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Summary: This study evaluated changes in spinal alignment and quality of life (QOL) after corrective spinal surgery for patients with postmenopausal osteoporosis and spinal kyphosis. Spinal global alignment and QOL were significantly improved after corrective spinal surgery but did not reach the level of non-operated controls. Introduction: With the increased aging of society, the demand for corrective spinal instrumentation for spinal kyphosis in osteoporotic patients is increasing. However, previous studies have not focused on the improvement of quality of life (QOL) after corrective spinal surgery in patients with osteoporosis, compared to non-operated control patients. The purposes of this study were thus to evaluate changes in spinal alignment and QOL after corrective spinal instrumentation for patients with osteoporosis and spinal kyphosis and to compare these results with non-operated patients. Methods: Participants comprised 39 patients with postmenopausal osteoporosis ≥50 years old who underwent corrective spinal surgery using multilevel posterior lumbar interbody fusion (PLIF) for symptomatic thoracolumbar or lumbar kyphosis, and 82 age-matched patients with postmenopausal osteoporosis without prevalent vertebral fractures. Spinopelvic parameters were evaluated with standing lateral spine radiography, and QOL was evaluated with the Japanese Osteoporosis QOL Questionnaire (JOQOL), SF-36, and Roland-Morris Disability Questionnaire (RDQ). Results: Lumbar kyphosis angle, sagittal vertical axis, and pelvic tilt were significantly improved postoperatively. QOL evaluated with all three questionnaires also significantly improved after 6 months postoperatively, particularly in domain and subscale scores for pain and general/mental health. However, these radiographic parameters, total JOQOL score, SF-36 physical component summary score, and RDQ score were significantly inferior compared with non-operated controls. Conclusions: The results indicate that spinal global alignment and QOL were significantly improved after corrective spinal surgery using multilevel PLIF for patients with osteoporosis and spinal kyphosis but did not reach the level of non-operated controls. [ABSTRACT FROM AUTHOR]

Summary: The associations between mid-femoral cross-sectional geometry and exercise characteristics were investigated in female athletes. The effects on bone geometry for weight-bearing sports with low-to-high-impact were greater than those for non-impact weight-bearing sports, whereas low-impact or high-strain-magnitude/low-strain-rate sports had less of an effect on bone geometry compared with higher-impact sports. Introduction: Many previous studies have investigated tibial geometry in athletes; however, few studies have examined the associations between femoral cross-sectional geometry and exercise characteristics. The aim of this study was to investigate these relationships using magnetic resonance imaging (MRI) at the femoral mid-shaft. Methods: One hundred and fifty-three female elite athletes, aged 18-34 years, were classified into five groups based on the characteristics of their sports. Sports were considered non-impact ( n = 27), low- or moderate-impact ( n = 39), odd-impact ( n = 38), high-strain-magnitude/low-strain-rate ( n = 10), or high-impact ( n = 39). Bone geometrical parameters, including cortical area, periosteal perimeter, and moment of inertia (bone strength index), were determined using MRI images. Results: Higher-impact groups displayed bone expansion, with significantly greater periosteal perimeters, cortical areas (~37.3 %), and minimum moments of inertia ( I, ~92.3 %) at the mid-femur than non- and low-impact groups. After adjusting for age, height, and weight, the cortical area and I of the low-impact and high-strain-magnitude/low-strain-rate groups were also significantly greater than those of the non-impact group. Conclusions: Higher-impact sports with high strain rates stimulated periosteal bone formation and improved bone geometry and strength indices at the femoral mid-shaft. Although our results indicate that weight-bearing sports are beneficial even if they are low impact, the effects of lower-impact or high-strain-magnitude/low-strain-rate sports on bone geometry were less pronounced than the effects of higher-impact sports at the femoral mid-shaft. [ABSTRACT FROM AUTHOR]

Summary: Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment. Introduction: Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear. Methods: Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70-150 pg/mL; C, 150-300 pg/mL; and D, ≥300 pg/mL). Results: The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex ( t = 3.24, P = 0.01; 95 % confidence interval [CI] 11.78 to 50.43) and phosphate level ( t = 2.13, P = 0.04; 95 % CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level ( t = 1.90, P = 0.06, 95 % CI −1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1 %), B (88.0 %), C (85.2 %), and D (90.5 %). Conclusion: Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment. [ABSTRACT FROM AUTHOR]

