PREGNANCY AND LACTATION ASSOCIATED OSTEOPOROSIS: BONE MICROSTRUCTURE AND METABOLISM, GENOTYPIC CHARACTERISTICS, NATURAL HISTORY AND BIOMARKERS OF DISEASE SEVERITY

Pregnancy and lactation associated osteoporosis (PLO) is a severe early presentation of osteoporosis in whichyoung women experience low trauma or spontaneous fractures, most commonly vertebral fractures, during latepregnancy or lactation. Information on characteristics and management is derived only from case reports andsmall series4-25. Before therapies for PLO can be developed, it is necessary to address several key gaps in ourknowledge about this disorder. Currently, there is little information available on the natural history of and riskfactors for PLO, the pathophysiological mechanisms of this acute fracturing syndrome, any biomarkers ofseverity, and risk of fracture with subsequent pregnancies. In our studies of the pathogenesis (AR49896)26-31and treatment (FD003902; FD005114)32,33 of premenopausal idiopathic osteoporosis (IOP), only 10 of 66women had PLO34. Premenopausal IOP is a rare orphan disease with an estimated prevalence 6 months after their initial fracture(s). Inclusion of both groups will allowus to compare patients who are at different stages of disease evolution. In Aim 1, we will conduct an onlinesurvey to obtain information on clinical characteristics and natural history of PLO, capitalizing on our long-termrelationship with a large (>135 women), international Facebook PLO support group. In Aims 2 and 3, we willrecruit 50 women with PLO, the largest cohort to date. Participants will undergo detailed phenotyping atColumbia University in terms of historical, biochemical, imaging and transiliac biopsy characteristics, andgenotyping by whole exome sequencing. All indices will be investigated as potential biomarkers of diseaseseverity. This study will provide the first comprehensive characterization of PLO, an essential step towards thedesign of future studies of targeted treatment strategies to improve skeletal recovery and bone quality.