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The aims of the present study were to clarify whether postmenopausal women with osteoarthritis (OA) of the knee show higher bone mineral density (BMD) than healthy controls, and to investigate the relationship between BMD and the Kellgren and Lawrence radiological grade in postmenopausal women with OA of the knee. A total of 674 postmenopausal women, 46–90 years of age, were enrolled in the study: 305 patients with OA of the knee and 369 healthy controls. Forearm (distal radius) BMD, measured by dual-energy X-ray absorptionetry (DXA), using a DTX-200 (Osteometer), was significantly higher in the OA group than in the control group (P < 0.001), even when adjusted for age, height, body weight, body mass index, years since menopause, and grip strength (P < 0.01). Analysis of variance (ANOVA) with Fisher's protected least significant difference (PLSD) test showed that BMD in radiological grades 2, 3, and 4 was significantly higher than that in grade 1 (P < 0.05, P < 0.001, and P < 0.05, respectively), and BMD in grade 3 was significantly higher than that in grade 2 (P < 0.01), but BMD in grade 4 was significantly lower than that in grade 3 (P < 0.05). These findings suggest that forearm BMD appears to be significantly higher in postmenopausal women with OA of the knee than in healthy controls. Although BMD may be increased in low to moderate radiological grades of OA, severe grade OA may not always develop from moderate grade OA. Some cases of severe grade OA may be associated with low BMD.

Platinum nanoparticles (Pt NPs) have been selectively anchored by photodeposition on titanium oxide (TiO2) matrix which is formed by hydrolysis of titanium isopropoxide on cup–stacked carbon nanotubes (CSCNT) in isopropanol, producing the composite Pt catalyst useful for oxygen reduction reaction (ORR) in acidic media, i.e., Pt NPs/TiO2/CSCNT. Using scanning transmission electron microscopy (STEM) with a high–angle annular–dark–field (HAADF) detector it has been clarified that Pt NPs are sunk into the TiO2 moieties and have the unique polyhedral shape surrounded mainly by the Pt (1 1 1) and Pt (1 0 0) facets. X–ray photoelectron spectroscopy (XPS) allowed us to confirm changes in electronic properties of both Pt NPs and TiO2 support, induced by the so-called strong metal–support interactions (SMSI) and the significantly increased ORR activity was attained in 0.1 M HClO4, compared with the Pt NPs deposited on CB (Vulcan carbon) and CSCNT. The surface structure of the Pt NPs was characterized by transmission electron microscopy (TEM), indicating the improved durability of the Pt NPs deposited on the TiO2/CSCNT, i.e., the only slight increase in the particle size after the durability test (typically 2000 times’ potential cycling at 10 mV s-1 in the potential ranges of 0.05 to 1.1 V and 1.0 to 1.5 V vs. RHE in 0.1 M HClO4). The results obtained demonstrate that the anchoring of Pt NPs on the TiO2 support material deposited on CSCNT is an effective way to enhance the ORR activity of Pt NPs by the SMSI as well as to prohibit Pt NPs from aggregating, i.e., the degradation of the ORR activity of Pt NPs.

The aim of the present review was to clarify the efficacy of currently available potent antiresorptive agents for preventing fractures in Japanese patients with an increased fracture risk. PubMed was used to search the literature for randomized controlled trials (RCTs), with the following search terms: fracture, etidronate, alendronate, risedronate, minodronate, raloxifene, bazedoxifene and Japan. The inclusion criteria were papers written in English, ≥50 subjects per group and a study period of ≥1 year. Fourteen RCTs met these criteria. The efficacy of antiresorptive agents for preventing vertebral, nonvertebral and hip fractures was investigated. There was evidence that raloxifene reduced the incidence of clinical vertebral fractures, while etidronate, alendronate and minodronate (but not bazedoxifene) reduced the incidence of morphometric vertebral fractures in patients with postmenopausal or involutional osteoporosis. Head-to-head trials showed that alendronate and raloxifene had similar efficacy for preventing vertebral fractures in patients with postmenopausal osteoporosis, while risedronate was not inferior to etidronate for reducing the incidence of morphometric vertebral fractures in patients with involutional osteoporosis. Alendronate reduced the incidence of hip fractures in patients with Parkinson's disease, and risedronate reduced the incidence of nonvertebral fractures and hip fractures in patients with Alzheimer's disease or stroke. In conclusion, the present review confirmed the efficacy of etidronate, minodronate and raloxifene for the prevention of vertebral fractures, the efficacy of alendronate for vertebral and hip fractures, and the efficacy of risedronate for vertebral, nonvertebral and hip fractures in Japanese patients with an increased fracture risk.

Osteoporosis in cases of rheumatoid arthritis (RA) is multifactorial, and the pathogenesis of bone loss induced by RA in postmenopausal women is not fully understood. The purpose of the present study was to determine the factors that affect forearm bone mineral density (BMD) in postmenopausal women with RA. In total, 839 postmenopausal women aged 46-90 years, were enrolled in the study; 470 patients with RA and 369 healthy controls (CON). Forearm (distal radius) BMD, measured by DXA using a DTX-200 (Osteometer, MediTech, CA, USA), was significantly lower in the RA group than in the CON group (P < 0.0001), even when adjusted for age, height, body weight, body mass index, and years since menopause (YSM) (P < 0.01). On multiple regression analysis, in the CON group, age and YSM were significantly correlated with BMD (P < 0.01 and P < 0.05, respectively). On the other hand, in the RA group, in addition to YSM, anatomic grade in the wrist, modified health assessment questionnaire (HAQ) score for the upper extremities, and erythrocyte sedimentation rate were each significantly correlated with BMD (P < 0.0001, P < 0.001, P < 0.0001, and P < 0.001, respectively), whereas functional class, duration of disease, dose of prednisolone used, modified HAQ score for the lower extremities, and the levels of c-reactive protein and rheumatoid factor were not. The present study with a large number of subjects shows that in addition to YSM, disuse (anatomic grade) of the wrist, arm function, and disease activity appear to be significant determinants of forearm BMD in postmenopausal women with RA.

