Life-threatening hypophosphataemia secondary to zoledronic acid implementation in a middle-age patient who presented with advanced osteolysis in the course of multiple myeloma

Abstract

A 40-year-old man with a history of chest pain, nausea, and palpitation was admitted to hospital due to hypercalcaemia and renal function exacerbation. On admission the patient's condition revealed signs of dehydration and tachycardia. Moreover, the patient complained of painful ribs. Laboratory tests revealed a high calcium level of 3.69 mmol/L, normal parathormone (PTH) -18.4 pg/mL, and vitamin D deficiency -22.14 ng/mL (Tab. 1). Serum phosphate, magnesium, potassium, and sodium were within the normal range, and there were no acid-base-balance disturbances. Abdominal ultrasound offered no important findings. However, low-dose whole-body computed tomography scanning displayed an advanced diffused osteolysis in numerous bones ( Fig. 1). Additionally, some rib fractures were present. Consecutively, further biochemical analyses found mild normocytic anaemia, an elevated erythrocyte sedimentation rate of 94 mm and lactate dehydrogenase of 325 U/L, monoclonal gammopathy features in protein electrophoresis, and a k/l serum ratio equal to 1696.1.The above led to a suspicion of non-PTH-mediated hypercalcaemia (NPTH-H) in the course of multiple myeloma (MM). Treatment then included intravenous fluids, forced diuresis, and calcitonin and zoledronic acid administered following an improvement of renal function (a glomerular filtration rate of 49 mL/min/1.73 m 2 ). Unexpectedly, a severe (0.2 mmol/L) hypophosphataemia with hypophosphaturia (< 0.1 mmol/L) occurred four days later. Tubular reabsorption of phosphate (TRP) was within the normal range -0.895 (0.85-0.95), while the tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) decreased significantly to 0.19 mmol/L (1.0-1.35). On the other hand, prior to bisphosphate administration, these parameters were consecutively 0.52 and 0.43 mmol/L, with phosphate concentration 0.82 mmol/L and its excretion in urine at 5.4 mmol/L, together with features of mild acute kidney injury (Tab. 1). The PTH level increased slightly.Despite the patient's relatively stable state, insufficient oral supplementation of phosphate and severity of observed hypophosphataemia accounted for resorting to the application of intravenous phosphate infusion, which was continued for four days. Concomitant treatment i.a. involved alphacalcidol and cholecalciferol.To confirm neoplastic disease, bone marrow biopsy was performed, revealing a level of infiltration of pathological plasma cells equal to 42.7%. DiscussionMultiple myeloma is a neoplastic disease characterised by lytic lesions of bones [1]. The diagnosis is rare in adults under 40 years old (approximately 2%), with average age at diagnosis being 70 years. MM-related hypercalcaemia is caused by osteoclast activation involving a receptor activator of the NF-kB (RANK) system, as accompanied by hydrogen and cytokine release -mainly of interleukin-6, sclerostin, and the glycoprotein Dickkopf-1 (DKK-1) [2]. Zoledronate therefore serves as a standard treatment because it binds to hydroxyapatite complexes at metabolically active