Hypovitaminosis D is a predictor of aromatase inhibitor musculoskeletal symptoms.

The aromatase inhibitor (AI)-associated musculoskeletal (MSK) pain symptoms are often debilitating and limit compliance with this important hormonal breast cancer therapy. The etiology of this syndrome is unknown. Hypovitaminosis D has been suggested as a possible risk factor for the development of MSK symptoms in women starting AIs. The objective of this substudy was to define the prevalence of low 25(OH)D in this population, to assess risk of low levels on developing pain and to define a target therapeutic goal for 25(OH)D in this population. This analysis was part of a 6-month prospective cohort study examining the MSK side effects of adjuvant AI therapy in postmenopausal women. Patients were evaluated by a rheumatologist with a joint examination, had 25(OH)D levels measured and completed quality of life questionnaires at baseline, 3 and 6 months. Symptomatic patients were defined as those that self-reported new or worsening MSK symptoms. Of 52 patients, 28 (54%) were symptomatic, and two (3.8%) stopped AIs due to MSK ailments. Thirteen patients had objective evidence of tendonitis on rheumatologic examination. Thirty-three percent of all subjects had baseline 25(OH)D levels <40 ng/mL, 19.2% had levels <30 ng/mL and 5.8% had levels <20 ng/mL. Symptomatic patients were more likely to have had baseline levels below 40 ng/mL, compared with asymptomatic patients (46.4% versus 16.7%, p = 0.037). In multivariate regression analyses, levels <40 ng/mL were associated with developing objective tenosynovitis (p = 0.033) but not with developing nonspecific myalgias. Our findings suggest hypovitaminosis D may be contributing to the AI-associated MSK pain syndrome and in particular to the development of tendonitis. Repletion to 25(OH)D levels >40 ng/mL is advisable. Further research should be carried out on identifying additional modifiable risk factors for this syndrome.

Defining the aromatase inhibitor musculoskeletal syndrome: a prospective study.

OBJECTIVE: To define the musculoskeletal syndrome associated with use of aromatase inhibitors (AIs), specifically, to describe its incidence, time to onset, risk factors, and clinical presentation. METHODS: Postmenopausal women with hormone-sensitive, nonmetastatic breast cancer starting AI therapy were enrolled in this prospective cohort study. They underwent complete rheumatologic evaluation and contrast-enhanced magnetic resonance imaging (MRI) of the hands and wrists prior to starting AI, at 3 and 6 months. The primary outcome was change in grip strength. RESULTS: Twenty-eight (54%) of 52 women reported new or worsening musculoskeletal symptoms. Two discontinued AIs due to pain. Mean time to symptom onset was 6 weeks (range 2-18 weeks), and 75% of symptomatic patients developed symptoms by 8 weeks. Later-stage cancer and worse quality of life (QOL) pretreatment were significantly associated with symptom development. Sixty-eight percent of symptomatic subjects had involvement of the hands; however, there was no difference in the mean change in grip strength (-2.9 kg versus -1.3 kg; P = 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, Rheumatoid Arthritis Magnetic Resonance Imaging Scoring did not significantly change. CONCLUSION: The incidence of AI-associated musculoskeletal syndrome is more than 50%, with most women developing symptoms by 8 weeks. The key finding in symptomatic women was focal tenosynovitis of the hands and feet, without evidence of autoimmune disease or systemic inflammation. Later-stage cancer and poorer QOL were predictive of symptom development.