Post-Transplant Bone Disease in Kidney Transplant Recipients: Diagnosis and Management.

Kidney transplantation is the preferred gold standard modality of treatment for kidney failure. Bone disease after kidney transplantation is highly prevalent in patients living with a kidney transplant and is associated with high rates of hip fractures. Fractures are associated with increased healthcare costs, morbidity and mortality. Post-transplant bone disease (PTBD) includes renal osteodystrophy, osteoporosis, osteonecrosis and bone fractures. PTBD is complex as it encompasses pre-existing chronic kidney disease-mineral bone disease and compounding factors after transplantation, including the use of immunosuppression and the development of de novo bone disease. After transplantation, the persistence of secondary and tertiary hyperparathyroidism, renal osteodystrophy, relative vitamin D deficiency and high levels of fibroblast growth factor-23 contribute to post-transplant bone disease. Risk assessment includes identifying both general risk factors and kidney-specific risk factors. Diagnosis is complex as the gold standard bone biopsy with double-tetracycline labelling to diagnose the PTBD subtype is not always readily available. Therefore, alternative diagnostic tools may be used to aid its diagnosis. Both non-pharmacological and pharmacological therapy can be employed to treat PTBD. In this review, we will discuss pathophysiology, risk assessment, diagnosis and management strategies to manage PTBD after kidney transplantation.

[Diagnosis and treatment of osteoporosis in patients with chronic kidney disease : Joint guidelines of the Austrian Society for Bone and Mineral Research (ÖGKM), the Austrian Society of Physical and Rehabilitation Medicine (ÖGPMR) and the Austrian Society of Nephrology (ÖGN)]. / Diagnose und Therapie der Osteoporose bei Patienten mit chronischer Niereninsuffizienz : Gemeinsame Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel (ÖGKM), der Österreichischen Gesellschaft für Physikalische Medizin und Rehabilitation (ÖGPMR) und der Österreichischen Gesellschaft für Nephrologie (ÖGN).

DEFINITION AND EPIDEMIOLOGY: Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T­score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T­score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C). DIAGNOSIS AND RISK STRATIFICATION OF OSTEOPOROSIS IN CKD: Densitometry (using dual X­ray absorptiometry, DXA): low T­score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T­score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m2) or CKD 5D (dialysis). SPECIFIC TREATMENT OF OSTEOPOROSIS IN PATIENTS WITH CKD: Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m2): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m2) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C). PHYSICAL MEDICINE AND REHABILITATION: Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B).

OSTEOPROTEGERIN AS AN EARLY SIGN OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER.

Chronic kidney disease (CKD) is among the most significant health problems, with the associated cardiovascular disease and bone metabolism disorders being the leading cause of morbidity and mortality in these patients. The aim of the study was to determine markers of bone turnover in patient sera (phosphates, calcium, alkaline phosphatase, parathyroid hormone and osteoprotegerin (OPG)) in all stages of kidney failure including kidney transplant recipients. We also wanted to determine whether dialysis vintage affects recovery of bone markers one year after transplantation. There were 164 study patients, whereas 30 healthy individuals served as a control group. Serum OPG progressively increased with decline of the glomerular filtration rate. The highest OPG concentration was recorded in dialysis group. We observed a statistically significant OPG increase in stage 2 CKD. In kidney transplant group, there was positive correlation between OPG and dialysis vintage. We also found that serum OPG was lower in patients treated with dialysis for less than 4 years prior to transplantation. We confirmed that CKD-mineral and bone disorder began in stage 3 CKD with parathyroid hormone and OPG elevation, and a statistically significant OPG increase in stage 2 CKD might be an early sign of CKD-mineral and bone disorder. Dialysis vintage longer than 4 years is associated with more significant disturbances in mineral and bone metabolism.

