Lani
07-31-2010, 11:49 AM
arthralgias are painful joints''
Breast Cancer Research and Treatment
© Springer Science+Business Media, LLC. 2010
10.1007/s10549-010-1075-9
Epidemiology
Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study
Daniel Prieto-Alhambra1, 3, 4, 5, 8 , M. Kassim Javaid3, Sonia Servitja6, 7, Nigel K. Arden3, Maria Martinez-GarcÃ*a6, 7, Adolfo Diez-Perez1, 2, Joan Albanell6, 7, Ignasi Tusquets6, 7 and Xavier Nogues1, 2
(1) Department of Internal Medicine, URFOA IMIM-Hospital del Mar, Parc de Salut Mar, Autonomous University of Barcelona, Barcelona, Spain
(2) RETICEF(Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad), Instituto Carlos III, Barcelona, Spain
(3) NIHR Musculoskeletal BRU, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
(4) Institut Catala de la Salut, Barcelona, Spain
(5) IDIAP Jordi Gol, Barcelona, Spain
(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
(7) RTIC (Red Temática de Investigación Cooperativa en Cáncer), Instituto Carlos III, Barcelona, Spain
(8) Travessera de Gracia,185,4 3, 08012 Barcelona, Spain
Daniel Prieto-Alhambra
Email: dprieto@camfic.org
Received: 15 July 2010 Accepted: 17 July 2010 Published online: 28 July 2010
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.
Keywords Breast neoplasms - Aromatase inhibitors - Arthralgia - Vitamin D - Cohort studies
Breast Cancer Research and Treatment
© Springer Science+Business Media, LLC. 2010
10.1007/s10549-010-1075-9
Epidemiology
Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study
Daniel Prieto-Alhambra1, 3, 4, 5, 8 , M. Kassim Javaid3, Sonia Servitja6, 7, Nigel K. Arden3, Maria Martinez-GarcÃ*a6, 7, Adolfo Diez-Perez1, 2, Joan Albanell6, 7, Ignasi Tusquets6, 7 and Xavier Nogues1, 2
(1) Department of Internal Medicine, URFOA IMIM-Hospital del Mar, Parc de Salut Mar, Autonomous University of Barcelona, Barcelona, Spain
(2) RETICEF(Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad), Instituto Carlos III, Barcelona, Spain
(3) NIHR Musculoskeletal BRU, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
(4) Institut Catala de la Salut, Barcelona, Spain
(5) IDIAP Jordi Gol, Barcelona, Spain
(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
(7) RTIC (Red Temática de Investigación Cooperativa en Cáncer), Instituto Carlos III, Barcelona, Spain
(8) Travessera de Gracia,185,4 3, 08012 Barcelona, Spain
Daniel Prieto-Alhambra
Email: dprieto@camfic.org
Received: 15 July 2010 Accepted: 17 July 2010 Published online: 28 July 2010
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.
Keywords Breast neoplasms - Aromatase inhibitors - Arthralgia - Vitamin D - Cohort studies