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

Abstract

Objectives: Excessive 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.

Methods: Twelve 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.

Results: At 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.

Fig. 1

Axial and sagittal PET images before and 12 weeks after the start of anti-TNF therapy (A) Baseline PET scan with ¹⁸F-fluoride accumulation throughout the spine. (B) After 12 weeks there was a heterogeneous effect of anti-TNF therapy on ¹⁸F-fluoride uptake: part of the AS lesions show a decrease (solid arrow) and others an increase (dashed arrow). Accumulation in the lumbar facet joints was regarded as OA (solid arrow head).

Fig. 2

H&E and Goldner stained histology images of vertebral bone biopsies (A) H&E staining overview of a PET-positive bone biopsy with the conjunction of connective tissue and bone matrix (20×). (B) H&E staining (detailed view of a PET-positive lesion; 200×) with cell infiltration in connective tissue. (C) Goldner staining of the same area with osteoid depositions (red) in areas with inflammation (40×). (D) Goldner staining of a PET-negative bone biopsy with minor osteoid depositions.