Summary: Serum undercarboxylated osteocalcin (ucOC)/intact osteocalcin (iOC) ratio increased >1.0 in the patients undergoing hemodialysis, particularly in those with high bone turnover state. Consequently, serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in hemodialysis patients. Introduction: Serum intact osteocalcin (iOC), undercarboxylated OC (ucOC), and the ucOC/iOC ratio are considered clinically relevant indices in pre-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, despite their accumulation in uremic serum. Methods: Serum iOC and ucOC were measured along with serum intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRACP)-5b in 89 pre-dialysis CKD and 189 HD patients. Results: Serum iOC and ucOC showed significantly negative correlations with estimated glomerular filtration rate in pre-dialysis CKD patients, although serum ucOC/iOC ratio did not correlate. Serum ucOC was significantly greater in HD patients than in pre-dialysis CKD patients, while serum iOC did not differ significantly, resulting in serum ucOC/iOC ratio >1.0 in 135 (71.4 %) out of 189 HD patients. HD patients with high serum ucOC/iOC ratio (>1.0) had a significantly younger age and significantly higher values of body mass index, serum creatinine, albumin, phosphate, iPTH, and TRACP-5b than those with low ucOC/iOC ratio (≤1.0). The baseline iPTH and P1NP correlated with the changes of the ucOC/iOC ratio during the 2 days of the inter-dialytic period. Multivariate analysis showed that log [ucOC/iOC] in HD patients was significantly associated with log [iPTH], log [BAP], or log [TRACP-5b]. Conclusions: Serum ucOC/iOC ratio >1.0 was observed in as high as 71.4 % of HD patients, preferentially with high bone turnover state, in comparison with pre-dialysis CKD patients. These data suggested that serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in HD patients. [ABSTRACT FROM AUTHOR]

Summary: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. Introduction: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. Methods: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. Results: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. Conclusions: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile. [ABSTRACT FROM AUTHOR]

Summary: Patients with rheumatoid arthritis showed greater response to 18-month administration of daily teriparatide especially in the increase of bone formation markers at 1 month and femoral neck bone mineral density at 18 months compared to postmenopausal osteoporosis patients. Introduction: The aim of this study was to evaluate the effects of 18-month administration of daily teriparatide (TPTD) in osteoporosis patients with rheumatoid arthritis (RA) by comparing that of postmenopausal osteoporosis patients (Porosis). Methods: The effects of TPTD were examined between RA ( n = 70; age 68.4 years; disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.8; rheumatoid factor [RF] positivity 75.5 %) with 77.1 % of prior bisphosphonate (BP), 84.3 % of oral prednisolone (PSL) (4.4 mg/day at baseline), 25.7 % of biologics, and Porosis ( n = 62; age 71.3 years) with 77.4 % of prior BP. Results: Femoral neck (FN) bone mineral density (BMD) increase at 18 months was significantly greater in RA compared to Porosis (4.7 vs. 0.7 %, P = 0.038), whereas it was 9.7 versus 7.9 % ( P = 0.736) in the lumbar spine (LS). The increase of bone formation markers (bone alkaline phosphatase [bone ALP] and N-terminal type I procollagen propeptide [PINP]) at 1 month were all significantly greater in RA compared to Porosis. A multivariate logistic regression analysis revealed that the significant indicator of 18-month BMD increase in RA was a 3-month increase of under-carboxylated osteocalcin (ucOC) for LS ( β = 0.446, P = 0.005) and baseline ucOC for FN ( β = 0.554, P = 0.001), in which both showed significant negative correlation with baseline PSL dose. Conclusions: RA showed greater response to daily TPTD administration, especially in the increase of bone formation markers at 1 month and FN BMD increase at 18 months compared to Porosis. [ABSTRACT FROM AUTHOR]

