particularly in the aging population. Declining renal function and skeletal fragility often coexist, because CKD-MBD may develop in a skeleton already compromised by preexisting osteoporosis. Adynamic bone, often resulting from excessive suppression of parathyroid hormone (PTH) and now a common form of renal osteodystrophy (ROD), may histologically resemble low-turnover osteoporosis; distinguishing between the 2 under light microscopy remains difficult, and reliable differentiation often depends on clinical context. Nevertheless, nephrologists and nonnephrologist bone specialists frequently work in parallel rather than in collaboration.This separation has contributed to persistent diagnostic gaps and fragmented management, especially in patients with advanced CKD. Advances in imaging, biochemical markers, and bone histomorphometry have improved insight into disease mechanisms; however, limitations in current diagnostic approaches remain. Osteoporosis therapies are frequently underused in CKD, despite growing evidence supporting efficacy and safety across a broader range of kidney function than previously assumed. Despite efforts to refine the definition of osteoporosis beyond bone mineral density (BMD) alone, clinical misclassification continues.Beyond skeletal health, vascular calcification (VC)—driven by disordered calcium–phosphate homeostasis—remains insufficiently prioritized in clinical decision-making, despite its strong association with cardiovascular morbidity and mortality in CKD. Emerging concepts, such as intermittent PTH administration, an established treatment in osteoporosis, illustrate the potential for interventions that may restore mineral balance and improve skeletal integrity in selected CKD populations. Whether such strategies can also favorably influence cardiovascular risk remains uncertain and warrant investigation. This integrated framework may improve interdisciplinary care.

Growing evidence suggests that chronic kidney disease (CKD) profoundly disrupts gut microbiome and its activity. This study explores how CKD affects colon microbial metabolism, focusing on (1) the representativeness of fecal metabolomics, (2) saccharolytic and proteolytic fermentation metabolites, and (3) the gut microbiome’s role in the partitioning of tryptophan in its metabolic pathways. Tryptophan’s main metabolic pathways include the indolic and the kynurenine pathways, which lead, respectively, to the formation of indoxyl sulfate and kynurenine, both contributing to uremic toxicity. Using a rat model of CKD, we evaluated whether fecal concentrations of microbial compounds, on which most studies are based, reflect the colonic concentrations in contact with the gut mucosa. Thus, we quantified the concentration and content of amino acids, indole, p-cresol, and also short-chain fatty acids, in different colon sections. We demonstrated that CKD promotes increased proteolytic fermentation and an augmented tryptophan partitioning into both the indolic and kynurenine pathways. Depletion of the indolic pathway obtained upon antibiotic treatment leads to a further enhancement of the kynurenine pathway.

Mineral and bone disease (MBD) is a frequent complication after solid organ transplantation. The rapid decline in bone mineral density (BMD) during the first year after kidney transplantation reflects complex interactions between immunosuppressive therapy, metabolic factors and pre-existing chronic kidney disease (CKD)-MBD. This narrative review summarizes the magnitude and time course of BMD loss after kidney transplantation, the underlying metabolic and pharmacologic mechanisms, and associated fracture risk. Diagnostic strategies including dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), high-resolution peripheral QCT(HR-pQCT), finite element analysis (FEA), and biochemical markers are reviewed alongside preventive and therapeutic approaches. Recent data highlight early deterioration of cortical bone structure, persistent hyperparathyroidism, and the limited predictive value of DXA alone. Integration of advanced imaging and bone-turnover markers as well as markers of mineral metabolism could improve risk stratification. Emerging artificial intelligence-based modeling and HR-pQCT-guided phenotyping may enable individualized prevention strategies in kidney transplant recipients (KTRs).

