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

  • Epidemiology
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Abstract

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 D3 (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D3 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; P < 0.001) and the increase was significantly (P = 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.

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Acknowledgments

Daniel Prieto-Alhambra receives support from the IDIAP Jordi Gol and Institut Catala de la Salut (“4rt Ajut per una estada en un centre de recerca a l’estranger”), and from the Instituto de Salud Carlos III, Government of Spain (BAE Grant 2009, Exp Number BA09/90023). Dr MK Javaid and Professor NK Arden receive support from the NIHR (National Institute of Health Research)—Musculoskeletal BRU, Oxford. The Medical Oncology Department receives support from the RTIC (Red Temática de Investigación Cooperativa en Cáncer, Instituto Carlos III, Government of Spain). The Internal Medicine Department and the URFOA IMIM receive support from the RETICEF (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, Instituto Carlos III, Government of Spain). The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, URFOA IMIM-Hospital del Mar, Parc de Salut Mar, Autonomous University of Barcelona, Barcelona, Spain

    Daniel Prieto-Alhambra, Adolfo Diez-Perez & Xavier Nogues

  2. RETICEF(Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad), Instituto Carlos III, Barcelona, Spain

    Adolfo Diez-Perez & Xavier Nogues

  3. NIHR Musculoskeletal BRU, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

    Daniel Prieto-Alhambra, M. Kassim Javaid & Nigel K. Arden

  4. Institut Catala de la Salut, Barcelona, Spain

    Daniel Prieto-Alhambra

  5. IDIAP Jordi Gol, Barcelona, Spain

    Daniel Prieto-Alhambra

  6. Medical Oncology Department, Breast Cancer Unit. Molecular Therapeutics and Biomarkers in Breast Cancer, Cancer Research Program, IMIM-Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain

    Sonia Servitja, Maria Martinez-García, Joan Albanell & Ignasi Tusquets

  7. RTIC (Red Temática de Investigación Cooperativa en Cáncer), Instituto Carlos III, Barcelona, Spain

    Sonia Servitja, Maria Martinez-García, Joan Albanell & Ignasi Tusquets

  8. Travessera de Gracia,185,4 3, 08012, Barcelona, Spain

    Daniel Prieto-Alhambra

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  1. Daniel Prieto-Alhambra
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Prieto-Alhambra, D., Javaid, M.K., Servitja, S. et al. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat 125, 869–878 (2011). https://doi.org/10.1007/s10549-010-1075-9

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