Safety of alternating denosumab and zoledronic acid for osteonecrosis of the femoral head in children

Osteonecrosis, or avascular necrosis, of the femoral head (ONFH) results from an avascular insult of traumatic or non-traumatic origin and can lead to significant morbidity, including pain, arthritis and the need for joint replacement at a young age. Non-surgical management of ONFH focuses on preservation of femoral head shape to reduce the need for arthroplasty or delay the age at which it is performed. Thirty patients diagnosed with ONFH on bone scan were prospectively studied to determine the safety of alternating denosumab and zoledronic acid over a 66-week treatment period. Patients underwent 6-weekly scheduled biochemical monitoring and assessment of bone mineral density at baseline and after twelve months. Mild hypercalcaemia (range 2.65-2.85 mmol/L) was noted in 5 patients (16%) during the treatment period. One of these patients was subsequently diagnosed with familial hypocalciuric hypercalcaemia. Asymptomatic hypocalcaemia (range 1.79-2.00 mmol/L) was detected on routine biochemical testing in a total of 15 patients (48%). All episodes responded to an increase in oral calcium supplementation. Bone mineral density (BMD) increased in all patients following treatment, with maximum total body height-adjusted Z-score +2.4 and lumbar spine +3.3. There were no episodes of medication-related osteonecrosis of the jaw, atypical femoral fracture or hypophosphataemia. Our study demonstrates that, with regular monitoring and management of serum calcium, alternating doses of denosumab and zoledronic acid can be administered safely for ONFH in children.