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Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture.

ABSTRACT: Emerging evidence demonstrates that microRNAs, as important endogenous posttranscriptional regulators, are essential for bone remodeling and regeneration. Undoubtedly, microRNA-based gene therapies show great potential to become novel approaches against bone-related diseases, including osteoporosis and associated fractures. The major obstacles for continued advancement of microRNA-based therapies in clinical application include their poor in vivo stability, nonspecific biodistribution, and unwanted side effects. Appropriate chemical modifications and delivery vectors, which improve the biological performance and potency of microRNA-based drugs, hold the key to translating miRNA technologies into clinical practice. Thus, this review summarizes the current attempts and existing deficiencies of chemical modifications and delivery systems applied in microRNA-based therapies for osteoporosis and osteoporotic fractures to inform further explorations.

SUBMITTER: Sun X

PROVIDER: S-EPMC6431398 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture.

Sun Xi X Guo Qi Q Wei Wenhua W Robertson Stephen S Yuan Ying Y Luo Xianghang X

International journal of endocrinology 20190306

Emerging evidence demonstrates that microRNAs, as important endogenous posttranscriptional regulators, are essential for bone remodeling and regeneration. Undoubtedly, microRNA-based gene therapies show great potential to become novel approaches against bone-related diseases, including osteoporosis and associated fractures. The major obstacles for continued advancement of microRNA-based therapies in clinical application include their poor <i>in vivo</i> stability, nonspecific biodistribution, an ...[more]

PMID: 30962808

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Project description:BackgroundOsteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies.ObjectiveTo assess the relationship between BMD and fracture and all common single-nucleotide polymorphisms (SNPs) in previously proposed osteoporosis candidate genes.DesignLarge-scale meta-analysis of genome-wide association data.Setting5 international, multicenter, population-based studies.ParticipantsData on BMD were obtained from 19 195 participants (14 277 women) from 5 populations of European origin. Data on fracture were obtained from a prospective cohort (n = 5974) from the Netherlands.MeasurementsSystematic literature review using the Human Genome Epidemiology Navigator identified autosomal genes previously evaluated for association with osteoporosis. We explored the common SNPs arising from the haplotype map of the human genome (HapMap) across all these genes. BMD at the femoral neck and lumbar spine was measured by dual-energy x-ray absorptiometry. Fractures were defined as clinically apparent, site-specific, validated nonvertebral and vertebral low-energy fractures.Results150 candidate genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9 gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11) were associated with BMD at either site. For most genes, no SNP was statistically significant. For statistically significant SNPs (n = 241), effect sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and TNFRSF11A loci were significantly associated with fracture risk; odds ratios ranged from 1.13 to 1.43 per allele. These effects on fracture were partially independent of BMD at SPP1 and SOST.LimitationOnly common polymorphisms in linkage disequilibrium with SNPs in HapMap could be assessed, and previously reported associations for SNPs in some candidate genes could not be excluded.ConclusionIn this large-scale collaborative genome-wide meta-analysis, 9 of 150 candidate genes were associated with regulation of BMD, 4 of which also significantly affected risk for fracture. However, most candidate genes had no consistent association with BMD.

Project description:This study aimed to evaluate the association between treatment duration of osteoporosis medications and clinical outcomes of patients with hip fracture. We found that the risk of subsequent osteoporotic fractures and all-cause mortality showed a decreasing trend as the treatment duration of osteoporosis medications increased.PurposeTo assess the risk of subsequent osteoporotic fracture (SOF) and all-cause mortality (ACM) in elderly patients with hip fracture in South Korea and to evaluate the potential reduction in the risk of SOF and ACM with varying durations of osteoporosis treatment.MethodsNewly diagnosed patients with hip fracture (age ≥ 60 years) who initiated osteoporosis medication within 3 months after the hip fracture from 2003-2014 were identified from the National Health Insurance Service-Senior cohort. The risk of SOF and ACM was estimated after the 1-year exposure-measurement period. Adjusted hazard ratios (aHRs) were calculated for treatment duration of osteoporosis medications categorized as short-term treatment (ST, < 3 months), early discontinuation (ED, ≥ 3- < 6 months), late discontinuation (LD, ≥ 6- < 12 months), and treatment continuation (TC, ≥ 12 months).ResultsA total of 4,421 patients were included in the analysis. The 3-year cumulative incidence of SOF was 22.4%, 22.0%, 23.9%, and 21.6%, and that of 3-year ACM was 29.8%, 27.0%, 19.7%, and 18.9% in the ST, ED, LD, and TC groups, respectively. Compared with the ST group, the risk of SOF showed a decreasing trend in the TC group (aHR [95% CI], 0.77 [0.58-1.00]). The risk of ACM was significantly reduced in the LD (aHR 0.68 [0.57-0.82]) and TC (aHR 0.65 [0.50-0.84]) groups.ConclusionThese findings underscore the importance of early and continuous osteoporosis treatment for elderly patients with hip fracture to improve health outcomes. The benefits of long-term osteoporosis treatment should be discussed in clinical practice to improve overall health outcomes.

Dataset Information

Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture.

Publications

Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture.

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