Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Daniel Prieto-Alhambra (1, 2, 3, 4) , M. Kassim Javaid (2) , Sonia Servitja (5, 6) , Nigel K. Arden (2) , Maria Martinez-García (2) , Adolfo Diez-Perez (1, 7) , Joan Albanell (5, 6) , Ignasi Tusquets (5, 6) , Xavier Nogues (1, 7)

1 Department of Internal Medicine
2 NIHR Musculoskeletal BRU, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
3 Institut Catala de la Salut
4 IDIAPJGol - Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina
5 Medical Oncology Department, Breast Cancer Unit. Molecular Therapeutics and Biomarkers in Breast Cancer, Cancer Research Program
6 RTIC (Red Temática de Investigación Cooperativa en Cáncer)
7 RETICEF(Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad)

Aromatase inhibitor (AI)-associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia. We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D orally every 2 weeks. The primary outcome was incident or worsening joint pain derived from baseline and 3-month visual analogic scale (VAS) for joint pain. Regression models were used to analyse the association between vitamin D concentrations at 3 months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs. letrozole/anastrozole), prior tamoxifen therapy, baseline NTX, and previous fracture. 90% of women had a 25(OH)D <30 ng/ml at baseline. After supplementation (daily 800 IU and additional 16,000 IU every 2 weeks), 50% of them still failed to reach adequate concentrations at 3 months. In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66;  < 0.001) and the increase was significantly ( = 0.02) attenuated in those that reached concentrations of 25(OH)D of ≥40 ng/ml, with a lower risk of incident arthralgia (OR 0.12 ** [0.03 to 0.40]). A target concentration of 40 ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.

Mots clés: Breast neoplasms; Aromatase inhibitors; Arthralgia; Vitamin D; Cohort studies

Daniel Prieto-Alhambra, M. Kassim Javaid, Sonia Servitja, Nigel K. Arden, Maria Martinez-García, et al.. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Research and Treatment, 2010, 125 (3), pp.869-878. ⟨10.1007/s10549-010-1075-9⟩. ⟨hal-00561321⟩