Can transient neonatal osteosclerosis be differentiated from malignant infantile osteopetrosis?

Abstract

Osteosclerosis in infancy requires careful evaluation as it may indicate the presence of osteopetrosis. Osteopetrosis is a rare disorder of high bone density due to impaired osteoclast resorption. Infantile forms of osteopetrosis have neurological and hematopoietic defects. However, some infants may present with a transient neonatal osteosclerosis (TNO) appearance without skeletal consequences. The aim of this case series is to compare TNO with infantile osteopetrosis. Radiographic reports of infants less than 12 months old were searched for the terms osteosclerosis and osteopetrosis from 2006 to 2025 at a single tertiary care children's hospital. Serial radiographs performed clinically were extracted and assessed for resolution and the clinical features described. TNO was identified in 7 infants and osteopetrosis was identified in 6 infants. The children with TNO presented at younger age (median age 6 days) than those with osteopetrosis (median age 73 days). All infants with osteopetrosis had genetic confirmation (TCIRG1 n = 3, CLCN7 n = 2 [one dominant, one recessive], IKBKG n = 1). Four of 6 infants with autosomal recessive osteopetrosis had thrombocytopenia and 3 had hypocalcemia, 5 had elevated parathyroid hormone, and 3 had elevated alkaline phosphatase. One of the 7 infants with TNO had thrombocytopenia and 2 had mild hypocalcemia. Rachitic changes were present in 3 infants with osteopetrosis, and metaphyseal widening in all 6 infants, but none of the TNO infants had these features. In TNO, resolution was evident by mean age of 8.5 months (range 1 to 31 months). TNO and infantile osteopetrosis have distinguishing clinical, radiographic and laboratory features.