HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation-associated osteoporosis (PLO)

Pregnancy and lactation-associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma and spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture, and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO-in comparison to both healthy premenopausal controls (n = 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (non-PLO IOP; n = 50). Women with PLO (aged 34 ± 6 yr) had a more severe clinical presentation than non-PLO IOP: 80% had vertebral and 92% had multiple fractures (p<.001). They had lower DXA aBMD at all sites vs Controls (all p<.001) and non-PLO IOP (all p<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters and lower bone strength than controls (all p<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all p ≤ .01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3 radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n = 25) evaluated ≤12 M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than distant PLO (n = 34) evaluated >12 M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.