INTRODUCTION:An iliac bone biopsy with semi-quantitative histomorphometry is the gold standard for evaluating renal osteodystrophy (ROD). However, lack of standardization of the bone biopsy procedure, sample handling, reading and reporting represent barriers to research synthesis and clinical collaboration. This study assessed diagnostic agreement across European laboratories performing histomorphometry for evaluation of ROD. METHODS:Five-millimeter transiliac biopsy slides from 5 cases were converted to digital images for analysis by experts from 7 laboratories. Parameters included quantitative histomorphometry, bone turnover, mineralization and volume (TMV) classification, and a concluding diagnosis. Agreement was analysed using Kappa statistics for categorical and intraclass correlation coefficients (ICC) for continuous variables. RESULTS:Agreement on histomorphometric variables ranged from poor to excellent. High agreement was observed for the static parameters bone area (ICC 0.91), osteoid area (ICC 0.95) and osteoid perimeter (ICC 0.84). For dynamic parameters, agreement was high for mineralizing surface (ICC 0.87) and bone formation rate (ICC 0.74), but poor for mineral apposition rate (ICC -0.13) and mineralization lag time (ICC 0.07). Agreement on the TMV classification was substantial for bone turnover (Kappa 0.77), slight for bone mineralization (Kappa 0.14), and substantial for bone volume (Kappa 0.73). The concluding diagnoses showed a high degree of consistency. CONCLUSIONS:Despite considerable inter-reader variability in bone histomorphometric measures, the clinical diagnoses of ROD were consistent across laboratories. Key sources of variability included analytical methods, disagreement on reference values, and differences in the definition of mineralization disorder. Further work should be undertaken to reach consensus on these points.

BACKGROUND:Fracture risk in patients with chronic kidney disease (CKD) is excessively high. A recent European consensus provides guidance on the comprehensive screening for CKD-associated osteoporosis in patients with CKD stages G4-5D. However, data on the yield and therapeutic implications of this approach in patients with kidney failure is lacking. METHODS:All prevalent dialysis patients aged >50 years or postmenopausal with life expectancy >1 year at a single center were invited for comprehensive bone health assessment, including the evaluation of risk factors, calcium intake, mineral metabolism parameters, bone turnover markers, fracture history, bone mineral density and vertebral fractures by dual-energy X-ray absorptiometry (DXA), handgrip strength and self-reported physical activity. RESULTS:Of 203 patients screened, 121 (mean age 75 years, 55% male) were eligible, of whom 71 underwent comprehensive phenotyping including DXA. CKD-associated osteoporosis was identified in 73% of participants, based on a T-score ≤-2.5 at the hip or lumbar spine (65%), history of fragility fracture (41%) and/or finding of a vertebral fracture (13%). Vitamin D insufficiency (<30 ng/mL) and insufficient calcium intake (<800 mg/day) were observed in 35% and 29%, respectively. Despite bio-intact parathyroid hormone levels exceeding the KDIGO target range in only 17%, bone turnover markers suggested high bone turnover in 53% of patients. Handgrip strength was below sarcopenia threshold in 65%, while physical activity was low in 55% of participants. Only 21% of patients with CKD-associated osteoporosis were treated with bone targeting therapy. CONCLUSION:Comprehensive bone health assessment identified CKD-associated osteoporosis in 7 out of 10 patients with kidney failure and unveiled several therapeutic opportunities ranging from optimization of mineral metabolism to non-pharmacological and pharmacological bone-targeting interventions. The present single-center findings call for reflection and confirmation.

Introduction Sex steroids in male patients decrease along with the progression of chronic kidney disease (CKD) and are associated with worse outcomes. This study aimed to increase the knowledge of the pathophysiology of biochemical hypogonadism in male CKD and its reversibility after kidney transplantation (KT). Methods We comprehensively mapped the hypothalamic-pituitary-gonadal (HPG) axis in 120 male patients (age 65 yrs, body mass index [BMI]: 26.8 kg/m(2)) with CKD stage 1 to 5, and 120 kidney-healthy controls, matched (1:1) for age and BMI. Additionally, we monitored the HPG axis in 50 male kidney transplant recipients (age 60 yrs) from the time of transplantation up to 12 months. Testosterone (T) was measured by liquid chromatography tandem mass-spectrometry. Luteinizing hormone (LH), follicle stimulating hormone (FSH), and inhibin B levels were assessed by immunoassay. T/LH ratio and inhibin B/FSH ratio served as a proxy for the function of Leydig and Sertoli cells, respectively. Results Hypogonadism is prevalent in CKD and is characterized by depressed T/LH ratio (1.75 [0.71-2.96] vs. 3.99 [2.39-5.20], P < 0.0001) and inhibin B/FSH ratio (14.40 [1.24-33.64] vs. 32.24 [16.27-56.72], P < 0.0001). T levels showed a steady increase shortly after transplantation, whereas LH levels decreased, resulting in a higher T/LH ratio (P < 0.0001). Inhibin B levels decreased after 3 months, resulting in a lower inhibin B/FSH ratio after 3 months (P < 0.0001), with partial recovery after 12 months. Conclusion Male patients with CKD showed low T/LH and inhibin B/FSH ratios pointing towards testicular failure as underlying pathophysiological mechanism. Male CKD can be considered a state of premature testicular ageing. Leydig cell function rapidly recovered after KT suggesting a functional cause of CKD-induced hypogonadism. In contrast, Sertoli cell function showed a deterioration, especially in the early post-transplant period.

