Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography

Abstract

ObjectivesExcessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment.MethodsTwelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks.ResultsAt baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC −1.0; P < 0.001) and SI joints (mean SUVAUC −1.2; P = 0.03) in contrast to non-responders.Conclusions 18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment.

HLA-B27–mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis

“…First, in the BM of AS patients, most TNAP-positive cells are of myelocyte/monocyte lineages and MSCs. Although we found a diffuse enhancement of TNAP expression in MSCs of the BM of AS, it was reported that only the BM near cortical bone in AS showed localized enhancement of osteogenesis (58). This discrepancy might be explained by a report stating that the unique microenvironmental niche of BM favored the stemness of MSCs and prevented their spontaneous osteogenesis (59).…”

Performance of 18F-sodium fluoride positron emission tomography with computed tomography to assess inflammatory and structural sacroiliitis on magnetic resonance imaging and computed tomography, respectively, in axial spondyloarthritis

“…In a recent study, biopsy procedures were used to collect material from PET-positive lesions in the spine for immunohistochemistry. These PET-positive lesions corresponded to osteoid formation and osteoclasts along with cell infiltrates in areas with both bone and connective tissue, which were largely absent in PET-negative lesions [22]. This study also showed that 18 F-NaF PET/CT may detect changes in bone formation in AS during treatment, as one third of the PET-positive lesions in the spine disappeared after 12 weeks of TNF blocker treatment in their population of 12 patients with AS.…”

Quantitative Imaging in Inflammatory Arthritis: Between Tradition and Innovation

“…In this latter study, 12 patients had a significant decrease in SUV-AUC values (i.e., SUV corrected for individual integrated whole blood activity concentration) in the sacroiliac and costovertebral joints after treatment with tumor necrosis factor (TNF)α inhibitors. 127 Aiming to further increase the diagnostic accuracy at diagnosis and after treatment of PET/CT, several alternative tracers have been explored, in particular in animal models. For instance, it was demonstrated that 68 Ga-citrate has a Fig.…”