Vitamin D Improves Pain From Aromatase Inhibitors

Nick Mulcahy

August 16, 2011

August 16, 2011 — High-dose vitamin D supplementation significantly improves musculoskeletal pain and discomfort caused by aromatase inhibitors (AIs) and may have a positive effect on bone health, according to a single-center, phase 2 study reported in the August issue of Breast Cancer Research and Treatment.

Musculoskeletal pain occurs in up to 50% of patients taking the drugs and is reportedly the most common reason for AI discontinuation, say the study authors, led by Antonella Rastelli, MD, from Washington University School of Medicine in St. Louis, Missouri.

"Women usually report that 'every bone in my body hurts' and that, since starting AIs, they feel like they 'have become 100 years old,'" they write.

In the new study of 60 patients with breast cancer who had been receiving the AI anastrozole (Arimidex, AstraZeneca) for at least 2 months, all the women took the recommended daily dose of vitamin D2 — 400 IU — plus 1000 mg of calcium a day.

For the study, patients randomly assigned to treatment received an additional high dose of vitamin D2 (50,000 IU capsule), which was given once a week; pain was measured at baseline and at 8-week intervals for up to 6 months.

At 8 weeks, pain scores were better for patients randomly assigned to high-dose vitamin D2 than for those assigned to placebo. The scores with significant improvement included pain measured by the Fibromyalgia Impact Questionnaire (P = .0045) and the Brief Pain Inventory-Short Form (BPI), which included BPI worst pain (P = .04), BPI average pain (P = .0067), BPI pain severity (P = .04), and BPI interference (P = .034).

The positive effect of high-dose vitamin D supplementation was not maintained at 4 and 6 months once the women were switched to a less frequent dose (50,000 IU once a month), as required by the study protocol.

"The apparent decline in efficacy may reflect the relatively short half-life and weak potency of Vitamin D2," write the authors about the once-monthly dose.

The study is the first randomized trial to assess the efficacy of high-dose vitamin D supplementation in women with breast cancer taking AIs. Two previous observational studies have "reported a potential role of vitamin D" for reducing musculoskeletal pain in this setting, say the authors.

It is uncertain how exactly vitamin D is helpful in these patients. "The pathogenesis of aromatase inhibitor-induced musculoskeletal symptoms and why it may respond to vitamin D is unclear," say the authors.

However, there is a "prevalence of vitamin D insufficiency or deficiency in women with breast cancer despite standard supplementation (e.g. oral vitamin D2; 400 IU/day)," the authors point out. And "clinical observation" — along with the 2 observational studies — has suggested that high-dose vitamin D may ameliorate musculoskeletal pain, they add.

Bone Impact Too

At enrollment, study participants had hormone receptor–positive invasive breast cancer (stage I to IIIB) and, after taking an AI for 2 months, were experiencing new or worsening musculoskeletal pain unrelated to any history of trauma. Other eligibility criteria included serum 25OHD level between 10 and 29 ng/mL, which is a range that covers both "insufficient" and "deficient" vitamin D levels.

A secondary goal of the study was to assess the efficacy of high-dose vitamin D supplementation in protecting bone health in patients with breast cancer receiving AI therapy.

"It is well known that AIs cause bone loss and are associated with an increased risk of fragility fractures," write the authors. Also, vitamin D deficiency/insufficiency is a risk factor for bone loss through the development of secondary hyperparathyroidism, they add, suggesting that this is a one-two punch on bone health for women in the study.

The investigators found that women taking placebo showed a decline in bone mineral density (BMD) of the femoral neck at 6 months (mean change, –1.4% ± 0.68%), while women receiving vitamin D supplementation maintained BMD (0.35% ± 0.72%; P = .06). No significant changes were observed at the lumbar spine or total femur.

"The favorable effect of vitamin D on BMD at the femoral neck potentially reflects increased mineralization of bone matrix from improved calcium absorption," they write.

One of the adverse effects of high-dose vitamin D supplementation came into play in the study.

There was a "relatively high dropout rate due to hypercalciuria." At 8 weeks, 5 patients (4 in the vitamin D group and 1 in the placebo group) developed abnormally high 24-hour urinary calcium excretion, which underscores the importance of monitoring patients taking high-dose vitamin D for this abnormality, advise the authors.

The study was supported by AstraZeneca. The authors have disclosed no relevant financial relationships.

Breast Cancer Res Treat. 2011;129:107-116. Abstract

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