In ultra-rare bone diseases, information on growth during childhood is sparse. Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin (OPG). OPG inhibits osteoclast activation via the receptor activator of nuclear factor-κB (RANK) pathway. In JPD, overactive osteoclasts result in inflammatory-like bone disease due to grossly elevated bone resorption. Knowledge on the natural history of JPD, including final height and growth, is limited. Most affected children receive long-term antiresorptive treatment, mostly with bisphosphonates, to contain bone resorption, which may affect growth. In this study, we report the follow-up of height, growth velocity, and skeletal maturation in a 16-year-old female patient with JPD. The patient was treated with cyclic doses of pamidronate starting at 2.5 years of age and with 2 doses of denosumab at the age of 8 years, when pamidronate was paused. In the following years, a sustainable decline in a height <i>z</i>-score and a stunted pubertal growth spurt; despite appropriate maturation of the epiphyseal plates of the left hand, the proximal right humerus and both femora were observed. Whether this reflects the growth pattern in JPD or might be associated to the antiresorptive treatments is unclear, since there is very limited information available on the effect of bisphosphonates and denosumab on growth and the growth plate in pediatric patients. Studies are needed to understand the natural history of an ultra-rare bone disease and to assess the effects of antiresorptive treatment on the growing skeleton.

Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin. Osteoprotegerin inhibits osteoclast activation via the receptor activator of nuclear factor κB (RANK) pathway. Severely affected children suffer from bone deformities and pain and require long term anti-resorptive treatment. Due to the rarity of the disease, few long-term follow-up data on the clinical course in children are available. In this report, motor development during infancy and early childhood and the activity of the bone disease based on clinical, radiographic and biochemical parameters are reported in 2 children with severe forms of JPD during long term treatment (4 and 14 years) with bisphosphonates. Results of a bone biopsy in patient 1 after 10 years of treatment and video material of the motor development of patient 2 are provided. Doses per year of pamidronate ranged from 4 to 9 mg/kg bodyweight and were administered in 4–10 courses, yearly. Treatment was adjusted individually according to the presence of bone pain. Motor development was delayed in both children before treatment with bisphosphonates was commenced and improved thereafter. Bone histology revealed a significantly higher heterogeneity of mineralization which was mainly attributed to the increased percentage of low mineralized bone areas. Individualized intravenous treatment with pamidronate resulted in sufficient control of bone pain and suppression of bone turnover with few side effects over the observation period.