There are other diseases where high homocysteine is found at the scene of the crime. It's still not clear if its just piling on during some other disease process or implicated as cause. Many studies look at homocysteine as a biomarker but others, like those above, see direct effects so my guess it's some type of signaling molecule (try putting homocysteine in PubMed - almost 22000 articles). Someday, I'll go down that rabbit hole.
High homocysteine is implicated in inflammation (brought about by high insulin and blood glucose levels) and increasing IL-6.
The other example is the hypomethylation in CpG islands within the IL-6 promoter gene in monocytes. IL-6 is a pro-inflammatory cytokine that participates in B cell response. When this promoter is hypermethylated, there is an overexpression of IL-6 that will cause an overexpression of pro-inflammatory cytokines at the same time. This will be associated with a local hyperactive of the inflammation circuit. But there is evidence that we can also find a hypermethylation mechanism in monocytes such as in the case of the CpG islands with the promoter of death receptor 3 (DR-3). DR-3 is a protein that cause apoptosis and activation of transcription factor NF-kappa-M. However, when there is a downregulation of tis protein because of the hypermethylation of its promoter, the RA synovial cell will be resistant to apoptosis.
Glucose and insulin levels are determinants of methylation. They alter homocysteine metabolism by increasing cell homocysteine production through its inhibition of trans-sulfuration. When there is an increase in the levels of homocysteine, methionine in cells will be catalyzed by DMNTs in S-adenosylmethionine. This will enhance DNMT activity that will subsequently lead to increased global DNA methylation.
High homocysteine is implicated in osteoporosis.
Our analyses of data from three cohorts of subjects in two independent studies show a strong association between increased homocysteine levels and the risk of osteoporotic fracture. The age- and sex-adjusted risk of fracture increased by 30 percent for each increase of 1 SD in the homocysteine level. A serum homocysteine level in the highest quartile doubled the risk of fracture. The magnitude of this effect is similar to that previously observed for the increase in the risk of cardiovascular disease and dementia according to homocysteine level.12-14,28
According to a long-standing hypothesis, the mechanism underlying the association between the homocysteine level and the risk of fracture may involve interference by homocysteine in collagen cross-linking.7
Besides B vitamins, look at D:
Serum vitamin D was a significant positive explanatory variable for HDLC (partial R (2) = 1.4%, P < 0.0001), and a significant inverse explanatory variable for homocysteine (partial R (2) = 6.0-12.6%).
Since my family history includes CVD and AD, and I am now in the osteopenia camp, I watch mine closely.