Association between the 110-kDa C-terminal agrin fragment and skeletal muscle decline among community-dwelling older women.

BACKGROUND: C-terminal agrin fragment (CAF) is a biomarker for neuromuscular junction degradation. This study aimed to investigate whether 110-kDa CAF (CAF110) was associated with the presence and incidence of low muscle mass and strength. METHODS: This cross-sectional retrospective cohort study comprised women aged ≥65 years. We measured muscle mass using a dual-energy X-ray absorptiometry scanner, hand-grip strength, and blood sampling between 2011 and 2012. A follow-up study with the same measurements was conducted between 2015 and 2017. Low muscle mass and strength were defined as an appendicular skeletal muscle mass index <5.4 kg/m2 and hand-grip strength <18 kg, respectively. The CAF110 level was measured using enzyme-linked immunosorbent assay kits. RESULTS: In total, 515 women (74.3 ± 6.3 years) were included in this cross-sectional analysis. Of these, 101 (19.6%) and 128 (24.9%) women presented with low muscle mass and strength, respectively. For low muscle mass, the odds ratios (ORs) of the middle and highest CAF110 tertile groups, compared with the lowest group, were 1.93 (95% confidence interval: 1.09-3.43; P = 0.024) and 2.15 (1.22-3.80; P = 0.008), respectively. After adjusting for age, the ORs remained significant: 1.98 (1.11-3.52; P = 0.020) and 2.27 (1.28-4.03; P = 0.005), respectively. Low muscle strength ORs of all the CAF110 tertile groups were not significant. In the longitudinal analysis, 292 and 289 women were assessed for incidents of low muscle mass and strength, respectively. Of those, 34 (11.6%) and 20 (6.9%) women exhibited low muscle mass and strength, respectively. For incident low muscle mass, the crude OR of the CAF110 ≥ the median value group was marginally higher than that of the CAF110 < median value group (median [interquartile range]: 1.98 [0.94-4.17] (P = 0.072). After adjusting for age and baseline muscle mass, the OR was 2.22 [0.97-5.06] (P = 0.058). All low muscle strength ORs of the median categories of CAF110 were not significant. CONCLUSIONS: CAF110 was not associated with low muscle strength. However, CAF110 may be a potential marker for the incidence of low muscle mass.

Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.

Combined results of three physical performance tests predict incident fracture independently of aBMD in community-dwelling elderly Japanese men: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

BACKGROUND: Several studies have examined the association between physical performance and fracture in women, but few such studies have targeted elderly men. This study aimed to determine whether the combined results of several physical performance tests can predict the subsequent incidence of fractures in elderly men after adjusting for confounding factors. METHODS: Of the 2174 elderly men who participated in this study, 2012 completed the baseline study visit, including physical performance tests (walking speed, hand grip strength, and one-leg standing) and measurement of bone mineral density by dual-energy X-ray absorptiometry. Follow-up study visits were conducted five and ten years later, during which incident fractures were identified by detailed interviews. We excluded 140 men with diseases or who took medications known to affect bone metabolism at baseline, 185 with missing values for predictors and potential confounding factors, and one who did not participate in any of the follow-up study visits. The remaining 1686 men were analyzed. Each physical performance test was analyzed by quartiles. Poor performance was defined as belonging to the worst quartile of performance. The association between physical performance and fracture was assessed using Cox proportional hazards models. RESULTS: We identified 175 clinical fractures (osteoporotic fracture: 77, major osteoporotic fracture: 48) in 1686 men during a mean follow-up period of 8.4 years. After adjusting for potential confounding factors including bone mineral density, men who performed poorly on all three physical performance tests had a 3.7-fold higher risk of osteoporotic fracture and a 6.6-fold higher risk of major osteoporotic fracture than men who did not perform poorly on any of the tests. CONCLUSIONS: Japanese elderly men who performed poorly on all three physical performance tests had a significantly higher risk of incident osteoporotic fracture independently of bone mineral density. The combined results of several physical performance tests may be useful for predicting incident fractures in elderly men.

Determinants of bone health in elderly Japanese men: study design and key findings of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study.

