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Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk for fractures. The strategies for preventing osteoporotic fractures are maximizing peak bone mass, counteracting age- and menopause-related bone loss, minimizing the increase in spinal kyphosis, and preventing falls. Thus, the aim of sport and exercise appears to differ among ages in the maintenance of bone health in females. Given that maximizing peak bone mass is the most important strategy for preventing fractures in later life, interventions may therefore be needed before the menarche (during the growth spurt) in children. The efficacy of sport activity and exercise in all strategies has been established, although there is no evidence that sport and exercise are able to prevent hip fractures. However, sport activity and exercise across the life span of the average female should be encouraged in the maintenance of bone health.

The purpose of this study was to investigate effects of the varied starting block angle for the start performance in competitive swimming. Ten well-trained college swimmers participated in this study. They performed twice at each 4 types of swim-start trials which were GS (grab start) with 7.5 and 10 degrees of block angle, TS (track start) with 7.5 and 10 degrees. The trials were recorded by high-speed camera (125Hz). Joint motions were calculated by using 2D-DLT methods. Comparisons of kinematical variables were performed by using the two-way repeated-measures analysis (block angle and start technique) of variance. Significant main effect of the block angle were observed in the horizontal and resultant take-off velocity (7.5deg 10deg). Significant main effects of the start technique were observed block time (GS > TS), coordinates of center of gravity at the takeoff (horizontal GS > TS, vertical GS TS). Significant interaction were not observed in each variable. These results suggested that an increase of the block angle and using of track start resulted in an advantage for start performance until water entry.

Objective: Neurological diseases, including Alzheimer's disease, stroke, and Parkinson's disease have been reported to increase the risk for fractures. The purpose of the present study was to clarify the efficacy of risedronate against hip fracture in patients with neurological diseases.Methods: The literature was searched with PubMed from 1995 to the present, with respect to strictly conducted randomized controlled trials (RCTs) with narrow confidence intervals (CIs), and a meta-analysis was conducted.Results: Four RCTs met the criteria; one RCT for Alzheimer's disease (n = 461, mean age = 78 years), two RCTs for stroke (n = 267, mean age = 76 years for men; n = 345, mean age = 71 years for women), and one RCT for Parkinson's disease (n = 223, mean age = 71 years). According to the results of RCTs, the relative risks (95% CI) for hip fracture with risedronate treatment compared with placebo treatment were 0.26 (0.10, 0.69) for Alzheimer's disease, 0.20 (0.04, 0.89) for stroke in men, 0.14 (0.02, ...

The purpose of this study was to investigate the relationship between plantar flexion angle and underwater dolphin kick performance using a simulation model, SWUM (SWimming hUman Model), in which the entire body was represented as a series of elliptic cylinders. Three unsteady fluid forces (added mass force, normal and tangential resistive force), buoyancy and gravity acting on the elliptic cylinders were computed from the shape and density of the cylinders, and from the joint motion for one cycle. Eight elite competitive swimmers participated in this study. Their body characteristics were measured and input as the simulation data (the shape and density of the elliptic cylinders). The joint motion data for one cycle were obtained by the 2-D DLT method during the underwater dolphin kick. To recreate the dynamics of the underwater dolphin kick in the simulation, three fluid coefficients, used to calculate the three unsteady fluid forces, were identified to minimize the difference between measured and simulated swimming velocity by the least-squares method. This identification was conducted for each of the input data. Simulations of the increased plantar flexion angle in the knee extension phase were executed with the optimal fluid coefficients for each swimmer in order to analyze the change in swimming velocity and thrust generated by the feet. The conclusions can be summarized as follows : (1) Swimming velocity during the underwater dolphin kick increased due to the increment of the thrust generated by the feet after an increase in the plantar flexion angle. (2) It was suggested that flexibility of plantar flexion is important, although it is not a determinant of underwater dolphin kick performance. (3) Swimmers with low flexibility of plantar flexion tended to achieve a faster swimming velocity after increasing the plantar flexion angle.

The purpose of the present study was to examine the effects of combined administration of alendronate (ALN) and alfacalcidol (ALF) on the cancellous and cortical bone mass of the tibia in orchidectomized rats. Fifty male Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into five groups: age-matched control, orchidectomy, and orchidectomy with administration of ALN (2.5 μg/kg, s.c., 5 times a week), ALF (0.05 μg/kg, p.o., 5 times a week), or ALN+ALF. The total experimental period was 12 wk. Orchidectomy reduced the cancellous bone mass of the proximal tibial metaphysis and maturation-related cortical bone gain of the tibial diaphysis as a result of increased trabecular bone resorption and decreased periosteal bone formation and also increased endocortical bone erosion and formation. ALN suppressed trabecular bone resorption and endocortical bone erosion and formation and increased periosteal bone formation, while ALF increased the number of osteoblasts and suppressed trabecular bone resorption and markedly increased periosteal and endocortical bone formation. Thus, both ALN and ALF prevented the orchidectomy-induced reduction in the cancellous bone mass and maturation-related cortical bone gain. Combined administration of ALN and ALF increased the cancellous bone mass as compared with the values observed in age-matched controls by causing more marked suppression of trabecular bone resorption. The present study showed the beneficial effects of combined administration of ALN and ALF on the cancellous bone mass of the tibia in orchidectomized rats.

