Severe Refractory Hypocalcemia After Administering Zoledronic Acid for Osteoporotic Fracture in Primary Hyperparathyroidism That Is Complicated Into Hungry Bone Syndrome: A Case Report

Zoledronic acid is a very effective (IV) amino bisphosphonate which is indicated in osteoporosis, hypercalcemia of malignancy, multiple myeloma, Paget’s disease, and bone metastases from solid tumors. Bisphosphonate inhibits bone resorption through actions on osteoclast activity resulting in increasing bone density. Unfortunately, there are side effects associated with zoledronic acid one of those is mild to moderate hypocalcemia. Hungry Bone Syndrome (HBS) is defined as a severe drop in calcium levels less than 2.1 mmol/L and/or prolonged hypocalcemia for more than 4 days post parathyroidectomy. Most seen in patients’ who have secondary hyperparathyroidism compared to primary hyperparathyroidism. The sudden drop of parathyroid (PTH) levels post parathyroid resection after a prolonged duration of high PTH levels causes net calcium to move into the bone, this is the most proposed hypothesis. The authors report a case of a 32 years old female known case of severe osteoporosis presented to the emergency department complaining of left hip pain after a short height fall admitted as a case of pathological fracture. Furthermore, upon admission was vitally stable although on examination the patient had left side hip pain and tenderness otherwise unremarkable. Initial lab investigation showed a calcium level of 2.57 mmol/L and PTH level 37 pmol/L otherwise electrolytes and full blood count were unremarkable. Radiological investigations were done, and an X-ray has shown a left hip fracture where the patient underwent an operating room for fixation. In addition, a 99mTc-HDP bone scan revealed hyperparathyroidism and brown tumor. 99m Tc SESTA-MIBI whole body scan suggested metabolic bone disease. Furthermore, the parathyroid showed suggested typical parathyroid adenoma below and lateral to the lower pole of the left thyroid lobe. The ultrasound of the thyroid showing a well-defined hypoechoic nodule 2.5x1.15 cm with significant hypervascularity is seen, which is most likely to be enlarged left parathyroid gland. Thus, diagnosis of primary hyperparathyroidism has been reached with parathyroid adenoma which was resected during a hospital stay. The patient received pre-op zoledronic acid as a treatment for osteoporosis prior to the hip operation. After the parathyroid adenoma resection, the patient had a sudden drop of PTH and developed hypocalcemia which was 1.1 mmol/L. Thus, the complication of post operated parathyroid adenoma of HBS diagnosis has been made. Interestingly the patient needed to increase the length of stay of the hospital due to refractory hypocalcemia where the patient has been receiving IV calcium and vitamin D supplementation which hadn’t improved until a month of IV calcium gluconate. Although, the patient didn’t develop any signs or symptoms of hypocalcemia.

Calciphylaxis in Association With Hungry Bone Syndrome. A Possible Risk Factor?

Background: Calciphylaxis (calcific uremic arteriolopathy) is a rare complication seen in, although not limited to, patients with end-stage renal disease (ESRD). The abnormal regulation of calcium (Ca) and phosphorus (P) homeostasis in this patient group results in intravascular Ca deposition. These patients often develop secondary/tertiary hyperparathyroidism, presenting unique treatment challenges. When patients do not respond to medical therapy, parathyroidectomy is an option that may be complicated by hungry bone syndrome (HBS). We present a case of a patient with calciphylaxis with HBS post-parathyroidectomy. Case Report: The patient is a 41 y.o. male with ESRD on hemodialysis who presented with lower extremity ulcers complicated by calciphylaxis. On admission, the PTH was elevated at 2200 U with a normal corrected Ca 8.7 and P 8.5. He was found to have a non-displaced pathologic fracture of the right femoral neck. CT scan of the neck revealed nodular parathyroid hyperplasia affecting all four glands. His hyperparathyroidism was managed medically with cinacalcet, phosphate binder, and sodium thiosulfate to optimize his condition before surgery. He underwent a subtotal parathyroidectomy, with post-op course complicated by HBS. Repeat labs showed PTH 444, P 6.1, corrected Ca 7.4, and ionized Ca <4. Despite frequent repletion with IV Ca and addition of calcitriol, he remained persistently hypocalcemic with symptoms (paresthesia, perioral numbness) and prolonged QTc (560 ms) on 12-lead EKG. After weighing the more imminent risk of unstable arrhythmia versus exacerbation of HBS by targeting too high of a Ca level post-op, ICU admission was decided where Ca levels could be more closely monitored and titrated. The patient eventually demonstrated an improvement in his Ca level and symptoms. Discussion: This patient with ESRD complicated by hyperparathyroidism presented with ulcers and calciphylaxis refractory to medical therapy, requiring parathyroidectomy. HBS was a concern in this particular patient given his risk factors. Hypocalcemia is an expected electrolyte imbalance that usually resolves within 2–4 days after parathyroidectomy. Severe and persistent hypocalcemia on day 4 after the procedure should raise concern for HBS. It has been shown that the risk is higher in patients who have secondary hyperparathyroidism, prolonged duration of elevated PTH, age >60, and radiologic evidence of bone disease. ConclusionCalciphylaxis is an uncommon but potentially fatal illness seen in ESRD patients associated with Ca and P abnormalities. Whether this may increase the risk of HBS status-post parathyroidectomy is unknown; however, HBS requiring ICU management to treat refractory hypocalcemia has been reported in this group1. It is arguable that calciphylaxis may serve to identify such patients. (1) Hassanein M, et al. BMJ Case Rep 2018;11:e226696. doi:10.1136/bcr-2018–226696