Background: Juvenile Pagets disease is a rare autosomal recessive osteopathy. Patients presenting in infancy develop severe bone deformities and may never walk. Bisphosphonate therapy is used to decrease bone turnover and it has generally good responses in milder forms of the disease. However there is no long-term experience of bisphosphonates in severe infantile forms.
Case report: A 9 month-old boy was referred to our clinic for bone deformities. He was the third child of first degree cousins. He had bilateral sensorineural hearing loss and delay in neuromotor development. His height and weight were below the 3rd percentile. He couldnt move his extremities, even his mother couldnt cuddle him due to severe bone pain. Laboratory results showed normal serum calcium, phosphate, parathormon levels but very high alkaline phosphatase (1692 U/l; normal: 133347). Bone ALP was also very high. Radiographic findings demonstrated bowing of femurs, widening of metaphysis and diaphysis of long bones, thickening calvarium, and periosteal reaction. Genetic analysis showed a large homozygous deletion in TNFRSF11B gene. Intravenous pamidronate therapy was started at a dose of 1 mg/kg every 3 months. The bone pain alleviated, motor development improved, ALP and periosteal reaction in bones decreased with the treatment. After 2 years of treatment, clinical findings began to deteriorate, so yearly dose of pamidronate was increased with a more frequent infusion schedule (every 2 months).
At 4.5 years of age, bilateral humerus fractures developed and bone pain recurred restricting his movements. ALP was high (1577 U/l). Switching to another bisphosphonate zoledronic acid had a quick effect in alleviating bone pain.
Conclusion: Intravenous pamidronate therapy is very effective in reducing bone pain, improving the bone deformities and motor development in infantile onset, severe form of juvenile Pagets disease. However this effect is transient. Changing to another bisphosphonate is an alternative treatment in case of resistance to pamidronate therapy.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology