High-dose Vitamin D May Relieve Joint Pain from Aromatase Inhibitors (AI)

TON - April 2010 Vol 3, No 2 — June 2, 2010

High doses of vitamin D can relieve musculoskeletal pain associated with aromatase inhibitors (AIs) in women with breast cancer, according to a study presented at the 32nd Annual San Antonio Breast Cancer Symposium in San Antonio, Texas.

"Our pilot data suggest that high-dose vitamin D significantly improves muscle and joint tenderness associated with anastrozole, and that this beneficial effect disappears once vitamin D is given monthly rather than weekly," said principal investigator Antonella Rastelli, MD, an internist with the survivorship program of the Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.

Musculoskeletal pain is a class effect of AIs, and breast cancer patients have been found to have deficient or insufficient levels of 25-OH vitamin D, she said.

The randomized, double-blind, placebo-controlled study evaluated high-dose vitamin D supplementation versus placebo for 6 months in 60 early breast cancer patients taking anastrozole as hormonal therapy for hormone receptor-positive disease. Patients were required to have serum calcium ≤10.3 mg/dL, marginal 25-OH vitamin D levels (10 ng/mL-29 ng/mL), 24-hour urinary calcium excretion ≤250 mg/g, and a history of generalized musculoskeletal pain that developed or worsened since starting anastrozole.

All patients received calcium (1000 mg/day) and standard vitamin D supplementation (400 IU/day). The active group also received highdose vitamin D (50,000 IU/week), administered for 8 weeks if they had 25-OH vitamin D ≥20 ng/mL and <30 ng/mL or for 16 weeks if they had 25-OH vitamin D ≥10 ng/mL and <20 ng/mL.

Patients were given questionnaires for pain and impairment at baseline and at 2, 4, and 6 months, including the Brief Pain Inventory (BPI), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Dis ability Index (HAQDI). Bone mineral density (BMD) measurements of the lumbar spine and proximal femur were taken at baseline and at 6 months.

Pain relieved in high-dose group
At the 2-month follow-up visit, subjects in the high-dose vitamin D group experienced a significant reduction in pain, compared with those in the placebo arm, on both the BPI questionnaire (P = .009) and the FIQ (P = .01). Significantly better scores were also reported for walking on flat ground and climbing steps (P = .04) in the HAQ-DI. Rastelli also reported favorable trends on the BPI-interference score, the FIQ total score, and the HAQ-DI total score.

Patients in the placebo group also derived some improvements in pain. "They were getting some vitamin D, and they seemed to be getting some relief," she said. For patients in the active groups, most of the beneficial effects disappeared at 4 and 6 months after the dosing was cut back from weekly to monthly.

Subjects receiving high-dose vitamin D supplementation also showed a trend for maintaining BMD of the femoral neck, compared with those in the placebo group, she added.

Need to monitor urine
Although high-dose vitamin D was well tolerated, some patients showed a propensity for higher urinary calcium excretion, which can lead to kidney stones, Rastelli reported. Four of the 30 active-treatment patients were excluded at 2 months because of this, as was one patient in the control group.

"You have to monitor for urinary calcium when you are giving 50,000 IU/week of vitamin D long-term, which is very potent," she emphasized.

Secondary hyperparathyroidism was also observed in a few patients. At baseline, 6 patients (10%) had secondary hyperparathyroidism from low 25-OH vitamin D levels, which resolved for two patients during treatment but persisted in four (8.5%). Secondary hyperparathyroidism can lead to bone loss.

The group hopes to conduct a multicenter trial to confirm their findings, and perhaps using cholecalciferol, which keeps serum levels more stable than ergocalciferol.

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