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<p>Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by elevated serum calcium and parathyroid hormone levels, frequently leading to bone loss and increased fracture risk. Although para-thyroidectomy is the definitive treatment, only a subset of patients exhibits significant bone mineral density (BMD) improvement after surgery. To address the unmet need for predictive biomarkers for BMD improvement, we developed the ExoBONE assay, a microfluidic-based diagnostic platform that integrates selective isolation and molecular analysis of extracellular vesicles (EVs). Using a horseshoe-shaped micro-mixer chip, we efficiently isolated flotillin-1-positive EVs from the plasma of PHPT patients. We then profiled EV-associated microRNAs and identified hsa-miR-125b-5p and hsa-miR-19b-3p as predictive markers for postoperative BMD recovery at the femoral neck and total hip, respectively. Notably, hsa-miR-125b-5p retained its predictive performance even after adjusting for key clinical covariates, such as age, sex, and baseline PTH and P1NP levels, supporting its robustness as a functional EV cargo marker. The ExoBONE assay enables minimally invasive and target-specific prediction of skeletal response to surgery, offering a clinically translatable strategy for personalized bone health monitoring. This study highlights the potential of microfluidic EV isolation and integrated molecular profiling in metabolic bone disease and postoperative outcome assessment.</p>

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Microfluidic ExoBONE Assay for Predicting Bone Mineral Density Improvement in Primary Hyperparathyroidism

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Seunghyun Lee,
  • Sunyoung Park,
  • Namki Hong,
  • Yongnyun Kim,
  • Jongju Jeong,
  • Hogyeong Gwak,
  • Hyo-Il Jung,
  • Yumie Rhee

摘要

Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by elevated serum calcium and parathyroid hormone levels, frequently leading to bone loss and increased fracture risk. Although para-thyroidectomy is the definitive treatment, only a subset of patients exhibits significant bone mineral density (BMD) improvement after surgery. To address the unmet need for predictive biomarkers for BMD improvement, we developed the ExoBONE assay, a microfluidic-based diagnostic platform that integrates selective isolation and molecular analysis of extracellular vesicles (EVs). Using a horseshoe-shaped micro-mixer chip, we efficiently isolated flotillin-1-positive EVs from the plasma of PHPT patients. We then profiled EV-associated microRNAs and identified hsa-miR-125b-5p and hsa-miR-19b-3p as predictive markers for postoperative BMD recovery at the femoral neck and total hip, respectively. Notably, hsa-miR-125b-5p retained its predictive performance even after adjusting for key clinical covariates, such as age, sex, and baseline PTH and P1NP levels, supporting its robustness as a functional EV cargo marker. The ExoBONE assay enables minimally invasive and target-specific prediction of skeletal response to surgery, offering a clinically translatable strategy for personalized bone health monitoring. This study highlights the potential of microfluidic EV isolation and integrated molecular profiling in metabolic bone disease and postoperative outcome assessment.