Idiopathic juvenile osteoporosis (IJO) is a rare metabolic bone disorder characterized by bone fragility in otherwise healthy children and adolescents, with typical onset before puberty. To our knowledge, this represents the first documented case of IJO in Georgia, with a delayed diagnosis in adulthood despite a clinical history suggestive of earlier onset. A 24-year-old male with a history of childhood nephrolithiasis and intermittent vitamin D deficiency presented with progressive bone pain, joint crepitus, and worsening mobility. Imaging revealed severe osteopenia and osteoporosis, prompting an extensive metabolic and endocrine evaluation. Laboratory findings were largely unremarkable aside from episodic hypercalciuria, normal parathyroid hormone levels, and fluctuating vitamin D levels. Major secondary causes, including malignancy, hyperparathyroidism, thyroid dysfunction, chronic inflammatory disease, and malabsorption syndromes, were ruled out. A diagnosis of IJO was made by exclusion. The patient was started on calcium and vitamin D supplementation with close monitoring. This case highlights the diagnostic challenges of IJO when presentation extends into adulthood and underscores the importance of considering this condition in young adults with unexplained bone fragility, particularly in regions where it remains undocumented.

This case report describes the rare occurrence of idiopathic juvenile osteoporosis (IJO) in an 11-year-old boy with bone fragility and fractures, particularly in the thoracic and lumbar vertebrae. After excluding discernible underlying causes, the diagnosis was confirmed using clinical and radiological assessments. Treatment commenced with oral bisphosphonates, leading to notable bone mineral density (BMD) improvements and the absence of subsequent fractures. IJO presents diagnostic challenges owing to its multifaceted nature, necessitating the exclusion of other common causes of pediatric osteoporosis. Although the pathophysiology of IJO remains poorly understood, this case underscores the potential efficacy of bisphosphonate therapy in managing the condition and improving patient outcomes. Notably, the patient's symptoms ameliorated as puberty commenced, aligning with the typical IJO patterns reported in the literature. Although the long-term impact of bisphosphonate treatment in pediatric IJO cases warrants further investigation, this case exemplifies the potential to enhance the quality of life of affected individuals.

Idiopathic juvenile osteoporosis (IJO) is a rare condition presenting with vertebral and metaphyseal fractures that affects otherwise healthy prepubertal children. Bone mineral density (BMD) measurements are very low. The primary problem appears to be deficient bone formation, with a failure to accrue bone normally during growth. The onset in childhood suggests IJO is a genetic disorder, and a number of reports indicate that some children carry heterozygous pathogenic variants in genes known to be associated with defective osteoblast function and low bone mass, most commonly LRP5 or PLS3. However, a positive family history is unusual in IJO, suggesting the genetic background can be complex. We describe a young man with classical IJO who was investigated with a bone fragility gene panel and whole genome sequencing. The proband was found to carry four variants in three different genes potentially affecting osteoblast function. From his mother he had inherited mutations in ALPL (p.Asn417Ser) and LRP5 (p.Arg1036Gln), and from his father mutations in LRP5 (p.Asp1551Alsfs*13) and activating transcription factor 4 (ATF4) (p.Leu306Ile). His sister had also inherited the LRP5 (p.Asp1551Alsfs*13) from her father, but not the ATF4 mutation. Their spinal BMD z-scores differed substantially (sister -1.6, father -3.2) pointing to the potential importance of the ATF4 mutation. Activating transcription factor 4 acts downstream from RUNX2 and osterix and plays an important role in osteoblast differentiation and function. This case, together with others recently published, supports the view that IJO can result from clustering of mutations in genes related to osteoblast development and function. Novel genes in these pathways may be involved. Our case also emphasizes the value of detailed study of other family members. After a bone biopsy had excluded a mineralization defect due to hypophosphatasia, the proband was treated with zoledronate infusions with good clinical effect.

Idiopathic juvenile osteoporosis (IJO) is a rare condition characterized by low bone mass that can increase the risk of fractures in children. Treatment options for these patients are limited as the molecular mechanisms of disease initiation and progression are incompletely understood. Sclerostin inhibits canonical Wnt signaling, which is important for the bone formation activity of osteoblasts, and elevated sclerostin has been implicated in adult osteoporosis. To evaluate the role of sclerostin in IJO, high-resolution confocal microscopy analyses were performed on bone biopsies collected from 13 pediatric patients. Bone biopsies were stained with sclerostin, and β-catenin antibodies showed elevated expression across osteocytes and increased sclerostin-positive osteocytes in 8 of the 13 total IJO patients (62%). Skeletal sclerostin was associated with static and dynamic histomorphometric parameters. Further, colocalization analyses showed that bone sclerostin colocalized with phosphorylated β-catenin, a hallmark of Wnt signaling that indicates Wnt inhibition. In contrast, sclerostin-positive osteocytes were not colocalized with an "active" unphosphorylated form of β-catenin. These results support a model that altered levels of sclerostin and Wnt signaling activity occur in IJO patients.

Zoledronic acid (ZA), used for treatment of children with osteoporosis, can cause acute phase reaction (APR) following the first infusion. Many institutions have a policy to admit and monitor all children for their first ZA infusion. To determine if the APR with the first ZA dose warrants hospital-level care and evaluate if its severity correlates with the underlying condition. Retrospective cross-sectional analysis. Two tertiary centres across the UK that run paediatric metabolic bone disease services. Children who received first ZA infusion as inpatients at these centres. Nil. The Paediatric Early Warning Score (PEWS) and length of hospital stay to assess the severity of APR. 107 patients were included. Peak PEWS≤3 was found in 85% of children. 83% required admission for <24 hours. The various patient populations (osteogenesis imperfecta (OI), immobility-induced osteoporosis, idiopathic juvenile osteoporosis, systemic inflammatory disorders and steroid-induced osteoporosis, Duchenne muscular dystrophy (DMD)) did not differ significantly in the mean peak PEWS and the length of hospital stay. However, when compared directly, the group with DMD and that with systemic inflammatory disorders and steroid-induced osteoporosis differed significantly in the mean peak PEWS (p=0.011) and the length of hospital stay (p=0.048), respectively, as compared with the OI group. Most patients had a mild APR not requiring overnight hospital admission, after their first ZA dose. However, certain groups seem to suffer more severe APR and may warrant consideration of inpatient monitoring with the first infusion.