CYP27B1 is the rate-limiting enzyme in the activation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3. This study aimed to characterize the spatial expression of CYP27B1 in mouse and human kidneys and to investigate the contribution of renal CYP27B1 to systemic vitamin D metabolism using inducible conditional knockout models. Immunofluorescent co-staining with segment-specific markers was used to localize CYP27B1 in kidney tissue. Mice with selective Cyp27b1 knockdown in renal tubular cells were generated by crossing Cyp27b1lox/lox mice, in which exon 8 was flanked with loxP sites, with inducible Pax8-Cre or Cdh16-Cre lines. In mice, CYP27B1 immunoreactivity was detected in proximal and distal tubules under basal conditions but increased specifically in proximal tubules under elevated enzyme activity. In healthy human kidneys, CYP27B1 staining was confined to proximal convoluted tubules. Cyp27b1lox/lox mice showed no overt phenotype, however, loxP insertion significantly reduced full-length Cyp27b1 mRNA expression in the kidney and various other tissues, which in some cases was accompanied by a PTH-independent increase in incomplete Cyp27b1 transcripts, as detected by exon 2–3 spanning primers. In Pax8-Cre+;Cyp27b1lox/lox mice, doxycycline-induced Cre expression further reduced full-length Cyp27b1 transcripts selectively in the kidney. In contrast, tamoxifen-induced deletion in Cdh16-Cre+;Cyp27b1lox/lox mice was less effective and showed more off-target effects. Circulating 1,25(OH)₂D₃ levels remained stable, and calcium and bone homeostasis were preserved or minimally affected. Kidney-selective Cyp27b1 knockdown by inducible Cre-mediated recombination is insufficient to silence 1,25(OH)2D3 synthesis, suggesting potent compensatory mechanisms that buffer loss of renal Cyp27b1 transcription.

Bone turnover abnormalities are common in chronic kidney disease (CKD) and contribute to bone fragility. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) introduced the term CKD-associated osteoporosis to describe bone fragility in CKD and highlighted the role of bone turnover markers (BTM) in clinical evaluation and management of bone fragility. However, current clinical practice guidelines lack specific treatment targets for bone turnover in the setting of CKD. The aim of this consensus was to present recommendations for the use of BTM in the management of CKD-associated osteoporosis. The consensus was conducted by members of relevant working groups of the European Renal Association (ERA), International Osteoporosis Foundation (IOF), European Foundation for Clinical Chemistry and Laboratory Medicine (EFLM) and European Society of Pediatric Nephrology (ESPN). Bone-specific alkaline phosphatase and tartrate resistant acid phosphatase isoform 5b are not renally cleared and considered reliable diagnostic tools for bone evaluation in CKD-associated osteoporosis. Both have been proposed as reference BTM in CKD by a recent international consortium. Intact N-terminal telopeptide of type I collagen can also be used in CKD. The current consensus describes methodological considerations and the clinical usefulness of BTM in risk prediction, choice of therapeutic strategy, and treatment evaluation in CKD-associated osteoporosis. Specific diagnostic ranges for bone turnover abnormalities are provided. Future research should focus on the integration of these reference BTM with other diagnostic tools, establishment of concrete treatment targets, and development of treatment strategies to reach these targets.

