Aromatase Inhibitors, Musculoskeletal Pain and Vitamin D

Keith Block, MD

Arimidex (anastrozole), Aromasin (exemestane) and Femara (letrozole) are aromatase inhibitors (AIs) used to treat post-menopausal breast cancer patients whose cancer is estrogen receptor positive. These medications block aromatase, an enzyme that converts androgens to estrogen, thus reducing the risk of cancer recurrence in this population. However, aromatase inhibitors come with unwanted side effects – including musculoskeletal pain, which in some cases is severe, and bone loss.

Several recent studies have noted that post-menopausal women taking aromatase inhibitors have a decrease in serum vitamin D and more musculoskeletal pain and arthralgia (joint pain) than their counterparts who are not taking AIs. Moreover, since estrogen depletion is associated with arthralgia as well, and since AIs work by ensuring extra estrogen is further depleted, it follows that some women will exhibit this common side effect. This is cause for concern, since it’s often difficult for patients to be compliant with this therapy.

A recent prospective study by Singer et al published in the journal Arthritis Care and Research (June 21, 2012) noted that more than 50 % of women experience this AI-associated musculoskeletal syndrome, with symptoms typically developing within eight weeks of therapy. Other studies have also noted this association and some, including a study published in 2009 in Current Oncology by Robidoux et al and a 2010 study by G. Moxley in the journal Clinical Breast Cancer, note that these symptoms are worse in women who already have pre-existing conditions, such as rheumatoid arthritis or osteoarthritis. Moxley noted that the syndrome occurred in patients who may not previously have had arthritis symptoms, but that the AI therapy made them more sensitive to this pain.

A study from Barcelona published March 21, 2012 in Breast Cancer Research and Treatment (Prieto-Alhambra D et al) looked at vitamin D and calcium supplementation and whether it could have an effect on AI-related bone loss. The participants were given 1 gram of calcium and 800 IUs of vitamin D daily. If initial serum vitamin D was lower than 30 ng/ml, these individuals were given additional vitamin D (16,000 IU) every two weeks. the participants in the study experienced 1.68% bone loss in their lumbar spine over the course of a year. However, when the bone loss was measured at 3 months, those subjects with higher concentrations of serum vitamin D had less bone loss and those with the highest concentrations – more than 40 ng/ml - reduced this bone loss by 1.70%, compared with those who had low serum vitamin levels. The researchers concluded that the use of vitamin D supplementation above target recommendations could sustain this reduction in bone loss for the full year.

Another study published in the British Journal of Nutrition in April 2012 (Hirani V) looked at the role of vitamin D levels and pain in 2,070 community-dwelling adults. They found that of this patient population 53% had symptoms of moderate/extreme pain and suggested this symptom was associated with poor vitamin D status, independent of other possible causes. The author suggested that older individuals should be screened for vitamin D status and provided supplementation where needed.

Other studies have been less conclusive about vitamin D’s role, particularly for cancer patients, nonetheless, they do suggest that further study is warranted and there appears to be enough evidence to support supplementation to see if it helps for both pain and bone loss for individual patients.

At the Block Center, we continue to recommend supplemental vitamin D to our patients – based on each patient’s individual needs. A general range is between 800 – 2000 IU a day. Maintaining strong bones is a complex process and one we will address in greater detail in a future blog article. However, we recommend the following to help keep bones strong and help prevent osteoporosis:

Do weight bearing exercises (such as walking or weight training) every day for 15 minutes for the purpose of bone maintenance. Of course, for aerobic and overall health benefits, 30 to 45 minutes on most days is more optimal.
If you smoke, quit. Limit alcohol and caffeine intake.
Take 750 (no more than 800) mg per day of a calcium supplement (calcium citrate, not calcium carbonate). The balance of your daily needs – 1000 mg for women under 50, 1200 mg per day for women over 50 and those diagnosed with osteopenia, and 1500 mg per day if you’ve been diagnosed with osteoporosis – should come from food. For patients taking aromatase inhibitors, we recommend 1,200-1,500 mg a day of calcium. Eat Vitamin D-rich foods, including salmon, mackerel, almonds, green vegetables, sardines and tuna.
We synthesize vitamin D through our skin. Fifteen minutes of unprotected sun exposure each day can help increase vitamin D stores, but no longer than this without sun block as sun exposure carries skin cancer risk. Also, as we age, our skin does not synthesize vitamin D as well, so supplementation is generally necessary.
Regular bone density tests may also be recommended.

We have seen the same risks for osteoporosis in men taking Lupron (leuprolide) and Zoladex (goserelin) to treat prostate cancer since these therapies deplete estrogen stores in men and therefore recommend they adopt the same exercise, diet and supplement regimen above.

While researchers will continue to explore the associate between vitamin D levels and musculoskeletal pain in women taking aromatase inhibitors, as well as vitamin D’s role in pain and bone loss prevention in general, there is still sufficient evidence to make the reasonable lifestyle changes suggested above during cancer therapy and beyond in an effort to maintain bone health.

For more information on The Block Center for Integrative Cancer Treatment, visit BlockMD.com.