(Nitrosyl)(salen)ruthenium(II) complex 1 was found to serve as an efficient catalyst for the epoxidation of conjugated olefins under photoirradiation, with 2,6-dichloropyridine N-oxide (2) or tetramethylpyrazine N,N'-dioxide as a stoichiometric oxidant. High enantioselectivity was achieved irrespective of the substitution pattern of olefins. The choice of solvent depends on stability of the resulting epoxides: high enantioselectivity is generally observed in the reaction with ethereal solvents, but use of benzene is recommended when the resulting epoxides are acid-sensitive.

The effect of the systemic administration of prostaglandin (PG) E(1) on physical activity and bone resorption was examined in patients with intermittent claudication (gait disturbance). Twenty male patients (age, 67.2 +/- 7.8 years; mean +/- SD) with neurogenic intermittent claudication caused by lumbar spinal canal stenosis were included in the study. Lipo-PG E(1) was administered intravenously, at a daily dose of 10 microg, on 3 days a week, for 6 months in all patients. Clinical symptoms, levels of urinary cross-linked N-telopeptides of type I collagen (NTx), and metacarpal cortical bone mineral density (BMD) were assessed before and just after the 6 months of treatment. Subjective symptoms, including leg pain and/or tingling and gait disturbance, and restrictions of the activities of daily living were significantly improved. However, no significant changes were observed in either urinary NTx levels or metacarpal cortical BMD. These findings suggest that the systemic administration of PG E(1) appears to improve subjective symptoms and activities of daily living in elderly male patients with neurogenic intermittent claudication, but does not affect either bone resorption or metacarpal cortical BMD. Short-term systemic administration of PG E(1) and increased physical activity in elderly male patients with gait disturbance caused by lumbar spinal canal stenosis may not affect bone resorption.

The aim of the present study was to investigate the relationships between physical activity and metacarpal cortical bone mineral density (BMD) and bone resorption in hemiplegic patients. Seventy-two male hemiplegic patients with cerebrovascular disease (mean age, 67.0 years; range 48–83 years) were recruited. Metacarpal cortical BMD in bilateral hands was measured by computed X-ray densitometry, and the levels of urinary cross-linked N-telopeptides of type I collagen (NTx), as a bone resorption marker, were measured by an enzyme-linked immunosorbent assay (ELISA). BMD (mean ± SD) in the paralyzed hand was significantly lower than that in the nonparalyzed hand (2.52 ± 0.46 and 2.64 ± 0.45 mmAl; P < 0.05). On multiple regression analysis, BMD was significantly positively correlated with Brunnstrom stage (assessment of degree of paralysis) in the hand (P < 0.05), whereas urinary NTx levels were significantly negatively correlated with Brunnstrom stage in the hand, arm, and leg, and with walking ability (P < 0.05, P < 0.05, P < 0.01, and P < 0.01, respectively). These findings suggest that, in male hemiplegic patients, although metacarpal cortical BMD may be affected by only local physical activity, urinary NTx appears to be responsive to local and general physical activity.

The potential of benidipine hydrochloride (BH), a 1,4-dihydropyridine calcium antagonist and a possible vasodilator, to protect against renal damage in the stroke-prone spontaneously hypertensive rat (SHR-SP) was examined using fifty-five males (10 weeks old). The animals were allotted into experiments 1 and 2, in each case subdivided into three groups (control and BH at doses of 3 and 10 mg/kg). Administration of BH was initiated before identification of clinical stroke in Experiment 1 and after its onset in Experiment 2. Measurement of body weight (BW) and systolic blood pressure (SBP) indicated that treatment of BH was associated with increased BW gain and reduced blood pressure in both experiments. Histopathological assessment revealed significant and dose-dependent decrease in the degree of fibrinoid necrosis in renal blood vessels, sclerosis, hyalinization, edematous thickening and Bowman's space dilatation in glomeruli, as well as protein casts, dilated or regenerative tubules, and interstitial inflammatory infiltration with fibrosis in tubulointerstitium in the BH treated groups as compared with the control group. These results indicated that BH exerts vasodilative effects on the kidney with improvement of regional blood flow, then preventing and ameliorating renal damage.

A modified Warthin-Starry (mWS) method was developed to stain apoptotic cells in tissue sections. Essentially the classical WS method is applied except for a minor change to prevent fading. In order to clarify the relationship between mWS-positive cells and apoptosis, apoptotic thymic tissues were examined on the rats treated with dexamethasone. The results clearly showed the distribution of mWS-positive cells to coincide well with that for apoptotic cells observed by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick end labeling (TUNEL) method. An additional characteristic is that nuclei of mitotic thymocytes, with highly condensed chromatin, are always stained. These observations suggest that the mWS method might be useful and convenient to detect condensed chromatin during apoptosis.

Objective To evaluate the existence of Epstein-Barr virus (EBV) infection in the synovial tissue of patients with rheumatoid arthritis (RA). Methods Synovial tissues were obtained at synovectomy or arthroplasty from 32 patients with RA and 30 control patients with osteoarthritis (OA). EBV DNA was detected by Southern blot hybridization and/or polymerase chain reaction (PCR) amplification. To localize the EBV-infected cells, tissue sections were studied by RNA in situ hybridization (ISH) for the EBV-encoded small RNA 1 (EBER-1), by DNA ISH for the Bam HI W region of EBV DNA, and by immunohistochemistry for EBV lytic proteins BZLF1 and gp350/220. Results EBV DNA was detected by PCR in 15 of the 32 samples from RA patients (47%), but in none of those from the 30 OA patients (P 1 EBV copy/1,000 cells (referred to as EBV 2+), and 6 contained 1 copy/1,000–5,000 cells (EBV 1+). Among the 9 EBV 2+ samples, 3 were also positive for EBV DNA by Southern blot hybridization, 5 were positive for EBER-1 by RNA ISH, and 3 were positive for EBV DNA by DNA ISH. Immunohistochemical analysis showed positive signals in all samples for BZLF1 and in 7 samples for gp350/220. In each examination, the positive signals were detected not only in lymphocytes, but also in synovial lining cells. Conclusion EBV was frequently detected in the synovial tissue of RA patients. The infected cells were both lymphocytes and synovial cells, and expressed EBV proteins associated with virus replication. These findings suggest that EBV may play a role in the pathogenesis of RA.

