The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women

Abstract

Regulation of osteoclastic activity is critical for understanding bone loss associated with the postmenopausal period. In vitro and animal studies have revealed the role of OPG as a decoy receptor that neutralizes the effect of RANKL on the differentiation and activation of osteoclasts. However, the role of the OPG-RANKL system in postmenopausal osteoporosis is controversial. Thus, the aim of this study was to investigate the relationship among circulating levels of OPG, RANKL, bone turnover markers (BTM), bone mineral density (BMD) and vertebral fractures in postmenopausal women. We determined anthropometric parameters, circulating OPG and RANKL, BTM, estradiol, BMD by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN), and pre-existing vertebral fractures in 206 ambulatory postmenopausal women of a mean age of 62 years (SD 7). Circulating OPG was significantly related to age (r =0.158; P =0.023), years since menopause (r =0.167; P =0.016) and BMD (LS Z-score: r =0.240; P =0.001, FN Z-score: r =0.156; P =0.025). Over half of the women had undetectable RANKL (n =113; 54.9%). There were no significant differences in clinical variables, BTM or BMD among women with detectable vs. undetectable RANKL. OPG was found to be independently associated with osteoporosis (OR: 2.9, 1.4-5.9) and prevalent vertebral fractures (OR: 2.5, 1.2-5.4). We conclude that serum OPG levels are independently associated with bone mass and prevalent vertebral fractures in postmenopausal women.

The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor κB legend with bone mineral density in older adults: the Rancho Bernardo Study

“…Neither OPG nor RANKL predicted 5 to 10 year change in BMD. The absence of a positive association of OPG with BMD in women who were not using estrogen is concordant with five of six previous studies (3,11,14,16,21,28). Only one prior study explicitly assessed women using estrogen.…”

“…OPG levels reported here are within the wide range published in other studies. Mean values of OPG (for assays that detect all OPG forms) have ranged from 10 to 246 pg/ml (3,(14)(15)(16)21), with the exception of one study reporting 1359 and 1229 pg/ ml for pre-and postmenopausal women respectively (28). Wide ranges in reported values likely reflect differences in study populations, collection and storage methods, assay detection levels, and improved detection levels in newer assays (2).…”

“…Until recently, RANKL assays were not sensitive enough to detect levels for a large proportion of healthy individuals (21). One study reported that 55% of postmenopausal women had undetectable levels (21). Mean values using the less sensitive assays ranged from 7 (3) to 26 pg/ml (20,21,36,37).…”

“…Published findings of serum OPG-bone mineral density (BMD) associations in humans have been inconsistent (3,(11)(12)(13)(14)(15)(16)(17)(18), and few studies have assessed the associations of RANKL (18)(19)(20) and the RANKL/ OPG ratio (20,21) with BMD. To test the a priori hypotheses that OPG-BMD associations are positive and RANKL-BMD associations are negative in humans, we conducted a cross-sectional and prospective study of the associations of serum levels of OPG, RANKL, and their ratio with BMD in older men and postmenopausal women, stratified by use of estrogen.…”

The RANK/ RANKL/ OPG interaction in the repair of autogenous bone grafts in female rats with estrogen deficiency

“…However, the literature presents conflicting results concerning the period after menopause, when bone loss is related to favoring RANKL activity over that of OPG. In a cohort study, Mezquita-Raya et al 21 and Chiba et al 22 found no correlation between OPG and bone resorption markers in women, regardless of their menopause status. According to the results, this study also demonstrated that the expression of bone markers during repair of autogenous bone grafts was not altered by estrogen deficiency.…”