Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone.
BACKGROUND
Recently, hyperhomocysteinemia (HHCY) has been suggested to have adverse effects on bone. This study investigated if an experimental HHCY in rats induces an accumulation of homocysteine (HCY) in bone tissue that is accompanied by bone loss and reduced bone strength.


METHODS
HHCY was induced in healthy rats by either a methionine (Meth)- or a homocystine (Homo)-enriched diet and compared with controls. Homocystine is the product of two disulfide linked HCY molecules. Tissue and plasma concentrations of HCY, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were measured. Bones were assessed by biomechanical testing, histomorphometry, microCT and the measurement of biochemical bone turnover markers in plasma.


RESULTS
Meth and Homo animals developed a significant HHCY that was accompanied by a tissue specific accumulation of HCY (1300 to 2000% vs. controls). 65% of HCY in bone was bound to collagen of the extracellular matrix. The SAH / SAM-ratio in bone and plasma of Meth and Homo animals exhibited a tissue specific increase indicating a reduced methylation capacity. Accumulation of HCY in bone was characterized by a distinct reduction of cancellous bone (proximal femur: -25 to -35%; distal femur -56 to -58%, proximal tibia: -28 to -43%). Accordingly, bone strength was significantly reduced (-9 to -12%).


CONCLUSIONS
A tissue specific accumulation of HCY in bone may be a promising mechanism explaining adverse effects of HHCY on bone. A reduced methylation capacity of bone cells might be another relevant pathomechanism.
Herrmann
Markus
M
Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, Homburg, Germany. markusherr@aol.com
Tami
Andrea
A
Wildemann
Britt
B
Wolny
Martin
M
Wagner
Alexandra
A
Schorr
Heike
H
Taban-Shomal
Omid
O
Umanskaya
Natalia
N
Ross
Steffen
S
Garcia
Patric
P
Hübner
Ulrich
U
Herrmann
Wolfgang
W
D000368:Aged; D000818:Animals; D001842:Bone and Bones / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006710:Homocysteine / Q000378:metabolism*; D006711:Homocystine / Q000008:administration & dosage; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D009206:Myocardium / Q000737:chemistry; D010024:Osteoporosis / Q000378:metabolism; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013314:Stress, Mechanical
D006710:Homocysteine; D006711:Homocystine; D012436:S-Adenosylmethionine; D003094:Collagen; D012435:S-Adenosylhomocysteine; D008715:Methionine