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Background: Few randomized controlled trials (RCTs) report interventions targeting improvement of frailty status as an outcome. Methods: This RCT enrolled 117 older adults (65-79 years of age) in Toufen, Taiwan who scored 3-6 on The Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version and then score ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF). With a two by two factorial design, subjects were randomly assigned to interventions (Exercise and nutrition, EN, n = 55 or problem solving therapy, PST, n = 57) or controls (non-EN, n = 62 or non-PST, n = 60). Educational booklets were provided to all. EN group subjects received nutrition consultation and a twice-weekly exercise-training program while PST group subjects received 6 sessions in 3 month. Subjects were followed at 3, 6, and 12 months. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline assessments. One hundred and one completed final assessments. Intention-to-treat analysis with the generalized estimating equation model was applied with adjustment for time and treatment-by-time interactions. Results: Mean age was 71.4 ± 3.7 years, with 59% females. Baseline characteristic were generally comparable between groups. EN group subjects had a higher improvement rate on the primary outcome than non-EN group subjects (45% vs 27%, adjusted p = 0.008) at 3 months, but not 6 or 12 months. They also had more increase of serum 25(OH) vitamin D level (4.9 ± 7.7 vs 1.2 ± 5.4, p = 0.006) and lower percentage of osteopenia (74% vs 89% p = 0.042) at 12 months. PST group subjects had better improvement (2.7 ± 6.1 vs 0.2 ± 6.7, p = 0.035, 6-month) and less deterioration (-3.5 ± 9.7 vs -7.1 ± 8.7, p = 0.036, 12-month) of dominant leg extension power than non-PST subjects. Some secondary outcomes were also improved in control groups (non-EN or non-PST). No adverse effects were reported. Conclusions: The three-month EN intervention resulted in short-term (3-month) frailty status improvement and long-term effect on bone mineral density and serum vitamin D (12-month) among Taiwanese community-dwelling elders. The effect of PST was less pronounce. Trial registration: ClinicalTrials.gov: EC0970301 [ABSTRACT FROM AUTHOR]

Caffeine-containing beverage consumption has been associated with low bone mass and increased fracture risk in some, but not most, observational studies. The effects of caffeine on bone metabolism are still controversial. We investigated the effects of caffeine on the differentiation of bone progenitor cells and bone mineral density (BMD) by in vitro and in vivo experiments. Low-concentration caffeine (0.005-0.1 mM) did not affect the bone marrow cell viability and alkaline phosphatase activity during osteoblast differentiation from bone marrow stromal cells, but it effectively enhanced the osteoclastogenesis from bone marrow hematopoietic cells and the bone resorption activity by pit formation assay. Moreover, caffeine effectively enhanced the receptor activator of NF-κB ligand (RANKL), but reduced the osteoprotegerin protein expressions in osteoblast MC3T3-E1 cells. Caffeine could also increase the cyclooxygenase-2 (COX-2) protein expression and prostaglandin (PG)E production in cultured neonatal mouse calvariae. In animal study, BMD in lumbar vertebra, femur, or tibia was significantly lowered in growing rats supplemented with 0.2% caffeine in diets for 20 weeks compared with the control group. The calcium contents in tibia and femur of caffeine-treated rats were also lower than that in the control group. The osteoclastogenesis of bone marrow cells isolated from caffeine-treated rats was markedly enhanced as compared with the control group. Taken together, these results suggest that caffeine may reduce BMD in growing rats through the enhancement in osteoclastogenesis. Caffeine may possess the ability to enhance a COX-2/PGE-regulated RANKL-mediated osteoclastogenesis. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:954-960 [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. METHODS: From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. RESULTS: The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 ± 2.3 months compared with 23.4 ± 14.9, 12.2 ± 8.5, and 6.6 ± 4.3 months in Groups 1, 2, and 3, respectively. CONCLUSIONS: This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts. [ABSTRACT FROM AUTHOR]

The subvastus and midvastus approaches are two of the most commonly performed quadriceps preserving approaches for total knee arthroplasty (TKA), which can hasten functional recovery and rehabilitation. However, there has not been sufficient investigation with respect to a quantitative comparison between the two approaches in terms of muscle strength. To compare outcomes with respect to muscle strength between these two approaches, quadriceps and hamstring muscle torques of 20 patients who underwent primary TKA with the subvastus (SV) approach and 10 patients who received the midvastus (MV) approach were measured after surgery. The median age of patients in the SV group (68 years, range 53–77 years) was significantly different that the median age of patients in the MV group (61 years, range 50–73 years) ( P = 0.0141). There was no significant difference in patient weight, height, or postoperative duration before muscle testing between the SV and MV groups. There were no significant differences in peak muscle torque or hamstring/quadriceps (H/Q) ratio between the groups. We thus conclude peak muscle torque and H/Q ratios were not statistically different with the SV or MV approach, therefore functional outcome is comparable. [ABSTRACT FROM AUTHOR]

