Background <p>Sodium [¹⁸F]Fluoride Positron Emission Tomography (Na[¹⁸F]F PET) is a promising imaging biomarker for evaluating bone metabolism in spondyloarthritis (SpA) and other bone affecting diseases. Accurate quantification of tracer uptake is essential for assessing disease activity and treatment response. This study aimed to determine optimal simplified metrics for Na[¹⁸F]F uptake and evaluate their performance compared to net influx rate (<i>K</i>_<i>i</i>).</p> Results <p>A prospective study included 54 SpA patients undergoing Na[¹⁸F]F PET/CT scans at baseline and after 12 weeks of therapy. Dynamic PET in combination with venous blood sampling was analyzed to derive kinetic parameters, including <i>K</i>_<i>i</i> in 43 scans that included pathological uptake in the dynamic field of view. Semi-quantitative standardized uptake values (SUVs) corrected body weight (BW), lean body mass (LBM), body surface area (BSA) and skeletal volume (SV) were compared and correlations between <i>K</i>_<i>i</i> and SUVs were assessed cross-sectionally and longitudinally. Based on analysis of the blood sample data, there was a significant difference between SUV corrected for BW between patients who weighted more and less than 85 kg (p &lt; 0.01 at all sample moments). When LBM or SV was used, this difference disappeared (p &gt; 0.05). There was a significant correlation between <i>K</i>_<i>i</i> and various SUV-metrics, with SUV_peak-LBM at 25–30 min yielding the highest correlation both cross-sectionally (R² = 0.77, p &lt; 0.01), and longitudinally (R² = 0.54, p &lt; 0.01).</p> Conclusions <p>Na[¹⁸F]F uptake quantification of lesions in the axial skeleton of SpA patients can be performed cross-sectionally and longitudinally with simplified uptake measures, particularly SUV_peak, normalized using LBM or SV. This offers a more reliable approach to evaluating disease activity and treatment responses compared to BW.</p>