BACKGROUND: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study was launched to investigate risk factors for osteoporotic fractures, interactions of osteoporosis with other non-communicable chronic diseases, and effects of fracture on QOL and mortality. METHODS: FORMEN baseline study participants (in 2007 and 2008) included 2012 community-dwelling men (aged 65-93 years) in Nara prefecture, Japan. Clinical follow-up surveys were conducted 5 and 10 years after the baseline survey, and 1539 and 906 men completed them, respectively. Supplemental mail, telephone, and visit surveys were conducted with non-participants to obtain outcome information. Survival and fracture outcomes were determined for 2006 men, with 566 deaths identified and 1233 men remaining in the cohort at 10-year follow-up. COMMENTS: The baseline survey covered a wide range of bone health-related indices including bone mineral density, trabecular microarchitecture assessment, vertebral imaging for detecting vertebral fractures, and biochemical markers of bone turnover, as well as comprehensive geriatric assessment items. Follow-up surveys were conducted to obtain outcomes including osteoporotic fracture, cardiovascular diseases, initiation of long-term care, and mortality. A complete list of publications relating to the FORMEN study can be found at https://www.med.kindai.ac.jp/pubheal/FORMEN/Publications.html .

Associations between trunk-to-peripheral fat ratio and cardiometabolic risk factors in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Body mass-independent parameters might be more appropriate for assessing cardiometabolic abnormalities than weight-dependent indices in Asians who have relatively high visceral adiposity but low body fat. Dual-energy X-ray absorptiometry (DXA)-measured trunk-to-peripheral fat ratio is one such body mass-independent index. However, there are no reports on relationships between DXA-measured regional fat ratio and cardiometabolic risk factors targeting elderly Asian men. METHODS: We analyzed cross-sectional data of 597 elderly men who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study, a community-based single-center prospective cohort study conducted in Japan. Whole-body fat and regional fat were measured with a DXA scanner. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: Both TAR and TLR in the group of men who used ≥ 1 medication for hypertension, dyslipidemia, or diabetes ("user group"; N = 347) were significantly larger than those who did not use such medication ("non-user group"; N = 250) (P < 0.05). After adjusting for potential confounding factors including whole-body fat, both TAR and TLR were significantly associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting serum insulin, and the insulin resistance index in the non-user group and non-overweight men in the non-user group (N = 199). CONCLUSION: The trunk-to-peripheral fat ratio was associated with cardiometabolic risk factors independently of whole-body fat mass. Parameters of the fat ratio may be useful for assessing cardiometabolic risk factors, particularly in underweight to normal-weight populations.

Circulating osteocalcin levels were not significantly associated with the risk of incident type 2 diabetes mellitus in elderly Japanese men: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

INTRODUCTION: Cross-sectional studies have shown that patients with type 2 diabetes mellitus (T2DM) have low circulating levels of osteocalcin (OC) and undercarboxylated OC (ucOC). This longitudinal study aimed to examine whether low OC or ucOC levels at baseline are associated with the risk of incident T2DM. METHODS: We examined 1700 community-dwelling Japanese men (≥65 years) after excluding those with history of diseases (other than T2DM) or medications that affect bone and glucose metabolism. T2DM was defined as fasting plasma glucose (FPG) ≥126 mg/dl or glycated hemoglobin A1c (HbA1c) ≥6.5%. Participants without prevalent T2DM at baseline were invited to follow-up surveys 5 and 10 years after baseline. RESULTS: Among the participants, 309 with prevalent T2DM showed significantly lower serum OC and ucOC levels at baseline than those without. After excluding these participants, 46 and 57 participants with incident T2DM were identified in the first and second follow-up surveys, respectively. These participants did not show significantly different OC and ucOC levels at baseline relative to those without T2DM, although their FPG and HbA1c levels at baseline were significantly higher compared to those without incident T2DM. Increase in glycemic indices preceded decrease in OC and ucOC levels. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM identified in the follow-up surveys. CONCLUSIONS: OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.