Background: There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. Methods: From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. Results: The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 ± 2.3 months compared with 23.4 ± 14.9, 12.2 ± 8.5, and 6.6 ± 4.3 months in Groups 1, 2, and 3, respectively. Conclusions: This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts. [ABSTRACT FROM AUTHOR]

Heme-oxygenase-1 (HO-1), an important enzyme involved in vascular disease, transplantation, and inflammation, catalyzes the degradation of heme into carbon monoxide and biliverdin. It has been reported that overexpression of HO-1 inhibits osteoclastogenesis. However, the effect of HO-1 on osteoblast differentiation is still not clear. We here used adenoviral vector expressing recombinant human HO-1 and HO-1 inducer hemin to study the effects of HO-1 in primary cultured osteoblasts. The results showed that induction of HO-1 inhibited the maturation of osteoblasts including mineralized bone nodule formation, alkaline phosphatase activity and decreased mRNA expression of several differentiation markers such as alkaline phosphatase, osteocalcin, and RUNX2. Furthermore, downstream products of HO-1, bilirubin, carbon monoxide, and iron, are involved in the inhibitory action of HO-1. HO-1 can be induced by H2O2, lipopolysaccharide and inflammatory cytokines such as TNF-α and IL-1β in osteoblasts and also in STZ-induced diabetic mice. In addition, endogenous PPARγ ligand, 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2) markedly increased both mRNA and protein levels of HO-1 in osteoblasts via PI3K-Akt and MAPK pathways. Blockade of HO activity by ZnPP IX antagonized the inhibitory action on osteocalcin expression by hemin and 15d-PGJ2. Our results indicate that upregulation of HO-1 inhibits the maturation of osteoblasts and HO-1 may be involved in oxidative- or inflammation-induced bone loss. J. Cell. Physiol. 222: 757–768, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the effects of non-weight-bearing exercise on growing bone. Male Wistar rats (7 week-old) were assigned to one baseline control group, one control group and two swimming training groups, which were trained with 2 and 4% body-weight mass added, respectively. After an 8-week training period, three groups showed significant development compared to the baseline control group. Among the three 15-week-old groups, swimming-trained rats were lower in body weight (BW), densitometry and size-related measurements. In femoral biomechanical testing, swimming training groups were significantly lower in yield moment and ultimate moment, which may be due to a significantly lower long bone cross-sectional moment of inertia. However, the two swimming groups were higher in post-yield energy absorption and displacement. Further, in estimated tissue-level biomaterial properties, no differences were shown in yield stress, strain or toughness among the three groups. Using BW as a covariate, results of ANCOVA showed no differences in size-related parameters among the three groups, and some parameters were even higher in the two swimming groups. Regarding Pearson’s correlation, size-related parameters correlated well to BW and whole bone strength but not to tissue post-yield behaviors. In conclusion, when compared to age-matched control group, swimming rats showed lower bone strength and lower yield energy absolutely at the structural level, but similar yield stress and yield toughness at the tissue level. Moreover, swimming training benefited growing bone in post-yield behaviors. Further studies should investigate the parameters that contribute to this exercise-induced post-yield behavior. [ABSTRACT FROM AUTHOR]

Sarcomatoid hepatocellular carcinoma (HCC) is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum a-fetoprotein level was never elevated beyond normal limit (< 20 ng/mL) through the whole course of treatment. We considered sarcomatoid hepatocellular carcinoma bone metastasis a highly aggressive lesion with unusual metastatic pattern. Surgical treatment with adequate safe margin in such a huge tumor with hypervascularity and extensive invasion in the pelvis was difficult; and radiotherapy maybe refractory regarding the sarcomatous nature. Therefore, debulking operation with local symptoms control may provide a better quality of life. And the clinical course suggests sarcomatoid hepatocellular carcinoma is derived from the transition of an ordinary hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possible prognostic factors of survival outcomes in patients with granulocytic sarcoma (GS). Methods: We retrospectively investigated the prognostic factors determining survival in 24 patients with GS using Kaplan-Meier survival analysis followed by log rank tests. We evaluated gender, age, location, GS antedating leukemia, underlying disorders, treatment type and stem cell transplantation. Results: The 5-year survival rate for the patients with GS was 21%. The patients undergoing chemotherapy had a significantly longer survival time compared to those who did not (p = 0.0009). We found no difference in the 5-year survival rate among the patients undergoing chemotherapy combined with radiation or surgery. Patients with chronic myelogenous leukemia and myelodysplastic disorders had worse survival rates (p = 0.0028). Conclusion: Early diagnosis with biopsy and early chemotherapy can improve survival outcome. Local radiation or surgery can improve symptoms but does not influence survival outcomes. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of exercise therapy on quality of life in postmenopausal women with osteoporosis or osteopenia. Methods: We searched MEDLINE, CINAHL, PEDro, EMBASE and the Cochrane library from January 1966 to March 2007. Two reviewers independently selected all studies that met predetermined inclusion criteria. Randomized controlled trials that used the Short Form 36 of the Medical Outcome Study (SF-36) questionnaire or the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) as outcome measures were selected. The PEDro Scale was applied to rate the quality of each article. All studies had a quality score above 5/10. Meta-analysis was facilitated by RevMan 4.1. Results: Four randomized controlled trials met the inclusion criteria, involving a total of 256 participants. Results revealed that the exercise groups showed significant improvements in the domains of physical function, pain, role physical and vitality (P<0.05). Furthermore, intervention with combined exercise programmes had better effects on physical function, pain and vitality domains than controls. Group exercise programmes also produced better results in these three domains. A short-duration exercise programme produced more improvement in physical function, role physical and vitality, whereas a long-duration exercise programme resulted in more improvement in physical function and pain domains. Conclusions: This meta-analysis revealed better improvement in physical function, pain, role physical and vitality in the exercise groups. Combined exercise and group exercise programmes showed better outcomes in the physical function, pain and vitality domains, but different durations of exercise programme showed improvement in different domains. [ABSTRACT FROM AUTHOR]

