Background and aims Reduced vitamin D levels may play a significant role in the development of fractures and musculoskeletal pains reported in patients on aromatase inhibitors (AIs) for breast cancer. In this study, we evaluated the vitamin D status in postmenopausal women with non-metastatic breast cancer who were about to start AI therapy. Methods This study was conducted on community dwelling postmenopausal subjects, aged 35–80 years, with early non-metastatic breast cancer (up to stage IIIA), who were about to start therapy using third generation AIs. Symptoms of joint and muscle pains were obtained using a modified Leuven menopausal questionnaire. 25-hydroxyvitamin D [25(OH)D] was evaluated by radioimmunoassy while bone mineral density (BMD) of the lumbar spine and the proximal femur by dual energy X-ray absorptiometry (DXA) Results Of the 145 participants (mean age = 60.96 ± 0.88 years), 63/145 (43.5%) had baseline levels of 25(OH)D of < 20 ng/ml (deficient), 50/145 (34.5%) had levels between 20–29 ng/ml (insufficient), and only 32/145 (22%) had > 30 ng/ml (sufficient); thus, 113/145 (78%) had low 25(OH)D levels (i.e. < 30ng/ml). Arthralgias and myalgias were found in 61.3% and 43% of patients, respectively; and of those, 83.3% and 88.1% had 25(OH)D of < 30ng/ml, respectively. Conclusions Prevalence of vitamin D deficiency is high in breast cancer women and this may increase the risk of bone loss and fractures in those who are going to start AIs. Moreover, musculoskeletal pains are common in breast cancer women, even before the initiation of AIs and in association with low vitamin D in the majority. Future studies may be needed to establish the contribution of low vitamin D, if any, on the prevalence of musculoskeletal pains in women on AIs.

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Purpose Polymorphisms in the CYP19A1 (aromatase) gene influence disease-free survival and bone loss in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER+) breast cancers. Because AI use results in profound estrogen deficiency which may lead to changes in body composition, the objective of this study was to determine the effect of the rs700518 polymorphism in the CYP19A1 gene, on the changes in body composition among postmenopausal women who were treated with AIs for ER+ breast cancer. Methods This is a 1-year prospective study of changes in body composition in postmenopausal women who were initiated on third-generation AIs for ER+ breast cancer. Body composition was measured by dual energy absorptiometry at 6 and 12 months, serum estradiol by radioimmunoassay and genotyping by Taqman SNP allelic discrimination assay. Results Eighty-two women were able to provide at least one follow-up body composition measurement. Women with the GG genotype for the rs700518 (G/A at Val80) developed a significant increase in Truncal fat mass index (p=0.03) and a significant decrease in fat-free mass index (p=0.01) at 12 months relative to patients carrying the A allele (GA/AA). There was no significant difference in the changes in estradiol levels among the genotypes. Conclusion Patients with the GG genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for significant loss of fat-free mass and increase in truncal fat with AI therapy. Whether there are associated metabolic abnormalities and whether changes would persist with long-term AI therapy, need to be confirmed in a larger study with a longer duration of follow-up.

Menopause is associated with changes in bone, muscle and fat mass. The importance of postmenopausal estrogen metabolism in bone health has been established. However, its relationship to body composition in postmenopausal women remains undetermined. The objective of this study is to determine the association between estrogen metabolism and body composition in postmenopausal women. This is a cross sectional study of 97 postmenopausal Caucasian women, 49–80 y.o., ≥ 1 year from the last normal menstrual period or those who have had oophorectomy. Inactive [2-hydroxyestrone (2OHE1)] and active [16α-hydroxyestrone (16α-OHE1)] urinary metabolites of estrogen were measured by ELISA. The whole and regional body composition was measured by DXA. We have found that both 2OHE1,, and 2OHE1/16α-OHE1 ratio were negatively correlated with % total fat, and % truncal fat but positively correlated with % total lean mass. Comparing the fat and lean parameters of body composition according to tertiles of 2OHE1 and 2OHE1/16αOHE1 ratio showed that subjects in the lowest tertiles, had the highest % total fat, and % truncal fat and the lowest % total lean mass. Multiple regression analysis also showed 2OHE1 and calcium intake as statistically significant predictors of all body composition parameters. In conclusion, in postmenopausal women, an increase in the metabolism of estrogen towards the inactive metabolites is associated with lower body fat and higher lean mass than those with predominance of the metabolism towards the active metabolites.

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