Monthly minodronate inhibits bone resorption to a greater extent than does monthly risedronate

AbstractAs a bisphosphonate, minodronate (MIN) is one of the strongest inhibitors of bone resorption. However, there have been no reports directly comparing the antiresorptive effects of monthly MIN with those of monthly risedronate (RIS). We enrolled 30 cases of osteoporosis (OP; 16 in the MIN group [mean age: 68.2 years] and 14 in the RIS group [mean age: 68.1 years]) to investigate the early effects of treatment by monthly MIN or RIS over a 4-month period using bone turnover marker values. Only female patients were enrolled to avoid gender bias. Urinary cross-linked N-telopeptide of type I collagen (NTX) before treatment and at 1, 2, and 4 months of therapy, as well as serum bone alkaline phosphatase and alkaline phosphatase before treatment and at 4 months afterwards, were evaluated. All bone turnover marker values were significantly decreased at 4 months in both groups. The changes in urinary NTX at the study end point for RIS and MIN were −30.1% and −63.1%, respectively. From 2 months of treatment, the antiresorptive effects on urinary NTX by MIN were significantly higher than those by RIS, indicating that MIN more immediately and strongly inhibited bone absorption. Thus, monthly MIN seems to suppress bone resorption faster and more strongly than RIS in OP treatment

Drosophila Tbx6-related gene, Dorsocross, mediates high levels of Dpp and Scw signal required for the development of amnioserosa and wing disc primordium

AbstractRegional differentiation along the dorsoventral (DV) axis of the Drosophila embryo primarily depends on a graded BMP signaling activity generated by Decapentaplegic (Dpp) and Screw (Scw). We have identified triplicated Dpp and Scw target genes Dorsocross1, 2 and 3 (Doc1, 2, 3) that have a conserved T-box domain related to the vertebrate Tbx6 subfamily and act redundantly to induce dorsal structures. Doc genes are expressed in the dorsal region in the early blastoderm. After gastrulation, newly expressed Doc appears in a segmental pattern in the ectoderm. This expression correlates spatially with the second phase of Dpp expression in the ectoderm. Doc expression in the early blastoderm is abolished in either dpp or scw mutant embryos, whereas the ectodermal segmented expression depends only on Dpp. Inactivation of Doc genes with RNAi dramatically affected the development of amnioserosa and wing disc primordia, both of which depend on high levels of BMP signaling, although leg disc primordium, which depends on low levels of BMP, remained intact. Doc1 mRNA expressed in Xenopus embryos induced ventral mesoderm, suppressed activin-induced events and induced Xvent genes, which are analogous to the effects of native Tbx6 and its upstream regulator, BMP-4. These results suggest that the Tbx6 subfamily act in the BMP signaling pathway required for embryonic patterning in both animals

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men) with femoral neck fracture and 21 patients (17 women and 4 men) with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX), as well as urine levels of C-terminal telopeptide of type I collagen (CTX) and deoxypyridinoline (DPD), were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX), five weeks (serum NTX and DPD), and 2–3 weeks (CTX) after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures

High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly

Carpal tunnel syndrome is the most common type of entrapment neuropathy. However, the cause of carpal tunnel syndrome remains unclear in most cases. Senile systemic amyloidosis, induced by wild-type transthyretin deposition, is a prevalent aging-related disorder and often accompanied by carpal tunnel syndrome. In this study, we measured the frequency of unrecognized wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome. One hundred twenty-three patients with carnal tunnel syndrome, including 100 idiopathic patients, treated by carpal tunnel release surgery were analyzed. Tenosynovial tissues obtained at surgery were analyzed by Congo red and immunohistochemical staining. If staining for transthyretin was positive, the entire transthyretin gene was analyzed by direct DNA sequencing. We also analyzed tenosynovial tissues from 32 autopsy cases as controls. Thirty-four patients (34.0%) with idiopathic carpal tunnel syndrome showed amyloid deposition in the tenosynovial tissue, and all amyloid showed specific immunolabeling with antitransthyretin antibody. Direct DNA sequencing of the entire transthyretin gene did not reveal any mutations, indicating that all amyloid deposits were derived form wild-type transthyretin. Statistical analysis using logistic regression showed that the prevalence of transthyretin deposition in the idiopathic carpal tunnel syndrome group was significantly higher than that in controls (odds ratio, 15.8; 95% confidence interval, 3.3-75.7), and age and male sex were independent risk factors for transthyretin amyloid deposition. Our results demonstrate that wild-type transthyretin deposition is a common cause of carpal tunnel syndrome in elderly men. It is likely that many patients develop carpal tunnel syndrome as an initial symptom of senile systemic amyloidosis.ArticleHUMAN PATHOLOGY. 42(11):1785-1791 (2011)journal articl

