International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 185-194 http://medscipublisher.com/index.php/ijmms 186 2 Vitamin D supplementation and Fracture Risk 2.1 Findings from major global research and summary reports A large amount of evidence from research and summary analysis shows that for generally healthy elderly people in the community, taking vitamin D alone does not significantly reduce the occurrence of fractures throughout the body, hip fractures, or other non-spinal fractures (Kahwati et al., 2018; Yao et al., 2019). For instance, large-scale VITAL studies and some recent summary analyses have found that regardless of the initial vitamin D level or factors such as race, the occurrence of fractures in people taking vitamin D and those taking placebos is similar (Bolland et al., 2018; LeBoff et al., 2022; De Souza et al., 2024). Conversely, when vitamin D is taken together with calcium, it shows that although the effect is not significant, it does statistically reduce the risk of overall and hip fractures, especially for those elderly people living in institutions such as nursing homes or with a high risk of fractures. The summary analysis report states that this combined supplementation can reduce the risk of fractures by 15%-30%, supporting its use in specific populations, although the effect in ordinary community elderly people is not so clear (Boonen et al., 2007; Chung et al., 2011; Weaver et al., 2015; Chakhtoura et al., 2021). 2.2 Effect differences: dosage, consumption method, and Population characteristics The effectiveness of vitamin D supplementation is influenced by the amount consumed and how it is taken. A daily dose of 800 to 1 000 international units (IU) has most consistently shown a reduced risk of fractures and falls. However, eating less or more - especially taking large doses at intervals - may be ineffective and even harmful (Bischoff-Ferrari et al., 2012; Anagnostis et al., 2020). Taking a large dose every day is better than taking it every other day. The latter has not shown any effect of preventing fractures and may even increase the risk of falls (Khaw et al., 2017; Kong et al., 2022; Myung and Cho, 2023). The characteristics of the crowd itself are also very crucial. The effect is more obvious in elderly people who are already deficient in vitamin D, those living in institutions such as nursing homes, or those who do not consume enough calcium on a regular basis. On the contrary, elderly people who live in their own homes, are generally healthy and do not lack vitamin D do not seem to benefit from it. Some studies have even found that giving healthy women large doses of vitamin D at intervals may actually increase the risk of hip fractures (Zhao et al., 2017; Kahwati et al., 2018; Chakhtoura et al., 2021; De Souza et al., 2024). 2.3 Deficiencies of existing research and the necessity of conducting new summary and analysis There are some problems with the existing research, such as significant differences in the research subjects (heterogeneity), varying dosages and methods of intake, different initial vitamin D levels, and inconsistent calcium supplementation at the same time. Many studies recruited individuals who were not clearly deficient in vitamin D or had a low risk of fractures, which might weaken the observed effects and make the results more difficult to generalize to everyone (Bolland et al., 2018; Kahwati et al., 2018; De Souza et al., 2024). The differences in methods, such as the varying lengths of tracking time, the different degrees to which people eat as instructed, and the different criteria for judging results, also make the interpretation of results and the formulation of guidelines more complicated (Anagnostis et al., 2020; Chakhtoura et al., 2021). In addition, the quality of various summary analyses (systematic reviews and meta-analyses) also varies. Contradictions often arise in the results due to different criteria for which studies were selected, what analytical methods were used, and which population subgroups were analyzed. These inconsistent situations indicate that a comprehensive and up-to-date summary analysis (meta-analysis) is highly necessary to truly understand the actual impact of vitamin D supplementation (alone or with calcium) for the elderly on fracture risk, and to identify which small groups are most likely to benefit from this intervention (Boonen et al., 2007; Weaver et al., 2015; Yao et al., 2019; Chakhtoura et al., 2021; Kong et al., 2022). 3 Introduction to the Design and Methods of Meta-analysis 3.1 Data sources and search methods A rigorous comprehensive analysis (meta-analysis) first requires a comprehensive search plan to identify all relevant studies. This usually requires systematically searching multiple electronic databases, such as PubMed, Embase and the Cochrane Library, using pre-determined keywords (like vitamin D, supplements, fractures, elderly)
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