Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

Abstract

Postmenopausal osteoporosis is characterized by the occurrence of fragility fracture with an increase in morbidity and mortality. Recently, microRNAs (miRNAs) have raised interest as regulators of translational repression, mediating a number of key processes, including bone tissue in both physiological and diseased states. The aim of this study was to examine the serum levels of 32 preselected miRNAs with reported function in bone and their association with osteoporotic fracture. We performed cross-sectional and longitudinal analyses from the OFELY Cohort. Serum levels of the miRNAs were quantified by qRT-PCR in 682 women: 99 premenopausal and 583 postmenopausal women, with 1 and 122 women with prevalent fragility fractures in each group, respectively. We have collected clinical variables (such as age, prevalent, and incident fractures), bone turnover markers (BTMs), BMD by dual X-ray absorptiometry, and bone microarchitecture with HRpQCT. We observed a number of miRNAs to be associated with fragility fractures (prevalent or incident), BTMs, BMD, and microarchitecture. This effect, however, was negated after age adjustment. This may be because age was also strongly associated with the serum levels of the 32 miRNAs (correlation coefficient up to 0.49), confirming previous findings. In conclusion, in a well-characterized prospective cohort with a sizeable sample size, we found no evidence that these 32 preselected miRNAs were not associated with BTMs, BMD, microarchitecture, and or fragility fractures. Ã CTX, mg/L (min-max) 0.466 (0.057-1.470) 0.374 (0.107-1.030) 0.481 (0.057-1.470) Ã Osteocalcin, ng/mL (min-max) Ã Ã p value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. Journal of Bone and Mineral Research LACK OF ASSOCIATION BETWEEN miRNAs AND BONE: DATA FROM THE OFELY COHORT 5 FEURER ET AL. Ã Radius Tt.vBMD, mg/cm 3 (min-max) 245.6 (122.9-482.1) 278.1 (101.9-515.8) Ã Radius Ct.vBMD, mg/cm 3 (min-max) 771.9 (556.9-956.4) 803.0 (572.6-1004.8) Ã Radius Tb.vBMD, mg/cm 3 (min-max) 123.2 (50.3-264.0) 141.8 (17.5-262.8) Ã Tibia Tt.vBMD, mg/cm 3 (min-max) 228.3 (124.2-371.2) 252.8 (109.0-417.4) Ã Tibia Ct.vBMD, mg/cm 3 (min-max) 702.6 (437.7-912.7) 744.6 (376.7-976.6) Ã Tibia Tb.vBMD, mg/cm 3 (min-max) 133.6 (52.0-212.6) 149.3 (31.9-254.7) Ã CTX, mg/L (min-max) 0.463 (0.057-1.16) 0.484 (0.062-1.470) NS Osteocalcin, ng/mL (min-max) 28.6 (4.2-90.2) 27.7 (6.5-86.2) NS P1NP, ng/mL (min-max) 49.0 (8.1-138.6) 21.5 (10.0-139.7) NS BAP, UI/L (min-max) 39.3 (15.2-69.4) 38.8 (10.1-88.6) NS Ã p-value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. 8 FEURER ET AL.

Circulating MicroRNAs as Novel Biomarkers for Osteoporosis and Fragility Fracture Risk: Is There a Use in Assessment Risk?

“…At the time of the PubMed medline, only four studies had evaluated c-miR signatures in PM OP patients by comparing them with PRM CTR subjects. However, one of these [54] did not identify any significant variation between the two groups in the serum levels of 33 selected miRs.…”

Circulating miRNAs: A New Opportunity in Bone Fragility

“…Feurer et al [ 63 ] attempted to evaluate the relationship between the expression levels of 32 miRNAs, selected according to the previous literature, and bone turnover, bone density, volumetric BMD, and incident fragility fractures in the serum of 123 premenopausal or postmenopausal women with fragility fractures (1 metatarsal fracture, 40 vertebral fracture, 2 hip fracture, 40 wrist fracture, 18 lower end tibia fracture, 6 proximal humerus fracture, and 1 pelvic fracture), and 559 without fractures, by using qPCR. Out of 32 miRNAs tested, only two miRNAs (miR-145-5p and miR-503-3p) were associated with a positive history of fracture as well as with BTMs, BMD, and microarchitecture parameters, but this association was no longer significant after age-adjustment.…”

The Clinical Potential of Circulating miRNAs as Biomarkers: Present and Future Applications for Diagnosis and Prognosis of Age-Associated Bone Diseases

“…Interestingly, the evaluation of 32 miRNAs, previously associated with both OP fractures and bone function, in serum samples from 682 women (a prospective cohort composed by pre and postmenopausal groups with or without prevalent fragility fracture) revealed that none of the selected miRNAs, after age adjustment, were significantly associated with fragility fractures [96].…”

“…For example, recently, Feurer et al reveal that, after age adjustment, most of the miRNAs previously associated with OP fractures lose their relationship with this condition [96].…”