Use of zoledronate for treatment of hypercalcemia with subcutaneous fat necrosis of the newborn – A case-based narrative review

Subcutaneous fat necrosis (SFN) of the newborn can be complicated by life-threatening hypercalcemia. Evidence for use of bisphosphonates (BP) in this cohort is limited. We have presented a case report of an infant who was admitted with SFN and hypercalcemia and managed with zoledronate. We performed a literature search in PubMed/MEDLINE using the search terms (subcutaneous fat necrosis) AND ((hypercalcemia) OR (hypercalcemia) from inception until April 2025. We included patients diagnosed with SFN with hypercalcemia who were treated with BP. The study objective was to assess the efficacy and safety of BP in the management of this condition. Literature search revealed 199 cases of SFN with hypercalcemia. Seventy percent of patients treated for hypercalcemia required further therapy with steroids and/or BP. There were 30 patients of SFN and hypercalcemia who received BP. The mean age at first presentation of SFN was 14.8 days (range day 1 to 2 months of life). The mean age at diagnosis of hypercalcemia was 29.7-12.8 days. The mean duration of hypercalcemia was 13.8 days (range 18 hours to 46days). Pamidronate (60%) was the most common BP used. Resolution of hypercalcemia with BP was seen in all the cases with a median response time of 3 days (range 12 hours-12 days). Zoledronate was given as a single dose in all cases and had faster mean response time (2.5 days) while other BPs required more than one dose with longer response times. No serious adverse effects were reported. BPs are safe and effective in the management of hypercalcemia due to SFN.