The small study reviewed here suggests that very high doses of vitamin D taken each week may help ease muscle and joint pain associated with taking an aromatase inhibitor as part of the treatment plan for hormone-receptor-positive breast cancer. These results were presented at the 2009 San Antonio Breast Cancer Symposium.
Hormonal therapy medicines -- either an aromatase inhibitor or tamoxifen -- are commonly prescribed after surgery for early-stage, hormone-receptor-positive breast cancer in post-menopausal women to lower the risk of the cancer coming back (recurrence). Hormonal therapy medicines are also sometimes used to treat advanced-stage, hormone-receptor-positive breast cancer.
Muscle and joint pain are common side effects of the aromatase inhibitors Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole). For some women this pain can be severe. Doctors aren't sure why aromatase inhibitors cause muscle and joint pain. Aromatase inhibitors work by lowering the amount of estrogen in the body -- this estrogen decrease is probably part of the cause of these side effects. Lower estrogen levels also can cause weakened bones while you're taking an aromatase inhibitor.
In this small study, 60 post-menopausal women diagnosed with hormone-receptor-positive breast cancer that wasn't metastatic were treated with Arimidex for at least 8 weeks after surgery. All the women had muscle and bone pain that began after they started taking Arimidex. All the women took over-the-counter supplements of calcium (1,000 mg) and vitamin D3 (400 IU) each day.
The women were split into two groups:
Women with kidney problems or other medical conditions that could be made worse by high doses of vitamin D weren't allowed in this study.
The doctors used several tools to rate the women's pain at the start of the study and then 2, 4, and 6 months later:
A spine and leg bone mineral density test, which evaluates the health of bones, was done when the study started and 6 months later.
After 2 months, women who got high doses of vitamin D weekly had notably less muscle and joint pain and were better at walking and climbing stairs compared to women who got the placebo. But after 4 and 6 months, when the women got high doses of vitamin D monthly instead of weekly, the improvements in pain and movement they had at 2 months went away.
Women who got high doses of vitamin D tended to maintain bone health (as measured by the bone mineral density test) better than women who got the placebo.
Two women developed high calcium levels in their urine and stopped taking the high doses of vitamin D; other than that, the high doses of vitamin D didn't cause any side effects.
The researchers aren't sure how high doses of vitamin D each week helps ease muscle and joint pain that can be caused by Arimidex.
High doses of vitamin D can be safe as long as you are closely monitored by a doctor. Too much vitamin D can cause dangerously high calcium levels in your blood and urine, kidney stones, and kidney damage. While the results of this study seem promising, more research is needed to better understand the benefits and risks of high doses of vitamin D, especially over longer periods of time. Researchers also need to study which form of vitamin D is best for this type of treatment.
If you're a post-menopausal woman taking an aromatase inhibitor as part of your treatment for hormone-receptor-positive breast cancer, you might be having muscle and joint pain. If these side effects are a problem, talk to your doctor about how to manage them. You might be able to switch to a different medicine. Don't start taking high doses of vitamin D on your own. And don't let side effects stop you from staying on track with the treatment plan that is best for you and your unique situation.
SAN ANTONIO (MedPage Today) -- High-dose vitamin D significantly reduced muscle and joint pain in breast cancer patients treated with the aromatase inhibitor anastrozole (Arimidex), results of a small, randomized clinical trial showed.
Weekly vitamin D supplementation led to significant improvement in pain and mobility after two months. The improvement began to dissipate after patients were switched to a monthly supplementation schedule and had largely disappeared by four to six months.
"Larger studies are needed to confirm these findings, but this pilot study suggests that high-dose vitamin D significantly improves anastrozole-induced muscle and joint tenderness and that this beneficial effect disappears once vitamin D is supplemented monthly, rather than weekly," Antonella Rastelli, MD, of Washington University in St. Louis, said at the San Antonio Breast Cancer Symposium.
"Moreover, bone mineral density of the femoral neck appears to be preserved at six months in patients who receive high vitamin D supplementation."
High-dose vitamin D was well tolerated and did not cause any toxicity," she added. "Some patients who received high-dose vitamin D demonstrated a propensity for higher urinary calcium excretion, which may lead to kidney stones."
Musculoskeletal pain is a class adverse effect of aromatase inhibitors. The St. Louis group previously had reported a high prevalence of vitamin D deficiency and insufficiency in breast cancer patients with musculoskeletal pain (SABCS 2004; Abstract P2-443), along with anecdotal evidence that weekly high-dose vitamin D might relieve it.
In follow-up to the earlier work, Rastelli and colleagues conducted a randomized clinical trial to evaluate the safety and efficacy of high-dose vitamin D for patients in these circumstances.
Eligibility criteria included postmenopausal, hormone receptor-positive breast cancer; at least eight weeks of anastrozole therapy prior to enrollment; serum calcium ≤10.3 mg/dL; marginal 25-OH vitamin D level (10 to 29 ng/mL); 24-hour urinary calcium excretion ≤250 mg/g; and a history of generalized musculoskeletal pain that began or worsened since starting treatment with the aromatase inhibitor.
Investigators excluded patients with metastatic breast cancer and those with a history of kidney stones, active primary hyperparathyroidism, Paget's disease, or severe arthritis or neuropathy, as well as patients with serum 25-OH vitamin D levels ≥30 ng/mL.
All patients received 1,000 mg calcium and 400 IU vitamin D3 daily.
Patients randomized to vitamin D supplementation received 50,000 IU/week for 8 or 16 weeks, depending on baseline 25-OH vitamin D levels. They were then switched to monthly vitamin D doses of 50,000 IU. The remaining patients received matching placebo supplementation.
All patients completed validated pain and impairment questionnaires at baseline and after two, four, and six months. Bone mineral density (BMD) of the lumbar spine and proximal femur was assessed at baseline and six months.
The primary outcome was the change from baseline in aromatase inhibitor-induced musculoskeletal symptoms. The secondary outcome was change in BMD.
The study involved 60 patients, 30 assigned to each treatment group. Vitamin D patients with hypercalciuria at the two-month follow-up visit withdrew from the study.
At two months, patients randomized to vitamin D had significant improvement in pain compared with the placebo group, as assessed by scores on the Brief Pain Index (P=0.009) and the Fibromyalgia Impact Questionnaire (P=0.01). Patients in the vitamin D group also had significantly better scores on an assessment of walking and climbing stairs (P=0.04).
Most of the benefit in the vitamin D group disappeared at four to eight months after a majority of the patients had switched to monthly supplementation, said Rastelli.
BMD assessment revealed a trend toward maintenance of bone density in the femoral neck in the vitamin D group (P=0.08).
Future studies should evaluate the impact of continuing weekly supplementation for a longer period, Rastelli and colleagues concluded in a poster presentation.
Additionally, inclusion criteria should be expanded to accommodate women with normal vitamin D levels, in light of recent evidence of significant differences in aromatase inhibitor-induced musculoskeletal pain in women with serum vitamin D levels >66 ng/mL (Breast Cancer Res Treat 2010; 119: 111-118).
Researchers should also consider other forms of vitamin D, they added. Cholecalciferol, for example, maintains more stable serum vitamin D levels than the ergocalciferol used in the study.
The study was supported by AstraZeneca.
Rastelli disclosed relationships with AstraZeneca and Lilly.
Primary source: San Antonio Breast Cancer Symposium Source reference: Rastelli A et al. "A double-blind, randomized, placebo-controlled trial of high dose vitamin D therapy on musculoskeletal pain and bone mineral density in anastrozole-treated breast cancer patients with marginal vitamin D status" SABCS 2009; Abstract 803.
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