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. 2020 Jun 15;17(12):4260.
doi: 10.3390/ijerph17124260.

Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density

Massimo De Martinis  1   2 , Maria Maddalena Sirufo  1   2 , Cristina Nocelli  3 , Lara Fontanella  4 , Lia Ginaldi  1   2
Affiliations

Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density

Massimo De Martinis et al. Int J Environ Res Public Health. .

Abstract

Osteoporosis is an age-related bone disease, affecting mainly postmenopausal women, characterized by decreased bone mineral density (BMD) and consequent risk of fractures. Homocysteine (Hcy), a sulfur-aminoacid whose serum level is regulated by methylenetrahydrofolate reductase (MTHFR) activity and vitamin B12 and folate as cofactors, is a risk factor for inflammatory diseases. Literature data concerning the link between Hcy and osteoporosis are still debated. The aim of our study was to assess the relationship among Hcy and BMD, inflammation, vitamin status and bone turnover in postmenopausal osteoporosis. In 252 postmenopausal women, BMD was measured by dual-energy X-ray absorptiometry (DXA). In addition to serum Hcy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and bone turnover markers (bone alkaline phosphatase-BAP, osteocalcin-OC, C-terminal telopeptide of type I collagen (CTX), vitamin deficiencies and MTHFR-C677T polymorphism were evaluated. Hcy, inflammation, bone resorption markers and prevalence of C677T polymorphism were higher, whereas vitamin D, B12, folate, and bone formation markers were lower in women with decreased BMD compared to those with normal BMD. Our results suggest a significant association between Hcy, BMD and inflammation in postmenopausal osteoporosis. The regulation of Hcy overproduction and the modulation of the inflammatory substrate could represent additional therapeutic approaches for osteoporosis prevention.

Keywords: MTHFR; bone; bone mineral density; folate; hyperhomocysteinemia; inflammation; osteoporosis; postmenopausal women; vitamin B12; vitamin D.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Serum levels of Homocysteine (Hcy, µmol/L) in women with low and normal bone mineral density.
Figure 2
Figure 2
Mean values of inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) in women with low bone mineral density (BMD) compared to women with normal BMD.
Figure 3
Figure 3
Serum concentrations of vitamin B12 and C-terminal telopeptide of type I collagen (CTX) (A), osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) (B), and vitamin D and folate (C) in women with low and normal BMD.
Figure 4
Figure 4
Prevalence of methylenetrahydrofolate reductase (MTHFR)gene C677T polymorphism (MTHFR mutation) in women with low bone mineral density (BMD) compared to women with BMD in the normal range.
Figure 5
Figure 5
Comparison between mean T-score values in women with normal (n. 105) and increased (n. 147) levels of serum homocysteine (Hcy).
Figure 6
Figure 6
Scatter plot showing significant negative correlation between homocysteine (Hcy) levels and BMD (T-score values) in postmenopausal women. Pearson’s correlation coefficients (R) and p-values related to unfractured (blue dots) and fractured (red dots) women are reported.
See this image and copyright information in PMC

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