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

Abstract

Purpose: 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. Methods: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 two weeks. The primary outcome was incident or worsening joint pain derived from baseline and three month 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.Results: 90% of women had a 25(OH)D <30 ng/ml at baseline. After supplementation (daily 800 IU and additional additional 16,000 IU every two week), 50% of them still failed to reach adequate concentrations at three 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]).Conclusion: A target concentration of 40ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper

“…While the association between vitamin D levels and breast cancer risk/prognosis is still controversial, the U-shaped relationship between 25-OH vitamin D levels and cancer or mortality risk observed in different studies suggests the need to avoid both deficient and too high levels [52,60,61]. A serum concentration of 25-OH vitamin D ≥40 ng/ml was associated with lower incidence of arthralgia in a specific prospective cohort study specifically designed to establish optimal levels of vitamin D for the prevention of AI-induced arthralgia [62], while the risk of arthralgia in patients with low concentration of 25-OH vitamin D (≤30 ng/ml) was confirmed in a separate study [63]. A weekly dose of up to 10,000 IU may thus be recommended in women with breast cancer based on recent international guidelines [64].…”

Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis

“…Only six cohort studies had full-text available for assessment with the Newcastle Ottowa Scale. Of these six studies, two were assessed as high methodological quality (37,38); two studies were median methodological quality (17,39,40); and one study was of poor methodological quality (41).…”

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

“…Hence, the estrogen synthesis pathway can play an important role in the final amount of available estrogen. In addition, serum 25-hydroxy-vitamin D (25(OH)D) status affects the rate of bone loss in patients with AI therapy and vitamin D supplementation to target threshold of R40 ng/ml protects against AI-related bone loss (AIBL) (Prieto-Alhambra et al 2011). Therefore, both the vitamin D metabolism and the response to vitamin D treatment may be essential to the regulation of bone metabolism.…”