Background: The author intended to clarify the therapeutic effect and prognostic factors of metastasectomy and timing of pulmonary metastases in osteosarcoma patents. Methods: Data was obtained retrospectively on all consecutive osteosarcoma patients from 1985 to 2005 in author's institute. Fifty-two patients with pulmonary nodules were identified, including 24 patients undergoing pulmonary metastasectomy treatment. These patients were categorized into four groups: group 1, patients with lung metastases at the initial presentation; group 2, lung metastases identified during the period of pre-operative chemotherapy; group 3, lung metastases identified during period of the post-operative chemotherapy; group 4, lung metastases identified after therapy for the primary osteosarcoma completed. Results: In our study, the 2-, 3-, and 5-year overall survival rates for 52 patients were 49%, 39% and 20%. The 2-year overall survival rates were 18% for group 1, 32% for group 3, and 70% for group 4 (p < 0.001). The 5-year overall survival rate was 34% for group 4. Patients who underwent metastesectomy showed a better survival outcome as compared with the patients not undergoing metastasectomy (p = 0.003). The 2-year and 5-year overall survival rates of only one lung metastatic nodule were 62% and 50%, and for initially multiple lung metastatic nodules, 45% and 5%, respectively. In addition, the patients presented with lung metastases had a worse prognosis as compared with those without initial lung metastases (p = 0.0001). Conclusions: The patients having single metastatic nodule showed a better prognosis than those with multiple lung nodules. Furthermore, those patients who underwent metastasectomy survived longer than those not undergoing metastasectomy. Patients who had late metastases after complete chemotherapy had a better prognosis; whereas those who had metastases identified at the initial presentation predicted a poor prognosis. [ABSTRACT FROM AUTHOR]

Abstract  This study investigated the effects of endurance running training on the bones of growing rats. Thirty-two male Wistar rats (7 weeks old) were assigned to a sedentary control group (CON, n = 10), a continuous endurance running group (CEN, n = 10), or an intermittent endurance running group (IEN, n = 12). After an 8-week training period, both exercise groups had significantly less body weight (BW) gain but higher aerobic capacity, shown by increased muscle citrate synthase (CS) activity. Bone area (BA), areal bone mineral density (aBMD), and bone mineral content (BMC) were measured by dual-energy Xray absorptiometry (DXA) in the total femur and sections of femora. Except for showing a significantly higher aBMD in total femora, the CON group was only slightly and nonsignificantly higher in other DXA measurements. In tissue weight measurements, the CON group showed a nonsignificantly higher tissue dry weight (P = 0.146), but a significantly lower tissue water content ratio (WCR, %) as compared to the exercise group. Despite having nonsignificantly lower long bone cross-sectional parameters, both exercise groups showed significantly better biomaterial properties, as measured by a three-point bending test. In extrinsic analysis, femora of the two exercise groups showed no difference in bending load and stiffness, but were significantly higher in post-yield bending energy and total ultimate bending energy (P P [ABSTRACT FROM AUTHOR]

We invented a standardization method to measure the cup's anteversion after total hip arthroplasty without the influence of patient's position. We measured 68 radiographs of 10 patients after total hip replacement (THR) and calculated the error of each measurement, defined as the difference with the average of the same measuring method on the same patient. We also calculated the repeatability standard deviation (RSD) of each method according to the American Society for Testing and Materials, ASTM E691. Mean absolute inter-examination angle error, defined as the average of the absolute deviations, was 0.75° for standardized anteversion (range 0.03-2.51°), as compared with those without standardization, 2.30° (range 0.04-13.04°). The inter-examination measurement reliability (precision), defined as one RSD, was 0.99° for standardized anteversion, as compared with those without standarization, 3.50°. There is no difference between patients four and five without (p = 0.097). There is a significant difference with standardization (p < 0.0001). Our study demonstrated that this mathematical method is a precise tool to measure the anteversion of the acetabular cup. We hope that it can be used widely in the future. [ABSTRACT FROM AUTHOR]

The article examines how osteoblast-derived TGF-ß1 stimulates IL-8 release through AP-1 and NF-kB in human cancer cells. The scientists' purpose for this research paper was to examine whether osteoblast-derived TGF-ß1 is associated with osteolytic bone diseases. Chemokine interleukin (IL)-8 mRNA levels were measured using RT-PCR analysis.

