Homocysteine as a Predictive Factor for Hip Fracture in Older Persons

McLean, Robert R.; Jacques, Paul F.; Selhub, Jacob; Tucker, Katherine L.; Samelson, Elizabeth J.; Broe, Kerry E; Hannan, Marian T.; Cupples, L. Adrienne; Kiel, Douglas P.

doi:10.1056/nejmoa032739

Cited by 521 publications

(340 citation statements)

References 37 publications

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“…This also appears to be important in the pathogenesis of the osteoporosis seen in patients with hereditary CTDs. Recent population studies done in Framingham, Massachusetts (31) and Rotterdam, The Netherlands (32), with more than 2,000 patients in each, showed the predictive value of homocysteine levels as a fracture risk in osteoporosis. In Japan, Sato et al (33) showed a statistically significant reduction of hip fracture after treatment with folic acid and vitamin B12 when compared with placebo in 628 patients with hemiplegia secondary to stroke.…”

Section: Discussionmentioning

confidence: 99%

Clinical study of hereditary disorders of connective tissues in a Chilean population

Bravo¹,

Wolff²

2006

Arthritis & Rheumatism

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Objective. To demonstrate the high frequency and lack of diagnosis of joint hypermobility syndrome (JHS) and the seriousness of vascular Ehlers-Danlos syndrome (VEDS).Methods. Two hundred forty-nine Chilean patients with hereditary disorders of the connective tissues (CTDs) and 64 control subjects were evaluated for the diagnoses of JHS and VEDS using the validated Brighton criteria, as compared with the traditional Beighton score. In addition, the presence of blue sclera was determined, with the degree of intensity graded as mild, moderate, or marked.Results. The frequency of hereditary CTDs was 35%, with diagnoses of JHS in 92.4% of subjects, VEDS in 7.2%, and osteogenesis imperfecta in 0.4%. The Beighton score proved to be insufficient for the diagnosis of JHS (35% of subjects had a negative score), whereas the Brighton criteria yielded positive findings (a diagnosis of JHS) in 39% of control subjects. Blue sclera was frequent, being identified in 97% of JHS patients and 94% of VEDS patients. Moderate osteopenia/osteoporosis was observed in 50% of patients with VEDS and 26% of those with JHS. Dysautonomia, dyslipidemia, and scoliosis were more frequent in VEDS patients than in JHS patients. The typical JHS facial appearance and the "hand holding the head sign" were identified. Raynaud's phenomenon was extremely rare in JHS patients (2%). Ruptured uterus and cerebral aneurysm occurred in 12% and 6% of VEDS patients, respectively. Spontaneous pneumothorax was more frequent in VEDS patients (11%) than in JHS patients (0.9%).Conclusion. JHS is very frequent but usually undiagnosed. The Beighton score is an insufficient method for JHS diagnosis. We recommend that physicians learn to recognize the typical facial features of JHS and be able to identify blue sclera. We also propose that validated hypermobility criteria be routinely used. Further research is needed to determine why the prevalence of JHS is so high in Chile.Hippocrates first described hypermobile joints 2,400 years ago, but the condition of joint hypermobility was not described as a medical problem until 1967, by Kirk et al (1). Although many people have hypermobile joints, the general public as well as many physicians consider hypermobility to be a curiosity rather than a potentially serious medical problem (2,3). The prevalence of hypermobility is difficult to evaluate because it varies with age, sex, and ethnic background and because multiple criteria are being used. It is more frequent in female subjects and children, is more frequent in Asian than in black populations, and is more frequent in both Asian and black populations than in whites. It is generally agreed that it exists in ϳ10% of individuals in Western populations (4) and up to 25% in Iraqis (5). Most cases of joint hypermobility are pauciarticular rather than generalized, which makes the diagnosis more difficult. Because of this, many people are unaware of having lax joints (6). In spite of this laxity in the joints, most people with hypermobility do not experience joint or musculoskelet...

