Of those, 15 were performed at 6 months and 6 were performed as an interim MRI. weeks (range 2 to 18) and 75% of symptomatic patients designed symptoms by 8 weeks. Later stage malignancy and worse quality of life (QOL) pre-treatment were significantly associated with symptom development. Sixty-eight percent of symptomatic subjects experienced involvement of the hands however, there was no difference in the mean switch in grip strength (?2.9 kg vs ?1.3 kg, p-value=0.6). Among symptomatic subjects, 46% had evidence of focal tenosynovitis of the hands and feet on examination. Although some symptomatic subjects had new MRI abnormalities, RAMRIS scores did not significantly switch. Conclusion The incidence of AI associated musculoskeletal syndrome is over 50% with nearly all women developing symptoms by 8 weeks. The key obtaining in symptomatic women was focal tenosynovitis of the hands Narcissoside and feet, without evidence of autoimmune disease or systemic inflammation. Later stage Narcissoside malignancy and poorer QOL were predictive of symptom development. Third generation aromatase inhibitors (AIs) are quickly replacing tamoxifen as the standard adjuvant endocrine therapy for hormone receptor positive, post-menopausal breast cancer. Adherence to this crucial therapy has been limited by debilitating musculoskeletal side effects. Adverse event reporting from large randomized controlled trials (RCTs) has consistently shown higher rates of arthralgia in patients taking AIs.[1-7] Of RCT participants, 5-10% discontinued therapy due to musculoskeletal symptoms. In several practice based studies, the incidence rates of AI-associated arthralgia were higher than those reported in RCTs ranging from 32-47% with a concerning rate of discontinuation of 13-50%.[9-11] Despite its clinical significance, the AI-associated musculoskeletal syndrome remains poorly Narcissoside defined. Reports on time to onset of symptoms have a broad range from 6 weeks to 6 months.[7,9] Case series have described arthralgia, myalgia and stiffness in women on AIs, predominantly involving the hands and wrists.[12-14] In 2 small studies, Morales et. al describe tenosynovitis presenting as trigger finger, carpal tunnel syndrome (CTS) and deQuervains tendonitis. [15-16] Other studies however, describe a more common anatomic involvement presenting as osteoarthritis and tendonitis . Risk factors for symptom development have also been discordant in the literature. While some studies have suggested an increased risk with lesser BMI, chemotherapy and previous hormone replacement therapy [7,10] others have not demonstrated this relationship.  We conducted a 6-month, prospective, pilot study of breast malignancy patients starting adjuvant AI therapy with the goal of describing the associated musculoskeletal syndrome. In this study we aim specifically to define the incidence, time to onset and risk factors for symptoms development as well as to describe the clinical presentation. To achieve our objective, and provide a comprehensive description of the syndrome, we performed and considerable rheumatologic work-up including QOL Narcissoside questionnaires, physical examination, laboratory studies and MRI. Grip strength, a well-validated, objective measure of hand impairment was chosen as the main end result measure based on the existing AI literature which suggests that this musculoskeletal effects of AIs are seen predominantly in the hands. [15,16] Choosing the same end result measure allowed calculation of a rational sample size. We anticipate that description of this syndrome will guide physicians in counseling and treating patients with the hope of improving compliance with this important therapy. PATIENTS AND METHODS Patients Post-menopausal women with stage I – III hormone receptor positive breast malignancy, starting adjuvant AI therapy were enrolled. Exclusion criteria included previous use of AIs, corticosteroid use in the 4 weeks prior to enrollment, other active cancer not in remission (excluding non-melanomatous skin malignancy) or previous diagnosis of any systemic rheumatic diseases or crystal-induced arthritides. Study Design In this prospective, single center, observational, cohort study patients were evaluated by a rheumatologist before initiating AI therapy, at 3 months and at 6 months. Symptomatic patients were defined as those who either: (1) responded in the affirmative at their 3 or 6 months scheduled study visit to the question Have you developed new or worsening muscle mass and/or joint symptoms since starting AIs? (2) contacted an investigator to statement new or worsening symptoms at any time. If symptoms were reported between scheduled study visits, the patient was brought in for an additional interim visit within 7 days of symptom report. All patients without contraindication experienced contrast-enhanced magnetic resonance imaging (MRI) of bilateral hands and wrists at baseline and 6 months. Symptomatic participants had an additional interim MRI of the hands and wrists only if they also Ccr3 had an abnormal hand or wrist rheumatologic exam. The interim MRI.
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- The authors wish to acknowledge The Childrens Memorial Health Institute, Warsaw, Poland for the access to Q-TOF LC/MS; mass spectrometer purchase was supported by European POIG
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