High genetic predisposition and vertebral fracture burden in pregnancy and lactation-associated osteoporosis: clinical insights from a Taiwanese cohort

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.