Objective To examine the relationship between vertebral trabecular bone mineral density (tBMD), vertebral strength, and syndesmophytes in patients with ankylosing spondylitis (AS) using quantitative computed tomography (QCT). Methods We performed QCT of the spine to measure syndesmophytes and tBMD in 5 vertebrae (T11–L3) in 61 patients with AS. Finite element analysis was performed to measure vertebral strength in compressive overload, including in trabecular and cortical compartments. In cross‐sectional analyses, we examined associations of syndesmophyte height with tBMD and vertebral strength in each vertebra. In 33 patients followed up for 2 years, we investigated whether baseline tBMD and vertebral strength predicted syndesmophyte growth in the same vertebra, and vice versa. Results In the cross‐sectional analyses, 126 vertebrae had bridging, 77 vertebrae had nonbridging syndesmophytes, and 83 vertebrae had no syndesmophytes. There were strong inverse associations between syndesmophyte height and tBMD, total strength, and trabecular strength only among bridged vertebrae. In the longitudinal analysis, nonbridged vertebrae with low tBMD (adjusted β = –0.01 [95% confidence interval (95% CI) –0.019, –0.0012]) and low strength (adjusted β = –0.0003 [95% CI –0.0004, –0.0002]) had more syndesmophyte growth over time. Similar associations were absent among bridged vertebrae. Conversely, vertebrae with bridging at baseline had a significant loss in percent tBMD over time (adjusted β = –0.001 [95% CI –0.0017, –0.0004]). Conclusion Associations between syndesmophytes and vertebral density and strength in AS differ between bridged and nonbridged vertebrae. Among nonbridged vertebrae, low tBMD and strength are associated with syndesmophyte growth. Bridging is associated with large subsequent losses in tBMD, possibly due to mechanical offloading.

Background: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies—blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)—were employed to investigate their complementary roles. Methods: Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. Results: A total of 25 patients were included. We analyzed 534 samples by ddPCR (n = 25), 256 samples by NGS (n = 24) and 371 samples by eLB (n = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61–272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant EGFR by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. EGFR/ERBB2/MET/KRAS amplifications, EGFR C797S, PIK3CA E545K, PTEN V9del, and CTNNB1 S45P were key resistance mechanisms identified by NGS. Conclusion: Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles.

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