Hypocalcemia induced by bisphophonates in cancer patients with vitamin D deficiency

Abstract

19644 Background: The use of bisphosphonates for treatment of hypercalcemia, bone pain and reduction of skeletal morbidity in metastatic breast cancer is increasing. Moreover, vitamin D deficiency is commonly associated with cancer. Hypocalcemia has been reported following IV bisphosphonate use. Methods: We present the clinical and lab findings in 6 cases of bisphosphonate-induced hypocalcemia, caused by unmasked vitamin D deficiency. Results: Our 1st patient was diagnosed with breast cancer and developed metastases 6yrs later. She was given Zolendronic acid 4 mg IV with a baseline calcium level (Ca) of 9.7 mg/dl, normal albumin, and elevated alkaline phosphatase. 3 days later, she developed symptomatic severe hypocalcemia with tetany: Ca dropped to 6.1 mg/dl with recovery. After her 2nd dose of Zolendronic acid, Ca dropped again to 6 mg/dl with normal albumin, intact parathyroid hormone (PTH) of 637 pg/ml (range 10–65) and 25-hydroxy vitamin D levels (25-OHD) of 4 ng/ml (range 20–100). Our 2nd patient presented with metastatic breast cancer and was treated with Zolendronic acid for hypercalcemia with a baseline Ca of 13 mg/dl, PTH-related protein of 2.8 pmol/l (range <1.8) and PTH of 7 pg/ml. She then developed hypocalcemia with corrected Ca of 7.7 mg/dl and 25-OHD of 13 ng/ml. Our 3rd patient with breast cancer was also treated with Zolendronic acid for bone metastases and hypercalcemia. She then presented with symptomatic hypocalcemia: ionized Ca level of 1.09 mmol/l (range 1.13–1.32), PTH of 211 pg/ml and 25-OHD of 13 ng/ml. Our other 3 cases had similar presentations to the above and will be discussed in detail. All 6 cases were treated with ergocalciferol and long-term oral calcium and vitamin D therapy. All of our cases presented with symptomatic hypocalcemia with vitamin D levels less than 30ng/mL. Conclusions: Since bisphosphonate use is increasing in cancer patients and vitamin D deficiency is not an uncommon finding in this population, consideration should be given to routine checking of 25-OHD levels before initiating treatment with bisphosphonates and supplementing with calcium and vitamin D when necessary (<30ng/mL). This could potentially prevent further morbidity. Further prospective studies would be needed for early replacement with vitamin D and calcium in those with vitamin D deficiency. No significant financial relationships to disclose.