Bone mineral density and microarchitecture improvement in a young patient with Hajdu-Cheney syndrome and autosomal dominant polycystic kidney disease treated with alendronate.

Abstract

Osteoporosis, typically seen in postmenopausal women, can also affect younger individuals, a condition known as Early-Onset Osteoporosis (EOOP). EOOP may be secondary to various conditions or arise from rare genetic disorders such as Hajdu-Cheney Syndrome (HCS), characterized by systemic bone involvement and fragility fractures. A 14-year-old male presented with a distal left femur fragility fracture. His medical history included spina bifida and bilateral tarsal coalition, with no family history of osteoporosis, and polycystic kidneys associated with a positive family history of autosomal dominant polycystic kidney disease (ADPKD). Laboratory tests were unremarkable, but dual X-ray absorptiometry (DXA) revealed low bone mineral density (BMD), and high resolution peripheral quantitative computed tomography (HR-pQCT) showed decreased volumetric bone density (vBMD), particularly in the cortical bone. At age 17, his kidneys were cystic and mildly enlarged. Whole exome sequencing revealed a pathogenic variant in <i>NOTCH2</i>, confirming the diagnosis of HCS, and a very likely causative variant in <i>PKD1</i>, supporting the diagnosis of ADPKD.The treatment regimen included weekly alendronate, impact exercise, a calcium-rich diet, and vitamin D supplementation. After 3 years, follow-up DXA and HR-pQCT demonstrated significant improvements in BMD and vBMD, mainly in the cortical bone. This case highlights the effectiveness of alendronate in managing osteoporosis in a patient with HCS and ADPKD, despite the current lack of strong supportive evidence. Long-term monitoring revealed substantial improvements in bone density and microarchitecture, underscoring the importance of early diagnosis and intervention for genetic causes of osteoporosis to prevent fracture-related morbidity.