Altered calcium metabolism in patients on long-term bisphosphonate therapy for metastatic breast cancer.
BACKGROUND
Bisphosphonates (BPs) are considered the standard of care in metastatic breast cancer (MBC) patients with bone metastases. Because the survival for these patients may be prolonged compared with those patients with visceral metastases, they may be prescribed BPs for several years. The effects of this long-term BP use on calcium metabolism in MBC patients have not previously been described.


OBJECTIVE
The main objective of this study was to evaluate the effect of long-term BP use on calcium homeostasis in MBC patients. The secondary objective was to assess Vitamin D levels in these patients.


METHODS
An exploratory analysis of serum calcium, parathyroid (PTH), and 25 hydroxycholecalsiferol (25-(OH)D) levels and their inter-relationships was undertaken in 46 MBC patients who had been on prolonged BP therapy. These results were compared to a historical control group of 420 patients without bone or mineral disease who were matched for gender, age, baseline renal function and season of seological testing.


RESULTS
Patients were similar in the two groups with no significant difference in mean age, baseline creatinine or season of testing. Serum calcium was no different between the two groups. However, PTH was significantly higher in MBC patients, compared to controls (5.7 vs. 4.8 pmol/L, p=0.043). Linear regression analysis showed that PTH was significantly higher in the MBC group at lower serum calcium levels and fell sharply with increasing serum calcium levels (p=0.0001). Among the patients with MBC, 62% had suboptimal levels of vitamin D and 18% were found to have insufficient or deficient levels (25-(OH)D < 40 nM) despite taking dietary supplementation.


CONCLUSIONS
In MBC patients with prolonged BP use, there appears to be a state of hyperparathyroidism similar to that seen with BP use in benign bone disease. Supplementation with 400 IU per day of Vitamin D per day was not sufficient to correct this metabolic abnormality.
Simmons
Christine
C
Division of Medical Oncology Sunnybrook Health Sciences Centre Odette Cancer Centre Toronto, Ontario, Canada. Christine.simmons@sunnybrook.ca
Amir
Eitan
E
Dranitsaris
George
G
Clemons
Mark
M
Wong
Betty
B
Veith
Reinhold
R
Cole
David E C
DE
D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D014807:Vitamin D / Q000097:blood
D004164:Diphosphonates; D014807:Vitamin D; D002118:Calcium