Manifestaciones craneofaciales en pacientes con osteodistrofia renal / Craneofacial manifestaciones in patients with renal osteodystrophy

Introducción: La osteodistrofia renal es una osteopatía metabólica difusa, relacionada con la insuficiencia renal crónica, que incluye diversas patologías en el sistema musculoesquelético. Se produce en respuesta a trastornos metabólicos generados por cambios electrolíticos, la inflamación crónica y la alteración hormonal. Estas variaciones modifican el proceso de remodelación ósea. Las manifestaciones clínicas incluyen alteración en el parénquima y estroma óseo, y van desde lesiones expansivas, produciendo deformidad, hasta fracturas patológicas del hueso. Objetivo: Relacionar las manifestaciones clínicas, imagenológicas e histológicas en el componente óseo cráneo facial para el diagnóstico de la osteodistrofia renal. Presentación de caso: Se presentan dos casos clínicos de pacientes con enfermedad renal crónica e hiperparatiroidismo secundario de base, con múltiples masas en maxilares que causan asimetría facial y alteración funcional. Las imágenes tomográficas revelan alteración en la morfología ósea cortical y trabecular. Ambos individuos evidenciaron alteraciones en niveles de hormona paratiroidea, fosfatasa alcalina, fósforo y calcio sérico. La histopatología comprobó tejido fibroóseo con hueso neoformado y gran vascularización, con células multinucleadas tipo osteoclastos sin presencia de hemosiderina. Pacientes manejados de forma interdisciplinaria entre medicina interna, endocrinología y cirugía maxilofacial. Conclusiones: Los pacientes con enfermedad renal crónica avanzada presentan alteración de la estructura y del metabolismo óseo y mineral. Tal situación puede comprometer el complejo óseo craneofacial. Los casos graves de osteodistrofia renal se caracterizan por una marcada expansión de los maxilares, que genera asimetría y rasgos de leontiasis. Las imágenes tomográficas asociadas a osteodistrofia renal presentan óseos trabeculares con expansión de cortical, que evidencia el recambio óseo inmaduro presente. La histopatología no es específica y puede ser similar a los casos de displasia ósea craneofacial. Ante lo anteriormente planteado es fundamental relacionar estos hallazgos con la clínica para definir un diagnóstico adecuado(AU)

(AU)Introduction: Renal osteodystrophy is a diffuse metabolic osteopathy, related to chronic renal failure, which includes various pathologies in the musculoskeletal system. It occurs in response to metabolic disorders generated by electrolyte changes, chronic inflammation and hormonal alteration. These variations modify the process of bone remodeling. Clinical manifestations include alteration in the parenchyma and bone stroma, and range from expansive lesions, producing deformity, to pathological fractures of the bone. Objective: Relate the clinical, imaging and histological manifestations in the skull-facial bone component for the diagnosis of renal osteodystrophy. Case Presentation: Two clinical cases of patients with chronic kidney disease and secondary underlying hyperparathyroidism are presented, with multiple masses in the jaws that cause facial asymmetry and functional alteration. Tomographic images reveal alteration in cortical and trabecular bone morphology. Both individuals showed alterations in levels of parathyroid hormone, alkaline phosphatase, phosphorus and serum calcium. Histopathology verified fibro-bone tissue with neoformed bone and great vascularization, with multinucleated osteoclast-like cells without the presence of hemosiderin. Patients were attended in an interdisciplinary way between internal medicine, endocrinology and maxillofacial surgery. Conclusions: Patients with advanced chronic kidney disease present alteration of the structure and bone and mineral metabolism. Such a situation can compromise the craniofacial bone complex. Severe cases of renal osteodystrophy are characterized by a marked expansion of the jaws, which generates asymmetry and traits of leonthiasis. The tomographic images associated with renal osteodystrophy present trabecular bones with cortical expansion, which evidences the immature bone turnover present. Histopathology is not specific and may be similar to cases of craniofacial bone dysplasia. Given the above, it is essential to relate these findings to the clinic to define an adequate diagnosis(AU)

Time for Revival of Bone Biopsy with Histomorphometric Analysis in Chronic Kidney Disease (CKD): Moving from Skepticism to Pragmatism.

Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.

Manifestations of hyperparathyroidism in the jaws: Concepts, mechanisms, and clinical aspects.

Hyperparathyroidism is one of the most common endocrine disorders worldwide. In countries where routine biochemical screening is not common, symptomatic hyperparathyroidism predominates. Its manifestations include skeletal alterations, calcification of soft tissues, kidney stones, and functional alterations in other systems. Notably, jaw alterations can be the first clinical sign of hyperparathyroidism, including brown tumor, renal osteodystrophy, osteitis fibrosa, and leontiasis ossea, and knowing such conditions is of core importance for the multidisciplinary diagnosis and management of hyperparathyroidism. We aimed to perform a concise review, systematizing the concepts and mechanisms underlying hyperparathyroidism and associated gnathic alterations. In addition, a detailed description of the clinical aspects of the jaw manifestations is presented.

Diagnostic Accuracy of Noninvasive Bone Turnover Markers in Renal Osteodystrophy.

RATIONALE & OBJECTIVE: Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies. TESTS COMPARED: Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b). OUTCOME: Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99). RESULTS: All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis. LIMITATIONS: The single-center approach and heterogeneity of the study cohort are main limitations of this study. CONCLUSIONS: We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease.

Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation.

Bone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18-70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.

Static histomorphometry allows for a diagnosis of bone turnover in renal osteodystrophy in the absence of tetracycline labels.

A bone biopsy with prior tetracycline labeling is the gold standard to diagnose renal osteodystrophy. In cases of missing tetracycline labels, it is still paramount to gain clinically relevant information from the extracted bone sample, by evaluating the static histomorphometry. This study investigates the diagnostic performance of static histomorphometry for the evaluation of high and low bone turnover. Transiliac bone biopsies taken pre- or post- kidney transplantation, of sufficient quality for a full histomorphometric analysis were included (n = 205). The cohort was randomly split to provide separate exploration and validation subsets. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover, and all were significant predictors of both high and low bone turnover (AUC 0.71-0.84). Diagnostic performance was very good for high turnover, as a combination of static parameters resulted in negative and positive predictive values (NPV and PPV) of 80% and 96%, respectively. For low turnover, the combined model resulted in PPV of 71% and NPV of 82%. We conclude that in the absence of tetracycline labels, static histomorphometry provide an acceptable alternative for a diagnosis of bone turnover in renal osteodystrophy.

Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease.

Parathyroid hormone (PTH) is a key regulator of bone turnover but can be oxidized in vivo, which impairs biological activity. Variable PTH oxidation may account for the rather poor correlation of PTH with indices of bone turnover in chronic kidney disease. Here, we tested whether non-oxidized PTH is superior to total PTH as a marker of bone turnover in 31 patients with kidney failure included from an ongoing prospective observational bone biopsy study and selected to cover the whole spectrum of bone turnover. Receiver Operating Characteristic (ROC) curves, Spearman correlation and regression analysis of non-oxidized PTH, total PTH and bone turnover markers (bone-specific alkaline phosphatase, procollagen N-terminal pro-peptide and tartrate-resistant acid phosphatase 5b) were used to assess the capability of non-oxidized PTH vs. total PTH to discriminate low from non-low and high from non-high bone turnover, as assessed quantitatively by bone histomorphometry. Serum levels of non-oxidized PTH and total PTH were strongly and significantly correlated. Histomorphometric parameters of bone turnover and the circulating bone turnover markers showed similar correlation coefficients with non-oxidized PTH and total PTH. The area under the ROC (AUROC) values for discriminating between low/non-low turnover for non-oxidized PTH and total PTH were significant and comparable (0.82 and 0.79, respectively). For high/non-high turnover the AUROCs were also significant and of the same magnitude (0.76 and 0.80, respectively). Thus, measuring non-oxidized PTH using the currently available method provides no added value compared to total PTH as an indicator of bone turnover in patients with kidney failure.

Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA.