Type 2 diabetes mellitus (T2DM) is common in patients with chronic kidney disease (CKD). Both conditions are associated with an increased fracture risk, with the proposed etiology including impaired bone quantity and quality. This cross-sectional study examined the bone phenotype in patients with T2DM and kidney failure and explored the role of glycemic control on the bone phenotype. To do so, laboratory parameters of mineral metabolism (including sclerostin) and bone turnover markers (BTM) (bone-specific alkaline phosphatase [BALP], trimeric pro-collagen type I N-terminal propeptide [intact P1NP], and tartrate-resistant acid phosphatase isoform 5b [TRACP5b]) were assessed in 647 patients with kidney failure, of which 102 had T2DM (median hemoglobin A1c [HbA1c] of 6.2%), at the time of kidney transplantation. Patients with type 1 DM were excluded. BMD (n = 555) by densitometry, and bone histomorphometry (n = 188) were available for subsets, and correlations between HbA1c and both BTM and BMD were examined. This study found that intact P1NP was lower (68 vs 82 μg/L, p = .03) while sclerostin was higher (2.1 vs 1.8 ng/mL, p = .04) in T2DM versus non-T2DM in an unadjusted analysis. BMD at the lumbar spine (Z-score: -0.066 vs -0.760, p < .001) and femoral neck (Z-score: -0.680 vs -0.965, p = .04) were higher in T2DM, and T2DM was in multivariable regression analysis identified as a significant determinant of lumbar spine BMD, independent of age, sex, and BMI. Bone histomorphometric parameters did not differ between groups. A correlation between HbA1c and BTM and BMD was present, but only in non-T2DM (BALP [ρ = -0.12, p = .007], intact P1NP [ρ = 0.14, p = .002], TRACP5b [ρ = -0.13, p = .003], BMD at the lumbar spine [ρ = 0.12, p = .008], femoral neck [ρ = 0.11, p = .02], and total hip [ρ = 0.17, p < .001]). In conclusion, patients with kidney failure and T2DM have preserved BMD compared with patients without diabetes. Our findings suggest a role for hyperglycemia as a determinant of the bone phenotype.

Background:Serum total alkaline phosphatase (ALP) is a robust predictor of all-cause mortality in both the general population and in patients with chronic kidney disease (CKD). Individual ALP isozymes and isoforms exert specific physiological functions and may therefore inform separately on different disease processes and risks related to these. Serum ALP consists predominantly of bone and liver isoforms, with a smaller contribution from the intestinal isoenzyme. We aimed to characterize the impact of CKD on serum ALP fractions and to identify clinical and biochemical correlates. Methods:Serum ALP liver, bone and intestinal fractions were analysed by electrophoresis in 523 individuals across stages of CKD (stage G1-2: n = 90; G3: n = 100; G4-5: n = 139; G5D: n = 194) and in 21 kidney-healthy controls. Associations with demographics and parameters of mineral metabolism and inflammation were examined. In haemodialysis patients, we further explored the association between ALP isozymes and all-cause mortality. Results:Total ALP levels increased significantly across stages of CKD, with liver, bone and intestinal fractions all contributing. In patients with CKD G5D, circulating levels of all three fractions were more than two-fold higher than in controls. Bone ALP associated with PTH while liver ALP associated with C-reactive protein, both independent of demographics and kidney function. Higher liver ALP levels associated with increased mortality risk, independent of traditional risk factors and inflammation. Conclusions:In patients with CKD, elevations in liver, bone and intestinal ALP fractions reflect distinct biological pathways and may differentially inform on risk related to different disease processes. While bone ALP reflects bone metabolism, liver ALP is linked with inflammation. The elevation in CKD and the independent association of liver ALP fraction with mortality in patients treated with haemodialysis calls for additional clinical and mechanistic studies.

Fracture risk increases along the progression of chronic kidney disease (CKD) to become several-fold higher in patients with CKD G4-5D as compared to the kidney-healthy background population matched for age and sex. In 2023, Kidney Disease Improving Global Outcomes (KDIGO) introduced the term CKD-associated osteoporosis to acknowledge and emphasize the overlap in diagnostic workup and therapeutic choices when treating bone fragility in CKD versus other conditions of osteoporosis, while maintaining the need to individualise the treatment plan with knowledge of CKD. Although evidence-based practice guidelines promote management strategies that are widely accepted in postmenopausal women and elderly men, there is a clear need to perform randomized controlled trials to confirm or disprove the benefits of therapy in the setting of advanced CKD. Lifestyle modification, as a 'low risk/potentially high return' intervention, should be considered in all patients. Current evidence furthermore supports a sequential approach to treatment, where mineral metabolism should be optimised, including parathyroid hormone targeting therapy, before initiating bone targeting drugs. We review the current standards of treatment and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of CKD-associated osteoporosis and propose a pragmatic treatment algorithm, pending more definite evidence from appropriately designed and powered clinical trials.

