Bridging the Gap: Pregnancy-And Lactation-Associated Osteoporosis.

Early diagnosis of pregnancy- and lactation-associated osteoporosis (PLO) is mandatory for a good outcome. Standard care is not a matter of conventional guidelines, rather it requires an individualized strategy while true overall incidence and pathogeny remain open issues. This is a narrative review based on full-length English articles, published between January 2021 and March 2023 and accessed via PubMed (no traumatic fractures or secondary osteoporosis are included). Our case-sample-based analysis included 836 females with PLO (the largest cohort based on published cases so far) through 12 studies and 24 single case reports. Except for one survey, these involved retrospective cohorts of small size (6-10 females/study) to medium size (23-47 women/study), and large cohorts with >50 subjects per study (a maximum of 379). Age of diagnosis: from 24 to 40 years for case reports (most subjects being over 30 and primigravida), while original studies indicated an average age between 31 and 34.18 years. Type of fractures underlined a most frequent vertebral phenotype (a mean of 2 to 5.8 vertebral fractures per patient) versus a most severe non-vertebral phenotype (hip and femoral neck fractures mostly requiring surgery). Potential contributors varied: smoking (1/3-1/2 of subjects), family history of osteoporosis (1/3), heparin and glucocorticoid use in pregnancy, low body mass index (majority of cases), hypovitaminosis D; and (with a low level of statistical significance) anti-psychotic medication, gestational diabetes, lupus, thrombophilia, anemia, in vitro fertilization (1/3 in one study), twin pregnancy, tocolysis with MgSO4, and postpartum thyroiditis. Most remarkably, up to 50% of PLO patients harbor mutations of LRP5, WNT1 , and COL1A1/A2 (more damaged form with potential benefits from osteoanabolic drugs); gene testing might become the new norm in PLO. The low index of clinical suspicion should be supported by performing magnetic resonance imaging (gold standard in pregnancy) with DXA (in lactation). Low bone mineral density is expected (Z-score varying from -2.2 SD to -4 SD, unless normal which does not exclude PLO). Bone turnover markers might be useful in individuals with normal DXA, in pregnancy when DXA cannot be performed, and in following the response to anti-osteoporosis drugs. Alternatively, microarchitecture damage might be reflected by DXA-trabecular bone score and high-resolution peripheral quantitative computed tomography. Specific medical interventions are currently focused on teriparatide (TPT) use (3 studies; n = 99 females treated with TPT and an additional subgroup of 18 patients from the gene-analysis-based study, thus a total of 117 females) which seems to be the therapy of choice as reflected by these new data: 6-24 months, 20 µg/day, no sequential therapy needed; case selection based on high fracture risk is necessary). The first case using romosozumab was reported in 2022. PAO/LAO remains a challenging condition which is a battle for the wellbeing of two individuals, on one hand, considering maternal-fetal outcomes and taking care of the offspring, but it is a battle for a multidisciplinary team, on the other hand, since a standardized approach is lacking.