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Section: Discussionmentioning

confidence: 99%

Clinical study of hereditary disorders of connective tissues in a Chilean population

Bravo¹,

Wolff²

2006

Arthritis & Rheumatism

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“…In 2004, two landmark studies performed in the Netherlands and the USA produced consistent findings in terms of the magnitude of increased risk of fracture associated with mild elevations in homocysteine (36,37) . In subsequent years, further studies from the USA, the Netherlands and Norway similarly demonstrated increases in fracture risk associated with elevated homocysteine concentrations (31)(32)(33)35) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 91%

“…In the past decade, numerous large observational studies have provided evidence to support a role for homocysteine and/or low B-vitamin status in fracture risk (Table 1) (12,(29)(30)(31)(32)(33)(34)(35)(36)(37) . In 2004, two landmark studies performed in the Netherlands and the USA produced consistent findings in terms of the magnitude of increased risk of fracture associated with mild elevations in homocysteine (36,37) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 99%

B-vitamins and bone in health and disease: the current evidence

et al. 2014

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Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677C→T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

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“…Thus, there is evidence available to support that: (a) smoking is associated with a higher risk of fractures (Kanis et al, 2005); (b) an adverse serum lipid profile for CHD (high low-density lipoprotein-cholesterol level) is also associated with a higher risk of osteoporotic fractures (Hsu et al, 2006); (c) homocysteine concentration is a risk factor for hip fracture in older persons (McLean et al, 2004); (d) fat mass is related to a lower bone density and to a higher risk of fractures (Hsu et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Dietary fat intake and the risk of osteoporotic fractures in the elderly

et al. 2007

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Objective: To explore the association between fat intake, serum lipids and the risk of osteoporotic fractures in the elderly. Design: A hospital-based case-control study. Setting: The study was conducted at a tertiary centre and referral hospital for the province of Jaén (Spain). Subjects: Cases (n ¼ 167) were patients aged 65 years or more with a low-energy fracture selected from the population attended at the hospital. Controls (patients without antecedents of any fracture) were 1:1 matched to cases by sex and age (n ¼ 167). Methods: Diet was assessed by a semiquantitative food frequency questionnaire. Serum total cholesterol and high-density lipoprotein (HDL) cholesterol were also measured. Results: Participants in the two upper quartiles of polyunsaturated fat (PUFA) intake showed an increased risk of fracture, with statistically significant differences with respect to the first quartile in the adjusted model (odds ratio (OR) ¼ 3.59; 95% confidence interval (CI) ¼ 1.06-12.1 and OR ¼ 5.88; 95% CI ¼ 1.38-25.02); P ¼ 0.01 for the trend test). A higher ratio of monounsaturated fat (MUFA) to PUFA was associated with a reduced risk of fracture (OR ¼ 0.20; 95% CI ¼ 0.07-0.60 for the fourth quartile; P ¼ 0.002 for the trend test). The intake of omega-6 fatty acids was associated with an elevated risk of fracture (OR ¼ 3.41; 95% CI ¼ 1.05-11.15 for the fourth quartile; P ¼ 0.01 for the trend test). HDL-cholesterol levels were inversely associated with the risk of fracture (test for trend P ¼ 0.03 across quartiles). Conclusions: PUFA intake was associated with an increased risk of osteoporotic fractures in the elderly, whereas a high ratio of MUFA:PUFA was associated with decreased risk.

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Homocysteine as a Predictive Factor for Hip Fracture in Older Persons

Abstract: These findings suggest that the homocysteine concentration, which is easily modifiable by means of dietary intervention, is an important risk factor for hip fracture in older persons.

Cited by 521 publications

References 37 publications

Clinical study of hereditary disorders of connective tissues in a Chilean population

Clinical study of hereditary disorders of connective tissues in a Chilean population

B-vitamins and bone in health and disease: the current evidence

Dietary fat intake and the risk of osteoporotic fractures in the elderly

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