The association between cysteine, bone turnover, and low bone mass.
BACKGROUND
With the identification of hyperhomocysteinemia as a risk factor for developing osteoporosis, the contribution of thiols metabolically linked with homocysteine (tHcy) may be of importance. Cysteine (Cys) is formed from tHcy and is involved in bone metabolism via incorporation into collagen and cysteine protease enzymes.


METHODS
We investigated the association of plasma Cys and related thiols, the bone turnover markers C-telopeptide (CTX) and procollagen type 1 N propeptide (P1NP) and folate and vitamin B(6) with calcaneal bone mineral density (BMD) in 328 postmenopausal British women grouped according to their BMD measurement.


RESULTS
Subjects with low BMD had a significantly lower plasma Cys concentration (146.3 vs. 177.7 micromol/l, p < 0.0001), a significantly higher recent fracture rate (30.9% vs. 16.4%, p = 0.017), and a significantly higher percentage of current smokers (26.4% vs. 7.3%. p = 0.003) than those with normal BMD. Additionally, they had a significantly lower plasma Cys, and higher plasma tHcy and CTX, than those with osteopenia. In the whole population, Cys was significantly associated with BMD, weight, height, smoking habit, log creatinine, Cys-Gly, log tHcy, and log folate, but the significant positive association of Cys with BMD was maintained after correction for all other variables (r = 0.197, p = 0.003). After weight, Cys was the next most significant predictor of BMD in a stepwise multiple linear regression model.


CONCLUSIONS
Our study suggests a significant association between plasma Cys and BMD. A reduced Cys concentration, possibly modulated by smoking, or reduced flux from tHcy, may lead to reduced availability for collagen formation. Increased osteoclast activation, possibly as a result of relative hyperhomocysteinemia, may lead to increased Cys utilization in cysteine proteases.
Baines
M
M
Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK. Malcolm.baines@rlbuht.nhs.uk
Kredan
M-B
MB
Davison
A
A
Higgins
G
G
West
C
C
Fraser
W D
WD
Ranganath
L R
LR
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D015331:Cohort Studies; D024042:Collagen Type I / Q000097:blood; D003545:Cysteine / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism; D008875:Middle Aged; D010455:Peptides / Q000097:blood
D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D006710:Homocysteine; D003545:Cysteine