E. Kadowaki

Trabecular bone score (TBS) predicts vertebral fractures in Japanese women over 10 years independently of bone density and prevalent vertebral deformity: the Japanese Population-Based Osteoporosis (JPOS) cohort study.

Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow‐up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual‐energy X‐ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey‐Kanis criteria or Genants grade 2 fracture at follow‐up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/103 person‐years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings.

Alcohol intake and bone status in elderly Japanese men: Baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study

There are no data concerning a relationship between alcohol and bone status from a large-scale community-based study of elderly Japanese men. The baseline survey for the Fujiwara-kyo Osteoporosis Risk in Men Study was performed in 2174 male participants during the period from 2007 to 2008 in Nara Prefecture, Japan. Among them 1665 fitted the following inclusion criteria: (a) age ≥65years, (b) no diseases or drug therapy that could affect bone mineral density (BMD). We analyzed 1421 men with complete information about alcohol intake. We found that alcohol intake and BMD were positively correlated after adjustment for age, body mass index, natto intake, milk intake, smoking, physical activity, education, marital status, and hypertension. Adjusted total hip BMD of men with alcohol intake >39g/day was 0.90g/cm(2) and that of abstainers was 0.85g/cm(2). With regard to bone turnover markers, alcohol intake was inversely associated with serum levels of osteocalcin and tartrate-resistant acid phosphatase isoenzyme 5b. A two-piece linear regression model revealed a positive relationship between alcohol intake and crude mean BMD for the total hip in those with alcohol intake of less than 55g/day. In contrast, alcohol intake and BMD in those with an alcohol intake of 55g/day or more was inversely correlated. The present large-scale study of elderly Japanese men revealed that although an alcohol intake of <55g/day was positively correlated to BMD, alcohol intake of ≥55g/day was inversely correlated to BMD.

Design and baseline characteristics of a prospective cohort study for determinants of osteoporotic fracture in community-dwelling elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study

AbstractBackgroundOsteoporosis and osteoporotic fracture in men are significant public health problems in an aging society. However, information on male osteoporosis remains impressively lacking, especially for Asians. We designed the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study as an ancillary study of a cohort study, the Fujiwara-kyo study, to determine risk factors for osteoporotic fractures in Japanese men.Methods/DesignDesign: A community-based single-centre prospective cohort study with at least a 5-year follow-up Subjects: All the male participants of the Fujiwara-kyo study who were living in the four cities studied, aged 65 years and older, and able to walk without aid from others. Primary outcome: Incidence of osteoporotic fractures including vertebral and clinical non-vertebral fractures. Additional outcomes: Change in bone mineral density (BMD), change in hip geometry, onset of receiving benefits from Long-term Care Insurance (LCI), health-related quality of life, and mortality. Baseline measurements: BMD at the lumbar spine (LS) and hip (TH), hip geometry, vertebral deformity assessment, bone turnover markers, physical and cognitive performance, various medical and lifestyle factors, and geriatric psychosocial measures confirmed by interviews based on self-administrated questionnaires. Outcome surveillance: Annual mail surveys and a follow-up survey at the fifth year comprising similar items to the baseline study will be used to determine the outcomes. Receipt of benefits from LCI and mortality will be obtained from the city governments. Current status: The baseline study was conducted for 2174 eligible men, and 2012 completed the study and were eligible for follow-up. Prevalence rates of osteoporosis (BMD 2.5 SD or more below the young adult mean (YAM)) and low BMD (BMD 1 SD or more below YAM) in at least one of LS and TH were calculated to be 4.4% and 41.8%, respectively. The proportion of men with low BMD only at TH showed a significant increasing trend with aging (p < 0.0001) while that only at LS showed a decreasing trend (p = 0.0386). The prevalence rate of osteoporosis was underestimated when diagnosed using only BMD at LS. Other baseline measurements were successfully obtained.DiscussionFORMEN baseline study was performed as designed and the FORMEN cohort study was successfully launched.