Mineral and bone disorder (MBD) is widely prevalent in children with chronic kidney disease (CKD) and is associated with significant morbidity. CKD may cause disturbances in bone remodelling/modelling, which are more pronounced in the growing skeleton, manifesting as short stature, bone pain and deformities, fractures, slipped epiphyses and ectopic calcifications. Although assessment of bone health is a key element in the clinical care of children with CKD, it remains a major challenge for physicians. On the one hand, bone biopsy with histomorphometry is the gold standard for assessing bone health, but it is expensive, invasive and requires expertise in the interpretation of bone histology. On the other hand, currently available non-invasive measures, including dual-energy X-ray absorptiometry and biomarkers of bone formation/resorption, are affected by growth and pubertal status and have limited sensitivity and specificity in predicting changes in bone turnover and mineralization. In the absence of high-quality evidence, there are wide variations in clinical practice in the diagnosis and management of CKD-MBD in childhood. We present clinical practice points (CPPs) on the assessment of bone disease in children with CKD Stages 2-5 and on dialysis based on the best available evidence and consensus of experts from the CKD-MBD and Dialysis working groups of the European Society for Paediatric Nephrology and the CKD-MBD working group of the European Renal Association-European Dialysis and Transplant Association. These CPPs should be carefully considered by treating physicians and adapted to individual patients' needs as appropriate. Further areas for research are suggested.

The role of static bone histomorphometry in diagnosing renal osteodystrophy.

BACKGROUND: Bone biopsy is the gold standard test to diagnose renal osteodystrophy (ROD). There is a preference to perform bone biopsy during renal transplantation but tetracycline bone labelling is usually not possible. We aimed to test if histomorphometry static parameters can identify low and high bone turnover as assessed by dynamic measurement using double tetracycline labelling. METHODS: 43 CKD stages 4-5D had trans-iliac bone biopsy using a 4 mm Jamshidi trephine and needle after tetracycline labelling. Quantitative histomorphometry was performed using the Bioquant Osteo histomorphometry system. Normal bone turnover was defined as bone formation rate/bone surface (BFR/BS) of 18-38 µm3/µm2/year. Static parameters of bone turnover included osteoblast surface/bone surface (Ob.S/BS, %), osteoclast surface/bone surface (Oc.S/BS, %) and erosion surface/bone surface (ES/BS, %). Receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of these static parameters for low and high bone turnover (based on BFR/BS). RESULTS: Median (IQR) for BFR/BS in this study was 32.12 (17.76-48.25) µm3/µm2/year. 26% of patients had low, 34% had normal and 40% had high bone turnover. The area under the ROC curve (AUC) for Ob.S/BS, Oc.S/BS and ES/BS were non-significant indicating poor accuracy for identifying low bone turnover. The AUC for Ob.S/BS was 0.697 (95% CI 0.538 to 0.827) indicating fair accuracy for identifying high bone turnover. Oc.S/BS and ES/BS had non-significant AUCs for high bone turnover. CONCLUSIONS: Static histomorphometry parameters for bone turnover are unable to replace dynamic parameter in diagnosing ROD. Tetracycline bone labelling is still required.

'Bone within bone appearance' in a pathological fracture.

A 60-year-old man presented to our hospital with complaints of pain and deformity on his right thigh for the past 2 days following a history of accidental slip and fall. Radiological investigations suggested a pathological type 2 Seinsheimer subtrochanteric fracture of the right femur with a 'bone within bone' appearance, which posed a diagnostic dilemma as this radiological appearance is seen in a spectrum of conditions. Radiographic skeletal survey failed to identify a similar appearance elsewhere in the body. Laboratory investigations pointed in favour of bone mineral disease, and histopathological examination of the bone narrowed it down to Paget's disease. The fracture was fixed with a contralateral distal femur locking compression plate. The fracture site failed to show signs of union until 6 months postsurgery and hence the patient was advised for grafting procedure. The patient deferred surgery and remains without major complications until 18 months of follow-up.