Objective: To investigate the effects of a sensorimotor training programme in osteoarthritic patients. Design: Randomized, single-blind, controlled trial. Setting: Kinesiology laboratory at School of Physical Therapy. Participants: A total of 60 patients were randomly assigned to the training group and the control group. Only 29 patients (training group, 15; control group, 14) completed the study. Intervention: The training group underwent a sensorimotor training programme using a sling suspension system complemented by a routine physical therapy. The control group underwent a routine physical therapy. Main measures: Active joint repositioning, functional testings, and self-reported function with the Western Ontario & McMaster Universities Arthritis Index before and after the eight-week intervention. Results: There were significant differences between the two groups with respect to the improvement in proprioception as measured by active joint repositioning (the changes in the absolute error were 1.9 ± 1.7°, training group versus 0.1 ± 2.8°, control group (P<0.05), and in self-reported functional difficulty (33.2 ± 35.1, training group versus 8.0 ± 10.2, control group; P<0.05)). There was no significant difference between the two groups in other outcomes. Conclusion: A sensorimotor training using a sling suspension system improved the patients' proprioception in the knee joints and their self-reported function. Thus, these exercises may serve as an exercise programme for patients with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

It has been shown that ultrasound (US) stimulation accelerates fracture healing, bone maturation, and remodeling in the animal models and in clinical studies. One of the major factor involves in remodeling process is matrix metalloproteinases (MMPs) such as MMP-13 that has been shown to degrade the native interstitial collagens in several tissues. Here we found that US stimulation increased the secretion of MMP-13 in cultured rat osteoblasts, as shown by zymographic analysis. US stimulation also increased the mRNA level of MMP-13, c-Fos, and c-Jun. Cycloheximide (an inhibitor of protein translocation) and actinomycin D (an inhibitor of gene transcription) did not inhibit the MMP-13, c-Fos, and c-Jun mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. p38 inhibitor, SB203580 or JNK inhibitor, SP600125 but not ERK inhibitor, PD98059 attenuated the US-induced MMP-13, c-Fos, and c-Jun expression; these results were further substantiated by transfecting with the dominant negative mutants of p38 or JNK. The binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter and the enhancement of AP-1 luciferase activity was enhanced by US stimulation. Taken together, our results provide evidence that US stimulation increases MMP-13 expression through p38 and JNK signaling pathway to regulate bone remodeling. J. Cell. Physiol. 215: 356–365, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf ) is a grass crop, which has been used in traditional Chinese medicine and also as a nourishing food. Recently, some studies have indicated that adlay possesses some pharmacological effects including anti-allergic, anti-mutagenic, hypolipemic, and anti-diabetic effects. However, the effect of adlay on osteoporosis is still unknown. In this study, we investigated and evaluated the effect of adlay seed on the osteoporosis prevention. The methods of in vitro cultures of neonatal rat calvaria tissues or adult rat femoral metaphyseal tissues of bones isolated from normal or ovariectomized female rats were used for further investigation. Treatment with water extract of adlay seed could reverse the decreased alkaline phosphatase activities and calcium levels and increased tartrate-resistant acidic phosphatase activities induced by parathyroid hormone in cultured metaphyseal tissues. In ovariectomized rats, the alkaline phosphatase activities and calcium levels were significantly decreased and tartrate-resistant acidic phosphatase activities were increased in femoral metaphyseal tissues as compared with sham-control. Treatment with water extract of adlay seed could counteract these effects in ovariectomized rats. Taken together, these findings imply that adlay is capable of reversing the osteoporotic status in rats, and may be a helpful healthy food for osteoporosis prevention. [ABSTRACT FROM AUTHOR]

Background: Жobeljić et al. recently reported a numeric table method to provide precise rotational osteotomy which is a well established orthopaedic procedure. The numeric table requires four pages in length that is rather inconvenient during performing an osteotomy operation. Methods: We thus develop our own method by summarizing the data of the four-page table into a small ruler, which is easy to carry and use in operation room. An electrical version of this ruler is also available. We also build a computer model to verify Жobeljić et al. method. Results: The error of Жobeljić et al. is between -37% to 16% (mean ± SD = -6% ± 9%). We verify our ruler by calculating the absolute difference between our method and that of Жobeljić et al. The difference is less than 0.1 mm. Conclusion: Our ruler is convenient for practical use for the rotational osteotomy procedure with equal precision. Further clinical verification is needed to justify its real significance. [ABSTRACT FROM AUTHOR]

