Aims. Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex. Methods. Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed. Results. Expression of senescence markers (CDKN2A/p16, CDKN2D/p19) and EZH2 was significantly higher in tendinopathies compared to fracture or healthy tissue controls and positively correlated with the degree of tissue degeneration. Immunofluorescent stainings demonstrated colocalization of p16 and p19 with EZH2 in tenocytes. Treatment of tendon biopsies with EPZ-6438 reduced secretion of a panel of SASP factors, including interleukin-6 (IL6), IL8, matrix metalloproteinase-3 (MMP3) or GRO1, similarly to the senotherapeutic compound AG490. Conclusion. We demonstrate that senescence traits accumulate in pathological tendon tissues and positively correlate with tissue degeneration. Increased expression of CDKN2A/p16 and CDKN2D/p19 coincides with EZH2 expression, while its inhibition decreased the secretion of SASP factors, indicating a possible regulatory role of EZH2 in tenocyte senescence in tendinopathies. Reduction of cellular senescence, e.g. with EPZ-6438, opens ways to new potential therapeutic approaches for enhancing regeneration in chronic tendinopathies. Cite this article: Bone Joint Res 2025;14(2):143–154

Aims. The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy. Methods. A total of 16,238 preoperative OSS were available in the National Joint Registry (NJR) for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey dataset (April 2012 to April 2022). Prior to CAT, the foundational item response theory (IRT) assumptions of unidimensionality, monotonicity, and local independence were established. CAT compared sequential item selection with stopping criteria set at standard error (SE) < 0.32 and SE < 0.45 (equivalent to reliability coefficients of 0.90 and 0.80) to full-length patient-reported outcome measure (PROM) precision. Results. Confirmatory factor analysis (CFA) for unidimensionality exhibited satisfactory fit with root mean square standardized residual (RSMSR) of 0.06 (cut-off ≤ 0.08) but not with comparative fit index (CFI) of 0.85 or Tucker-Lewis index (TLI) of 0.82 (cut-off > 0.90). Monotonicity, measured by H value, yielded 0.482, signifying good monotonic trends. Local independence was generally met, with Yen’s Q3 statistic > 0.2 for most items. The median item count for completing the CAT simulation with a SE of 0.32 was 3 (IQR 3 to 12), while for a SE of 0.45 it was 2 (IQR 2 to 6). This constituted only 25% and 16%, respectively, when compared to the 12-item full-length questionnaire. Conclusion. Calibrating IRT for the OSS has resulted in the development of an efficient and shortened CAT while maintaining accuracy and reliability. Through the reduction of redundant items and implementation of a standardized measurement scale, our study highlights a promising approach to alleviate time burden and potentially enhance compliance with these widely used outcome measures. Cite this article: Bone Joint Res 2024;13(8):392–400