Bone turnover in elderly men: relationships to change in bone mineral density

BACKGROUND: It is not clear whether bone turnover markers can be used to make inference regarding changes in bone mineral density (BMD) in untreated healthy elderly men. The present study was designed to address three specific questions: (i) is there a relationship between bone turnover markers and femoral neck BMD within an individual; (ii) is there a relationship between baseline measurements of bone turnover markers and subsequent change in BMD; and (iii) is there a relationship between changes in bone turnover markers and changes in femoral neck BMD? METHODS: The present study was part of the on-going Dubbo Osteoporosis Epidemiology Study, which was designed as a prospective investigation. Men who had had at least 3 sequential visits with serum samples available during follow-up were selected from the study population. Serum C-terminal telopeptide of type I collagen (sICTP), N-terminal propeptide of type I collagen (sPINP) and femoral neck BMD were measured by competitive radioimmunoassays. Femoral neck bone mineral density (BMD) was measured by a densitometer (GE Lunar Corp, Madison, WI). Various mixed-effects models were used to assess the association between the markers and changes in BMD. RESULTS: One hundred and one men aged 70 ± 4.1 years (mean ± SD) met the criteria of selection for analysis. On average, sPINP decreased by 0.7% per year (p = 0.026), sICTP increased by 1.7% per year (p = 0.0002), and femoral neck BMD decreased by 0.4% per year (p < 0.01). Within-subject analysis indicated that changes in BMD were significantly associated with changes in sPINP (p = 0.022), but not with changes in sICTP (p = 0.84). However, neither baseline sPINP (p = 0.50) nor baseline sICTP (p = 0.63) was associated with subsequent changes in BMD. Moreover, changes in BMD were not significantly associated with previous changes in sPINP (p = 0.13) or sICTP (p = 0.95). CONCLUSION: These results suggest that in elderly men of Caucasian background, changes in sPINP were inversely related to changes in BMD within an individual. However, neither sPINP nor sICTP was sufficiently sensitive to predict the rate of change in BMD for a group of individuals or for an individual

The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians

BACKGROUND: Although vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f allele), abolishing the first translation initiation site and resulting in a peptide lacking the first three amino acids (F allele). We examined the role of this polymorphism in insulin sensitivity and beta cell function. This study included 49 healthy Caucasian subjects (28 females, age 28 ± 1 years old, body mass index 24.57 ± 0.57 kg/m(2), waist-hip ratio 0.81 ± 0.01 cm/cm). They were all normotensive (less than 140/90 mmHg) and glucose tolerant, which was determined by a standard 75-gm oral glucose tolerance test. Their beta cell function (%B) and insulin sensitivity (%S) were calculated based on the Homeostasis Model Assessment (HOMA). Their genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism analysis. Phenotypes were compared between genotypic groups. RESULTS: There were 18 FF, 21 Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were pooled with the Ff subjects during analyses. The FF and Ff/ff groups had similar glucose levels at each time point before and after a glucose challenge. The Ff/ff group had higher insulin levels than the FF group at fasting (P=0.006), 30 minutes (P=0.009), 60 minutes (P=0.049), and 90 minutes (P=0.042). Furthermore, the Ff/ff group also had a larger insulin area under the curve than the FF group (P=0.009). While no difference was noted in %B, the Ff/ff group had a lower %S than the FF group (0.53 vs. 0.78, P=0.006). A stepwise regression analysis confirmed that the Fok I polymorphism was an independent determinant for %S, accounting for 29.3% of variation in %S when combined with waist-hip ratio. CONCLUSIONS: We report that the Fok I polymorphism at the VDR gene locus is associated with insulin sensitivity, but has no influence on beta cell function in healthy Caucasians. Although this polymorphism has been shown to affect the activation of vitamin D-dependent transcription, the molecular basis of the association between this polymorphism and insulin resistance remains to be determined

The Rotterdam Study: 2010 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in close to a 1,000 research articles and reports (see www.epib.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

Screening for low bone mass with quantitative ultrasonography in a community without dual-energy X-ray absorptiometry: population-based survey