Mounting evidence suggests that inflammation contributes to bone mineral density (BMD) loss, not only in patients with chronic autoimmune conditions but also in postmenopausal women. Chronic kidney disease (CKD) is also a state of low-grade systemic inflammation. A plethora of endogenous and exogenous mediators seems to be involved, with metabolic endotoxemia gaining much interest in recent years. This study explores the association between metabolic endotoxemia, inflammation and bone mass in patients with kidney failure. This cross-sectional observational study included patients with kidney failure eligible for kidney transplantation. Data on demographics, comorbidities, parameters of mineral and bone disorder, high-sensitivity C-reactive protein (CRP, as a marker of inflammation), lipopolysaccharide-binding protein (LBP, as a marker of metabolic endotoxemia), plasma bone turnover markers (BALP, iPINP and TRAP5b by IDS-iSYS) and bone mineral density (BMD), assessed by Dual-energy X-ray absorptiometry (DXA) at lumbar spine (LS), total hip (TH), femoral neck (FN), 1/3 distal radius and ultradistal radius, were collected. Univariate and multivariate analyses were conducted to investigate the determinants of bone loss and inflammation. The cohort included 649 patients (age 57 ± 12 years, 63% male). Median CRP was 3 (IQR 1, 7) mg/L and median LBP (subset only, n = 190) was 19 (14, 23) . Higher BMI and elevated LBP were associated with increased CRP (P < 0.01), independently of age and sex. High CRP was a risk factor for low BMD at all skeletal sites, after adjustment for traditional risk factors (age, BMI, sex) and PTH, remaining significant at all sites except LS after additional adjusting for any of the bone turnover markers BALP, iPINP or TRAP5b. Interestingly, the inverse association between CRP and BMD was only revealed after adjusting for BMI (Table 1 ). CRP emerged as a significant risk factor for low bone mass in patients with kidney failure, particularly when adjusting for BMI. While obesity is linked to higher BMD, through estrogen production from adipocytes and increased skeletal loading, obesity is also associated with chronic low-grade inflammation, underscoring the complex relationship between inflammation, BMI, and bone mass (Fig. 1 ). Present findings call for additional studies exploring the link between metabolic endotoxemia and bone health.

The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

INTRODUCTION:Bone disease after kidney transplantation is complex, converging features of senile, postmenopausal, glucocorticoid-induced, and chronic kidney disease (CKD)-associated osteoporosis. CASE PRESENTATION:We present a case of a 60-year-old female kidney transplant recipient with osteoporosis, who failed to show an improvement in areal bone mineral density (aBMD) after 5 years of annual intravenous therapy with 5 mg zoledronate. After thorough examination, persistent hyperparathyroidism and subsequent hypophosphatemia were pointed to as the most likely explanation. DISCUSSION:Persistent hyperparathyroidism is a common finding in kidney transplant patients. Therapy with antiresorptive agents may mask the bone phenotype of persistent hyperparathyroidism, delaying the initiation of parathyroid hormone (PTH) suppressive therapy. Meanwhile, PTH driven hypophosphatemia may be a cause of antiresorptive treatment failure. CONCLUSION:Present case emphasizes the importance of controlling CKD-mineral and bone disorders prior to initiating bone targeting drugs, as also has been recommended by recent consensus manuscripts. In an era in which bone turnover markers gain importance in guiding PTH suppressive and osteoporosis therapy, antiresorptive agents may complicate the diagnosis of hyperparathyroidism by masking the bone phenotype.

Zoccali, Carmine; Vervloet, Marc G; Evenepoel, Pieter; Massy, Ziad; Cozzolino, Mario; Mallamaci, Francesca; Lederer, Eleanor D.; Andia, Jorge Cannata; Drueke, Tilman B. Author Information