The Effects of Homocysteine on the Skeleton.

Abstract

PURPOSE OF REVIEW:

Homocystinuria is a congenital metabolic disorder in which cystathionine β-synthase deficiency results in a prominent increase in homocysteine (serum levels > 100 μM), causing mental retardation, atherosclerotic cerebral infarction, and osteoporosis accompanied by fragility fractures. Encountering a case with excessive homocysteinemia such as that seen in hereditary homocystinuria is unlikely during usual medical examinations. However, in individuals who have vitamin B or folate deficiency, serum homocysteine concentrations are known to increase. These individuals may also have a polymorphism in methylenetetrahydrofolate reductase, MTHFR (C677T: TT type), which regulates homocysteine metabolism. These changes in homocysteine levels may elicit symptoms resembling those of homocystinuria (e.g., Alzheimer's disease, atherosclerosis, osteoporosis).

RECENT FINDINGS:

High serum homocysteine has been shown to have detrimental effects on neural cells, vascular endothelial cells, osteoblasts, and osteoclasts. Homocysteine is also known to increase oxidative stress, disrupt cross-linking of collagen molecules, and increase levels of advanced glycation end products, which results in reduced bone strength through a mechanism that goes beyond low bone density and increased bone resorption. Therefore, high serum homocysteine may be regarded as a factor that can reduce both bone mass and impair bone quality. In this review, we outline the epidemiology and pathophysiology of osteoporosis associated with hyperhomocysteinemia.

• Authors: Mitsuru Saito, Keishi Marumo
• Journal: Current osteoporosis reports (Curr Osteoporos Rep) Vol. 16 Issue 5 Pg. 554-560 (10 2018) ISSN: 1544-2241 [Electronic] United States
• PMID: 30116976 (Publication Type: Journal Article, Review)

Chemical References

• Glycation End Products, Advanced
• Homocysteine
• Collagen
• MTHFR protein, human
• Methylenetetrahydrofolate Reductase (NADPH2)

Topics

• Bone and Bones (metabolism)
• Collagen (metabolism)
• Folic Acid Deficiency (metabolism)
• Glycation End Products, Advanced (metabolism)
• Homocysteine (metabolism)
• Homocystinuria (complications, genetics, metabolism)
• Humans
• Hyperhomocysteinemia (complications, metabolism)
• Methylenetetrahydrofolate Reductase (NADPH2) (deficiency, genetics, metabolism)
• Muscle Spasticity (complications, genetics, metabolism)
• Osteoblasts (metabolism)
• Osteoclasts (metabolism)
• Osteoporosis (etiology, metabolism)
• Polymorphism, Genetic
• Psychotic Disorders (complications, genetics, metabolism)
• Vitamin B Deficiency (metabolism)