Mitsuru Saito1, Keishi Marumo2. 1. Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan. xlink67@gol.com. 2. Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
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.
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.
Entities:
Keywords:
Advanced glycation end products; Bone quality; Collagen; Cross-links; Fracture risk; Homocysteine; Pentosidine
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