Relationships between serum uric acid concentrations, uric acid lowering medications, and vertebral fracture in community-dwelling elderly Japanese men: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

PURPOSE: The association between serum concentrations of uric acid (UA), a potent endogenous antioxidant, and fracture risk has not yet been examined for morphometric vertebral fracture (VF). This study aimed to determine whether serum UA concentrations are associated with risks of clinical osteoporotic fracture (OPF) and morphometric VF after adjusting for confounding factors including UA-lowering medications (ULMs). MATERIALS AND METHODS: A total of 2012 Japanese men aged ≥65 years completed the baseline study, which included serum UA measurement and X-ray absorptiometry-based VF assessment. We conducted a follow-up study five years later to identify incident OPFs and VFs. OPF was identified through interviews. Incident VF was defined as a vertebra which showed reduction in any of its anterior, central, or posterior heights by ≥20% during follow-up, and satisfied grade one or higher fracture criteria in Genant's method on follow-up images. Bone mineral density (BMD) of the hip and spine was measured by dual-energy X-ray absorptiometry at baseline and follow-up. RESULTS: We identified 45 clinical OPFs from 2000 men and 39 VFs from 1530 men during a mean follow-up period of 4.3 years. Hip BMD was significantly higher in higher UA concentration groups after adjusting for age and body mass index. A significantly decreased multivariate-adjusted odds ratio (OR) of incident VF was observed for the highest quartile groups of serum UA concentrations compared with the lowest quartile group (OR: 0.17, 95% confidence interval: 0.05-0.62). This OR remained significant after further adjusting for ULM use. ULM users in the lowest quartile group of serum UA concentrations had a significantly higher incidence rate of VF compared to the other quartile groups. CONCLUSIONS: Higher serum UA concentrations were associated with a lower risk of morphometric VF independently of ULM in Japanese elderly men. Excessive reduction of serum UA concentrations by ULM might increase VF risk.

Decreased bone mineral density and osteoporotic fractures are associated with the development of echogenic plaques in the carotid arteries over a 10-year follow-up period: The Japanese Population-based Osteoporosis (JPOS) Cohort Study.

OBJECTIVES: To investigate whether low bone mineral density (BMD) and history of fracture at baseline are associated with the development of echogenic carotid plaques over a 10-year follow-up period. STUDY DESIGN: A prospective cohort study. MAIN OUTCOME MEASURES: Development of echogenic plaques identified by ultrasonography of the carotid arteries. METHODS: Among 1048 women aged 40 or more who completed the baseline survey of the Japanese Population-based Osteoporosis (JPOS) cohort study, 500 women who completed the first decade of follow-up and 267 women who completed the second decade of follow-up were included. We identified history and incidence of clinical osteoporotic fracture during the follow-up through medical interviews, and determined vertebral fractures by morphometry of absorptiometric images. RESULTS: We identified 67 (13.4%) and 31 (11.6%) women with echogenic plaques at the end of first and second decade of follow-up, respectively. Participants with echogenic plaques were significantly older, exhibited lower spine BMD, and had a higher prevalence of osteoporotic fracture, diabetes, and hypertension. A generalized estimating equation analysis was used to combine the participants from the two follow-up periods into a single cohort, and showed that osteoporotic BMD and osteoporotic fractures were significantly associated with the development of echogenic plaques, after adjusting for atherosclerosis risk factors (odds ratio (OR): 2.15, 95% confidence interval (95% CI): 1.04, 4.44; OR: 1.84, 95% CI: 1.03, 3.28, respectively). CONCLUSION: Osteoporotic BMD and osteoporotic fracture history were significantly, and independently, associated with an increased occurrence of echogenic plaques. Ultrasonographic screening of the carotid artery may benefit patients with osteoporosis.

Trends in Serum Lipid Levels of a 10- and 13-Year-Old Population in Fukuroi City, Japan (2007-2017).

BACKGROUND: Current trends in serum lipid levels among children are likely to be important predictors of future cardiovascular disease prevalence. However, no studies have examined trends in low-density lipoprotein cholesterol (LDL-C) levels in Japanese children. METHODS: We investigated trends in LDL-C levels from 2008 through 2017 and HDL-C levels from 2007 through 2017 in a population of 10- and 13-year-old children in Fukuroi City, Japan. We analyzed 17,838 children, accounting for 93.8% of all fifth and eighth graders in the entire city. Adverse lipid levels were defined as follows: 130 mg/dL or higher for LDL-C, and lower than 40 mg/dL for HDL-C. The Jonckheere-Terpstra and Cochran-Armitage tests were used to evaluate secular trends in mean serum lipid levels and prevalence of dyslipidemia, respectively. RESULTS: There were no significant trends in BMI during the study period. In children aged 10 years, serum levels of LDL-C and HDL-C showed significant positive associations with calendar year during the study period for both sexes. A significant increase in HDL-C levels was observed in girls aged 13 years. On the other hand, no significant trends were observed in the prevalence of high LDL-C or low HDL-C regardless of sex or age, while the prevalence of high non-HDL-C showed a significant increase in boys. CONCLUSIONS: In the Fukuroi population, serum levels of LDL-C and HDL-C slightly increased in both boys and girls aged 10 years, and HDL-C levels slightly increased in girls aged 13 years, during the past decade.