Use of anthropometric indicators in screening for undiagnosed vertebral fractures: A cross-sectional analysis of the Fukui Osteoporosis Cohort (FOC) study

BackgroundVertebral fractures are the most common type of osteoporotic fracture. Although often asymptomatic, each vertebral fracture increases the risk of additional fractures. Development of a safe and simple screening method is necessary to identify individuals with asymptomatic vertebral fractures.MethodsLateral imaging of the spine by single energy X-ray absorptiometry and vertebral morphometry were conducted in 116 Japanese women (mean age: 69.9 ± 9.3 yr). Vertebral deformities were diagnosed by the McCloskey-Kanis criteria and were used as a proxy for vertebral fractures. We evaluated whether anthropometric parameters including arm span-height difference (AHD), wall-occiput distance (WOD), and rib-pelvis distance (RPD) were related to vertebral deformities. Positive findings were defined for AHD as ≥ 4.0 cm, for WOD as ≥ 5 mm, and for RPD as ≤ two fingerbreadths. Receiver operating characteristics curves analysis was performed, and cut-off values were determined to give maximum difference between sensitivity and false-positive rate. Expected probabilities for vertebral deformities were calculated using logistic regression analysis.ResultsThe mean AHD for those participants with and without vertebral deformities were 7.0 ± 4.1 cm and 4.2 ± 4.2 cm (p < 0.01), respectively. Sensitivity and specificity for use of AHD-positive, WOD-positive and RPD-positive values in predicting vertebral deformities were 0.85 (95% CI: 0.69, 1.01) and 0.52 (95% CI: 0.42, 0.62); 0.70 (95% CI: 0.50, 0.90) and 0.67 (95% CI: 0.57, 0.76); and 0.67 (95% CI: 0.47, 0.87) and 0.59 (95% CI: 0.50, 0.69), respectively. The sensitivity, specificity, and likelihood ratio for a positive result (LR) for use of combined AHD-positive and WOD-positive values were 0.65 (95% CI: 0.44, 0.86), 0.81 (95% CI: 0.73, 0.89), and 3.47 (95% CI: 3.01, 3.99), respectively. The expected probability of vertebral deformities (P) was obtained by the equation; P = 1-(exp [-1.327-0.040 × body weight +1.332 × WOD-positive + 1.623 × AHD-positive])-1. The sensitivity, specificity and LR for use of a 0.306 cut-off value for probability of vertebral fractures were 0.65 (95% CI: 0.44, 0.86), 0.87 (95% CI: 0.80, 0.93), and 4.82 (95% CI: 4.00, 5.77), respectively.ConclusionBoth WOD and AHD effectively predicted vertebral deformities. This screening method could be used in a strategy to prevent additional vertebral fractures, even when X-ray technology is not available.

Renal function and bone mineral density in community-dwelling elderly Japanese men: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study

End-stage renal failure deteriorates bone mass and increases fracture risk. However, there are conflicting reports in the literature regarding the effects of mild to moderate renal dysfunction on bone mineral density (BMD). We investigated the association between renal function and BMD at the spine and hip and bone metabolism markers in community-dwelling elderly Japanese men. From 2174 male volunteers aged ≥65 years, we examined 1477 men after excluding those with diseases or medications known to affect bone metabolism. Renal function was assessed by serum cystatin C and estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease Study equation. Bone metabolism was evaluated using levels of serum amino-terminal propeptide of type I procollagen (PINP) and tartrate-resistant acid phosphatase isoenzyme 5b (TRACP-5b), which represent bone metabolic status independent of renal function. eGFR was inversely associated with BMD after adjusting for potential confounders (P < 0.01). Cystatin C showed a weaker but significant association with BMD. eGFR was modestly positively associated with PINP levels (P = 0.04), although cystatin C concentrations were neither associated with PINP nor TRACP-5b levels. Since BMD integrates bone metabolism from the past to present, inverse associations between renal function and BMD may be attributed to past factors, such as obesity. Our findings suggest that low renal function does not affect bone metabolism in a population of community-dwelling elderly Japanese men. Longitudinal studies will be necessary to clarify whether low renal function affects bone loss.

