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

## TL;DR

A 14-year-old boy with Hajdu-Cheney Syndrome and kidney disease showed improved bone density after three years of alendronate treatment.

## Contribution

First long-term follow-up of bone mass in HCS using DXA and HR-pQCT, showing treatment effectiveness.

## Key findings

- Alendronate treatment improved BMD and cortical bone density in a patient with HCS and ADPKD.
- HR-pQCT showed significant volumetric bone density improvements after three years of treatment.
- Early diagnosis and intervention led to substantial bone microarchitecture improvements.

## 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 NOTCH2, confirming the diagnosis of HCS, and a very likely causative variant in PKD1, 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.

•A 14-year-old male with Hajdu-Cheney Syndrome (HCS) had a fragility fracture and low BMD.•Genetic testing identified a pathogenic NOTCH2 variant, confirming HCS diagnosis.•Treatment with alendronate, exercise, calcium, and vitamin D improved BMD.•HR-pQCT revealed significant cortical bone density improvement after 3 years.•First long-term HCS bone mass follow-up using DXA and HR-pQCT.

A 14-year-old male with Hajdu-Cheney Syndrome (HCS) had a fragility fracture and low BMD.

Genetic testing identified a pathogenic NOTCH2 variant, confirming HCS diagnosis.

Treatment with alendronate, exercise, calcium, and vitamin D improved BMD.

HR-pQCT revealed significant cortical bone density improvement after 3 years.

First long-term HCS bone mass follow-up using DXA and HR-pQCT.