No previous investigation has explored preventive behaviors among women with First-Degree Relatives (FDRs) diagnosed with osteoporosis, particularly Asian women. This study investigates osteoporosis knowledge, health beliefs and preventive behaviors of women with a family history of osteoporosis, and the different knowledge and health beliefs regarding preventive behaviors of women with such a history. Women were recruited at a large public health center in northern Taiwan. A questionnaire was administered to women with FDRs with osteoporosis with a focus on osteoporosis knowledge, health beliefs and preventive behaviors. Descriptive analysis was initially conducted. Correlation and differences between demographics, knowledge, health beliefs and preventive behaviors were rated for continuous variables, and the χ⊃2 test was performed for categorical variables. A total of 251 who women satisfied the sampling criteria were invited to engage in the study. Two hundred and one women agreed to take part in the study, and the participation rate was around 80%. This work stresses the insufficiency of information on osteoporosis, constraining beliefs and ignorance of healthy preventive behaviors among women with FDRs with osteoporosis. Overall, the likelihood that women would take positive preventive behaviors is associated with their demographics and knowledge. The variables most strongly correlated with preventive behaviors for community-dwelling women are, in order, knowledge, number of children, educational level, knowledge of osteoporosis, experience of bone density examination, and whether or not women believed they had kyphosis. The results of this work can be applied to provide effective implementation guidelines for preventing osteoporosis, especially for women with a family history of the disease. [ABSTRACT FROM AUTHOR]

Long-term exposure to particulate air pollution has been implicated as a risk factor for cardiovascular disease and mortality. Short-term exposure has also been suggested to contribute to complications of atherosclerosis. Aberrant regulation of smooth muscle cell proliferation is thought to associate with the pathophysiology of vascular disorders such as atherosclerosis. In this study, we investigate the influence of organic extracts of motorcycle exhaust particulates (MEPE) on rat vascular smooth muscle cell (VSMC) proliferation and related regulation signaling. Exposure of VSMCs to MEPE (10–100 µg/mL) enhanced serum-induced VSMC proliferation. The expression of proliferating cell nuclear antigen (PCNA) was also enhanced in the presence of MEPE. VSMCs treated with MEPE induced the increase in the extent of cyclooxygenase (COX)-2 mRNA and protein expression and prostaglandin E 2production, whereas the level of COX-1 protein was unchanged. Moreover, MEPE increased the production of reactive oxygen species (ROS) in VSMCs in a dose-dependent manner. MEPE could also trigger time-dependently extracellular signal-regulated kinase (ERK)1/2 phosphorylation in VSMCs, which was attenuated by antioxidants N-acetylcysteine (NAC) and pyrrolidinedithiocarbamate (PDTC). The level of translocation of nuclear factor (NF)-κB-p65 in the nuclei of VSMCs was also increased under MEPE exposure. The potentiating effect of MEPE on serum-induced VSMC proliferation could be abolished by COX-2 selective inhibitor NS-398, specific ERK inhibitor PD98059, and antioxidants NAC and PDTC. Taken together, these findings suggest that MEPE may contribute to the enhancement of the pathogenesis of cardiovascular diseases by augmenting proliferation of VSMCs through a ROS-regulated ERK1/2-activated COX-2 signaling pathway. [ABSTRACT FROM AUTHOR]

