Vitamin D Counters Bone Density Loss With Aromatase Inhibitors

Jim Kling

December 14, 2021

Among women with breast cancer being treated with aromatase inhibitors (AI), supplementation with vitamin D and calcium protected against bone loss after 5 years, according to results from a prospective cohort study in Brazil. The study found no difference in bone mineral density outcomes at 5 years between women with hormone receptor–positive cancers treated with aromatase inhibitors (AIG) and triple negative or HER-2 positive patients who were treated with another therapy (CG).

About two-thirds of women with breast cancer have tumors that are positive for hormone receptors, and so are often treated with endocrine therapy such as selective estrogen receptor modulators or AI. However, there are concerns that AI treatment may lead to a loss of bone mineral density and impacts on quality of life. This loss is influenced by a range of factors, including body weight, physical activity, smoking, alcohol consumption, corticosteroid use, calcium in the diet, and circulating levels of vitamin D.

Vitamin D helps to regulate absorption of calcium and phosphorus, ensuring that their plasma concentrations are high enough for adequate bone health. But vitamin D deficiency is a common problem, even in tropical areas such as Brazil. "It is high in the general population and especially in postmenopausal breast cancer patients. Thus, vitamin D and calcium supplementation has an impact on these women's lives," said lead author Marcelo Antonini, MD, who presented the study (abstract P1-13-04) at the San Antonio Breast Cancer Symposium. He is a researcher at Hospital Servidor Publico Estadual in São Paulo, Brazil.

Although the findings are encouraging, more work needs to be done before it leads to a change in practice. "Larger studies must be carried out to prove this theory; however, in noncancer patients we have already well established the benefits of vitamin D and calcium supplementation," Antonini said in an interview

The researchers examined women before the start of treatment, at 6 months, and at 5 years. Those with vitamin D levels below 30 ng/mL received 7,000 IU/day for 8 weeks, followed by a 1,000 IU/day maintenance dose. Subjects with osteopenia received a calcium supplement (500 mg calcium carbonate), and those with osteoporosis received 4 mg zoledronic acid (Zometa, Novartis).

There were 140 patients in both the AIG and CG groups. The average age was 65 years. Sixty-four percent of the AIG group and 71% of the CG group were vitamin D deficient at baseline. At 5 years, the frequencies were 17% and 16%, respectively. Both groups showed significant declines in bone mineral density in the femoral neck and femur at both 6 months and 5 years, but there was no significant difference between them. There was no significant difference between the two groups with respect to bone density loss in the spine.

The study is limited by the fact that it was conducted at a single center and had a small population size.

Another prospective observational study, published earlier this year, looked at vitamin D supplementation in 741 patients (mean age 61.9 years) being treated with aromatase inhibitors, whose baseline vitamin D levels were less 30 ng/mL. They received 16,000 IU dose of oral calcifediol every 2 weeks. At 3 months, individuals who achieved vitamin D levels of 40 ng/mL or higher were less likely to have joint pain (P < .05). At 12 months, data from 473 patients showed that for every 10-ng/mL increase in serum vitamin D at 3 months, there was a reduction in loss of bone marrow density in the lumbar spine (adjusted beta = +0.177%, P < .05), though there were no associations between vitamin D levels and BMD of the femur or total hip.

"Our results suggest that optimal levels of vitamin D are associated with a reduced risk of joint pain related to AI treatment. A target threshold (of vitamin D) levels was set at 40 ng/mL to significantly reduce the increase in joint pain." The authors noted that this threshold is well above the goal of 20 ng/mL recommended by the 2010 Institute of Medicine report.

The study did not receive external funding. Antonini has no relevant financial disclosures.

This article originally appeared on, part of the Medscape Professional Network.


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