Association of Aromatase Inhibitor-Associated Musculoskeletal Symptoms with Ultrasonographic Changes at the Wrist.
Authors: Henry N. , Jacobson J. , Banerjee M. , Hayden J. , Smerage J. , Stearns V. , Hayes D. 
Published: December 2010

Background: About 40% of aromatase inhibitor (AI)-treated women develop AI-associated musculoskeletal symptoms (AIMSS) such as arthralgias, but the etiology is unclear. Tendon sheath fluid and tenosynovial changes have been demonstrated by imaging in symptomatic AI-treated patients. It is unclear if these changes correlate with development of AIMSS.Methods: Thirty consecutive patients (pts) initiating therapy with letrozole or exemestane on a prospective clinical trial were enrolled to this substudy. Pts with prior wrist trauma or who declined to provide informed consent were excluded. Pts underwent high resolution ultrasonography (US) of the wrists bilaterally and completed the Health Assessment Questionnaire (HAQ), pain Visual Analog Scale (VAS), and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire at baseline (BL) and after 3 mo of AI. AIMSS was defined as increase in HAQ or pain VAS score during AI therapy that exceeded a predefined cutoff. Analysis of US images was performed in a blinded manner. Imaging abnormalities included the following: presence of fluid, synovitis, and/or hyperemia in the tendon sheath or joint recess. Statistical analysis was performed using univariate chi-square tests and logistic regression analyses.Results: Of the 30 enrolled subjects, 25 completed both BL and 3 mo assessments. Eight of 30 (27%) discontinued therapy because of AIMSS (2 before and 6 after the 3 mo timepoint), and 3 patients discontinued therapy for unrelated reasons. All patients have been followed for at least 6 mo. We observed a significant association between early treatment discontinuation and change in HAQ (Odds Ratio (OR) 1.525, p=0.0006) and VAS (OR 1.307, p=0.0096) but not DASH (OR 1.001, p=0.96) scores between BL and 3 mo. The proportion of pts with abnormalities on US at BL or that developed during therapy is given in tables 1 and 2, respectively. We did not observe a statistically significant correlation between objective abnormalities on US at BL or following initiation of AI therapy and the development of AIMSS or early treatment discontinuation because of AIMSS.Conclusions: Clinically relevant musculoskeletal symptoms develop in AI-treated women, leading to treatment discontinuation in a substantial percentage. However, patient-reported symptoms were not associated with inflammatory changes visible on wrist US in this pilot study.Proportion of pts with US abnormalities at BL # with abnl/total ptsof pts with AIMSS, # with US abnlof pts without AIMSS, # with US abnlof pts who d/c AI b/c AIMSS, # with US abnlof pts who continued AI, # with US abnlAny anatomic site27/30 (90%)9/10 (90%)18/20 (90%)7/8 (88%)20/22 (91%)--Tendon sheath14/30 (47%)7/10 (70%)7/20 (35%)5/8 (63%)9/22 (41%)--Joint recess24/30 (80%)6/10 (60%)18/20 (90%)6/8 (75%)18/22 (82%) Proportion of pts who developed new abnormalities on US during AI therapy # with abnl/total ptsof pts with AIMSS, # with US abnlof pts without AIMSS, # with US abnlof pts who d/c AI, # with US abnlof pts who continued AI, # with US abnlAny anatomic site13/25 (52%)5/9 (56%)7/16 (44%)4/6 (67%)7/19 (37%)--Tendon sheath5/25 (20%)2/9 (22%)3/16 (19%)0/6 (0%)5/19 (26%)--Joint recess12/25 (48%)5/9 (56%)6/16 (38%)4/6 (67%)6/19 (32%) 

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 802.