Fibronectin (Fn) is involved in early stages of bone formation and basic fibroblast growth factor (bFGF) is an important factor regulating osteogenesis. bFGF increased Fn expression, which was attenuated by phosphatidylinositol phospholipase inhibitor (U73122), protein kinase C inhibitor (GF109203X), Src inhibitor (PP2), NF-κB inhibitor (PDTC), IκBα phosphorylation inhibitor (Bay 117082), or IκB protease inhibitor (TPCK). bFGF-induced increase of Fn-luciferase activity was antagonized by cells transfected with Fn construct without NF-κB regulatory site. Stimulation of osteoblasts with bFGF activated IκB kinase α/β (IKK α/β) and increased IκBα phosphorylation, IκBα degradation, p65 and p50 translocation from the cytosol to the nucleus, the formation of an NF-κB-specific DNA-protein complex and κB-luciferase activity. bFGF-mediated an increase of IKKα/β activity and DNA-binding activity was inhibited by U73122, GF109203X, or PP2. The binding of p65 to the NF-κB element, as well as the recruitment of p300 and the enhancement of p50 acetylation on the Fn promoter was enhanced by bFGF. Overexpression of constitutively active FGF receptor 2 (FGFR2) increased Fn-luciferase activity, which was inhibited by co-transfection with dominant negative (DN) mutants of PLCγ2, PKCα, c-Src, IKKα, or IKKβ. Our results suggest that bFGF increased Fn expression in rat osteoblasts via the FGFR2/PLCγ2/PKCα/c-Src/NF-κB signaling pathway. J. Cell. Physiol. 211: 45–55, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Malignant melanoma occurs infrequently in Taiwan. Once it has progressed into osseous metastases, the prognosis is poor. There are no reported clinical experiences of surgical management in this area. Methods: To improve our understanding of the rare clinical experiences, we retrospectively investigated clinical characteristics, radiological findings, treatment modalities, survival outcomes and prognoses of 11 Taiwanese patients with osseous metastasis of melanoma treated surgically at two national medical centers, National Taiwan University Hospital and National Cheng Kung University Hospital from January 1983 to December 2006. Results: Six patients suffered from acral-lentiginous melanoma. Nine patients sustained multiple osseous metastases and most lesions were osteolytic. Nine patients also had sustained metastases to other organs including liver, lungs, lymph nodes, brain and spleen. Second malignancies including lung cancer, thyroid papillary carcinoma, renal cell carcinoma and cervical cancer co-existed in four patients. The interval from the initial diagnosis of melanoma to the clinical detection of osseous metastases varied from 0-37.8 months (mean 9.75 months). Metastatic melanoma was invariably fatal; the mean survival time from bone metastases to death was 5.67 months. Conclusion: Due to the high morbidity and poor survival of Taiwanese patients with osseous metastases of melanoma, surgical treatment should be directed towards pain relief and the prevention of skeletal debilitation in order to maintain their quality of life. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: OBJECTIVE.: To investigate the effects of biologic age, as well as chronologic age, on the vertebral ultimate load (strength) and risk score of vertebral fracture (Φ) between the genders.SUMMARY OF BACKGROUND DATA.: Previous studies have shown a good correlation between the biomechanical strength of vertebral bodies and measured bone mineral parameters, whereas other factors also contribute to the bone strength and risk of fractures. Combining multiple factors into a single assessment may provide more comprehensive and individualized estimations of the fracture risk. In this study, we applied the measured bone mineral content (BMC) and bone projection area of the second through the fourth lumbar vertebrae (L2–L4) to assess the biomechanical strength of lumbar vertebrae. In addition, we used the body segment model to estimate the load of the L3 vertebral body during a bending-forward activity, to then estimate the risk score (Φ) of vertebral compression fracture in healthy Chinese volunteers in Taiwan, and to analyze the effects of gender and age on the risk score (Φ).METHODS.: A total of 611 females and 235 males aged 22–80 years were included in this study. The anteroposterior BMC and projection area of lumbar spine were measured by a Norland XR-26 dual energy radiograph absorptiometer (Norland Corp., Ft. Atkinson, WI). The estimated ultimate strength (L) of lumbar spine was calculated from the regression equation using anteroposterior lumbar BMC and bone area according to Bassman et al (Paper presented at: 39th Annual Meeting of Orthopedic Research Society; February 1993; San Francisco, CA). The estimated spinal load (F) for a person bending over with back horizontal, either with hand free (F0), lifting a 20 kg weight (F20), or a 30 kg weight (F30), was calculated from a force diagram according to William and Lissner. Risk score (Φ) was defined as the quotient of F/L.RESULTS.: The results showed an age-related decrease of bone mineral density (P < 0.001) in both genders corrected for weight and height. Using the multiple linear regression analysis and analysis of covariance, Φ for F0, F20, and F30 increased significantly, with increasing age only in females (P < 0.0001), especially after menopause, but not in males. The Φ of postmenopausal females was significantly larger than those of younger females (i.e., F0 (Φ) 0.533 ± 0.075 vs. 0.458 ± 0.064, P < 0.001; F20 (Φ) 0.903 ± 0.101 vs. 0.789 ± 0.080, P < 0.001; and F30 (Φ) 1.087 ± 0.117 vs. 0.954 ± 0.090, respectively, P < 0.001). In females, the ultimate load of the spine and Φ began to decrease to a significant level since the fifth decade, whereas in the males, the similar trends occurred since the sixth decade. Comparing both genders, the F0 (Φ) was slightly yet significantly larger in the young males (<50 years) than the premenopausal females with similar ages (P < 0.001), but older females had higher F0 (Φ) values than males older than 60 years. Moreover, the Φ increased more prominently in the postmenopausal females with the weight lifted. As a result, both F20 (Φ) and F30 (Φ) were significantly larger in females older than 50 years as compared to males with the similar ages (P < 0.001).CONCLUSIONS.: Our findings emphasize the importance of Φ, which considers BMC, bone size, body weight, body height, and weight lifted, for evaluating a more individualized risk of spine fracture in elderly men and postmenopausal women. The Φ increased more prominently with lifting weight and increased with aging only in the early postmenopausal females. The study showed that a combination of bone mass and anthropometric parameters provides a more individualized assessment of fracture risk than bone mineral density alone. [ABSTRACT FROM AUTHOR]

