Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

A 41-year-old post-menopausal female with cerebral palsy and Trisomy 21 presented with asymptomatic scoliosis. She ambulates independently and had no prior fragility fractures. Apart from a wide-based gait, varus knees and scoliosis, there was no palpable bony tenderness or masses.

Biochemistry demonstrates persistently elevated bone remodeling markers over time, with peak levels of C-telopeptide (CTX) 3480ng/L (<800), procollagen type 1 N-propeptide (P1NP) 599ug/L (15.1-58.6), and bone-specific ALP of 144ug/L (5.5-24.6). She had normal renal function, parathyroid hormone, calcium, vitamin D and phosphate levels. She did not tolerate cannulation for attempted zoledronic acid infusion in 2021.

Plain imaging (Figure 1A) showed diffuse bony abnormality. Technetium-99m whole body bone scan (Figure 1B) demonstrated diffusely increased osteoblastic activity. She had normal bone mineral density with lowest Z-score of +0.9 at lumbar spine.

The findings above support the diagnosis of Idiopathic hyperphosphatasia, synonymous with Juvenile Paget’s disease. This is a rare genetic bone disease with significant variability in phenotype, thought to be caused by autosomal recessive inheritance of mutations in the TNFRSF11B gene encoding osteoprotegrin (OPG). Patients often have shortened, wide and deformed long bones, frequently with lateral bowing of the femur and anterior bowing of the tibia, and bone pain can be a frequent symptom (1). While replacement with recombinant OPG has limited evidence, case reports suggest bisphosphonates or denosumab may be therapeutic options (2). 

Juvenile Paget’s disease is a rare diagnosis presenting with a range of phenotypes. Decisions regarding therapy must be individualised to the patient’s case. Our patient did not undergo genetic testing in line with her family’s wishes, and the decision was made to delay anti-resorptive treatment as the patient was asymptomatic without evidence of bone pain or prior fragility fractures.