The cortical bone mineral density (BMD) of the first metatarsus was measured using computed x-ray densitometry in 84 hemiplegic subjects (35 men and 49 postmenopausal women) and 49 healthy age-matched controls (23 men and 26 postmenopausal women), and the determinants of paralysis-induced co

The effects of moderate intensity exercise of different duration on the cancellous and cortical bone mass of the tibia were investigated in mature ovariectomized rats by bone histomorphometry. A total of twenty 23-week-old female Wistar rats were used in this study. Ovariectomy (OV) was performed on 15 animals, and they were divided into three groups of five animals each: an OV group, an OV + exercise for 30 min a day (EX30) group and an OV + EX60 group. The other 5 animals served as a sham-operated (SH) control group. The exercise consisted of treadmill running at 16 m/min and was performed 5 days a week for 12 weeks after the operation. After 12 weeks of exercise, bone histomorphometry was used to evaluate the cancellous bone (secondary spongiosa) of the proximal tibia and the cortical bone of the tibial shaft. The OV group showed a significant decrease in cancellous bone volume, with increased resorption and formation, compared to the SH group (P < 0.01). Although the OV + EX30 group showed a significant increase in cancellous bone volume, with decreased resorption and increased osteoblastic activity, compared to the OV group (P < 0.05), cancellous bone volume in the OV + EX30 group remained significantly lower than that in the SH group (P < 0.05). There was not a significant difference in cortical bone area between the OV group and the SH group, whereas the OV + EX30 group showed a significant increase in cortical bone area, with decreased resorption on the endosteal surface, compared to the OV group (P < 0.05). There were no significant differences in cancellous bone volume or cortical bone area between the OV group and the OV + EX60 group. The data suggest that moderate intensity exercise of appropriate duration may attenuate ovariectomy-induced cancellous bone loss and increase cortical bone mass in mature ovariectomized rats.

We examined radiographs of the elbows of the pitching arms of 79 professional baseball pitchers (mean age, 25.1 years; mean duration of professional career, 4.7 years) and noted the frequency and size of spurs, bone fragments, and intra-articular loose bodies according to site. The influence of duration of professional baseball career on these osteoarthritic changes was also investigated. The olecranon tip was the most frequent site of spurs (62/79; 78.5%), and fragmentation of the spur was detected in 17 joints. The frequency of spurs was also high at the medial margin of the olecranon, the tip of the coronoid process, the medial margin of the sigmoid notch, the medial margin of the trochlea and the olecranon fossa. In 38 subjects, spurs were observed at the distal portion of the radial notch of the ulna. However, few pitchers had osteoarthritic changes in the humeral capitellum or radial head. Intra-articular loose bodies were detected in 4 of 79 joints (5.1%), and bone fragments were present below the medial humeral epicondyle in 25 of 79 joints (31.6%). Osteoarthritic changes in the elbow joint appeared to be attributable mainly to traction stress and impingement associated with extension and valgus strain. Significant osteoarthritic changes were often found in professional pitchers whose careers exceeded 5 years.

The influence of secondary damage to joint structures (menisci and articular cartilage) on return to sports activities following anterior cruciate ligament (ACL) reconstruction was investigated. Two hundred and sixty athletes who had undergone ACL reconstruction with the Leeds-Keio artificial ligament and had achieved satisfactory joint stability and range of motion were involved in this study. The follow-up period was 7–50 months (mean, 23.4 months). There was a clear correlation between the severity of damage to the joint structures (the menisci and articular cartilage) and the level of return to sports. The most common reason for not being able to return to the original level of sports activity was “pain”. Thus, it was concluded that irreversible secondary damage to joint structures was an important factor hindering return to sports after ACL reconstruction. This study showed that the incidence of meniscal injury and cartilage damage increased with the passage of time after ACL injury, and that, once meniscal injury develops, the incidence of cartilage damage increases. Since sports activity is a factor that accelerates or promotes processes that give rise to this meniscal injury and cartilage damage, it was concluded that it is vital to perform ACL reconstruction before irreversible secondary damage to joint structures occurs in athletes with ACL injuries who hope to continue their sports activities.

A microscopic technique combining spectral confocal laser scanning microscopy with a lipophilic fluorescent dye, Nile red, which can emit trans-polyisoprene specific fluorescence, was developed, and unmixed images of synthesized trans-polyisoprene in situ in Eucommia ulmoides were successfully obtained. The images showed that trans-polyisoprene was initially synthesized as granules in non-articulated laticifers that changed shape to fibers during laticifer maturation. Non-articulated laticifers are developed from single laticiferous cells, which are differentiated from surrounding parenchyma cells in the cambium. Therefore, these observations suggested that trans-polyisoprene biosynthesis first started in laticifer cells as granules and then the granules accumulated and fused in the inner space of the laticifers over time. Finally, laticifers were filled with the synthesized trans-polyisoprene, which formed a fibrous structure fitting the laticifers shape. Both trans- and cis-polyisoprene are among the most important polymers naturally produced by plants, and this microscopic technique combined with histological study should provide useful information in the fields of plant histology, bioindustry and phytochemistry.