Summary: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Introduction: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Methods: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. Results: The 10-year cumulative incidence of vertebral fractures was 0.67 %. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95 % CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95 % CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures ( P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not ( P for trend = 0.0729 and 0.4341, respectively). Conclusions: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures. [ABSTRACT FROM AUTHOR]

Summary: This multi-center, prospective, open-label, observational study evaluated the effects of once-monthly minodronate (50 mg) on treatment persistence, bone turnover markers, bone mineral density, low back pain, and upper gastrointestinal symptoms in outpatients with osteoporosis previously treated with daily or weekly bisphosphonate products. Introduction: The purposes of this study were to investigate the effects of once-monthly oral minodronate (MIN 50 mg) on bone turnover markers and bone mineral density, low back pain, and upper gastrointestinal symptoms, as well as preference for and treatment persistence of MIN 50 mg among Japanese osteoporosis patients currently treated with daily or weekly bisphosphonates. Methods: Study patients were allocated based on their preference to either the Switch group (patients willing to switch over to MIN 50 mg) or the Continue group (patients wanting to continue their current therapies). Patients' treatment persistence and satisfaction levels with the therapies were assessed using a self-administered questionnaire. The study endpoints were serum TRACP-5b, serum P1NP, bone mineral density, upper gastrointestinal symptoms, and low back pain. Results: In total, 264 and 133 patients were allocated into the Switch and Continue groups, respectively. Approximately, 65 % of patients were willing to switch to MIN 50 mg, with the predominant reason being 'less frequent dosing more convenient.' Treatment persistence was significantly higher in the Switch group (MIN 50 mg) than the Continue group. Almost all patients with abnormal bone metabolism markers demonstrated normalization after switchover. MIN 50 mg alleviated low back pain and upper gastrointestinal symptoms induced by prior bisphosphonate use. Conclusions: MIN 50 mg alleviates low back pain, reduces bone turnover markers and increases bone density, and induces fewer upper gastrointestinal symptoms after switchover from prior bisphosphonate products, and therefore, it may provide patients with a more convenient treatment option and enhance long-term treatment persistence. [ABSTRACT FROM AUTHOR]

Summary: This study examined the accuracy of thoracic and lumbar kyphotic angles as well as anthropometric indicators for discriminating patients with vertebral fracture among Japanese women >50 years old with back pain. Along with region-specific kyphotic angles and anthropometric indicators, the combination of thoracic and lumbar kyphotic angles offered the highest accuracy. Introduction: Vertebral fractures have been associated with thoracic kyphosis. However, reports on lumbar kyphotic changes in association with vertebral fracture are scarce. This study investigated the accuracy of thoracic kyphotic angle (TKA) and lumbar kyphotic angle (LKA) measurements as well as anthropometric indicators (wall-occiput distance (WOD) and rib-pelvis distance (RPD)) in discriminating patients with vertebral fracture. Methods: Lateral radiographs of the spine were obtained in 70 postmenopausal Japanese women who visited an orthopedic clinic with low back pain (mean age, 76.2 ± 9.0 years). Radiographic vertebral fracture was diagnosed using quantitative measurement according to Japanese criteria. Osteoarthritis (OA) was defined as Kellgren-Lawrence (KL) grade 3 or higher. TKA and LKA were measured using SpinalMouse®. WOD and RPD were also measured. Results: At least one vertebral fracture was present in 49 subjects (70 %). Women with vertebral fractures showed significant increases in LKA, TKA + LKA, and WOD and decreases in RPD. Logistic regression analysis showed significant association between TKA + LKA and vertebral fracture independent of the presence of OA. Receiver operating characteristic analysis revealed that TKA was useful for discriminating thoracic fractures (area under the curve (AUC), 0.730) and LKA was useful for lumbar fractures (AUC, 0.691). The combination of TKA + LKA offered the highest accuracy for detecting thoracic, lumbar, and any vertebral fractures, with AUCs of 0.779, 0.728, and 0.783, respectively. WOD and RPD showed low-to-moderate accuracies for thoracic, lumbar, and any vertebral fractures. Conclusions: Assessment of spinal kyphosis by SpinalMouse® as well as anthropometric indicators proved useful in discriminating subjects with vertebral fractures. These convenient and radiation-free methods could contribute to early diagnosis of vertebral fractures and subsequent appropriate treatment, thus preventing additional osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Summary: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk. Introduction: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture. Methods: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from −30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture. Results: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9 %) and when analyzed separately by femoral neck fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4 %) Conclusions: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture. [ABSTRACT FROM AUTHOR]