Fibronectin (Fn) is involved in the early stages of bone formation, and prostaglandin E (PGE) is an important factor regulating osteogenesis. Here we found that PGE2 enhanced extracellular Fn assembly in rat primary osteoblasts, as shown by immimofluorescence staining and enzyme-linked immunosorbent assay. PGE2 also increased the protein levels of Fn by using Western blotting analysis. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptor, antisense oligonucleotides revealed that the EP1 receptor but not other PGE receptors is involved in PGE2-mediated up-regulation of Fn. At the mechanistic level, Ca2+ chelator (1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester)), phosphatidylinositol-phosphalipase C inhibitor (U73122), or Sre inhibitor (PP2) attenuated the PGE2-induced Fn expression. Protein kinase C (PKC) inhibitor (GF109203X) also inhibited the potentiating action of PGE2 Furthermore, treatment with antisense oligonucleotides of various PKC isoform& including ɑ, β, ∈ and δ, demonstrated that ɑ isozyme plays an important role in the enhancement action of PGE2 on Fn assembly. Flow cytometry and reverse transcription-PCR showed that PGE2 and 17-phenyl trinor PGE2 (EP1/EP3 agonist) increased the surface expression and mRNA level of ɑ5 or β1 integrins. Fn promoter activity was enhanced by PGE2 and 17-phenyl trinor PGE2 in cells transfected with pGL2F1900-Luc. Cotransfection with dominant negative mutants of PKCɑ or c-Src inhibited the potentiating action of PGE2 on Fn pro-rooter activity. Local administration of PGE2 or 17-phenyl trinor PGE2 into the metaphysis of the tibia via the implantation of a needle cannula significantly increased the Fn and ɑ5β1 integrin immunostaining and bone volume of secondary spongiosa in tibia. Taken together, our results provided evidence that PGE2 increased Fn and promoted bone formation in rat osteoblasts via the EP1/phospholipase C/PKCɑ/c-Src signaling pathway. [ABSTRACT FROM AUTHOR]

We have found that the concentration of titanium (Ti) in the blood of patients with loosened Ti-alloy prostheses is elevated. An increase in the levels of elemental Ti in the blood and lung tissues of rats with an alloyed-Ti implant also has been found. The cellular reaction to elevated elemental Ti in the circulation remains unclear. We further performed experiments to examine the changes of inducible nitric oxide synthase (iNOS) expression in alveolar macrophages from alloyed-Ti-implanted rats. The elevation of nitrite and iNOS expression induced by lipopolysaccharide (LPS) was suppressed. The in vitro effect of a soluble form of Ti was further investigated. Ti (0.01–0.06 mM) inhibited the LPS-induced nitrite production and iNOS expression in alveolar macrophages from normal rats without any cytotoxic effects. LPS induced protein tyrosine phosphorylation, tyrosine-phosphorylation of lyn (a CD14-receptor-associated-tyrosine kinase), and degradation of IκB-α protein (inhibitor of NF-κB) in alveolar macrophages. These events were inhibited by co-incubation with Ti. These results indicate that elemental Ti may impair iNOS expression in alveolar macrophages through the alteration of protein tyrosine phosphorylation and NF-κB activation. The inhibitory action of Ti on cellular responses of alveolar macrophages may be anti-inflammatory and thus may depress local defense mechanisms related to microbial killing. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 802–810, 2003 [ABSTRACT FROM AUTHOR]