Real World Use and Effects of Calcimimetics in Treating Mineral and Bone Disorder in Hemodialysis Patients.

BACKGROUND: Calcimimetics are used to treat mineral and bone disorder by reducing parathyroid hormone (PTH), calcium (Ca), and phosphorus (Phos). The study objectives were to assess the control of PTH, Ca, and Phos over time in patients receiving cinacalcet or etelcalcetide as well as dosing and time to discontinuation for etelcalcetide. METHODS: This was a retrospective cohort study using electronic medical records from small and independent dialysis centers. Adults ≥18 years of age were identified as cinacalcet or etelcalcetide users based on the first calcimimetic received in 2018 (index date). Patients were followed from the index date until parathyroidectomy, kidney transplant, death, or end of data (December 31, 2018). Analyses of mean PTH, Ca, and Phos, as well as target achievement of PTH, Ca, and Phos were conducted over a 9-month period. Discontinuation with etelcalcetide was measured with the Kaplan-Meier estimator. RESULTS: There were 1,346 cinacalcet patients (mean age 60.5 years, 43.5% female, and 47.1% Black) and 1,255 etelcalcetide patients (mean age 63.4 years, 46.6% female, and 38.5% Black). At baseline, the proportions in target were similar for etelcalcetide versus cinacalcet: 36 versus 38% for PTH, 79 versus 80% for Ca, and 43 versus 44% for Phos. Overall, 40-47% of cinacalcet users and 48-62% of etelcalcetide users were observed to be in target for PTH over 9 months. The proportion in target for Phos ranged from 41 to 46% for cinacalcet and 46-51% for etelcalcetide. The proportion in target for Ca ranged from 74 to 78% for cinacalcet and 60-73% for etelcalcetide. Etelcalcetide 12-month discontinuation was 37.4%. CONCLUSION: Both calcimimetics were effective in keeping PTH, Ca, and Phos levels within target. Patients receiving etelcalcetide tended to have lower laboratory values for PTH, Ca, and Phos over time, while patients receiving cinacalcet tended to be more likely to be in target for Ca over time.

Quantitative histomorphometric analysis of halved iliac crest bone biopsies yield comparable ROD diagnosis as full 7.5mm wide samples.

BACKGROUND AND OBJECTIVES: Histomorphometric analysis of a transiliac bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (ROD). This procedure is costly, invasive and usually performed with a trephine with an internal diameter of 7.5 mm. Our objective was to evaluate the accuracy of ROD diagnosis on halved histological bone sections to determine if they are comparable to the standard 7.5 mm samples. DESIGN: We included 68 bone biopsies performed in CKD patients for diagnostic purposes with a 7.5 mm diameter trephine. Quantitative histomorphometric analysis of the whole bone samples was performed including assessment of bone mineralization, turnover and volume. Each histological section (representing the whole 7.5 mm diameter biopsy) was then divided lengthwise in two hemisections (representing the 3.5 mm diameter biopsy). Histomorphometric analysis was repeated this time on the two hemibiopsies for each sample, blinded from initial results. Diagnoses were classified as osteitis fibrosa, adynamic bone disease, mixed uremic bone disease, osteomalacia or other. Correlations between the whole sample and the hemibiopsies for each parameter were studied. Concordance between the various bone parameters and final ROD diagnosis obtained from the whole section versus the two hemi sections was evaluated. RESULTS: Highly significant correlations were found between parameters measured on the whole section and the corresponding hemisections, with r coefficient of 0.98 for osteoid surface and thickness and bone formation rate, 0.97 for osteoclast surface, and 0.96 for bone volume (p < 0.001). Final diagnosis was in full accordance between the whole biopsy and the two corresponding hemi-biopsies in 91% of cases. CONCLUSIONS: Accurate diagnosis of ROD type was obtained by evaluation of bone surface areas of 3 mm diameter. These data suggest that small invasive bone biopsies might provide accurate ROD diagnostics while decreasing both invasiveness and cost of the procedure.