SAT-365 Severe, Symptomatic Hypocalcemia Due to Denosumab and Vitamin D Deficiency in an Osteopenic Post-Menopausal Female

BACKGROUND: Denosumab is a monoclonal antibody used in the treatment of osteoporosis to prevent bony injuries by increasing bone density. It has a very rare side effect of severe hypocalcemia (1) and a patient should take supplemental Vitamin D and calcium for prevention. There is debate among experts on when denosumab should be discontinued and if so, whether an alternative therapy should be started (2). Case Report: A female in her 8th decade of life presented to the ED with a complaint of intermittent and diffuse numbness and confusion. She had a history of MGUS and osteoporosis; however, her most recent SPEP did not detect MGUS and her most recent bone scan showed a T score indicating osteopenia. She had been receiving denosumab for the past four years with her last injection three weeks prior. Physical exam revealed 5/5 strength and intact sensation in all four extremities. Her serum calcium level on presentation was 4.3 mg/dL (8.5-10.1), ionized calcium was 3.9 mg/dL (4.6-5.4), 25 Hydroxy Vitamin D 8.8 ng/ML (30-100), and intact PTH was appropriately elevated at 702.7 pg/mL (14.0-72.0). Her phosphorus level was also appropriately low at 2.1mg/dL (2.5/4.9). She had a serum creatinine level of 0.9 mg/dL (0.6-1.0) and an eGFR 63 mL/min. ECG showed normal sinus rhythm without any QT changes. She received 4 grams of calcium gluconate intravenously over the next 24 hours without improvement in her calcium, as trending chemistries continually showed a calcium level less than 5.0. She was started on a calcium gluconate continuous infusion along with calcitriol, Vitamin D3 5,000 IU per day, and oral calcium 500 mg with Vitamin D 600 IU three times daily. Her calcium levels improved, albeit still low, to 6.5 mg/dL and the calcium continuous infusion was stopped. A 1, 25-Dihydroxy Vitamin D level showed improvement as well resulting at 82 pg/mL (20-79). Her numbness and confusion symptoms resolved, and she was discharged on the aforementioned oral calcium and vitamin D regimen with instructions to follow up and discontinue use of denosumab. Conclusion: There are two primary takeaways from this clinical case. The first is to ensure a patient receiving denosumab is also taking supplemental Vitamin D and calcium to prevent hypocalcemia and to periodically measure serum levels to rule out deficiency. The second is the emphasis on having a provider-patient discussion on alternative therapies when the patient may no longer be a candidate for denosumab while considering the patient’s risk for fracture. References: Bone, Henry G. et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trail and open-label extension. Lancet Diabetes Endocrinology. 2017. 5: 513-23 Tsourdi, E. et al. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone 2017. 105: 1-17.