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Re: Serum 25(OH)D levels in breast cancer patients with bone metastases

Dear Editor

We read with interest the study reported by Palmieri et al in the January 10th issue of this journal.¹ In their study, serum calcium, PTH and 25(OH)D levels were measured prospectively in 279 Caucasian women with breast cancer, 75 of whom had locally advanced or metastatic disease, but patients receiving bisphosphonates were excluded. Overall, the authors found that women with early-stage breast cancer had significantly higher 25(OH)D and lower PTH than those with advanced disease, in keeping with experimental data indicating direct inhibition of parathyroid function by 25(OH)D itself.² That the authors found no difference in serum calcium levels between the two groups is consistent with unaltered coupling of extracellular calcium concentrations to PTH secretion by the calcium-sensing receptor.³

We have prospectively assessed the same parameters in 45 patients with progressive bone metastases while on bisphosphonate therapy (pamidronate or clodronate) for a median interval of 20 months. We also found that 25(OH)D levels were low in many patients. However, we found that serum calcium levels were elevated compared to age-matched controls. Moreover, PTH levels did not show the same coupling to 25-hydroxyvitamin D, but were elevated among those with low normal calcium, irrespective of vitamin D status. When given to normocalcemic individuals, bisphosphonates are known to provoke a short-lived hyperparathyroid response to drug-induced hypocalcemia⁴, but the long-term effects of high-dose bisphosphonates are little studied. If there is a tendency toward chronic secondary hyperparathyroidism amongst metastatic breast cancer survivors on long-term bisphosphonates, even when serum calcium is within the normal range, then maintenance of a ‘normal’ 25OHD level is important. At first glance, this would appear to be a simple matter of recommending a daily supplement, but considerable controversy now surrounds the adequacy of current recommendations. Some authorities are now suggesting that 25OHD levels of 75 nmol/L be considered the minimum for optimal health outcomes, a value that may require more than 2000 IU/day to achieve.⁵

We are currently investigating further the role of Vitamin D in metastatic breast cancer patients with bone involvement to determine if it can act as an adjunct to bisphosphonate therapy in these patients and enhance the benefits of bisphosphonates as well as investigating its potential cytostatic role in metastatic bone disease.⁶ This remains an interesting and challenging area of research in breast cancer patients with advanced metastatic bone disease.

References:

1 Palmieri C, MacGregor T, Girgis S, Vigushin D. Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. J Clin Path.2006;59;1334-1336.

2 Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int. 2006 Aug;70(4):654-9.

3 Chattopadhyay N, Brown EM. Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium-sensing. Mol Genet Metab. 2006 Nov;89(3):189-202.

4 Tanvetyanon T, Stiff PJ. Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol. 2006 Jun;17(6):897-907.

5 Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. Review

6 Wigington DP, Strugnell SA, Knutson JC. Pamidronate and 1,24(S)-dihydroxyvitamin D2 synergistically inhibit the growth of myeloma, breast and prostate cancer cells. Anticancer Res. 2005;25:1909-17.