Women With Pregnancy and Lactation–Associated Osteoporosis (PLO) Have Low Bone Remodeling Rates at the Tissue Level

Abstract

Pregnancy and lactation–associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low‐trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non‐PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue‐level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2/mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.

Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF

“…The latest and largest bone biopsy study in PLAO women where bone biopsies were performed 12 months postpartum, aimed to assess the baseline state of bone remodeling. Transiliac bone biopsies in these women, showed a low bone turnover state, which was also confirmed by circulating bone turnover markers compared to patients affected by idiopathic osteoporosis, itself already a state of low bone formation (97). This study showed a dissociation between low PINP in PLAO compared to controls, while the concentration of C-terminal telopeptide of type 1 collagen did not significantly differ (97).…”

“…These novel findings suggest the possibility of an underlying defect in osteoblast function taking into consideration the lower bone formation reported in PLAO women in the absence of lower osteoblast number (97).…”

Severe Bone Microarchitecture Impairment in Women With Pregnancy and Lactation-Associated Osteoporosis

“…Cohen et al evaluated a group of women with PLO and observed that they had lower tissue mineral apposition rates and bone formation rates assessed by transiliac bone biopsy in comparison with women with premenopausal osteoporosis. Based both on serum remodeling markers and micro-CT findings, they reported that women with PLO had evidence of low bone formation, in absence of lower osteoblast numbers, suggesting the possibility of an underlying defect in osteoblast function [ 41 ].…”

β-Hydroxy-β-Methylbutyrate (HMB) Supplementation Prevents Bone Loss during Pregnancy—Novel Evidence from a Spiny Mouse (Acomys cahirinus) Model

“…These observations are in agreement with a previous study in which a slight increase in the concentration and activity of bone turnover markers (osteocalcin, alkaline phosphatase, C-telopeptide of type I collagen) associated with the presence and healing of fresh bone fractures were observed in some women with PLO [ 60 , 61 , 62 ]. Moreover, bone biopsies of some PLO patients have indicated increased resorption or decreased activity of osteoblasts [ 40 , 63 , 64 ].…”