Up to half of patients on AI therapy experience musculoskeletal symptoms, and up to 20% will discontinue therapy because of intolerable side effects; therefore, AIMSS has become an important clinical issue requiring effective management.
Effective management of AIMSS is still a mystery in clinical practice, as the mechanisms behind AIMSS are not clearly understood. A number of small interventional trials investigating acupuncture
[19, 20], vitamin D
, short-term low-dose prednisolone
, thymosin α1
 and yoga
 have provided various treatment strategies. However, most of these trials have had some methodological and practical limitations, including small sample sizes, larger-than-anticipated drop-out, a single-center design, lack of control group and blinding, and a short follow-up period. Therefore, developing appropriate management strategies for AIMSS will require further investigation. To date, there is still a lack of prospective, randomized, controlled trials to provide powerful evidence supporting the use of various treatment modalities. Our study will be the first randomized, double-blind, placebo-controlled clinical trial analyzing the efficacy and safety of TCM in patients with AIMSS.
There are several limitations to our study. One limitation is the absence of specific measures for AIMSS. AIMSS is a set of symptoms involving the bone, muscles and joints. There are no questionnaires specially designed for AIMSS. Through reviewing the literature and reported studies
[20, 23, 26], rheumatological questionnaires may be validated in the longitudinal assessment of joint symptoms, although the pathological processes are likely to be different. We selected WOMAC and M-SACRAH that focus on joint pain, stiffness, and functional status in the hands and knees, which are the most common locations of pain. Another limitation is the indeterminate diagnostic criteria of AIMSS. Musculoskeletal symptoms are reported according to different terms (for example, arthralgia, joint symptoms, joint pain, and musculoskeletal symptoms) in the literature. Because of the lack of clear diagnostic criteria, various clinical trials have reported a wide range of AIMSS incidence and research objects, which confuses physicians and investigators and makes it challenging to recognize the manifestations of AIMSS and to establish acceptable inclusion criteria. In order to clear the clinical characteristics of AIMSS and inclusion criteria, we defined AIMSS, through reviewing the literature
[10, 11, 27, 28], as self-reported ongoing musculoskeletal symptoms, including arthralgia, joint stiffness, joint swelling, bone pain, myalgia, carpal tunnel syndrome, and trigger finger, which started or worsened after taking an AI.
The results of this study will provide a new evidence-based treatment strategy for patients suffering from AIMSS.