Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.

Download Full-text

MO568STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE EVALUATION OF BONE TURNOVER IN RENAL OSTEODYSTROPHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab086.006 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Hanne Skou Jørgensen ◽

Geert Behets ◽

Patrick D'Haese ◽

Pieter Evenepoel

Keyword(s):

Bone Turnover ◽

Diagnostic Accuracy ◽

Renal Osteodystrophy ◽

Bone Biopsy ◽

Bone Formation Rate ◽

Suitable Alternative ◽

Predictive Values ◽

Bone Biopsies ◽

Low Bone Turnover ◽

Tetracycline Labeling

Abstract Background and Aims A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover. Method Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100). Results All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p < 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1. Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm>5.4%, OcPm>1.5%, and OAr>2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%. Conclusion Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.

Download Full-text

The Calcemic Response to Continuous Parathyroid Hormone (PTH)(1-34) Infusion in End-Stage Kidney Disease Varies According to Bone Turnover: A Potential Role for PTH(7-84)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1909 ◽

2010 ◽

Vol 95 (6) ◽

pp. 2772-2780 ◽

Cited By ~ 45

Author(s):

Katherine Wesseling-Perry ◽

G. Chris Harkins ◽

He-jing Wang ◽

Robert Elashoff ◽

Barbara Gales ◽

...

Keyword(s):

Los Angeles ◽

Bone Turnover ◽

Healthy Volunteers ◽

Serum Calcium ◽

Bone Biopsy ◽

Dialysis Patients ◽

High Bone Turnover ◽

Dihydroxyvitamin D ◽

High Bone ◽

Adynamic Bone

Abstract Context: Factors contributing to PTH resistance in dialysis patients remain elusive. Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients. Design: The study was a prospective, controlled assessment of response to PTH(1-34). Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center. Participants: Nineteen dialysis patients and 17 healthy volunteers were studied. Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg · h for 46 h. Bone biopsy was performed in all dialysis patients. Main Outcome Measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion. Results: Serum calcium levels rose in healthy volunteers (9.2 ± 0.1 to 11.9 ± 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 ± 0.3 to 10.7 ± 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 ± 0.1 to 3.5 ± 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 ± 0.4 to 8.0 ± 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover. Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.

Download Full-text

Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation

Calcified Tissue International ◽

10.1007/s00223-021-00917-1 ◽

2021 ◽

Author(s):

Satu M. Keronen ◽

Leena A. L. Martola ◽

Patrik Finne ◽

Inari S. Burton ◽

Xiaoyu F. Tong ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Bone Turnover ◽

Kidney Transplant ◽

Bone Biopsy ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Bone Biomarkers ◽

High Turnover ◽

High Bone Turnover ◽

High Bone

AbstractBone 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.

Download Full-text

Changes in Bone Histomorphometry after Kidney Transplantation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.09950818 ◽

2019 ◽

Vol 14 (6) ◽

pp. 894-903 ◽

Cited By ~ 11

Author(s):

Satu Keronen ◽

Leena Martola ◽

Patrik Finne ◽

Inari S. Burton ◽

Heikki Kröger ◽

...

Keyword(s):

Kidney Transplantation ◽

Bone Turnover ◽

Kidney Transplant ◽

Bone Biopsy ◽

Bone Volume ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mineral Density ◽

Low Bone Turnover ◽

High Bone

Background and objectivesOver 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, & measurementsSixty 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.ResultsA 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.ConclusionsBone 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.

Download Full-text

High bone turnover markers and disturbances of bone mineral density in children with hypophosphataemic rickets

Bone Abstracts ◽

10.1530/boneabs.6.p074 ◽

2017 ◽

Author(s):

Agnieszka Rusinska ◽

Izabela Michalus ◽

Izabela Woch ◽

Paulina Adamiecka ◽

Danuta Chlebna-Sokol

Keyword(s):

Bone Mineral Density ◽

Bone Turnover ◽

Bone Mineral ◽

Bone Turnover Markers ◽

Mineral Density ◽

Hypophosphataemic Rickets ◽

High Bone Turnover ◽

High Bone ◽

Turnover Markers

Download Full-text

The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves’ Disease

PLoS ONE ◽

10.1371/journal.pone.0144599 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0144599 ◽

Cited By ~ 10

Author(s):

Sun Wook Cho ◽

Jae Hyun Bae ◽

Gyeong Woon Noh ◽

Ye An Kim ◽

Min Kyong Moon ◽

...

Keyword(s):

Bone Turnover ◽

Graves Disease ◽

Blocking Antibody ◽

High Bone Turnover ◽

High Bone ◽

Premenopausal Patients

Download Full-text

Raloxifene Has No Efficacy in Reducing the High Bone Turnover and the Risk of Spontaneous Vertebral Fractures after Denosumab Discontinuation

Case Reports in Rheumatology ◽

10.1155/2018/5432751 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Elena Gonzalez-Rodriguez ◽

Delphine Stoll ◽

Olivier Lamy

Keyword(s):

Bone Loss ◽

Bone Turnover ◽

Aromatase Inhibitors ◽

Vertebral Fractures ◽

Bone Markers ◽

Rebound Effect ◽

High Bone Turnover ◽

Antiresorptive Agent ◽

High Bone

At denosumab discontinuation, an antiresorptive agent is prescribed to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report the case of a woman treated with aromatase inhibitors and denosumab for 5 years. Raloxifene was then prescribed to prevent the rebound effect. Raloxifene was ineffective to reduce the high bone turnover and to avoid spontaneous clinical vertebral fractures. We believe that among the antiresorptive treatments, the most powerful bisphosphonates should be favored, and their administration adapted according to the serial follow-up of bone markers.

Download Full-text