Endocrine Abstracts

JOINT2223

Background: Juvenile Paget’s Disease (JPD; OMIM 239000) is a rare autosomal recessive disorder characterized by accelerated bone remodeling and elevated serum alkaline phosphatase (ALP) levels. Mutations in TNFRSF11B, which encodes osteoprotegerin (OPG), have been implicated in JPD.

Methods: This report describes two siblings with compound homozygous loss-of-function mutations in TNFRSF11B, leading to OPG deficiency and consequent typical symptoms of JPD. Case 1 (male, 7 years 3 months) presented with severe bone deformities with multiple fractures and hearing impairment. He cannot walk indecently without any help. Case 2 (female, 4 months) presented with minor bone deformities and initial hearing impairment. Whole exon gene examination confirmed the homozygous mutation of TNFRSF11B gene c.412C>T (p. R138X). Their parents were non-consanguious. Traditional calcium and vitamin D treatments have limited effects on JPD patients. After alendronate sodium was administered, the symptoms of the siblings were alleviated, they could stand and walk without any help, and the serum total alkaline phosphatase (ALP) level was significantly decreased.

Results: After bisphosphonate treatment, ALP levels decreased significantly and skeletal symptoms improved in both cases.

Conclusions: Early identification and treatment of JPD caused by TNFRSF11B gene mutation can significantly improve the quality of life of patients. Bisphosphonates are effective therapeutic agents, and early intervention can prevent severe bone deformities and functional impairment.

Keywords: Juvenile Paget’s Disease; Alkaline Phosphatase; Bone Remodeling; Bisphosphonates; TNFRSF11B.