Association between hand-grip strength and site-specific risks of major osteoporotic fracture: Results from the Japanese Population-based Osteoporosis Cohort Study.

OBJECTIVES: To investigate the association between hand-grip strength and site-specific risks of major osteoporotic fracture. STUDY DESIGN: Prospective cohort study. MAIN OUTCOME: Associations between low hand-grip strength and increased risk of fracture at the distal forearm, vertebrae, and hip. MEASURES: We enrolled 1342 postmenopausal women aged 50 years or more into baseline and follow-up surveys of the Japanese Population-based Osteoporosis Cohort Study in 1996, 1999, 2002, or 2006. Fracture events were ascertained by follow-up surveys until 2011 or 2012. The Cox proportional hazards model was used to estimate hazard ratios (HRs) of hand-grip strength on fracture event. RESULTS: During a median follow-up of 15.2 years, 162 women sustained at least one osteoporotic fracture and 135 of these women sustained at least one major osteoporotic fracture, the larger group including 65, 38, 35, and 8 women with fractures of the distal forearm, vertebrae, hip, and proximal humerus, respectively. In the crude models, the associations between low hand-grip strength and increased risk of fracture at the distal forearm, vertebrae, and hip were significant; the HRs (95% confidence interval) of the lowest tertile of hand-grip strength were 2.02 (1.10-3.71), 11.35 (4.07-31.63), and 4.72 (1.79-12.47), respectively. Age adjustment attenuated the significance of hip fracture risk, and adjusting for bone mineral density attenuated the significance of distal forearm fracture risk. After additional adjustment for body mass index, history of diabetes mellitus, and calcium intake, the HR for vertebral fracture risk was 4.55 (1.56-13.27). When limiting the follow-up period to 5 and 10 years, low hand-grip strength was associated with an increased risk of distal forearm fracture independently of the aforementioned covariates; the HRs were 4.22 (1.12-15.95) and 2.52 (1.03-6.17), respectively. CONCLUSIONS: Low hand-grip strength is specifically associated with the risk of distal forearm fractures within 10 years and clinical vertebral fractures within 15 years or more in Japanese postmenopausal women.

Increased risk of osteoporotic fracture in community-dwelling elderly men 20 or more years after gastrectomy: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

PURPOSE: Many studies have reported that patients with a history of gastrectomy (gastrectomized patients) have lower areal bone mineral density (aBMD) and higher fracture risk than those without. However, population-based studies on this topic are scarce, and little is known regarding the bone metabolic status of gastrectomized patients in the long-term. This study aimed to clarify the association of gastrectomy with aBMD, bone metabolism markers, and fracture risk in community-dwelling elderly Japanese men. METHODS: A total of 1992 men aged ≥65 years completed baseline measurements including aBMD at the spine and hip, serum levels of intact parathyroid hormone (PTH), intact osteocalcin (OC), tartrate-resistant acid phosphatase isoenzyme 5b (TRACP5b), and undercarboxylated OC (ucOC), and an interview regarding past medical history including gastrectomy. Osteoporotic fractures (OPFs) that occurred during the 5-year follow-up period were determined through structured interviews. RESULTS: After excluding participants with type 1 diabetes mellitus and those with missing values, 1985 men, including 132 gastrectomized men, were analyzed. Gastrectomized men had significantly higher PTH, TRACP5b, and ucOC levels, and lower aBMD, than non-gastrectomized men. Gastrectomy was associated with a significantly higher risk of OPF after adjusting for confounding variables (hazard ratio (HR): 2.55, 95% confidence interval (CI): 1.17, 5.55), and the risk was no longer significant when further adjusted for PTH and aBMD. Even in this model, however, increase in OPF risk was significant in gastrectomized men who survived 20 years or more after the surgery (HR: 3.56, 95% CI: 1.33, 9.52). CONCLUSIONS: History of gastrectomy was associated with elevated bone resorption, decreased aBMD, and increased fracture risk in community-dwelling elderly Japanese men. This increase in fracture risk was more prominent long after gastrectomy.

