Denosumab-associated symptomatic hypophosphatemia in normal kidney function: two case reports

We report two cases of symptomatic severe hypophosphatemia requiring hospitalization and intravenous phosphate supplementation following denosumab therapy for osteoporosis. The two patients had normal kidney function and no previously reported risk factors for hypophosphatemia, both presented neurological symptoms and severe fatigue. After hospital admission, they were treated with intravenous phosphate: serum phosphate improved to normal levels and the patients were discharged with oral phosphate supplements and—in one patient—with oral calcitriol therapy. As prescription rates of denosumab therapy increase, attention should be paid to the risk of developing hypophosphatemia: the risk of such complication may be lower by early and regular monitoring of Ca, Pi, and PTH, as well as early supplementation of phosphate and/or vitamin D as needed. Whenever a patient receiving denosumab therapy complains otherwise unexplained fatigue, exercise intolerance, muscle pain, cramping, and paresthesias, we suggest hypophosphatemia as a potential complication to be ruled out.