Association of Self-reported Height Loss and Kyphosis with Loss of Teeth in Japanese Elderly

Study background: Height loss and kyphosis are useful surrogate markers of osteoporotic vertebral fractures in the elderly. Loss of teeth in the elderly also is associated with osteoporosis. These imply the possibility that self-reported these indices may be associated with loss of teeth in the elderly. This study aimed to clarify the associations of self-reported height loss and kyphosis with number of teeth lost in Japanese elderly. Subjects and Methods: Among patients who visited dispensing pharmacies in Matsumoto, Japan, 307 patients (75 men and 232 women) aged 50–97 years participated in the study. They completed a structured questionnaire including covariates related to loss of teeth. Self-reported height loss and kyphosis were simply defined as three categories: no; mild-to-moderate; severe. Results: Analyses of covariance adjusted for covariates revealed that there were no significant differences in the numbers of teeth lost in total, or during the past 1 year among the three self-reported height loss categories. Significant differences were observed in the total numbers of teeth lost among the three self-reported kyphosis categories (p<0.001). Subjects who were conscious of severe kyphosis had significantly larger number of teeth lost (mean ± SEM, 16.1 ± 1.8) than those who were conscious of no kyphosis (8.7 ± 0.6, p<0.001) and mild-to-moderate kyphosis (8.3 ± 0.7, p<0.001). Furthermore, there were significant differences in the number of teeth lost during the past 1 year among the three self-reported kyphosis categories (p=0.031). Subjects who were conscious of severe kyphosis had significantly greater number of teeth lost during the past 1 year (0.9 ± 0.2) than those who were conscious of no kyphosis (0.3 ±0.1, p=0.03). Conclusions: Our results suggest that Japanese elderly with self-reported severe kyphosis may lost more teeth than those without self-reported severe kyphosis

Validation of the Japanese Society for Surgery of the Hand Version of the Quick Disability of the Arm, Shoulder, and Hand (QuickDASH-JSSH) questionnaire

AbstractBackgroundThe Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) questionnaire is a region-specific, selfadministered questionnaire, which consists of a disability/symptom (QuickDASH-DS) scale, and the same two optional modules, the work (DASH-W) and the sport/music (DASHSM) modules, as the DASH. After the Japanese version of DASH (DASH-JSSH) was cross-culturally adapted and developed, we made the Japanese version of QuickDASH (QuickDASH-JSSH) by extracting 11 out of 30 items of the DASH-JSSH regarding disability/symptoms. The purpose of this study was to test the reliability, validity, and responsiveness of QuickDASH-JSSH.MethodsA series of 72 patients with upper extremity disorders completed the QuickDASH-JSSH, the 36-Item Short-Form Health Survey (SF-36), and the Visual Analog Scale (VAS) for pain. Thirty-eight of the patients were reassessed for test–retest reliability 1 or 2weeks later. Reliability was investigated by the reproducibility and internal consistency. To analyze the validity, a principal component analysis and the correlation coefficients between the QuickDASH-JSSH and the SF-36 were obtained. The responsiveness was examined by calculating the standardized response mean (SRM; mean change/SD) and effect size (mean change/SD of baseline value) after carpal tunnel release of the 17 patients with carpal tunnel syndrome.ResultsCronbach’s alpha coefficient in the QuickDASH-DS was 0.88. The intraclass correlation coefficient (ICC) for the same was 0.82. The unidimensionality of the QuickDASH-DS was confirmed. The correlation coefficients between the QuickDASH-DS and the DASH-DS, DASH-W, or the DASH-SM were 0.92, 0.81, or 0.76, respectively. The correlation coefficients between the QuickDASH-DS score and the subscales of the SF-36 ranged from −0.29 to −0.73. The correlation coefficient between the QuickDASH-DS score and the VAS for pain was 0.52. The SRM/effect size of QuickDASHDS was −0.54/−0.37, which indicated moderate sensitivity.ConclusionThe Japanese version of QuickDASH has equivalent evaluation capacities to the original QuickDASH