PtPb ordered intermetallic nanoparticles (NPs) was deposited on titanium oxide (TiO2)/cup-stacked carbon nanotube (CSCNT) for improvement of the activity of the electrochemical oxygen reduction reaction (ORR). Employment of CSCNT as a support material caused high loading of PtPb NPs/TiO2. The PtPb NPs/TiO2/CSCNT which was prepared by the step-by-step preparation method; annealing under inert gas atmosphere with Ti-alkoxide for TiO2, photodeposition for Pt NPs and microwave synthesis to prepare ordered intermetallic PtPb NPs on TiO2 via the reaction of Pb2+ with Pt/TiO2, exhibited the enhancement of ORR electrocatalytic activity. Scheme 1 shows a schematic depiction of the step-by-step preparation method of PtPb NPs/TiO2/CSCNT by annealing under inert gas atmosphere with Ti-alkoxide for TiO2, photodeposition for Pt NPs and microwave synthesis to prepare ordered intermetallic PtPb NPs on TiO2 via the reaction of Pb2+ with Pt/TiO2. A commercially available CSCNT (100 nmf, Sankei Giken Kogyo Co., Ltd., Japan) was treated with an acidic mixture solution of H2SO4 (6 M) and HNO3 (6 M) at 90 °C for 6 h to introduce a carboxylic acid functional group on the surfaces and then washed with water, followed by drying overnight at 110 °C. A Ti precursor solution was prepared by dissolving Titanium (IV) isopropoxide (TTIP, 0.2 g) in iso-propanol (100 mL). Functionalized carbon was added to the solution under vigorous stirring. De-ionized water (1.0 mL) was used to accelerate the reaction of TTIP. After further stirring for 6h, the resulting mixture was collected and dried overnight under vacuum condition, followed by heat-treatment at 450 °C for 1 h under Ar atmosphere to yield CSCNT-supported TiO2 (TiO2/CSCNT). Pt NPs were photochemically deposited on TiO2/CSCNT to prepared Pt NPs/TiO2/CSCNT. The Pt NPs/TiO2/CSCNT (0.030 g) and Pb(CH3COO)2 ¥3H2O (0.022 mmol) were dissolved in 50 mL of ethylene glycol. The mixture was then sonicated in a bath-type ultrasonicator and treated in the flask with a reflux set for 1 min under 300-W microwave radiation. The mixture in the flask was cooled to room temperature with water. The mixture was again treated under microwave (focused microwave instrument, CEM) radiation of 300 W for 9 min. After the mixture cooled, the PtPb NPs/TiO2/CSCNT was collected via centrifugation, washed sequentially with methanol and dried under vacuum. Figure 1 shows linear-sweep ORR voltammograms for (a) PtPb NPs/TiO2/CSCNT and (b) Pt NPs/CB in O2-saturated 0.1 M HClO4 solution. Here, CB-supported Pt NPs (b) was used as a control. The ORR curve (a) obtained with PtPb NPs/TiO2/CSCNT shifts to the positive direction, owing to the interaction between PtPb NPs and TiO2when compared with one of Pt/CB (b). Scheme 1. Schematic representation of the step-by-step methode to prepare ordered intermetallic PtPb NPs/TiO2/CSCNT Figure 1. Linear sweep voltammograms (LSV) for ORR on (a) PtPb/TiO2/CSCNT and (b) Pt/CB in O2-saturated 0.1 M HClO4 aqueous solution at 10 mVs-1. Inset: a TEM image of PtPb/TiO2/CSCNT used to obtain the LSV. Figure 1

SUMMARY Fas antigen (CD95) is a membrane-associated molecule that mediates apoptotic cell death and may play a role in the induction and maintenance of T cell tolerance. To elucidate the involvement of Fas antigen in human autoimmune diseases, we analysed Fas antigen expression by peripheral T cells from patients with SLE and rheumatoid arthritis (RA), using three-colour flow cytometry. Both CD4+ and CD8+ T cell from SLE patients expressed Fas antigen in a higher density than did these cell from healthy donors and from RA patients. Enhancement of Fas antigen density was noted in Fas+CD45RO+ memory T cell from SLE patients. More remarkably, a significant expression of Fas antigen was observed in CD45RO− naive T cells from SLE patients CD4+CD45RO− T cells from SLE patients co-expressed Fas antigen and early to intermediate activation antigens such as CD25 and CD71, and late activation antigen HLA-DR in only FashiCD4+ naive T tells. Such up-regulation of Fas antigen expression in SLE patients seems to be clinically meaningful, because mean fluorescence intensity (MFI) of Fas antigen on CD4+ T cell subsets inversely correlates with the absolute size of CD4+ T tell subsets in peripheral blood of SLE patients. These results suggest that T cells with increased Fas antigen expression may be highly susceptible to apoptotic cell death, in vivo. A putative mechanism for lymphopenia in SLE patients is discussed.

The temporal evolution of a wave packet in electron-beam-plasma is observed experimentally. It is shown that the packet develops on electron time scales not into self-contraction but into asymmetrical widening. Particle trapping, indicated the distribution function of electron-beam, plays an important role in causing this phenomenon. When the waves in an electron-beam-plasma system are strong, nonlinear phenomena characteristi- cally appear. In regard to this phenomena, it is important to discuss solitary waves or modulation instabilities (1). A. Y. Wong et al. (2) showed experimentally a 3-D Langmuir-wave collapse of ion time scales driven by a pulsed electron-beam. T. Intrator et al. (3) reported the longitudinal self-contraction of modulationally unstable electron wave packets developing on electron time scales. We (4) showed that a wave packet can be stabilized by emitting a series of several burst waves. In order to investigate nonlinear phenomena at long distances, we introduce a new beam-plasma device, the length of which is 2 times longer than that of the previous one. In this paper, we report the nonlinear behavior of the electron time scales of the packet in plasma, induced by a low density electron-beam, and the distribution function of the electron-beam.

