Measuring bone metabolic activity in dialysis patients with renal osteodystrophy using [18F]-Sodium Fluoride positron emission tomography- comparison between static and dynamic measurements

AUTHORS

Louise Aaltonen, Niina Koivuviita, Marko Seppänen, Vesa Oikonen, Anna K. Kirjavainen, Heikki Kröger, Eliisa Löyttyniemi, Kaj Metsärinne

ABSTRACT

Background

Dynamic [18F]NaF PET has shown promising results in the measurement of bone metabolism in patients with renal osteodystrophy. Dynamic PET scans are challenging in clinical practice, and the objective of this study was to evaluate whether standardized uptake values measured by [18F]NaF PET could be a feasible method.

Methods

Twenty-eight patients on maintenance dialysis with confirmed renal osteodystrophy underwent a dynamic [18F]NaF PET scan. As a reference for bone metabolism, a bone biopsy was obtained from the anterior iliac crest (AIC). Tracer activity in bone was measured using Patlak analysis and standardized uptake values (SUV). SUV was also adjusted to tracer activity measured from the aorta 48–60 min after injection (SUVR).

Results

SUV measured in the lumbar spine (L1-L4) and at the AIC did not correlate with histomorphometric parameters obtained by bone biopsy. There was no statistically significant difference between SUV in different turnover groups. When adjusting the mean bone uptake of fluoride in the lumbar spine, there was a strong correlation with the blood clearance of tracer to bone (Ki). SUVR also correlated significantly with histomorphometric markers obtained by bone biopsy.

Conclusions

These results suggest that measurements of tracer activity in the blood 48–60 min after tracer injection could be used to correct SUVs from static [18F]NaF PET scans. However, further research and validation of the method is needed.

Retrospective Characterization of Bone Histomorphometric Findings in Clinical Patient Specimens

AUTHORS

Linnea Sellman, Xiaoyu Tong, Inari S Burton, Heikki Kröger

ABSTRACT

Background

Bone histomorphometry provides comprehensive information on bone metabolism and microstructure. In this retrospective study, we aimed to obtain an overview of the typical indications, referring hospitals, and histomorphometric quantification-based diagnoses of the bone tissue in our histomorphometry laboratory, the only laboratory in Finland carrying out histomorphometric examination of clinical bone biopsies.

Methods

Between January 1, 2005 and December 31, 2020, 553 clinical bone biopsies were sent to our histomorphometry laboratory for histomorphometric examination. The median age of the patients was 55 years (range, 0.2–89.9 years), 51% of them were males, and 18% comprised pediatric patients. We received bone biopsy specimens from 23 hospitals or healthcare units. The majority of the samples we sent by nephrologists.

Results

The most common bone biopsy indications were suspicion of renal osteodystrophy (ROD), unknown bone turnover status in osteoporosis, and several or untypical fractures. The most common quantitative bone histomorphometry-based diagnosis was ROD.

Conclusions

This study provides information on the clinical application of bone histomorphometry in Finland. Precise and quantitative ROD evaluation is the most common indication for bone histomorphometry, being crucial in clinical decision-making and targeted treatment of this patient group.

Bone Histomorphometry and 18F-Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and...

AUTHORS

Louise Aaltonen, Niina Koivuviita, Marko Seppänen, Inari S. Burton, Heikki Kröger, Eliisa Löyttyniemi & Kaj Metsärinne

ABSTRACT

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.

Infrared spectroscopy indicates altered bone turnover and remodeling activity in renal osteodystrophy

Authors

Hanna Isaksson, Mikael J Turunen, Lassi Rieppo, Simo Saarakkala, Inari S Tamminen, Jarno Rieppo, Heikki Kröger, Jukka S Jurvelin

Abstract

Renal osteodystrophy alters metabolic activity and remodeling rate of bone and also may lead to different bone composition. The objective of this study was to characterize the composition of bone in high-turnover renal osteodystrophy patients by means of Fourier transform infrared spectroscopic imaging (FTIRI). Iliac crest biopsies from healthy bone (n = 11) and patients with renal osteodystrophy (ROD, n = 11) were used in this study. The ROD samples were from patients with hyperparathyroid disease. By using FTIRI, phosphate-to-amide I ratio (mineral-to-matrix ratio), carbonate-to-phosphate ratio, and carbonate-to-amide I ratio (turnover rate/remodeling activity), as well as the collagen cross-link ratio (collagen maturity), were quantified. Histomorphometric analyses were conducted for comparison. The ROD samples showed significantly lower carbonate-to-phosphate (p < .01) and carbonate-to-amide I (p < .001) ratios. The spatial variation across the trabeculae highlighted a significantly lower degree of mineralization (p < .05) at the edges of the trabeculae in the ROD samples than in normal bone. Statistically significant linear correlations were found between histomorphometric parameters related to bone-remodeling activity and number of bone cells and FTIRI-calculated parameters based on carbonate-to-phosphate and carbonate-to-amide I ratios. Hence the results suggested that FTIRI parameters related to carbonate may be indicative of turnover and remodeling rate of bone.

Link to Article

http://dx.doi.org/10.1002/jbmr.10