Summary: A 3-year follow-up study on 334 young Japanese females enrolled in a university at the age of 18 years revealed that discontinuation of leisure time impact-loading exercises performed in junior high and/or high school was associated with increased risk of reduction in calcaneus osteo-sono assessment index (OSI). Introduction: Bone strength rapidly increases during puberty and reaches its peak by the end of adolescence. The aim of this study was to determine the lifestyle factors that influence the maintenance of calcaneus OSI in young adult females around the time when peak bone mass is attained. Methods: Annual health checkups including OSI measurements, anthropometrics, lifestyle analysis, and blood examination were performed 4 times on 334 Japanese females enrolled in a university at the age of 18 years. According to the slope of OSI change during the 3-year follow-up, the subjects were grouped into two categories: OSI loss (the lowest tertile) and OSI gain/stable (the second and third tertiles). Results: At the baseline assessment, the OSI loss group had higher OSI and height and an earlier menarche age than the OSI gain/stable group. Performing leisure time impact-loading exercise in junior high and/or high school but discontinuing it at university was associated with increased risk of OSI loss, independent of OSI, height and weight at the age of 18 years, weight change during follow-up, age of menarche, energy-adjusted nutrient intake, and alcohol drinking; the odds ratios were 4.1-4.9 compared with those performing impact-loading exercise at university. In particular, duration, frequency, and subjective intensity of impact-loading exercise during high school were positively associated with OSI loss. Conclusion: Discontinuation of leisure time impact-loading exercises performed during late adolescence is associated with an increased risk of OSI loss in young adult females during the 3-year follow-up period. [ABSTRACT FROM AUTHOR]

Summary: Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism. Introduction: Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism. Methods: Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined. Results: ucOC correlated positively with BAP ( ρ = 0.489, p < 0.0001), TRACP-5b ( ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients ( p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose ( ρ = −0.303, p < 0.0001), hemoglobin A1C ( ρ = −0.214, p < 0.01), and glycated albumin ( ρ = −0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH]. Conclusion: Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Summary: This study aims to determine the relationship between advanced glycation end-product (AGE) accumulation in skin tissue and bone strength, assessed by quantitative ultrasound, among healthy adult Japanese men. The results of the study suggest that men with higher AGE accumulation in skin tissue have a lower osteo-sono assessment index. Introduction: AGE accumulate in bone collagen with age and diabetes and decrease the mechanical properties of bone. Although increased AGE levels are associated with fractures among diabetic patients and elderly women, it is unclear whether a relationship between increased AGE levels and bone strength is present in apparently healthy adult males. The aim of this study was to determine the relationship between AGE accumulation in tissue and the mechanical properties of bone among adult Japanese men, using quantitative ultrasound as a surrogate measure of the latter. Methods: Skin autofluorescence (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono assessment index (OSI), which is determined by quantitative ultrasound, were measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0-55.0 years). Results: Adjusted for age, BMI, calcium intake, physical activity, smoking status, and education level, log-transformed skin AF had a negative association with log-transformed OSI ( β = −0.218, P < 0.01). Adjusted geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75-2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66 (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared to be 5.0% lower than that for the lowest and middle skin AF tertiles ( P < 0.01). Conclusion: Among apparently healthy adult Japanese men, those with higher skin AF had a lower OSI, indicating a relationship between AGE accumulation and bone strength. A long-term prospective study is required to clarify the causality. [ABSTRACT FROM AUTHOR]

