title: Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study.
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 D(3) (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D(3) 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.
authors.affiliation: Department of Internal Medicine, URFOA IMIM-Hospital del Mar, Parc de Salut Mar, Autonomous University of Barcelona, Barcelona, Spain. dprieto@camfic.org
authors.forename: Daniel
authors.initials: D
authors.lastname: Prieto-Alhambra
authors.forename: M Kassim
authors.initials: MK
authors.lastname: Javaid
authors.forename: Sonia
authors.initials: S
authors.lastname: Servitja
authors.forename: Nigel K
authors.initials: NK
authors.lastname: Arden
authors.forename: Maria
authors.initials: M
authors.lastname: Martinez-García
authors.forename: Adolfo
authors.initials: A
authors.lastname: Diez-Perez
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Ignasi
authors.initials: I
authors.lastname: Tusquets
authors.forename: Xavier
authors.initials: X
authors.lastname: Nogues
mesh_terms: D000368:Aged; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D018771:Arthralgia / Q000139:chemically induced* / Q000473:pathology; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D015233:Models, Statistical; D011446:Prospective Studies; D013131:Spine / Q000378:metabolism; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047072:Aromatase Inhibitors; D014807:Vitamin D; C104450:25-hydroxyvitamin D