This study investigated the effects of both anterior-posterior position and inclination of a back plate positioned on a starting platform on swimming start performance. Ten male college swimmers performed eight starts with varying combinations of take-off angle (normal and lower), inclination angle (10 degrees, 25 degrees, 45 degrees, and 65 degrees) and position (0.29, 0.44, and 0.59 m from the front edge of the starting block). Two-way repeated measures analysis of variance (ANOVA; take-off angle x backplate) for four conditions with take-off angles (normal and lower) and inclinations (10 degrees and 45 degrees), and one-way ANOVA for comparisons between four inclinations and three positions were carried out. Multiple comparisons were made using Bonferroni's method. The main effects of the take-off angle were on the vertical and resultant take-off velocities [F(1,18) = 36.72, p0.001 and F(1,18) = 9.58, p = 0.013, respectively]. Comparisons between the plate positions showed that the 5 m time of the 0.29 m condition was significantly longer, the take-off angle and vertical take-off velocity of the 0.59 m condition were significantly lower, and horizontal and resultant take-off velocities of the 0.29 m condition were significantly less. Rear foot take-off times were significantly longer in the ascending order: 0.29, 0.44, and 0.59 m.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are well-established serological markers that show high sensitivity and specificity in early rheumatoid arthritis (RA) and are associated with bone erosions of RA. However, some patients subsequently progress to RA even if there is no presence of anti-CCP antibodies in an early stage. The aim of this study is to evaluate the diagnostic utility of matrix metalloproteinase-3 (MMP-3), high-sensitivity C-reactive protein (hsCRP) and IgM rheumatoid factor for predicting RA in anti-CCP-negative patients with recent-onset undifferentiated arthritis (UA). Baseline levels of those markers were measured at the entry of the study. A total of 99 patients with UA were included, among them 44 patients (44.4 %) had been classified as having RA by a skilled rheumatologist at some point during 1-year follow-up. Of these 99 patients, 34 patients (34.3 %) had anti-CCP antibodies and 65 patients (65.7 %) had no anti-CCP antibodies. Eleven patients who were anti-CCP-negative developed RA. We compared sensitivity, specificity, positive predictive value and negative predictive value of serum markers of these anti-CCP-negative RA patients. The combined usage of MMP-3 with hsCRP is relatively superior to other markers as predictors of RA.

A 63-year-old woman with Behçet disease presented with epigastric pain due to refractory gastric ulcers. Examinations indicated that these ulcers were caused by gastrointestinal Behçet disease. Steroid therapy proved ineffective, so we gave 5mg/kg of infliximab. However, since the patient responded poorly to the treatment the infliximab was discontinued and a total gastrectomy was performed. After surgery, a marginal ulcer developed and infliximab was again administered. Although this brought about improvement in the conditions of the marginal ulcer, infusion-related hypersensitivities in the patient caused polyarthralgia. We therefore discontinued the infliximab treatment and began 40 mg of adalimumab every other week. After 3 months of the new treatment, the patient's marginal ulcer completely healed and her epigastric pain disappeared. This case suggests that adalimumab may be as useful as infliximab for treating refractory gastrointestinal Behçet disease.

The aim of the present review was to clarify the efficacy of currently available potent antiresorptive agents for preventing fractures in Japanese patients with an increased fracture risk. PubMed was used to search the literature for randomized controlled trials (RCTs), with the following search terms: fracture, etidronate, alendronate, risedronate, minodronate, raloxifene, bazedoxifene and Japan. The inclusion criteria were papers written in English, ≥50 subjects per group and a study period of ≥1 year. Fourteen RCTs met these criteria. The efficacy of antiresorptive agents for preventing vertebral, nonvertebral and hip fractures was investigated. There was evidence that raloxifene reduced the incidence of clinical vertebral fractures, while etidronate, alendronate and minodronate (but not bazedoxifene) reduced the incidence of morphometric vertebral fractures in patients with postmenopausal or involutional osteoporosis. Head-to-head trials showed that alendronate and raloxifene had similar efficacy for preventing vertebral fractures in patients with postmenopausal osteoporosis, while risedronate was not inferior to etidronate for reducing the incidence of morphometric vertebral fractures in patients with involutional osteoporosis. Alendronate reduced the incidence of hip fractures in patients with Parkinson's disease, and risedronate reduced the incidence of nonvertebral fractures and hip fractures in patients with Alzheimer's disease or stroke. In conclusion, the present review confirmed the efficacy of etidronate, minodronate and raloxifene for the prevention of vertebral fractures, the efficacy of alendronate for vertebral and hip fractures, and the efficacy of risedronate for vertebral, nonvertebral and hip fractures in Japanese patients with an increased fracture risk.

A 57-year-old man presented with jaundice. Abdominal computed tomography showed a 10-cm left hepatic lobe heterogeneous solid mass with low attenuated areas in the mass, multiple liver metastases and lung metastasis. Serology for hepatitis B and C were negative. Serum alpha-fetoprotein, CEA and CA19-9 were normal. The patient died a few weeks later of progressive liver failure and an autopsy was performed. Histologically, the tumor consisted of sarcomatoid mononuclear cells and osteoclast-like giant cells. The liver tissue surrounding the tumor showed no cirrhotic pattern. The osteoclast-like giant cells were uniformly and strongly immunoreactive with CD68. The mononuclear cells demonstrated expression of vimentin but were negative for CAM5.2. The MIB-1 index was 20% for the mononuclear cells. In conclusion, the histopathological diagnosis revealed an osteoclast-like giant cell tumor of the liver.

Background and Objective: Chronic kidney disease is associated with an increased risk of fragility fractures. A retrospective study was conducted to compare outcomes after 3 years of alendronate treatment in postmenopausal osteoporotic Japanese women with or without renal dysfunction (RD). Methods: One hundred and thirty-five postmenopausal osteoporotic Japanese women (mean age at baseline: 68 years) who had been treated with alendronate in our outpatient clinic for more than 3 years were analysed. The lumbar spine bone mineral density (BMD) of patients was measured using dual energy x-ray absorptiometry, and urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and serum levels of alkaline phosphatase (ALP) were monitored during the 3-year treatment period. The incidence of osteoporotic fractures was also assessed. Results: Twenty-six women had RD with an estimated glomerular filtration rate (eGFR) of

症例は, 61歳男性.昭和60年11月,関節痛,紫斑,視力障害が出現し,当科第1回目の入院となった.患者血清は, 4°C静置で白色沈降物を形成し,この沈降物は顕微鏡下に結晶構造を呈していた.患者血清のアセテート膜電気泳動では, γ位にM-peakを認め,免疫電気泳動でmonoclonal IgG λ typeであることが明らかになった.さらに,種々の検索により,沈降物はこのM-peakより形成されていると思われた.基礎疾患を認めないため,本症例を本態性結晶性クリオグロブリン血症と診断し,血漿交換療法後,ステロイド治療を行ったところ臨床所見は改善し退院した.本例は,ステロイド剤の減量に伴い,その後2回にわたり再燃しており,それぞれ血漿交換療法,大量ステロイドおよび免疫抑制剤の投与で寛解した.

The present study investigated the difference in blood glucose concentration (Glu) response during an incremental swimming test before and after a ten-week training period and verified whether blood glucose threshold (GT) could be determined in competitive swimmers. 7 elite male university swimmers participated in this study. 2 incremental swimming tests were conducted in a swimming flume before and after a ten-week training period. Blood lactate concentration (Bla) and Glu were measured after each swimming step, and the velocities of the lactate threshold (VLT) and glucose threshold (VGT) were analyzed. VLT increased significantly after training (1.21±0.06 m x s(-1) pre-training, 1.31±0.10 m x s(-1) post-training, p

Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanPurpose: Combined treatment with alendronate and alfacalcidol is more useful to increase bone mineral density (BMD) than alendronate or alfacalcidol alone. A retrospective study was conducted to investigate the 3-year outcome of combined treatment with alendronate and alfacalcidol in patients with severe bone loss (BMD ≤ 50% of the young adult mean) and osteoporotic fracture.Methods: Thirty-four patients (six men and 28 postmenopausal women) with primary or secondary osteoporosis who had been treated with alendronate and alfacalcidol for more than 3 years were analyzed. The lumbar spine or total hip BMD and bone turnover markers were monitored, and the incidence of osteoporotic fractures was assessed.Results: The urinary level of cross-linked N-terminal telopeptides of type I collagen and serum level of alkaline phosphatase significantly decreased (-42.5% at 3 months and -18.9% at 3 years), and the lumbar spine BMD, but not the total hip BMD, significantly increased (14.8% at 3 years), compared with the baseline values. However, the incidence of vertebral and nonvertebral fractures was 26.5% and 2.9%, respectively, suggesting a high incidence of vertebral fractures.Conclusion: The results of the present study suggest that combined treatment with alendronate and alfacalcidol may be useful to reduce bone turnover and increase the lumbar spine BMD in patients with severe bone loss and osteoporotic fracture. However, its efficacy against vertebral fractures appears not to be sufficient. Thus, anabolic agents such as teriparatide should be taken into consideration as first-line drugs in patients with severe osteoporosis.Keywords: osteoporosis, fragility fracture, bone mineral density, bone turnover

Osteoarthritis (OA) of the knee is the most common type of arthritis and the major cause of chronic musculoskeletal pain and mobility disability in the elderly. The objective of this paper is to discuss the effectiveness of exercise for OA of the knee based on a review of the literature. We reviewed the relevant literature, i.e. systematic reviews and meta-analyses searched using PubMed. Muscle strengthening and aerobic exercises are effective in reducing pain and improving physical function in patients with mild to moderate OA of the knee.

Neurological diseases such as amyotrophic lateral sclerosis (ALS), stroke, and Parkinson's disease cause disability and immobilization that increases the risk of hip fracture. The purpose of the present study was to clarify the efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with such neurological diseases.A literature search (PubMed) was done from 1995 to the present for randomized controlled trials (RCTs), and a meta-analysis was conducted.Seven RCTs met the criteria, including two of etidronate (ALS and stroke), two of alendronate (stroke and Parkinson's disease), and three of risedronate (stroke and Parkinson's disease). All of the RCTs were performed on Japanese patients. According to the results of pooled data analysis, the relative risk (95% confidence interval) of hip fracture in patients receiving etidronate, alendronate, and risedronate treatment compared with placebo or active control treatment was 0.16 (0.03-0.87), 0.29 (0.10-0.80), and 0.24 (0.10-0.58), respectively, suggesting a reduction of risk by more than 70% with oral bisphosphonates. There was no statistical evidence of heterogeneity among RCTs, and publication bias was not identified by the funnel plot and Begg's rank correlation test. No severe adverse events due to oral bisphosphonate treatment were reported.It remains uncertain whether the findings are relevant for Western patients with an increased risk of hip fracture due to neurological diseases.A meta-analysis of RCTs suggested that oral bisphosphonate treatment prevents hip fracture in disabled Japanese patients with neurological diseases, including ALS, stroke, and Parkinson's disease. Oral bisphosphonate treatment was well tolerated by such patients.

Type 2 diabetic patients are at high risk of bone fractures even if their bone mineral density is normal or high. This is likely explained by poor bone quality and extraskeletal factors. The present review was conducted to provide an overview of the currently available preclinical and clinical evidence on the effect of vitamin K(2) on bone quality in persons with type 2 diabetes. Vitamin K(2) stimulates γ-carboxylation of osteocalcin and can increase bone formation through steroid and xenobiotic receptors. Clinical studies of type 2 diabetic patients have shown detrimental collagen cross-links in bone; low serum insulin-like growth factor-I and osteocalcin concentration are associated with an increased risk of fractures. A therapeutic strategy for preventing fractures in type 2 diabetic patients remains to be established. One recent preclinical study showed that vitamin K(2) administration in a type 2 diabetic rat model had the following skeletal benefits: increased serum osteocalcin, improved collagen cross-link profiles, and increased bone strength. These new findings suggesting a possible beneficial effect of vitamin K(2) supplementation on bone quality in type 2 diabetes warrant further investigation.