Summary: Recent animal studies have demonstrated that undercarboxylated osteocalcin upregulates insulin secretion via osteoblast-insulin signaling. However, it remains unclear whether such a pathway exists in humans. This study showed that serum undercarboxylated osteocalcin levels were inversely associated with fasting plasma glucose, hemoglobin A, and homeostasis model assessment of insulin resistance (HOMA-IR) levels in community-dwelling elderly Japanese men. Introduction: Undercarboxylated osteocalcin (ucOC) was reported to increase insulin secretion and improve glucose tolerance via osteoblast-insulin signaling in animal-based studies. Whether this pathway also exists in humans is unknown. We aimed to clarify whether serum ucOC levels are associated with glycemic status and insulin resistance in the general Japanese population. Methods: We included 2,174 Japanese men (≥65 years) who were able to walk without aid from others and lived at home in four cities of Nara Prefecture. We excluded participants with a history of diseases or medications that affect bone metabolism, other than type 2 diabetes mellitus (T2DM). Fasting plasma glucose, glycated hemoglobin A, and HOMA-IR levels were determined as outcome measures. Results: Of the 1,597 participants included in the analysis, both intact OC (iOC) and ucOC levels showed significant inverse correlations with all outcome measures, even after adjusting for potential confounders. Mean values of outcome measures showed a significant decreasing trend with higher quintiles of iOC or ucOC after adjusting for confounders. This trend remained significant for ucOC quintiles after further adjustment for iOC levels, but was not significant for iOC quintiles after adjusting for ucOC levels. These results were attenuated, but still apparent, after excluding participants receiving drug therapy for T2DM. Conclusions: Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies. [ABSTRACT FROM AUTHOR]

Summary: A cross-sectional analysis of 1,662 community dwelling elderly Japanese men suggested that habitual natto intake was significantly associated with higher bone mineral density (BMD). When adjustment was made for undercarboxylated osteocalcin levels, this association was insignificant, showing the natto-bone association to be primarily mediated by vitamin K. Introduction: Low vitamin K intake is associated with an increased risk of hip fracture, but reports have been inconsistent on its effect on BMD. Our first aim was to examine the association between BMD and intake of fermented soybeans, natto, which contain vitamin K1 (20 μg/pack) and K2 (380 μg/pack). Our second aim was to examine the association between undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K intake, and BMD to evaluate the role of vitamin K in this association. Methods: Of the Japanese men aged ≥65 years who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men study, 1,662 men without diseases or medications known to affect bone metabolism were examined for associations between self-reported natto intake or serum ucOC levels with lumbar spine or hip BMD. Results: The subjects with greater intake of natto showed significantly lower level of serum ucOC. Analysis after adjustment for confounding variables showed an association of greater intake of natto with both significantly higher BMD and lower risk of low BMD (T-score < −1 SD) at the total hip and femoral neck. This association became insignificant after further adjustment for ucOC level. Conclusion: Habitual intake of natto was associated with a beneficial effect on bone health in elderly men, and this association is primarily due to vitamin K content of natto, although the lack of information on dietary nutrient intake, including vitamin K1 and K2, prevented us from further examining the association. [ABSTRACT FROM AUTHOR]

Summary: Improvements in total content of enzymatic cross-linking, the ratio of hydroxylysine-derived enzymatic cross-links, and non-enzymatic advanced glycation end product cross-link formation from once-weekly administration of hPTH(1-34) for 18 months in OVX cynomolgus monkeys contributed to the improvement of bone strength. Introduction: Parathyroid hormone (PTH) is used for the treatment of osteoporosis. To elucidate the contribution of material properties to bone strength after once-weekly treatment with hPTH(1-34) in an ovariectomized (OVX) primate model, the content of collagen and enzymatic immature, mature, and non-enzymatic cross-links, collagen maturity, trabecular architecture, and mineralization in vertebrae were simultaneously estimated. Methods: Adult female cynomolgus monkeys were divided into four groups ( n = 18-20 each) as follows: SHAM group, OVX group, and OVX monkeys given once-weekly subcutaneous injections of hPTH(1-34) either at 1.2 or 6.0 μg/kg (low- or high-PTH groups) for 18 months. The content of collagen, enzymatic and non-enzymatic cross-linking pentosidine, collagen maturity, trabecular architecture, mineralization, and cancellous bone strength of vertebrae were analyzed. Results: Low-PTH and high-hPTH treatments increased the content of enzymatic immature and mature cross-links, bone volume (BV/TV), and trabecular thickness, and decreased pentosidine, compared with the OVX group. Stepwise logistic regression analysis revealed that BV/TV, the content of total enzymatic cross-links, and calcium content independently affected ultimate load (model R = 0.748, p < 0.001) and breaking energy (model R = 0.702, p < 0.001). BV/TV was the most powerful and enzymatic cross-link content was the second powerful determinant of both ultimate load and breaking energy. The most powerful determinant of stiffness was the enzymatic cross-link content (model R = 0.270, p < 0.001). Conclusion: Once-weekly preventive administration of hPTH(1-34) increased the total contents of immature and mature enzymatic cross-links, which contributed significantly to vertebral cancellous bone strength. [ABSTRACT FROM AUTHOR]

