A new study demonstrates that high-dose vitamin D helps to relieve debilitating joint and muscle pain in women with breast cancer who are taking estrogen-lowering drugs to shrink the tumors. This is yet another demonstration of vitamin D’s possible role in maintaining bone health while also aiding musculoskeletal aches and pains.
According to a news release from Washington University, St. Louis [here], drugs known as aromatase inhibitors are commonly prescribed to shrink breast tumors fueled by the hormone estrogen and help in preventing cancer recurrence. They are less toxic than chemotherapy but, for many patients, the drugs may cause severe musculoskeletal discomfort, including pain and stiffness in the hands, wrists, knees, hips, lower back, shoulders, and feet. It is unknown exactly why these discomforts occur but as many as half of treated women can experience the symptoms and the pain can be so debilitating that patients stop taking aromatase inhibitors. Vitamin D appears to offer some help in ameliorating the discomfort.
Writing in the journal Breast Cancer Research and Treatment, a research team from Washington University School of Medicine led by Antonella L. Rastelli, MD, describes a double-blind placebo-controlled randomized trial to determine whether in women receiving the aromatase inhibitor anastrozole high-dose vitamin D2 supplementation improves aromatase-inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss [Rastelli et al. 2011]. Sixty patients with early breast cancer and AIMSS were stratified according to their baseline 25(OH)D (25-hydroxyvitamin D) levels:
- Group A — 20–29 ng/mL 25(OH)D — received either 50,000 IU vitamin D capsules once-weekly for 8 weeks then monthly for 4 months, or placebo.
- Group B — 10–19 ng/mL 25(OH)D — received either 50,000 IU vitamin D capsules once-weekly for 16 weeks and then monthly for 2 months, or placebo.
Subjects in all groups also received a standard daily dose of vitamin D (400 IU) plus 1,000 mg of calcium each day throughout the study. AIMSS was assessed via several questionnaires at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change from baseline in musculoskeletal pain, and the secondary endpoint was the percent change in BMD at 6 months.
Baseline characteristics were comparable between the groups. At all time points, measures of pain, worst-pain, average-pain, pain-severity, and pain interference with daily activities were all significantly better in subjects receiving high-dose vitamin D2 than in the placebo groups. The positive effects of vitamin D2 on AIMSS were significantly stronger throughout the study in Group B — the patients with greater vitamin D deficiency at baseline — than in Group A. BMD at the femoral neck decreased in the placebo group but did not significantly change in the vitamin D groups (P = 0.06).
The authors conclude overall that weekly high-dose vitamin D supplementation improves AIMSS and may have a positive effect on bone health. According to Rastelli in the news release, “High-dose vitamin D seems to be effective in reducing the musculoskeletal pain caused by aromatase inhibitors. Patients who get the vitamin D weekly feel better because their pain is reduced and sometimes goes away completely. This makes the drugs much more tolerable. Millions of women worldwide take aromatase inhibitor therapy, and we may have another ‘tool’ to help them remain on it longer.”
COMMENTARY: Benefits of vitamin D for musculoskeletal pain have been extensively discussed in these Pain-Topics UPDATES [here]. This particular study was well-designed and carefully conducted, but the small numbers of subjects in each group call for further research with much larger sample sizes. The study was supported by Astra-Zeneca, which makes the aromatase inhibitor anastrozole under the brand name Arimidex®, so commercial bias cannot be ruled out. Two other FDA-approved aromatase inhibitors, letrozole and exemestane, also cause musculoskeletal pain, and patients on these drugs might also benefit from high-dose vitamin D.
The vitamin D used in this study was plant-derived vitamin D2, which the researchers believe achieves the best results when given weekly because the body metabolizes it in 7 to 10 days; whereas, vitamin D3 remains in the body considerably longer. The more rapid elimination of vitamin D2 also was considered a safety factor; however, other research has found D3 to have greater potency and there also might be some question as to whether daily moderately-high doses of vitamin D3 might be more effective than once-weekly ultra-high doses.
The protocol used in this study is of interest, in that patients with more deficient vitamin D levels (10-19 ng/mL) were administered weekly high-dose supplementation twice as long (16 vs 8 weeks) as those with what many consider inadequate levels (20-29 ng/mL). And, patients with greater vitamin deficiencies at the outset and receiving supplementation longer experienced the strongest positive effects.
Furthermore, all subjects also were provided supplemental calcium. Due to its role in calcium absorption, vitamin D supplementation at high weekly doses combined with the calcium did appear to help maintain bone density, although this beneficial effect did not reach significance (possibly reflecting a lack of statistical power in such small group sizes). However, it should be noted that too much vitamin D can cause elevated levels of calcium in the urine and potentially increase risks of kidney stones. This emphasizes a need to monitor patients for hypercalcemia while they are taking high-dose vitamin D, and especially if calcium supplementation also is provided.
This is an important study demonstrating the role of vitamin D in maintaining musculoskeletal health and helping to remediate aches and pains. In this particular case, because aromatase inhibitors reduce cancer recurrence, finding ways to help patients stay on them is important for long-term, relapse-free survival, according to Rastelli. Aromatase inhibitors are prescribed to post-menopausal women for at least 5 years or longer after a breast cancer diagnosis and there is some evidence, Rastelli notes, that patients who experience the drugs’ musculoskeletal side effects are actually less likely to see their cancer return. So alleviating such troublesome symptoms via vitamin D supplementation may offer considerable benefits.
Finally, we also should note that another study reported several years ago in these UPDATES [here] found preliminary evidence of increased joint pain in three-quarters of women with breast cancer, which was associated with (not necessarily caused by) insufficient levels of vitamin D. Supplementation with the vitamin reduced the pain and also decreased the amount of fatigue typically experienced by these patients.
REFERENCE: Rastelli AL, Taylor ME, Gao F, et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. 2011;129 (1):107-116 [abstract here].