Plasma dimethylglycine, nicotine exposure and risk of low bone mineral density and hip fracture: the Hordaland Health Study

Abstract

Summary

In the large community-based Hordaland Health Study, low plasma dimethylglycine was associated with low bone mineral density in both middle-aged and elderly subjects and to an increased risk of subsequent hip fracture among the elderly. These associations seemed to be particularly strong among subjects exposed to nicotine.

Introduction

Dimethylglycine (DMG) is a product of the choline oxidation pathway and formed from betaine during the folate-independent remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are associated with atherosclerotic cardiovascular disease and inflammation, which in turn are related to osteoporosis. High plasma total Hcy and low plasma choline are associated with low bone mineral density (BMD) and hip fractures, but the role of plasma DMG in bone health is unknown.

Methods

We studied the associations of plasma DMG with BMD among 5315 participants (46–49 and 71–74 years old) and with hip fracture among 3310 participants (71–74 years old) enrolled in the Hordaland Health Study.

Results

In age and sex-adjusted logistic regression models, subjects in the lowest versus highest DMG tertile were more likely to have low BMD (odds ratio [OR] 1.68, 95 % confidence interval [CI] 1.43–1.99). The association was stronger in participants exposed compared to those unexposed to nicotine (OR 2.31, 95 % CI 1.73–3.07 and OR 1.43, 95 % CI 1.16–1.75, respectively, p interaction = 0.008). In the older cohort, Cox regression analyses adjusted for sex showed that low plasma DMG was associated with an increased risk of hip fracture (hazard ratio [HR] 1.70, 95 % CI 1.28–2.26). A trend toward an even higher risk was found among women exposed to nicotine (HR 3.41, 95 % CI 1.40–8.28).

Conclusion

Low plasma DMG was associated with low BMD and increased risk of hip fractures. A potential effect modification by nicotine exposure merits particular attention.

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Correspondence to J. Øyen.

Electronic supplementary material

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Supplemental Table S1

Baseline characteristics in 1998 to 2000, follow-up and endpoint of participants (71–74 years at inclusion) included in the hip fracture analyses by tertiles of plasma dimethylglycine (DMG), in the Hordaland Health Study. (DOCX 14 kb)

Supplemental Table S2

Odds ratios (OR) for low femoral neck bone mineral density (lowest quintile in each sex and age group) according to tertilesa of plasma dimethylglycine (DMG) in the whole cohort and separately by baseline age group, sex and nicotine exposureb, in the Hordaland Health Study. (DOCX 31 kb)

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Øyen, J., Svingen, G.F.T., Gjesdal, C.G. et al. Plasma dimethylglycine, nicotine exposure and risk of low bone mineral density and hip fracture: the Hordaland Health Study. Osteoporos Int 26, 1573–1583 (2015). https://doi.org/10.1007/s00198-015-3030-4

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Keywords

  • Bone mineral density
  • Dimethylglycine
  • Hip fracture
  • Nicotine exposure
  • One-carbon metabolism
  • Smoking