Chronic Kidney Disease and Bone - Correlation Between 18F-PET-TT Imaging and Histomorphometry of Bone in CKD Patients
Chronic Kidney Disease and Bone - Correlation Between 18F-PET-TT Imaging and Histomorphometry of Bone in CKD Patients
Chronic kidney disease (CKD) is an increasing public health problem and the number of patient
 with chronic kidney disease is increasing worldwide. Bone abnormalities are found almost
 universally in patients with CKD requiring dialysis and in the majority of patients with CKD
 stages 3-5. Chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex disorder of
 bone and mineral metabolism, which is associated with disorder in circulating levels of
 hormones and development of secondary hyperparathyroid disease. The abnormalities of mineral
 homeostasis impair bone remodeling and mineralization and results in cortical and trabecular
 defects and an increased fracture risk. There is also an association with increased morbidity
 and mortality. CKD-MBD is also associated with development of calcification of the blood
 vessels. During the last decade it has been increasingly acknowledged that mineral and bone
 disorder contribute to the excessively high cardiovascular morbidity and mortality in
 patients with chronic kidney disease.

 The diagnosis of mineral bone disorder and the underlying bone histology in CKD patients is
 challenging. The treatment of renal osteodystrophy (ROD) and especially the treatment of
 fractures in this patient group, depends on the underlying bone histopathology and bone
 turnover. The gold standard for diagnosing the subtypes of ROD is bone biopsy, but it is
 invasive and requires considerable expertise regarding quantitative histomorphometry and
 interpretation. Plasma parathormone (PTH) measurement is commonly used to evaluate these
 patients, and generally extremely high or low PTH levels predict the underlying bone
 disorder. Still PTHs ability to correctly estimate turnover in bone is limited. Several
 biomarkers such as tartrate-resistant acid phosphatase 5b (TRAP5b) and procollagen type 1
 N-terminal propetide (PINP) has been investigated, but no biomarker in clinical use has yet
 been proven suitable or superior to PTH to estimate overall bone histology.

 18F-NaF positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging
 technique that allows assessment of regional bone turnover at clinically relevant sites.
 18F-NaF is a bone-seeking tracer, which reflects remodeling of bone and osteoblast
 activity25. 18F-NaF serves as an efficient tracer to measure metabolic changes in bone. A
 correlation between histomorphometric markers such as bone formation rate (BFR) and tracer
 activity in the 18F- NaF PET scan in CKD patients has previously been shown in one small
 study.

 This study's goal is to evaluate, if 18-NaF-Positron emission tomography-computed tomography
 (18F-PET-TT) can be used in the assessment of CKD patients. The hypothesis is that 18F-PET-TT
 correlates with the histomorphometry of bone biopsy and with the calcification score in CKD
 patients and that 18F-PET-TT maybe can be used as a diagnostic imaging technique in the
 future.
This is a cross-sectional prospective study. 10 - 20 patients with secondary/tertiary
 hyprparathyreoidism on oeritoneal dialysis, hemodialysis, predialysis patients and patients,
 who have received a kidney transplant will be included,. Data collection in the dialysis
 group is finnished and the first article published (Aaltonen et al, Bone 2020). A control
 group was recruited for validation of the PET-method.

 All participants undergo a 18F-PET-TT scan. PET, with the short half-life bone seeking
 18F-Sodium Fluoride (18F-NaF), provide an unique way of assessment of regional bone
 metabolism. 18F-NaF binds to sights of new bone formation and serves as a marker of bone
 blood flow and osteoblastic activity. A dynamic 18F-PET-TT imaging is first done of the
 lumbar region of the spine, following with a static PET-TT and also measurement of
 calcification score using PET-TT. 18F-NaF is injected intravenously by direct venipuncture or
 intravenous catheter. All the patients are also asked for permission to use DNA-samples if
 needed.

 Blood tests measuring the bone formation and turnover will be taken during the normal
 clinical controls of the patients or at the latest wheb the bone biopsy is takekn.
 Echocardiogram, which is reasonable sensitive, is done to detect and evaluate valvular
 calcification. Bone biopsy is done in the day care unit within one month from the PET-scan.
 To obtain information about dynamic parameters of the bone, the patients had double labeling
 with tetracycline. The biopsy is taken in local anesthesia from the anterior iliac spine
 vertically.
Inclusion Criteria:

 -  Patients with severely decreased kidney function (eGRF below 20ml/min) with secondary
 hyperparathyroidism. In addition a group of healthy volunteers.

 Exclusion Criteria:

 -  Pregnancy, parathyroidectomy, biphosphonate-medication.