Mishra et al. [1] in their work entitled “A comparative analysis of serologic parameters and oxidative stress in osteoarthritis and rheumatoid arthritis” demonstrated that lipid levels might modulate the susceptibility to the development of inflammatory diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). The progression of both disorders is known to be associated with inflammation and oxidative stress. The serum levels of both MDA (malondialdehyde) and CRP (C-reactive protein) are positively correlated with high cholesterol levels emphasizing the link between oxidative stress, inflammation, and dyslipidemia.

The mevalonate pathway is essential for the biosynthesis of cholesterol and non-sterol isoprenoids: the impairment of this pathway leads to a rare disease called mevalonate kinase deficiency (MKD). MKD is an inborn auto-inflammatory disorder, due to the mutations in second enzyme of the mevalonate pathway. The quality of life of MKD patients is poor because of frequent inflammatory episodes. The disease usually starts within the first year of life and shows a variable spectrum of clinical manifestation, characterized by fever, lymphadenopathy, joint and abdominal pain as well as rashes that periodically occur [2].

Recently, we developed an animal and cellular model of the MDK [3] using the aminobisphosphonate alendronate (ALD), able to inhibit farnesyl pyrophosphate synthase (FPPS), in association with bacterial muramyldipeptide (MDP) capable to induce an acute inflammatory condition (Fig. 1).

Fig. 1
figure 1

Schematic representation of mevalonate pathway

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The association between ALD and MDP in this mouse model involves a shortage of mevalonate pathway intermediate compounds, in particular of isoprenoids fundamental for cholesterol production. We observed a reduction of cholesterol levels in association with the inflammatory response. We hypothesize that the relative lack of cholesterol and isoprenoids probably causes the typical inflammatory phenotype of this disease. The inflammatory phenotype observed in MKD patients and in aminobisphosphonate-treated mice is comparable [4].

Although the inflammatory marker levels of CRP and SAA (serum amyloid A), respectively, evaluated in patients with RA [1] and in the animal model of MKD [3] shows the same trend, the relationship between cholesterol levels and inflammation is in opposite, probably because it is a peculiar event of this genetic disease. However, from all the foregoing, it is clear that both high and very low levels of cholesterol, respectively, observed in RA and MKD clearly indicates the natural and important link between the cholesterol homeostasis and the inflammatory condition (Fig. 1) [1, 3].

The main complications associated with chronic inflammatory conditions are metabolic disorder such as obesity, cardiovascular disease, and atherosclerosis characterized by the high cholesterol levels [5, 6].

Since patients with MKD disease present low cholesterol values, it is reasonable to assume that these patients will not provide evidence of the typical complications associated with the phenotype of the chronic inflammatory diseases.