Knot what you expected: a tender turn after Reclast

Erythema nodosum (EN) is a septal panniculitis commonly triggered by infections, autoimmune conditions, and medications, with zoledronic acid (ZA) being a rarely reported cause despite its widespread use as an intravenous bisphosphonate for osteoporosis and metastatic bone disease. We present the case of a 68-year-old woman with osteoporosis who developed acute onset of painful bilateral lower-extremity subcutaneous nodules 10 days following ZA infusion. Physical examination revealed tender, ill-defined subcutaneous nodules with overlying erythema on both lower legs. Punch biopsy demonstrated septal panniculitis with thickened fibrous septa, granulomatous inflammation, and scattered calcifications, consistent with EN. Workup excluded other common causes. The patient was managed supportively with nonsteroidal anti-inflammatory drugs, rest, ice, and avoidance of future bisphosphonate infusions. This case represents only the second reported instance of EN associated with ZA administration in the literature. The relationship between infusion and symptom onset, combined with the absence of alternative triggers, suggests a temporal correlation. Given the increasing use of bisphosphonates in clinical practice, early recognition of this rare adverse reaction can ultimately reduce patient morbidity.