BACKGROUND: Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy. OBJECTIVE: The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk. DESIGN: We conducted a case-control study in the Women's Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed. RESULTS: The risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61-4.87). CONCLUSIONS: This study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function.
BACKGROUND: Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy. OBJECTIVE: The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk. DESIGN: We conducted a case-control study in the Women's Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed. RESULTS: The risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61-4.87). CONCLUSIONS: This study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function.
Authors: Joyce B J van Meurs; Rosalie A M Dhonukshe-Rutten; Saskia M F Pluijm; Marjolein van der Klift; Robert de Jonge; Jan Lindemans; Lisette C P G M de Groot; Albert Hofman; Jacqueline C M Witteman; Johannes P T M van Leeuwen; Monique M B Breteler; Paul Lips; Huibert A P Pols; André G Uitterlinden Journal: N Engl J Med Date: 2004-05-13 Impact factor: 91.245
Authors: S H Mudd; F Skovby; H L Levy; K D Pettigrew; B Wilcken; R E Pyeritz; G Andria; G H Boers; I L Bromberg; R Cerone Journal: Am J Hum Genet Date: 1985-01 Impact factor: 11.025
Authors: Zhao Chen; Charles Kooperberg; Mary B Pettinger; Tamsen Bassford; Jane A Cauley; Andrea Z LaCroix; Cora E Lewis; Simon Kipersztok; Carolyn Borne; Rebecca D Jackson Journal: Menopause Date: 2004 May-Jun Impact factor: 2.953
Authors: C Lewerin; H Nilsson-Ehle; S Jacobsson; H Johansson; V Sundh; M K Karlsson; Ö Ljunggren; M Lorentzon; J A Kanis; U H Lerner; S R Cummings; C Ohlsson; D Mellström Journal: Osteoporos Int Date: 2013-10-16 Impact factor: 4.507
Authors: K Terzidis; A Panoutsopoulos; A Mantzou; P Tourli; G Papageorgiou; K Saltiki; G Tsagalis; C Mara; M Alevizaki Journal: J Endocrinol Invest Date: 2011-07-13 Impact factor: 4.256
Authors: Carolyn J Crandall; Sowmya Vasan; Andrea LaCroix; Meryl S LeBoff; Jane A Cauley; John A Robbins; Rebecca D Jackson; Douglas C Bauer Journal: J Bone Miner Res Date: 2018-06-19 Impact factor: 6.741