Summary: A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular calcification and mortality in hemodialysis patients. OPG and pulse wave velocity (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients who were prospectively followed for 6 years. In long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were strongly linked with both arterial stiffness and worse outcome. Introduction: A high circulating OPG level is reported to be a risk factor for vascular calcification and mortality in Western chronic kidney disease (CKD) patients but it is not known if this is true for Japanese CKD patients, where a different risk profile may operate. Methods: OPG and PWV were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age 62 years) who were prospectively followed for 6 years. Results: OPG levels were associated in multivariate analysis with age, dialysis vintage, history of cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein levels did not correlate with OPG. Patients with clinical history of CVD had significantly higher OPG levels and OPG levels were positively correlated to PWV, an index of arterial stiffness. These associations were independent of age, sex, dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including 25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase in OPG was associated with increased all-cause (hazard ratios 1.14, 95% confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality, respectively). Conclusions: In long-term normoalbuminemic Japanese hemodialysis patients, with low prevalence of inflammation, OPG levels were strongly linked with both arterial stiffness and worse outcome. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus. Introduction: We previously reported that the expression of macrophage migration inhibitory factor (MIF) was up-regulated during the fracture healing process in rats. However, its role in the pathophysiology of this process remained unclear. The aim of the present study was to clarify the role of MIF in the fracture healing process using MIF gene-deficient mice (MIF KO). Methods: Bone repair in wild-type mice (WT) and MIF KO ( n = 70, respectively) was investigated using a tibia fracture model. Radiographic, biomechanical, histological, bone histomorphometric, and molecular analyses were performed. Results: Post-fracture biomechanical testing showed that maximum load and stiffness were significantly lower in MIF KO than in WT on day 42. However, similar levels were observed between the two groups on day 84. Bone histomorphometric analysis revealed significantly higher osteoid volume, a lower mineral apposition rate, and smaller numbers of osteoclasts in the MIF KO callus compared to the WT callus. The messenger ribonucleic acid expressions of matrix metalloproteinase (MMP)-2, membranous type 1-MMP, cathepsin K, and tissue nonspecific alkaline phosphatase were found to be significantly suppressed in the MIF KO callus. Conclusion: The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization. [ABSTRACT FROM AUTHOR]

Summary: Postmenopausal hemodialysis patients are at risk of complications related to renal mineral and bone disorder, and postmenopausal osteoporosis. In 112 postmenopausal hemodialysis patients, free estrogen index was positively correlated with bone mineral density (BMD) Z-score and the annual percent change of BMD in multiple regression analysis. Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life. Introduction: Women on dialysis are not only at risk of developing mineral and bone disorder, but also suffer from postmenopausal osteoporosis. We assessed the effect of sex hormones on bone metabolism in postmenopausal hemodialysis patients. Methods: We enrolled 112 postmenopausal hemodialysis patients with a mean age of 68.4 ± 10.4 years. We measured the serum levels of estradiol, testosterone, sex hormone-binding globulin (SHBG), and intact parathyroid hormone (intact-PTH), as well as bone metabolism parameters and radial bone mineral density (BMD). The free estrogen index (FEI) was calculated from the estradiol and SHBG values. After conventional dialysis was performed for 12 months, BMD was measured again and the annual percent change was calculated. Estradiol and SHBG were also measured in 25 postmenopausal women without chronic kidney disease. Results: Estradiol levels were higher in the hemodialysis patients than in the postmenopausal women without chronic kidney disease. In patients with relatively normal bone turnover (intact-PTH: from 150 to 300 pg/ml), the FEI showed a positive correlation with the BMD Z-score. The annual percent change of BMD showed a positive correlation with the FEI according to multiple regression analysis. Conclusions: Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life. [ABSTRACT FROM AUTHOR]

