Circulating miR-34a and Bone Mineral Density of Brazilian Very-Old Adults

Abstract

The human aging is marked by several body changes, including in bone mineral density (BMD). Research shows that microRNAs are important modulators of bone metabolism. The present research aims to analyze the whole blood concentration of 10 selected microRNAs (miRs) and their association with absolute and relative scores of BMD in specific osseous site of Brazilian very-old adults. Forty noninstitutionalized and apparently healthy, very old (≥80 years) outpatients were eligible for research. Anthropometry, biochemistry, and densitometry measurements were performed along with coronary artery calcification (CAC) scores and tested across total circulating levels of microRNAs. As expected, the relative BMD scores for the lumbosacral region (L1 to S5) and for the femoral head and neck observed in the sample denote weakened bone architecture, compatible with prevalent osteopenia and osteoporosis. In this context, one single significant association was found, and negatively implicated the miR-34a-5p with both absolute (β = −0.36, P=0.001 for BMD) and relative (β = −0.43, P=0.001 for T-score) densitometry indexes of the femoral head (adjusted to sex and physical activity practice), but not with the other sites. No difference in total blood concentrations of the miRs was found according to CAC scores. Our findings indicate greater circulating levels for miR-34a-5p among very-old adults who display the lowest scores of BMD, being a finding consistent with a modest contribution of the miR (along with co-variables) to the mineralization of that site. Attesting clinical relevance of our findings demands forthcoming studies.

Sharing Circulating Micro-RNAs between Osteoporosis and Sarcopenia: A Systematic Review

“…None of the studies on sarcopenia defined the study design. Most of the studies (68%) were conducted in China, but participant ethnicity is stated in very few studies (25%) [ 29 , 30 , 35 , 42 , 43 , 52 , 53 , 54 , 55 , 57 , 60 , 65 , 81 , 82 ], thus limiting the generalizability of findings.…”

“…Some studies (17%) recruited younger participants in healthy control groups [ 38 , 41 , 42 , 44 , 47 , 59 , 60 , 71 , 78 ] and did not match for age, causing potential selection bias. Almost all the studies considered female osteoporotic and sarcopenic patients (76%), but 14/59 studies also included male patients [ 34 , 38 , 50 , 52 , 53 , 58 , 59 , 60 , 61 , 62 , 66 , 73 , 77 , 82 , 83 ]. Twelve studies on osteoporosis and two on sarcopenia did not state sex.…”

“…More than 60% of the studies on osteoporosis included in the current systematic review satisfied most of the items in the QUADAS2, which suggests that the overall quality of included studies was moderate-to-high ( Table 6 ). Six studies showed a high risk of bias in the patient selection [ 29 , 32 , 39 , 46 , 53 , 76 ] by not reporting, beyond the type of study, the allocation of the number of patients in the different experimental groups. Concerning the index text and how it was conducted and/or interpreted, most of the included studies showed a low risk of bias.…”

“…Concerning the index text and how it was conducted and/or interpreted, most of the included studies showed a low risk of bias. However, several studies did not specify the endogenous control used to perform the qRT-PCR, and thus they were scored to have a high risk of bias in relation to the index test [ 29 , 33 , 35 , 37 , 39 , 53 , 57 , 62 , 64 , 67 , 69 , 74 , 76 , 79 ]. The reference standard and the flow and timing risk of bias were low in all the examined studies.…”

Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging

“…( 47 ) Several studies have found miR‐34a to increase with age in EVs secreted by BMSCs, ( 48 , 49 ) and miR‐34a suppresses osteoblast differentiation as well as bone formation by differentiated osteoblasts. ( 50 , 51 ) Total circulating levels of miR‐34a (not solely EV‐derived miR‐34a) are inversely correlated with bone mineral density in older adults, ( 52 ) and circulating miR‐34a is increased with ovariectomy and positively correlated with bone loss in rodents. ( 53 ) Furthermore, EVs from aged bone matrix transfer microRNAs such as miR‐483‐5p and miR‐2861, which stimulate vascular calcification and bone marrow adipogenesis.…”