BACKGROUND: Dual-energy x-ray absorptiometry (DXA) is the criterion standard to identify low bone mineral density (BMD), but access to axial DXA may be limited or cost prohibitive. We screened for low bone mass with quantitative ultrasonography (QUS) in a community without DXA, analyzed its reliability and obtained reference values and estimated the prevalence of low QUS values. METHODS: We enrolled 6493 residents of Kinmen, Taiwan, and a reference group (96 men and 70 women aged 20–29 years) for this cross-sectional, community-based study. All participants completed a questionnaire and underwent ultrasonographic measurements. Reliability and validity of QUS measurements were evaluated. Broadband ultrasound attenuation (BUA) values were obtained and statistically analyzed by age, sex and weight. Annual loss of BUA was determined. Trends in the prevalence of QUS scores were evaluated. RESULTS: Two QUS were used and had a correlation coefficient of 0.90 (p < 0.001). Calcaneal BUA was significantly correlated with BMD in the femoral neck (r = 0.67, p < 0.001) and BMD of the total lumbar spine (r = 0.59, p < 0.001). BUAs in the reference group were 92.72 ± 13.36 and 87.90 ± 10.68 dB/MHz for men and women, respectively. Estimated annual losses of calcaneal BUA were 0.83% per year for women, 0.27% per year for men, and 0.51% per year for the total population. The prevalence of severely low QUS values (T-score = -2.5) tended to increase with aging in both sexes (p < 0.001). Across age strata, moderately low QUS values (-2.5 < T-score < -1.0) were 31.6–41.0% in men and 23.7–38.1% in women; a significant trend with age was observed in men (p < 0.001). CONCLUSION: Age-related decreases in calcaneal ultrasonometry, which reflected the prevalence of low bone mass, were more obvious in women than in men

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies

Type 2 diabetes mellitus (T2DM) influences bone metabolism, but the relation of T2DM with bone mineral density (BMD) remains inconsistent across studies. The objective of this study was to perform a meta-analysis and meta-regression of the literature to estimate the difference in BMD (g/cm2) between diabetic and non-diabetic populations, and to investigate potential underlying mechanisms. A literature search was performed in PubMed and Ovid extracting data from articles prior to May 2010. Eligible studies were those where the association between T2DM and BMD measured by dual energy X-ray absorptiometry was evaluated using a cross-sectional, cohort or case–control design, including both healthy controls and subjects with T2DM. The analysis was done on 15 observational studies (3,437 diabetics and 19,139 controls). Meta-analysis showed that BMD in diabetics was significantly higher, with pooled mean differences of 0.04 (95% CI: 0.02, 0.05) at the femoral neck, 0.06 (95% CI: 0.04, 0.08) at the hip and 0.06 (95% CI: 0.04, 0.07) at the spine. The differences for forearm BMD were not significantly different between diabetics and non-diabetics. Sex-stratified analyses showed similar results in both genders. Substantial heterogeneity was found to originate from differences in study design and possibly diabetes definition. Also, by applying meta-regression we could establish that younger age, male gender, higher body mass index and higher HbA1C were positively associated with higher BMD levels in diabetic individuals. We conclude that individuals with T2DM from both genders have higher BMD levels, but that multiple factors influence BMD in individuals with T2DM

Effect of self-reported walking difficulty on bone mass and bone resorption marker in Japanese people aged 40?years and over

Background: This study aimed to examine the association of walking difficulty with bone mass or bone turnover among community-dwelling Japanese people aged 40 years and older. Methods: We studied 1097 community-dwelling Japanese people aged 40 years and older (379 men and 718 women) who were invited to participate in periodic health examinations in 2006?2009. Walking difficulty was defined as having difficulty walking 100 m on a level surface (self-administered questionnaire). Calcaneal stiffness index (bone mass) was measured by quantitative ultrasound. Spot urine samples were collected, and urinary N-terminal cross-linking telopeptide of type I collagen (NTx) was measured. Values were corrected for creatinine (Cre) concentration. Results: The prevalence of walking difficulty was significantly higher in women than in men (7.4 vs. 3.4 %, p?=?0.011) and significantly increased with age in men (p for trend?=?0.02) and women (p for trend <0.001). In univariate analysis, men and women with walking difficulty were older (p?<?0.001) and had a lower stiffness index (p?<?0.001), compared with those without walking difficulty. Among women, individuals with walking difficulty had significantly higher urinary NTx/Cre than those without walking difficulty (p?<?0.001); however, this was not so among men (p?=?0.39). Multiple regression analysis adjusted for age, weight, and menopausal status showed a significant association between walking difficulty and lower stiffness index in men (p?=?0.004) and women (p?=?0.005). In women, walking difficulty was significantly associated with higher NTx/Cre (p?=?0.001), but not in men (p?=?0.35). Conclusions: Walking difficulty may contribute to low bone mass in both sexes but might cause high bone turnover in women only