Validation of the Japanese Society for Surgery of the Hand version of the Carpal Tunnel Syndrome Instrument

AbstractBackgroundThe Carpal Tunnel Syndrome Instrument (CTSI) is a disease-specific, self-administered questionnaire that consists of a symptom severity scale (SS) and a functional status scale (FS). The CTSI was cross-culturally adapted and developed by the Impairment Evaluation Committee, Japanese Society for Surgery of the Hand (JSSH). The purpose of this study was to test the reliability, validity, and responsiveness of the Japanese version of the CTSI (CTSI-JSSH).MethodsA consecutive series of 87 patients with carpal tunnel syndrome completed the CTSI-JSSH, the JSSH version of the Disability of the Arm, Shoulder, and Hand questionnaire (DASH-JSSH), and the 36-Item Short-Form Health Survey (SF-36). Seventy-two of the patients were reassessed for test–retest reliability 1 or 2 weeks later. Reliability was investigated by the reproducibility and the internal consistency. To analyze the validity, a factor analysis (principal axis factoring) of the CTSI-JSSH and the correlation coefficients between the CTSI-JSSH and DASH-JSSH were obtained. The responsiveness was examined by calculating the standardized response mean (SRM; mean change/SD) and effect size (mean change/SD of baseline value) after carpal tunnel release in 42 patients.ResultsCronbach’s alpha coefficients for the CTSI-JSSH-SS and the CTSI-JSSH-FS were 0.84 and 0.90, respectively, and the intraclass correlation coefficients were 0.82 and 0.83, respectively. The unidimensionality of the CTSI-JSSH-SS was barely confirmed; the unidimensionality of the CTSI-JSSH-FS was confirmed. The correlation coefficients between the CTSI-JSSH-FS and the CTSI-JSSH-SS or DASH-JSSH were 0.58 and 0.80, respectively. The correlation coefficient between the CTSI-JSSH-SS and DASH-JSSH was 0.54. The correlation coefficients between the subscales of SF-36 and the CTSI-JSSH-SS or the CTSI-JSSH-FS ranged from -0.23 to -0.66 and from -0.19 to -0.63, respectively. The SRMs/effect sizes of the CTSI-JSSH-SS and the CTSI-JSSH-FS were -0.85/-0.99 and -0.70/-0.61, which indicated that they were more than moderately sensitive.ConclusionsThe CTSI-JSSH has sufficient reliability, validity, and responsiveness to assess the health status in carpal tunnel syndrome

High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly

Carpal tunnel syndrome is the most common type of entrapment neuropathy. However, the cause of carpal tunnel syndrome remains unclear in most cases. Senile systemic amyloidosis, induced by wild-type transthyretin deposition, is a prevalent aging-related disorder and often accompanied by carpal tunnel syndrome. In this study, we measured the frequency of unrecognized wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome. One hundred twenty-three patients with carnal tunnel syndrome, including 100 idiopathic patients, treated by carpal tunnel release surgery were analyzed. Tenosynovial tissues obtained at surgery were analyzed by Congo red and immunohistochemical staining. If staining for transthyretin was positive, the entire transthyretin gene was analyzed by direct DNA sequencing. We also analyzed tenosynovial tissues from 32 autopsy cases as controls. Thirty-four patients (34.0%) with idiopathic carpal tunnel syndrome showed amyloid deposition in the tenosynovial tissue, and all amyloid showed specific immunolabeling with antitransthyretin antibody. Direct DNA sequencing of the entire transthyretin gene did not reveal any mutations, indicating that all amyloid deposits were derived form wild-type transthyretin. Statistical analysis using logistic regression showed that the prevalence of transthyretin deposition in the idiopathic carpal tunnel syndrome group was significantly higher than that in controls (odds ratio, 15.8; 95% confidence interval, 3.3-75.7), and age and male sex were independent risk factors for transthyretin amyloid deposition. Our results demonstrate that wild-type transthyretin deposition is a common cause of carpal tunnel syndrome in elderly men. It is likely that many patients develop carpal tunnel syndrome as an initial symptom of senile systemic amyloidosis.ArticleHUMAN PATHOLOGY. 42(11):1785-1791 (2011)journal articl