Hyperglycemic status is associated with an elevated risk of osteoporotic fracture in community-dwelling elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) cohort study.

PURPOSE: Patients with type 2 diabetes mellitus have an increased fracture risk. However, population-based studies on the association between glycemic status and fracture risk are scarce, and none have targeted a Japanese population. In addition, patients in the lowest category of hemoglobin A1c (HbA1c) do not always show the lowest risk. This study aimed to clarify the association between glycemic status and fracture risk in community-dwelling elderly Japanese men. METHODS: A total of 1992 men aged ≥65 years completed baseline measurements including fasting plasma glucose (FPG), HbA1c, bone density, and an interview regarding past disease history. Osteoporotic fractures (OPFs) that occurred during the 5-year follow-up period were determined through interviews. An OPF at the spine, hip, proximal humerus, or distal radius was defined as a major OPF (MOF). RESULTS: After excluding participants who had a history of type 1 diabetes mellitus and thiazolidinedione therapy, 1951 men were analyzed. Men with hyperglycemia in the diabetic range had a significantly higher risk of OPF compared with those with normoglycemia, after adjusting for confounding factors including insulin therapy (hazard ratio (HR): 2.76, 95% confidence interval (CI): 1.17, 6.50 in FPG ≥ 126 mg/dl; HR: 2.49, 95% CI: 1.07, 5.77 in HbA1c ≥ 6.5%). An elevated risk of MOF was observed in participants in the prediabetic HbA1c category (HR: 2.15, 95% CI: 1.00, 4.62 in 5.7% ≤ HbA1c < 6.5%) in addition to those in the diabetic category. The intermediate glycemic status group showed intermediate risk, suggesting that the association was linear. CONCLUSIONS: Hyperglycemia was associated linearly with elevated fracture risk in community-dwelling elderly men. MOF risk may be elevated in Japanese elderly men with prediabetic glycemic status.

Low bone mineral density is associated with an elevated risk of developing increased arterial stiffness: A 10-year follow-up of Japanese women from the Japanese Population-based Osteoporosis (JPOS) cohort study.

OBJECTIVE: Only a few longitudinal studies have assessed the relationship between bone mineral density (BMD) and arteriosclerosis. This study aimed to determine whether low BMD at baseline is associated with the development of increased arterial stiffness, as evaluated by brachial-ankle pulse wave velocity (baPWV), in Japanese women. METHODS: A baPWV value of ≥1800 cm/s was adopted as the criterion for increased arterial stiffness, i.e., the outcome of the study. Of the 725 women aged ≥50 years who completed the baseline survey, we excluded the 166 who already met this criterion. Of the remaining women, we analyzed data from the 446 who completed at least one of the follow-up surveys conducted 5 or 10 years after baseline. BMD at the lumbar spine (LS) and total hip (TH) was measured by dual-energy X-ray absorptiometry in the baseline survey. baPWV was measured both at baseline and at follow-up. Multivariate logistic regression was used to evaluate the independent effect of BMD at baseline on developing the outcome during 10-year follow-up. RESULTS: We identified 166 women who newly developed increased arterial stiffness. The odds ratios (OR) for a 1 SD decrease in BMD at LS and TH for developing the outcome were 1.20 (95% confidence interval [CI]: 0.91-1.50), and 1.44 (95% CI: 1.14-1.81), respectively, after adjusting for age and systolic blood pressure. After additionally adjusting for baPWV at baseline, the OR for a 1 SD decrease in BMD at TH remained significant (1.33, 95% CI: 1.02-1.72). CONCLUSION: Low BMD at TH was significantly associated with the development of increased arterial stiffness during a 10-year follow-up of Japanese women.

Muscle strength is associated with bone health independently of muscle mass in postmenopausal women: the Japanese population-based osteoporosis study.

