PubMed · 15972391
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Nandini Dendukuri, Caroline Reinhold. 2005. Correlation and regression.. https://doi.org/10.2214/ajr.185.1.01850003
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BACKGROUND: In a great many of observational studies, whether there is a relevance of resistin levels on bone mineral density (BMD) and fracture occurrence has been inconsistently reported, and the causality is unclear. METHODS: We aim to assess the resistin levels on BMD and fracture occurrence within a Mendelian randomization (MR) analysis. Exposure and outcome data were derived from the Integrative Epidemiology Unit (IEU) Open genome wide association studies (GWAS) database. Screening of instrumental variables (IVs) was performed subject to conditions of relevance, exclusivity, and independence. Inverse variance weighting (IVW) was our primary method for MR analysis based on harmonized data. Weighted median and MR-Egger were chosen to evaluate the robustness of the results of IVW. Simultaneously, heterogeneity and horizontal pleiotropy were also assessed and the direction of potential causality was detected by MR Steiger. Multivariable MR (MVMR) analysis was used to identify whether confounding factors affected the reliability of the results. RESULTS: After Bonferroni correction, the results showed a suggestively positive causality between resistin levels and total body BMD (TB-BMD) in European populations over the age of 60 [β(95%CI): 0.093(0.021, 0.165), P = 0.011]. The weighted median [β(95%CI): 0.111(0.067, 0.213), P = 0.035] and MR-Egger [β(95%CI): 0.162(0.025, 0.2983), P = 0.040] results demonstrate the robustness of the IVW results. No presence of pleiotropy or heterogeneity was detected between them. MR Steiger supports the causal inference result and MVMR suggests its direct effect. CONCLUSIONS: In European population older than 60 years, genetically predicted higher levels of resistin were associated with higher TB-BMD. A significant causality between resistin levels on BMD at different sites, fracture in certain parts of the body, and BMD in four different age groups between 0-60 years of age was not found in our study.
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While bone mineral density measurements play a central role in osteoporosis management, the degree to which increases in this parameter contribute to bone fragility, fracture risk, and the therapeutic efficacy of osteoporosis agents is controversial. Indeed, bone strength is also significantly dependent upon bone turnover and bone quality, including microarchitecture, mineralization, and geometry. Given the critical role of these factors, it is essential to understand how they are affected by therapeutic agents. Even though a number of technological advances, such as microcomputed tomography, magnetic resonance imaging, and computerized analysis of radiographic patterns, help to provide critical information toward a more comprehensive assessment of bone turnover and bone quality, clinical trials addressing these factors are scarce. This article provides a review of studies relating to how osteoporosis therapies impact parameters of bone strength and quality.