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

Abstract

<b><i>Introduction:</i></b> Invasive bone biopsy to assess bone metabolism in patients with chronic kidney disease-mineral and bone disorder may be replaced by the noninvasive <sup>18</sup>F-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 <sup>18</sup>F-NaF PET/CT and biomarkers (bone-specific alkaline phosphatase, osteocalcin, fibroblast growth factor 23, and osteoprotegerin). <b><i>Methods:</i></b> A cross-sectional study included 17 dialysis patients, and results from <sup>18</sup>F-NaF PET/CT scans and the biomarkers were directly compared with the results of histomorphometric analyses of tetracycline double-labeled trans-iliac bone biopsies. <b><i>Results:</i></b> 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 (K<sub>i</sub>) from <sup>18</sup>F-NaF PET/CT correlated with bone turnover parameters obtained by bone biopsy (activation frequency: <i>r</i> = 0.82, <i>p</i> < 0.01; bone formation rate/bone surface: <i>r</i> = 0.81, <i>p</i> < 0.01), and K<sub>i</sub> defined low turnover with high sensitivity (83%) and specificity (100%). CT-derived radiodensity correlated with bone volume, <i>r</i> = 0.82, <i>p</i> < 0.01. Of the biomarkers, only osteocalcin showed a correlation with turnover assessed by histomorphometry. <b><i>Conclusion:</i></b> In conclusion, <sup>18</sup>F-NaF PET/CT may be applicable for noninvasive assessment of bone turnover and volume in CKD-MBD.

Utility of a simplified [18F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications

“…For 18 F, this hypothesis is supported by a study by Reeve et al in patients with postmenopausal osteoporosis that reported correlations between bone blood flow measured using [ 18 F]NaF, bone turnover measured using [ 85 Sr]SrCl 2 , and dynamic bone histomorphometry performed at the iliac crest (11). It is also supported by more recent studies that have examined the correlations between K i measurements at the spine and hip and indices of bone formation measured by bone biopsy in patients with chronic kidney disease mineral and bone disorder (CKD-MBD) (3,4).…”

“…The link between quantitative measurements of [ 18 F]NaF kinetics and bone formation rate is supported by a study by Reeve et al that used both [ 18 F]NaF and [ 85 Sr]SrCl 2 together with dynamic bone histomorphometry to establish correlations between skeletal blood flow, calcium-surrogate bone mineral uptake, and mineral apposition rate in patients with postmenopausal osteoporosis (11). In more recent studies, bone metabolic flux (K i ) values obtained using [ 18 F]NaF PET have been compared with measurements of bone formation rate made by the gold standard method of bone biopsy in patients with CKD-MBD (Figure 4) (3,4). By comparison with [ 18 F]NaF PET-CT, bone biopsy is a painful and complex procedure that is limited to a single biopsy site at the iliac crest, is subject to significant measurement errors and is now rarely performed, with many centres not having the necessary resources.…”

“…Quantitative [ 18 F]NaF PET-CT is used as an imaging biomarker that is considered to provide a measure of the site-specific rate of bone formation ( 3 , 4 , 14 ). However, possible confounding artefacts include atherosclerosis, vascular calcification, and inflammation.…”

“…One application that has attracted interest is the potential of [ 18 F]NaF PET-CT scans to help with the investigation of patients with CKD-MBD, in particular whether measurements of lumbar spine K i can differentiate patients with high turnover disease such as secondary hyperparathyroidism from those with low bone turnover such as adynamic bone disease (ABD) ( 3 , 4 , 38 , 39 ) and improve on the sensitivity and specificity of existing diagnostic methods based on measurements of intact parathyroid hormone (iPTH) and other bone turnover markers ( 40 ). An interesting aspect of these studies is that, in addition to providing data on potential diagnostic thresholds for K i for the detection of ABD, they also involve measurements of bone turnover using bone biopsy with tetracycline labelling at the iliac crest.…”

“…Unlike the more familiar technique of [ 18 F]FDG, which images malignant disease, quantitative [ 18 F]NaF PET-CT scans measure bone metabolic flux (K i , alternatively known as regional bone plasma clearance), a measure that correlates with the rate of bone formation at the measurement site ( 3 , 4 ). The conventional protocol for performing the studies has involved an hour-long dynamic PET scan at a single bed position combined with arterial blood sampling to measure the arterial input function (AIF) ( 5 ).…”