Arm span increases predictive value of models for prevalent vertebral deformities: The Japanese Population-based Osteoporosis (JPOS) Study

OBJECTIVE We examined anthropometric indicators to improve predictive ability of asymptomatic vertebral fracture screening models. STUDY DESIGN AND SETTING Data were obtained from the 1996 Japanese Population-based Osteoporosis (JPOS) Study. McCloskey-Kanis criteria diagnosed vertebral deformities on X-ray absorptiometric images in 693 women aged > or =50.The multiple logistic regression model included age, height, weight, postmenopausal status, total hip BMD, and arm span (AS) or sitting height as explanatory variables. Akaikes information criterion (AIC) evaluated model goodness-of-fit. RESULTS Age-adjusted AS and sitting height in subjects with and without vertebral deformities were 147.2+/-0.6 cm and 148.5+/-0.2 cm (P=0.055), 78.5+/-0.5 cm and 79.9+/-0.2 cm (P=0.007), respectively. Every 5-cm increase in AS indicated 1.5-fold increased risk of prevalent vertebral deformity in the model including age, height, weight, postmenopausal status, and BMD. Including the explanatory variable AS in models yielded better predictive accuracy than excluding AS (AIC, 441.7 vs 446.6, respectively). Sitting height did not significantly influence model predictive ability. CONCLUSION Predictive accuracy of model for vertebral fracture including age, height, weight, postmenopausal status, and BMD improved when AS was added as an explanatory variable. Models to screen for asymptomatic vertebral fractures should include AS.

Response to “Effects of Vitamin K intake on gamma-carboxylated proteins, bone fractures, and vascular calcifications”

We would like to thank Maria Fusaro and colleagues for their suggestion that habitual intake of natto may have a beneficial effect on vascular health, as well as bone health, via vitamin K-dependent matrix Gla protein (MGP), a potent inhibitor of arterial calcification [1]. This is interesting because we know that MGP may be carboxylated only in the presence of vitamin K2, which is enriched in natto [2]. A systematic review of the relationship between vitamin K and coronary heart disease (CHD) showed no association between vitamin K1 intake and the incidence of CHD, whereas increased intake of vitamin K2 is associated with fewer CHD events [3]. Thus, vitamin K2 may be a more important factor in the prevention of CHD than vitamin K1. In addition, a usual portion size of natto (50 g) contains approximately 380 μg of vitamin K2 (menaquinone-7) [4], while the mean vitamin K2 intake in the cohort studies cited by Rees et al. [3] was only 30 μg/day, with a maximum intake of 128 μg/day [5, 6]. A Japanese population consuming natto would have a higher dietary vitamin K2 intake than other populations. The Japanese Population-based Osteoporosis Cohort Study showed that postmenopausal women with no or low natto intake exhibited significantly greater hip bone loss than those with habitual natto intake [7] and that low spine bone density or prevalent vertebral fractures in postmenopausal women are independently associated with increased intima–media thickness (IMT) at the carotid bifurcation [8]. These findings suggest that low natto intake may be associated with increased IMT, a surrogate marker for CHD. In contrast, another report in the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study showed that serum levels of undercarboxylated osteocalcin, a biomarker for vitamin K intake, are inversely associated with glycemic index and insulin resistance [9], suggesting that natto intake may increase the risk of diabetes mellitus, which is a potent risk factor for CHD [10]. Therefore, it is not clear whether vitamin K intake has beneficial effects on vascular health, in addition to bone health. As Fusaro and colleagues pointed out, we should investigate the effects of vitamin K on vascular calcification with a careful consideration of the interaction between vitamin K and intake of calcium and vitamin D. The risk of diabetes mellitus should also be investigated. We will conduct a follow-up survey on the FORMEN Study population for fracture assessment and IMT measurement and prospectively examine the association between natto This is a reply to the letter that can be found at doi 10.1007/s00198011-1689-8.