Summary: Although previous studies indicated that serum insulin-like growth factor-I (IGF-I) was inversely associated with the presence of vertebral fractures (VFs), little is known whether serum IGF-I is associated with multiple VFs. We report that serum IGF-I could be clinically useful for assessing the severity of VFs in type 2 diabetic postmenopausal women. Introduction: The number of VFs is associated with the mobility and mortality of the elderly people. Although serum IGF-I is inversely associated with the presence of VFs, little is known about the relationship between serum IGF-I and multiple VFs. Methods: In this cross-sectional study, we recruited 479 men and 334 postmenopausal women with type 2 diabetes mellitus and measured serum IGF-I, bone mineral density, and bone turnover markers. Lateral X-ray films of the thoracic and lumbar spine were taken to diagnose the VF. Results: In postmenopausal women, serum IGF-I level was decreased when the number of VFs was increased [no VFs; 138 ± 51 ng/ml (mean ± SD) vs. one VF; 119 ± 42 ( p = 0.006), two VFs; 103 ± 39 ( p = 0.002), and three and more VFs; 91 ± 40 ( p < 0.001)]. Multiple logistic regression analysis adjusted for age, duration of diabetes, body mass index, serum creatinine, and HbA showed that serum IGF-I level was inversely associated with the presence of one VF [odds ratio (OR) = 0.67, p = 0.029], two VFs (OR = 0.40, p = 0.017), as well as three and more VFs (OR = 0.27, p = 0.005). These associations were still significant after the additional adjustment for BMD at the lumbar spine. In contrast, no significant association of serum IGF-I level with VFs was found in men. Conclusions: Serum IGF-I level was inversely associated with the number of prevalent VFs in postmenopausal women with type 2 diabetes, suggesting that serum IGF-I could be clinically useful for assessing the severity of VFs in the population. [ABSTRACT FROM AUTHOR]

Summary: In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker. Introduction: Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients. Methods: Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT. Results: Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks. Conclusion: W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption. [ABSTRACT FROM AUTHOR]

Summary: A reference database for trabecular bone density, cortical thickness, and elastic modulus of trabecular bone for a novel ultrasonic bone densitometry system (LD-100) based on two longitudinal waves (fast and slow) was determined over a wide age range in a normal Japanese population. Introduction: A novel ultrasonic bone densitometry system (LD-100 system) was applied to create a reference database for trabecular bone density (TBD), cortical thickness (CoTh), and elastic modulus of trabecular bone (EMTb) for this device over a wide age range in a normal Japanese population. Methods: In a comparative study between LD-100 and peripheral quantitative computed tomography (pQCT) systems, 52 individuals were examined by both systems at the same radius simultaneously. To create a reference database, a total of 2,380 healthy subjects (1,179 men, 1,201 women), ages 18–99 years, were examined using the LD-100 system. Results: Highly significant correlations between the LD-100 and pQCT systems were found in TBD ( r = 0.877, p < 0.001) and CoTh ( r = 0.723, p < 0.001). For the reference database, peak values of TBD, CoTh, and EMTb were observed at 30–34 years (255.09 mg/cm), 20–24 years (5.23 mm), and 20–24 years (4.09 GPa) in men, and at 25–29 years (209.24 mg/cm), 25–29 years (3.98 mm), and 20–24 years (3.33 GPa) in women, respectively. The TBD fell significantly ( p < 0.05) beginning at 55–59 years in both sexes, with a relatively rapid decrease in women. The CoTh showed a significant decrease beginning at 40–44 years in men and 50–54 years in women. The EMTb showed a significant decrease beginning at 40–44 years in men and 55–59 years in women. Conclusions: The LD-100 system is a useful bone densitometry device and the database of age-related changes in TBD, CoTh, and EMTb established in this study will provide fundamental data for future studies related to bone status. [ABSTRACT FROM AUTHOR]