**6. Conclusions**

Since citrate is a ubiquitous metabolite with a multidimensional role in the human organism, it is not surprising that it is involved in the pathophysiology of tissues, organs and systems. In fact, recent data in the literature have highlighted the relationship between citrate defects and various medical conditions with considerable financial and social impact, e.g., cancer [153], dyslipidemia [154], vascular calcifications [155], and visual disabilities [156].

Overall, this review has highlighted the main functions of citrate, and, more specifically, focused on the role of citrate in the pathophysiology and medical managemen<sup>t</sup> of metabolic bone diseases, thus identifying some key points which are summarised in Table 4.

Although interest in the role of citrate is spreading, a consensus statement regarding the use of citrate supplementation for the managemen<sup>t</sup> of metabolic bone diseases is still lacking, since the heterogeneity of the current evidence is a major limitation in identifying the best practice. Even when the study design is well planned, there are some reasons which may explain the di fficulty in obtaining unique and compelling results from clinical trials.

First, dietary supplementation cannot be regarded as a pharmacological treatment, and therefore the e ffects on measurable clinical outcomes are expected to be less prominent. Hence, baseline di fferences between participants which are beyond the investigator's control become selection biases that attenuate the strength of randomisation and interfere with the interpretation of the results. On the other hand, current scientific knowledge provides a sufficient background, leading the clinician and the researcher to further investigate the beneficial effects of citrate-based treatment in depth, as proven by multiple studies which have dealt with this matter.

At present, it can be argued that the use of citrate supplementation should be considered in the medical managemen<sup>t</sup> of bone diseases, but it is also reasonable to assume that the effects could be maximised in a personalised approach in which the scientific knowledge and the clinical judgement of practitioners are essential in identifying patients who could reap real benefits.

**Table 4.** The role of citrate in the pathophysiology and medical managemen<sup>t</sup> of bone diseases.
