High genetic predisposition and vertebral fracture burden in pregnancy and lactation-associated osteoporosis: clinical insights from a Taiwanese cohort.
8 affiliations
- 1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
- 2Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- 3Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
- 4Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
- 5Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan.
- 6Department of Metabolism and Endocrinology, Taipei City Hospital, Renai Branch, Taipei, Taiwan.
- 7Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
- 8Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract
Background
Pregnancy and lactation-associated osteoporosis (PLO) is a rare disorder causing rapid bone loss and severe fragility fractures. While familial clusterings suggest genetic susceptibility, the specific clinical features, genetic landscape, and skeletal recovery trajectory of PLO remain poorly characterized in non-Caucasian populations. This study aimed to evaluate a Taiwanese PLO cohort to optimize diagnostic awareness.Methods
Eleven postpartum women with PLO were evaluated using bone densitometry and spinal imaging. Whole-exome sequencing was performed utilizing a targeted 398-gene skeletal disease virtual panel. Patients were followed longitudinally for a median of 25 months during lactation cessation and/or targeted bone therapy.Results
Seven women developed symptoms after their first pregnancy and four after their second. Vertebral fractures occurred in 91% (10/11) of patients, 80% (8/10) of whom had multi-level involvement predominantly localized to the thoracolumbar spine (T3-L5, peaking at T11-L2). Baseline lumbar bone mineral density (BMD) was significantly lower than hip sites (P = 0.018). Genetic variants were identified in 10 of 11 patients (91%), with six individuals harboring pathogenic variants in WNT1, LRP5, COL10A1, LTBP3, and CALCR. Patients with pathogenic variants exhibited significantly lower lumbar spine BMD than those without (Z-scores: -3.7 vs. -3.0; P = 0.043). Post-treatment, the cohort's median Z-score improved from -3.5 to -2.3 (P = 0.005), though none achieved a score above -1.0.Conclusions
Our findings suggest a significant genetic burden associated with PLO, potentially revealed by pregnancy and lactation stressors. The predominance of vertebral bone loss highlights acute postpartum back pain as a notable clinical sign warranting further investigation. Optimizing long-term maternal outcomes may require rapid diagnostic evaluation, prompt lactation cessation, and the future integration of genotype-informed management strategies.
Related
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BibTeX
@article{chiu2026high,
title = {{High genetic predisposition and vertebral fracture burden in pregnancy and lactation-associated osteoporosis: clinical insights from a Taiwanese cohort.}},
author = {Wei-Yih Chiu and Yu-An Chen and Shyang-Rong Shih and Rong-Sen Yang and Ming-Hsiao Hu and Wen-Ping Yang and Pei-Lung Chen and Keh-Sung Tsai and Wei-Shiung Yang},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1930247},
url = {https://europepmc.org/article/MED/42903217},
note = {CC BY},
}
RIS
TY - JOUR
TI - High genetic predisposition and vertebral fracture burden in pregnancy and lactation-associated osteoporosis: clinical insights from a Taiwanese cohort.
AU - Wei-Yih Chiu
AU - Yu-An Chen
AU - Shyang-Rong Shih
AU - Rong-Sen Yang
AU - Ming-Hsiao Hu
AU - Wen-Ping Yang
AU - Pei-Lung Chen
AU - Keh-Sung Tsai
AU - Wei-Shiung Yang
PY - 2026
DA - 2026/10/06
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1930247
UR - https://europepmc.org/article/MED/42903217
AB - Background Pregnancy and lactation-associated osteoporosis (PLO) is a rare disorder causing rapid bone loss and severe fragility fractures. While familial clusterings suggest genetic susceptibility, the specific clinical features, genetic landscape, and skeletal recovery trajectory of PLO remain poorly characterized in non-Caucasian populations. This study aimed to evaluate a Taiwanese PLO cohort to optimize diagnostic awareness.Methods Eleven postpartum women with PLO were evaluated using bone densitometry and spinal imaging. Whole-exome sequencing was performed utilizing a targeted 398-gene skeletal disease virtual panel. Patients were followed longitudinally for a median of 25 months during lactation cessation and/or targeted bone therapy.Results Seven women developed symptoms after their first pregnancy and four after their second. Vertebral fractures occurred in 91% (10/11) of patients, 80% (8/10) of whom had multi-level involvement predominantly localized to the thoracolumbar spine (T3-L5, peaking at T11-L2). Baseline lumbar bone mineral density (BMD) was significantly lower than hip sites (P = 0.018). Genetic variants were identified in 10 of 11 patients (91%), with six individuals harboring pathogenic variants in WNT1, LRP5, COL10A1, LTBP3, and CALCR. Patients with pathogenic variants exhibited significantly lower lumbar spine BMD than those without (Z-scores: -3.7 vs. -3.0; P = 0.043). Post-treatment, the cohort's median Z-score improved from -3.5 to -2.3 (P = 0.005), though none achieved a score above -1.0.Conclusions Our findings suggest a significant genetic burden associated with PLO, potentially revealed by pregnancy and lactation stressors. The predominance of vertebral bone loss highlights acute postpartum back pain as a notable clinical sign warranting further investigation. Optimizing long-term maternal outcomes may require rapid diagnostic evaluation, prompt lactation cessation, and the future integration of genotype-informed management strategies.
SN - 1664-2392
ER -