There are conflicting reports on whether muscle strength is associated with bone mineral density (BMD) independently of muscle mass. Here, we examined the association between muscle strength and BMD in a representative population of Japanese women. Cross-sectional data from 680 postmenopausal women, who were participants in the 15th-year follow-up survey of the Japanese Population-based Osteoporosis cohort study, were analyzed. Areal BMD (aBMD) at the femoral neck and lumbar spine, whole-body bone mineral density, and appendicular skeletal muscle mass (ASM, kg) were measured by dual-energy X-ray absorptiometry. The ASM index (ASMI, kg/m2) was calculated as ASM divided by height squared (m2). Grip strength (kg) was measured as an indicator of muscle strength. Grip strength showed significantly (P < 0.05) positive relationships with aBMDs at several skeletal sites after adjusting for ASMI and age (standardized partial regression coefficient (ß) = 0.102 at femoral neck, ß = 0.126 at lumbar spine). Adjusted means of aBMD at the femoral neck and lumbar spine showed significant increasing trends from the lowest to highest tertile of grip strength. Our findings indicate that muscle strength is associated with aBMD at several sites independently of muscle mass in Japanese postmenopausal women. Thus, postmenopausal women with strong muscle strength tend to have a healthy bone status regardless of muscle size.

Relationships between serum leptin levels and bone mineral parameters in school-aged children: a 3-year follow-up study.

Leptin regulates bone cell differentiation and functions via direct and indirect actions in experimental settings. Epidemiologically, however, the impact of leptin on the regulation of bone metabolism remains unclear. While some studies have reported a positive relationship between leptin and bone mineral parameters, other studies found an inverse or no association. We analyzed data from a population-based follow-up survey of community-dwelling children in Hamamatsu, Japan, to investigate relationships between leptin levels and bone mineral parameters. Multiple regression analysis was performed. Multicollinearity was quantified using the variance infiltration factor (VIF). Among 408 children who participated in the baseline survey (at age 11.2 years), 254 (121 boys and 133 girls) completed the follow-up survey (at age 14.2 years). Leptin levels were strongly related to fat mass (r = 0.87 in boys, r = 0.80 in girls). Leptin levels at baseline were significantly (P < 0.05) positively related to total body less head (TBLH) areal bone mineral density (aBMD) at follow-up in girls (standardized partial regression coefficient: ß = 0.302, VIF = 2.246), after adjusting for body fat percentage (%). On the other hand, leptin levels were inversely related to TBLH aBMD in boys (ß = - 0.395, VIF = 4.116), after adjusting for body fat mass (kg). Positive relationships between leptin levels and bone mineral parameters were observed with VIF values < 4.0, whereas inverse relationships were observed with VIF values ≥ 4.0. These findings suggest that positive relationships between leptin levels and bone mineral parameters are weak, or not always observed, due to statistical problems (i.e., multicollinearity) and other factors derived from adipose tissue.

Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study.

PURPOSE: Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. METHODS: A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. RESULTS: After excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. CONCLUSIONS: Hyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.

Relative Importance of Central and Peripheral Adiposities on Cardiometabolic Variables in Females: A Japanese Population-Based Study.

In epidemiological studies, there is little evidence regarding the relative impact of central adiposity and peripheral adiposity on cardiometabolic risk factors, especially in Asian populations. This study investigated associations between central-to-peripheral fat ratios and cardiometabolic variables using data from a population-based study of Japanese women. The source population was composed of 1800 women aged 50 yr or older at the 15th- to 16th-yr follow-up survey of the Japanese Population-Based Osteoporosis Cohort Study. This study analyzed cross-sectional data from 998 women for whom complete information about body fat variables according to dual-energy X-ray absorptiometry, cardiometabolic variables, and potential confounding factors was available. Both before and after adjusting for potential confounding factors, trunk-to-appendicular fat ratios showed significant (p < 0.05) correlations with brachial-ankle pulse wave velocity, serum lipids, and hemoglobin A1c levels. Relationships between fat ratios and cardiometabolic variables were independent of relationships between fat volumes (in whole body or in trunk) and cardiometabolic variables. Furthermore, relationships between trunk-to-appendicular fat ratios and cardiometabolic variables were observed among women in the lowest tertile of total body fat (brachial-ankle pulse wave velocity, ß = 0.08; high-density lipoprotein cholesterol, ß = -0.32; low-density lipoprotein cholesterol, ß = 0.15; and hemoglobin A1C, ß = 0.16; p < 0.05, respectively). Central adiposity is more related to cardiometabolic variables than peripheral adiposity. Information on central-to-peripheral fat ratios is particularly valuable for the evaluation of relatively thin Japanese women.