The objective of the present study was to identify factors correlated with the serum leptin concentration in women with knee OA. Fifty postmenopausal Japanese women with knee OA (age: 50–88 years) were recruited in our outpatient clinic. Plain radiographs of the knee were taken, and urine and blood samples were collected. Dual-energy X-ray absorptiometry (DXA) scanning was performed for the whole body and lumbar spine, and factors correlated with the serum leptin concentration were identified. A simple linear regression analysis showed that body weight, body mass index, whole-body bone mineral density (BMD), total fat mass, and total fat percentage, but not age, height, lumbar spine BMD, lean body mass, serum and urinary bone turnover markers, or the radiographic grade of knee OA, were significantly correlated with the serum leptin concentration. A multiple regression analysis showed that among these factors, only body weight and total fat mass exhibited a significant positive correlation with the serum leptin concentration. These results suggest that the serum leptin concentration might be related to increases in body weight and total fat mass, but not to BMD or bone turnover markers, in postmenopausal women with OA.

AIM: To clarify the efficacy of conservative and surgical treatment of spondylolysis in athletes. METHODS: PubMed was used to perform a search of the literature for studies published during the period from 1990 to 2009 that reported data on the outcome of conservative or surgical treatment of spondylolysis in athletes. The articles were examined for data on the percentage of athletes who returned to sports activities and the interval between the start of treatment and their return. RESULTS: Five studies were identified. Two studies were concerned with conservative treatment and the other three with surgical treatment (wire fixation or screw fixation with bone graft). The percentages of athletes who returned to sports activities ranged from 80.0% to 89.3% and from 81.9% to 100%, respectively, and the intervals until their return ranged from 5.4 to 5.5 mo and from 7 to 12 mo, respectively. CONCLUSION: The percentages of athletes who returned to sports activities after conservative and surgical treatment appeared to be satisfactory, but the interval until their return to sports activities was longer after surgery than after conservative treatment.

Aging, obesity, and female gender are risk factors for osteoarthritis (OA) of the knee. Basic research has suggested that leptin may play an important role in the pathological process of OA, and that interleukins (ILs) and growth factors may be related to this process. The objective of the present clinical study was to examine the possible correlations between the serum leptin concentration and gender, fat mass, and the IL and growth factor levels in synovial fluid among patients with knee OA. Forty-four patients with knee OA and hydrarthrosis (age: 50-88 yr) were recruited in our outpatient clinic. Plain radiographs of the knee were taken, and blood and synovial fluid of the knee joint were collected. The serum leptin concentration was significantly higher in women than in men. A simple linear regression analysis showed that body weight, body mass index, and total fat mass, but not age, height, radiographic grade of knee OA, lean body mass, or the levels of IL-6, transforming growth factor-beta (TGF-beta), or insulin-like growth factor-1 (IGF-1) in synovial fluid were significantly correlated with the serum leptin concentration. A multiple regression analysis showed that among gender and the three above-mentioned significant factors, only gender and total fat mass were significantly associated with the serum leptin concentration. These results suggested that the serum leptin concentration was higher in women than in men and that it was related only to an increased total fat mass in patients with knee OA. However, the present clinical study failed to show a significant correlation between the serum leptin concentration and the IL or growth factor levels in synovial fluid.

The purpose of the present study was to examine the effect of vitamin K₂ on cancellous and cortical bone mass in rats with streptozotocin (STZ)-induced type 1 diabetes. Twenty-seven male Sprague-Dawley rats aged 12 weeks were randomized by the weight-stratified method into the following three groups: age-matched control group, STZ + vehicle group, and STZ + vitamin K₂ group. STZ (40 + 50 mg/kg) was administered intravenously twice during the initial 1-week period. Vitamin K₂ (menatetrenone, 30 mg/kg) was administered orally 5 days a week. After 12 weeks of treatment, the serum glucose concentration and femoral length and weight were measured and histomorphometric analysis was performed on the cancellous and cortical bone of the distal femoral metaphysis and femoral diaphysis, respectively. STZ administration induced hyperglycemia and a decrease in femoral weight. The STZ + vehicle group also showed cancellous osteopenia due to a decrease in the number of osteoblasts/bone surface (N.Ob/BS) and the osteoblast surface (ObS)/BS without any significant changes in bone-resorption parameters, but it did not have a significant decrease in cortical bone mass. Administration of vitamin K₂ to STZ-treated rats prevented the development of hyperglycemia and a decrease in femoral weight. Vitamin K₂ also prevented cancellous osteopenia by inhibiting the decrease in N.Ob/BS and ObS/BS without significantly affecting bone-resorption parameters, but it did not significantly increase cortical bone mass. These results suggest that vitamin K₂ has beneficial effects on glucose concentration and cancellous bone mass in rats with STZ-induced type 1 diabetes.

ON + )(Salen)ruthenium(II) complex 1 was found to be an efficient catalyst for the epoxidation of conjugated olefins under sunlight coming through windows or incandescent light. The most suitable terminal oxidant was 2,6-dichloropyridine N-oxide 2. All the examined conjugated olefins showed high enantioselectivity greater than 80% ee, irrespective of their substitution pattern.

(Nitrosyl)(salen)ruthenium(II) complex 1 was found to serve as an efficient catalyst for the epoxidation of conjugated olefins under photoirradiation, with 2,6-dichloropyridine N-oxide (2) or tetramethylpyrazine N,N'-dioxide as a stoichiometric oxidant. High enantioselectivity was achieved irrespective of the substitution pattern of olefins. The choice of solvent depends on stability of the resulting epoxides: high enantioselectivity is generally observed in the reaction with ethereal solvents, but use of benzene is recommended when the resulting epoxides are acid-sensitive.

Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: A retrospective study was performed to evaluate the outcome of alendronate (ALN) treatment for seven years in postmenopausal Japanese women with osteoporosis. Forty-seven postmenopausal women with osteoporosis (mean age at baseline 65.7 years) treated with ALN for over seven years in our outpatient clinic were analyzed. Lumbar spine bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) were monitored during the seven-year treatment period. Urinary NTX and serum ALP levels decreased (-48.2% at three months and -15.7% at seven years, respectively) and lumbar spine BMD increased (+12.8% at seven years) compared with baseline values. No serious adverse events were observed, including osteonecrosis of jaw, atypical femoral diaphysis fractures, or atrial fibrillation. To our knowledge, this is the first report of the outcome of ALN treatment for seven years in Japanese patients with osteoporosis. ALN successfully suppressed bone turnover and increased lumbar spine BMD from the baseline value over the course of the seven-year treatment period without causing any severe adverse events.Keywords: alendronate, osteoporosis, long-term treatment, bone mineral density, bone turnover

The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

Background: The main challenge to the long-term treatment of osteoporosis with bisphosphonates has been patient adherence. The purposes of this cohort study were to investigate the 3-year outcome of alendronate treatment in postmenopausal Japanese women with osteoporosis and to identify factors that contributed to the discontinuation of alendronate treatment. Methods: A total of 72 postmenopausal Japanese women with osteoporosis and aged from 58 to 85 years were treated with alendronate in a 3-year trial. Metacarpal bone mineral density, serum alkaline phosphatase, and urinary crosslinked N-terminal telopeptides of type I collagen were monitored, and factors contributing to the discontinuation of alendronate treatment were determined. Results: Fourteen patients dropped out of the trial. The reasons for dropout were side effects (diarrhea [n = 1], gastric symptoms [n = 9], and inflammation of the mouth [n = 1]) or non-compliance (n = 3). Logistic regression analysis showed that the number of prevalent vertebral fractures was a significant factor affecting the discontinuation of alendronate treatment for the reasons listed above. In 58 patients who continued the 3-year treatment, urinary cross-linked N-terminal telopeptides of type I collagen level was reduced by 44.1% at 3 months and serum alkaline phosphatase level was decreased by 11.6%, 11.8%, and 12.5% at 1, 2, and 3 years, respectively. However, metacarpal bone mineral density did not change significantly. Conclusion: Alendronate treatment decreased urinary cross-linked N-terminal telopeptides of type I collagen and serum alkaline phosphatase levels, and maintained metacarpal bone mineral density in postmenopausal Japanese women with osteoporosis. The patients adhered well to alendronate treatment in our clinic. The number of prevalent vertebral fractures was an important factor affecting the discontinuation of alendronate treatment due to side effects and non-compliance. [J Chin Med Assoc 2009;72(12):619–624]

Hypovitaminosis D and K due to malnutrition or sunlight deprivation, compensatory hyperparathyroidism, increased bone resorption, low bone mineral density (BMD), and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Alzheimer's disease. The purpose of the present study was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer's disease.With respect to randomized controlled trials (RCTs) regarding Alzheimer's disease and hip fractures, the literature was searched with PubMed.Three RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for individual RCTs. Exposure to sunlight with calcium supplementation, menatetrenone (vitamin K2) plus calcium and vitamin D supplementation, and risedronate plus calcium and vitamin D supplementation improved hypovitaminosis D and hyperparathyroidism, contributing to a reduction in bone resorption. Risedronate itself strongly decreased bone resorption. Menatetrenone also decreased the serum level of undercarboxylated osteocalcin. The three interventions increased metacarpal BMD and reduced the incidence of hip fractures. The respective RRs (95% CI) were 0.22 (0.049-0.999), 0.13 (0.031-0.554), and 0.26 (0.100- 0.690).The present study clarified the efficacy of three interventions, including exposure to sunlight, menatetrenone, and risedronate with calcium and/or vitamin D supplementation against hip fractures in patients with Alzheimer's disease.

The objective of the present study was to investigate the nutritional status from the aspect of bone metabolism in Japanese elite male athletes with increased bone resorption. Urinary levels of a bone resorption marker, cross-linked N-terminal telopeptide of type 1 collagen (NTX), were measured in 71 professional baseball players (age, 18-39 years); the mean urinary NTX level was 65.6 (range, 17.5-269.0) nM BCE/mM Cr. Of 71 athletes, 9 with high levels of urinary NTX (greater than mean + 1 SD) were examined by measuring serum biochemical markers and nutritional assessment (simple food frequency questionnaire). Serum biochemical marker analysis showed that 7 of these 9 athletes had vitamin D insufficiency, as indicated by low serum levels of 25-hydroxyvitamin D, and that all 9 athletes showed vitamin K insufficiency as indicated by low levels of vitamins K(1) and K(2). Nutritional assessment revealed high intakes of protein and low intakes of calcium and vitamin D based on adequate intake (AI). However, daily vitamin K intake achieved the AI. These results suggest that there exist elite male athletes who show increased bone resorption and calcium and vitamin D insufficiency. However, there was a discrepancy between vitamin K intake and serum levels of vitamins K(1) and K(2). The present study raised an issue regarding the nutritional status from the point of view of bone metabolism in elite male athletes such as professional baseball players.

Patients with neurological diseases such as Alzheimer's disease, stroke and Parkinson's disease have been reported to have vitamin K deficiency secondary to malnutrition, which increases the risk of non-vertebral and hip fractures. The purpose of the present study was to clarify the efficacy of menatetrenone (vitamin K(2)) against non-vertebral and hip fractures in patients with neurological diseases.A literature search was conducted on PubMed from January 1995 to July 2008 to identify randomized controlled trials (RCTs) of use of menatetrenone against non-vertebral and hip fractures in patients with neurological diseases. A meta-analysis of all RCTs meeting these criteria was then performed.Three RCTs of patients with Alzheimer's disease (n = 178, mean age 78 years), stroke (n = 99, mean age 66 years) and Parkinson's disease (n = 110, mean age 72 years) met the criteria for meta-analysis. These RCTs did not include placebo controls but did have non-treatment controls. According to the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases. No severe adverse events were reported with menatetrenone treatment.The present meta-analysis of three RCTs suggests that there is efficacy for menatetrenone treatment against non-vertebral and hip fractures among patients with neurological diseases. Further larger placebo-controlled trials are needed to confirm the results of the present study.

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (-27.0%). Serum ALP levels decreased (-12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.