title: The association between plasma homocysteine levels and bone quality and bone mineral density parameters in older persons.
abstract: BACKGROUND
  High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters, rather than with bone mineral density.
  
  
  METHODS
  Cross-sectional data of the B-PROOF study (n=1227) and of two cohorts of the Rotterdam Study (RS-I (n=2850) and RS-II (n=2023)) were used. Data on bone mineral density of the femoral neck and lumbar spine were obtained in these participants using dual-energy X-ray assessment (DXA). In addition, participants of B-PROOF and RS-I underwent quantitative ultrasound measurement of the calcaneus, as a marker for bone quality. Multiple linear regression analysis was used to investigate the associations between natural-log transformed plasma levels of homocysteine and bone mineral density or ultrasound parameters.
  
  
  RESULTS
  Natural-log transformed homocysteine levels were inversely associated with femoral neck bone mineral density in the two cohorts of the Rotterdam Study (B=-0.025, p=0.004 and B=-0.024, p=0.024). In B-PROOF, no association was found. Pooled data analysis showed significant associations between homocysteine and bone mineral density at both femoral neck (B=-0.032, p=0.010) and lumbar spine (B=-0.098, p=0.021). Higher natural-log transformed homocysteine levels associated significantly with lower bone ultrasound attenuation in B-PROOF (B=-3.7, p=0.009) and speed of sound in both B-PROOF (B=-8.9, p=0.001) and RS-I (B=-14.5, p=0.003), indicating lower bone quality. Pooled analysis confirmed the association between homocysteine and SOS (B=-13.1, p=0.016). Results from ANCOVA-analysis indicate that differences in SOS and BUA between participants having a plasma homocysteine level above or below median correspond to 0.14 and 0.09 SD, respectively.
  
  
  CONCLUSIONS
  In this study, plasma levels of homocysteine were significantly inversely associated with both bone ultrasound parameters and with bone mineral density. However, the size of the associations seems to be of limited clinical relevance and may therefore not explain the previously observed association between plasma homocysteine and osteoporotic fracture incidence.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: Enneman
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: K M A
authors.initials: KM
authors.lastname: Swart
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Zillikens
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: van Dijk
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands.
authors.forename: R A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: T J M
authors.initials: TJ
authors.lastname: van der Cammen
authors.affiliation: Department of Internal Medicine/Endocrinology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands.
authors.forename: C P G M
authors.initials: CP
authors.lastname: de Groot
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: J B J
authors.initials: JB
authors.lastname: van Meurs
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: van Schoor
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands; Section of Geriatric Medicine, Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands. Electronic address: n.vandervelde@erasmusmc.nl.
authors.forename: N
authors.initials: N
authors.lastname: van der Velde
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D006710:Homocysteine
keywords: Bone mineral density; Homocysteine; Osteoporosis; Quantitative ultrasound