Endocrine Abstracts

Introduction: Denosumab, a human monoclonal antibody used in osteoporosis and second line treatment option for hypercalcaemia, can cause profound hypocalcaemia especially in Vitamin-D depleted and cancer patients.

Case history: 56 years female, with diabetes, hypertension on metformin, empagliflozin, amlodipine and ramipril, presented with 3 months history of backache, no red flag signs, clinically and hemodynamically stable except mild confusion and spinal tenderness but no other neurological deficit. Bloods showed hypercalcaemia with suppressed Parathyroid Hormone (PTH) and acute kidney injury (AKI) stage 3. X-ray spine showed possible wedge fracture and subsequent investigation confirmed spinal metastasis secondary to breast cancer. Hypercalcemia management with Denosumab led to severe hypocalcaemia within 14 days which was recurrent, requiring prolonged intravenous calcium infusions.

Investigations: Initial bloods: Urea: 32 (2.5-7.8 mmol/l), Creatinine: 382 (49-90umol/l), Corrected Calcium: 4.08 (2.20-2.60 mmol/l), PTH: 0.8 (1.3-7.3 pmol/l), Phosphate: 2.26 (0.8-1.5 mmol/l), Magnesium: 0.78 (0.7-1.0 mmol/l), Vitamin-D levels weren’t checked pre-Denosumab but 2 weeks later were 31 (>50 nmol/l). Bloods 1 month after Denosumab: Corrected Calcium: 1.58 (2.20-2.60 mmol/l), Phosphate: 1.45(0.8-1.5 mmol/l), Magnesium: 0.66 (0.7-1.0 mmol/l), 25OH-vitamin-D (post-replacement): 106 (>50 nmol/l). Full blood count, liver, thyroid, lipid, coagulation profile was normal. CT spine showed bone metastasis and pathological rib fractures. Biopsy of breast mass confirmed ductal carcinoma in situ.

Treatment: Given AKI, hypercalcaemia and bone metastasis she was treated with intravenous fluids (IVT) and Denosumab 120 mg subcutaneously which resulted in profound, recurrent, symptomatic hypocalcaemia with prolonged hospital stay (nearly 2 months) and frequent intravenous calcium infusions besides magnesium and Vitamin-D replacement. Calcium and Vitamin-D levels remained normal on high dose oral replacement on out-patient follow-up.

Conclusions: • IVT and bisphosphonates remains first line management for hypercalcemia unless contraindicated as per endocrine society guidelines.

• Vitamin-D must be replenished before giving Denosumab to prevent life threatening hypocalcaemia.

• Patient requires high dose vitamin-D and Calcium replacement post Denosumab to prevent hypocalcaemia and frequent monitoring.