Gene Variants and Bisphosphonates Treatment in Pregnancy and Lactation-Associated Osteoporosis (PLO): A Retrospective Study of 22 Chinese Patients.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare bone disorder with insufficient understanding on its pathogenesis and treatments. We retrospectively investigated 22 Chinese PLO patients diagnosed in our hospital. Whole exome sequencing was performed in 14 patients, and responses to bisphosphonates treatment were evaluated. The mean age of the patients was 30.8 ± 4.4 years. The mean number of vertebral fractures per patient was 4.0 ± 2.6. The bone mineral density (BMD) Z-scores were - 2.9 ± 0.9 at the lumbar spine (LS), - 1.7 ± 0.7 at the femoral neck, and - 1.8 ± 0.7 at the total hip. Trabecular bone score Z-score was - 2.2 ± 0.8. Genetic analysis identified relevant variants (RVs) in 11 of 14 patients, predominantly in LRP5, WNT1, and COL1A1/A2. Patients with RVs had significantly greater height loss (3.6 ± 2.1 cm vs. 0 cm, p = 0.028). All patients received bisphosphonate therapy, during which increases in BMD primarily at the LS were observed: 13.5 ± 8.8%, 17.8 ± 14.7%, 22.0 ± 17.0%, 27.0 ± 14.1% and 35.1 ± 18.5% at the 6-, 12-, 24-, 36-, and 48-month follow-ups. Patients with RVs demonstrated LS BMD percentage changes of 40.1 ± 22.1% (vs. no RVs group 26.2 ± 14.8%, p = 0.57) after 48-month follow-ups. In conclusion, our study highlights the significant clinical burden of PLO. Genetic RVs are prevalent in Chinese PLO patients. After bisphosphonate treatment, there is a significant increase in BMD, especially in LS. Patients with RVs have the potential of more robust therapeutic response.