Lung caner cells have a striking tendency to metastasize to bone. The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively secreted by osteoblasts and bone marrow stromal cells and plays a key role for homing of hematopoietic cells to the bone marrow. Reverse transcriptase–polymerase chain reaction and flow cytometry studies demonstrated SDF-1 receptor (CXCR4) messenger RNA (mRNA) and surface expression of CXCR4 in lung cancer cell lines, especially higher in those with high invasiveness (A549) as compared with lower level in H928 cells and H1299 cells. SDF-1, osteoblast-conditioned medium (OBCM) and stromal cell-conditioned medium all induced the invasiveness of lung cancer cells. Matrix metalloproteinase (MMP)-9 small interfering RNA inhibited the SDF-1α- or OBCM-induced MMP-9 expression and thereby significantly inhibited the SDF-1α- or OBCM-induced cell invasion. Furthermore, mitogen-activated protein kinase kinase inhibitor PD98059 suppressed SDF-1α-induced MMP-9 mRNA expression. Transient transfection with dominant-negative extracellular signal-regulated kinase (ERK) mutant also showed that the ERK-signaling pathway was involved in SDF-1α-induced MMP-9 expression. Moreover, nuclear factor-κB (NF-κB) decoy oligodeoxynucleotide suppressed the MMP-9 promoter activity enhanced by SDF-1α. Both mitogen-activated protein kinase kinase inhibitor and ERK mutant also antagonized SDF-1α-induced NF-κB-driven luciferase promoter activity. Taken together, our results indicated that bone marrow-derived-SDF-1α enhances the invasiveness of lung cancer cells by increasing MMP-9 expression through the CXCR4/ERK/NF-κB signal transduction pathway. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effects of a mechanical loading course (short-term free-fall landing) on femoral geometry and biomechanical properties in growing rats. Thirty-two female Wistar rats (7-week-old) were randomly assigned to three groups: L30 (n = 11), L10 (n = 11) and CON (n = 10) groups. Animals in the L10 and L30 groups were subjected to a 5-day free-fall landing program in which animals were dropped from a height of 40cm 10 and 30 times per day, respectively. Landing ground reaction force (GRF) was measured on the 1st and 5th days of landing training. All animals were subjected to two fluorescent labeling injections on the days before and after the 5-day landing training. Three days after the last labeling injection, animals were sacrificed under deep anesthesia. Methods of dynamic histomorphometry, tissue geometry and tissue biomechanical measurements were used to investigate the response in femora. A significant decrease in peak GRF in the hind-limb was shown from day 1 to day 5. No significant difference was shown among groups in dynamic histomorphometry. Biomechanical property analyses showed significantly lower maximal energy and post-yield energy in the L10 and L30 groups as compared to the CON group (p < 0.05). Moreover, geometric measurements revealed that crosssectional cortical areas and thicknesses were significantly lower in landing groups than in the CON group. Short-term (5-day) free-fall landing training resulted in minor compromised long bone tissue, as shown by reduced bending energy and cortical bone area but not in other mechanical properties or tissue measurements (e.g. weights and length) of growing female rats. Further studies would be valuable to investigate whether this compromised bone material represents the existence of a latency period in the adaptation of bone material to external mechanical loading. [ABSTRACT FROM AUTHOR]

It has been shown that ultrasound (US) stimulation accelerates fracture healing in the animal models and clinical studies. Nitric oxide (NO) is a crucial early mediator in mechanically induced bone formation. Here we found that US stimulation increased NO formation and the protein level of inducible nitric-oxide synthase (iNOS). US-mediated iNOS expression was attenuated by anti-integrin αvβ3 or β1 antibodies but not anti-integrin αvβ3 or β3 antibodies or focal adhesion kinase mutant. Integrin-linked kinase (ILK) inhibitor (KP-392), Akt inhibitor (1L-6-hydroxymethyl-chiro-inositol-2-[(R)-2-O-methyl-3-O-octadecylcarbonate]) or mammalian target of rapamycin (mTOR) inhibitor (rapamycin) also inhibited the potentiating action of US. US stimulation increased the kinase activity of ILK and phosphorylation of Akt and mTOR. Furthermore, US stimulation also increased the stability and activity of HIF-l protein. The binding of HIF-la to the HRE elements on the iNOS promoter was enhanced by US stimulation. Moreover, the use of pharmacological inhibitors or genetic inhibition revealed that both ILK/Akt and mTOR signaling pathway were potentially required for US-induced HIP-la activation and subsequent iNOS up-regulation. Taken together, our results provide evidence that US stimulation up-regulates iNOS expression in osteoblasts by an HIF-lα-dependent mechanism involving the activation of ILK/Akt and mTOR pathways via integrin receptor. [ABSTRACT FROM AUTHOR]

Decoy receptor 3 (DcR3), a soluble receptor for FasL, LIGHT, and TL1A, induces osteoclast formation from monocyte, macrophage, and bone stromal marrow cells. However, the function of DcR3 on bone formation remains largely unknown. To understand the function of DcR3 in bone formation in vivo, transgenic mice overexpressing DcR3 were generated. Bone mineral density (BMD) and bone mineral content (BMC) of total body were significantly lower in DcR3 transgenic mice as compared with wild-type controls. The difference in BMD and BMC between DcR3 transgenic and control mice was confirmed by histomorphometric analysis, which showed a 35.7% decrease in trabecular bone volume in DcR3 transgenic mice in comparison with wild-type controls. The number of osteoclasts increased in DcR3 transgenic mice. In addition, local administration of DcR3 (30 µg/ml, 10 µl, once/day) into the metaphysis of the tibia via the implantation of a needle cannula significantly decreased the BMD, BMC, and bone volume of secondary spongiosa in tibia. Local injection of DcR3 also increased osteoclast numbers around trabecular bone in tibia. Furthermore, coadminstration of soluble tumor necrosis factor receptor inhibitor/Fc chimera (TNFRSF1A) but not osteoprotegerin inhibited the action of DcR3. In addition, in an assay of osteoclast activity on substrate plates, DcR3 significantly increased the resorption activity of mature osteoclasts. Treatment with higher concentrations of DcR3 slightly increased nodule formation and alkaline phosphatase activity of primary cultured osteoblasts. These results indicate that DcR3 may play an important role in osteoporosis or other bone diseases. [ABSTRACT FROM AUTHOR]