Genetic contributors to osteoporosis in pregnancy and lactation associated osteoporosis (PLO)
Abstract
Pregnancy- and lactation-associated osteoporosis (PLO) describes a fragility fracture presentation around pregnancy/lactation. Presentation often includes multiple vertebral fractures, but can also involve hip, sacral/pelvic, or other fractures. Substantial bone structural deficits and low bone formation rate have been documented. Most have no known secondary cause. Many have a history of childhood fracture and/or family history of osteoporosis. These characteristics, together with early onset and disease severity, lead to the hypothesis that genetic factors may contribute to PLO. We enrolled 110 women with PLO (mean #fractures = 6, vertebral fractures in 88 %) in an exome sequencing (ES) study. Analyses identified rare (<1 % allele frequency in gnomAD) predicted deleterious variants (RPDV) in 33/110 (30 %) women. All were heterozygous; two participants had multiple RPDV. No RPDV in COL1A1/COL1A2 were identified. 28/110 (25 %) had RPDV in genes related to WNT signaling, critical to bone formation: LRP5 (n = 19), LRP6 (n = 6), WNT1 (n = 2) or WNT1&LRP5 (n = 1). Seven had RPDV related to renal/calcium handling (SLC34A1, SLC34A3, SLC9A3), or other osteoporosis mechanisms (PLS3 (n = 3), HGD (n = 1)). Those with RPDV did not differ from those without in terms of BMD, fracture characteristics, and most clinical characteristics. Among 110 PLO women, exome sequencing analyses identified a potential genetic osteoporosis contribution in 30 %, suggesting that many genetic contributors…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 110 participants or records.
Read the paper
Related studies
- A Coupled SYSTEM of Intracellular Ca 2+ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker
- A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin
- Cancer epigenetics: Moving forward
- Current developments in LC-MS for pharmaceutical analysis
- Myricetin: A comprehensive review on its biological potentials
- A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.