This paper introduces a novel multirate feedforward control method for robot manipulators with elastic joints. Perfect tracking control methodology using multirate feedforward control was proposed by H. Fujimoto, et al. Then, A. Shimada, et al. have prsented its application to robot manipulators; however, they only described the controller design process and gave a few simulation results. In addition, they did not provide details on how the state reference should be designed. Even if experiments were attempted, it would be difficult to evaluate control performance since generally manipulators have joint angle sensors mounted on the output side of reduction gears In order to solve this, this paper illustrates the design process for the state reference, and introduces a prototype robot manipulator that has precision rotary encoders installed on the output side of the joints. This means that the manipulator has not only the rotary encoders attached to servo motors but special precision rotary encoders. We describe experimental results obtained by applying this control technique.

Objective This study was to clarify the neuropathological findings of acute encephalomyelopathy with Sjogren's syndrome. Methods We examined an autopsied case of acute encephalomyelopathy with Sjogren's syndrome. Case Report A 40-year-old woman developed acute myelopathy and brainstem dysfunction. Magnetic resonance imaging (MRI) revealed high-intensity lesions on T2-weighted axial images (T2WI) in the medulla oblongata and cervical spinal cord. We established a diagnosis of Sjogren's syndrome (SjS) according to the European Community criteria. The patient was treated with intravenous methylprednisolone (500 mg/day) for three days, followed by oral prednisolone. Although her neurological symptoms improved, her general condition deteriorated after the onset of acute colonic pseudo-obstruction and she died of multiple organ failure associated with hemophagocytosis. Results Autopsy showed atrophy of the secretory glands and an accumulation of lymphocytes around the ducts, confirming the diagnosis of Sjogren's syndrome. Neuropathological examination revealed multifocal lesions in the cervical spinal cord and medulla, along with scattered perivascular lymphocytic infiltration. In addition, there was demyelination, spongy change and axonal swelling in the white matter, but no remarkable vasculitic changes were seen in the central nervous system. Conclusion Although the steroid therapy may have had a significant influence, the main pathological finding in this case was not vasculitis, but rather axonal degeneration with spongy change and axonal swelling.

The purpose of this paper is to discuss the effects of antifracture drugs on postmenopausal, male and glucocorticoid-induced osteoporosis, focussing on the efficacy and safety of alendronate and risedronate. A search of the literature was conducted using PubMed for strictly conducted systematic reviews published from 1995 to present with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with a narrow confidence interval. According to the results of the systematic reviews and meta-analyses, alendronate and risedronate are useful for the prevention of vertebral and non-vertebral fractures in postmenopausal women with osteoporosis. The results of RCTs have shown the antifracture efficacy of raloxifene and ibandronate against vertebral fractures and that of strontium and parathyroid hormone against vertebral and non-vertebral fractures in postmenopausal women with osteoporosis. In addition, the long-term safety of alendronate, risedronate and raloxifene has been established. On the other hand, RCTs have shown that, only alendronate prevents vertebral fractures in men with osteoporosis, and that alendronate and risedronate can prevent vertebral fractures in patients receiving glucocorticoid treatment. There seems to be less evidence of the antifracture efficacy of the drugs in male and glucocorticoid-induced osteoporosis. They have limitations related to long-term compliance, gastrointestinal intolerance and poor and variable absorption form gastrointestinal tract. Thus, intermittent intravenous administration of bisphosphonates such as ibandronate and zoledronate or subcutaneous administration of denosumab might address some of these problems, although the antifracture efficacy of these drugs needs be established. However, antifracture efficacy and long-term safety are important points in the choice of drugs for the treatment of osteoporosis. Thus, the evidence derived from the literature, based on strict evidence-based medicine guidelines, suggests the antifracture efficacy and safety of alendronate in postmenopausal, male and glucocorticoid-induced osteoporosis, and those of risedronate in postmenopausal and glucocorticoid-induced osteoporosis.

The purpose of the present study was to investigate the short-term effects of muscle strengthening exercises on the muscle strength in patients with osteoarthritis (OA) of the knee, and to determine whether the beneficial effects of the exercises on the muscles strength, if any, would be maintained over the long-term. Twenty-six patients (mean: 62.8 years) with mild-to-moderate OA of the knee were instructed to perform the exercises, which consisted of once-weekly facility-based strengthening exercises of the knee extensor and flexor muscles with a Medx knee machine at the intensity of 50% of the maximum peak torque (MPT) measured at the baseline (20 timesx3 sets per week), together with daily home-based isometric strengthening exercises (setting and straight leg raising) of the extensor and flexor muscles of the knee (30 times per day). The beneficial effects of the exercises on the MPT values of both the extensor and flexor muscles of the knee that began to be observed from 3 to 6 months after the start of the exercise regimen, regardless of the gender, age, body mass index, or baseline MPT values of the muscles, were maintained for up to 1-3 years, but tended to be no longer observed at 5 years. The present study showed the short-term efficacy of combined facility- and home-based muscle strengthening exercises for the muscle strength in patients with mild-to-moderate OA of the knee, as well as the loss of the beneficial effect of the exercise regimen on the muscle strength over the long-term.

The beneficial effects of alfacalcidol (ALF) on bone mass, bone formation, and bone resorption have been established in ovariectomized rats. Our previous studies showed that high-dose glucocorticoid (GC) administration (methylprednisolone sodium succinate, 5.0 mg/kg, s.c., 3 times a week) for 4 wk induced cancellous osteopenia without significantly affecting cortical bone mass in Sprague-Dawley rats, and that high-dose GC administration for 8 wk also resulted in cortical osteopenia. The purpose of the present study was to examine the effects of ALF on cancellous and cortical bone mass in GC-treated rats. Forty female Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into four groups of 10 rats each, as follows: age-matched control group (CON); 8-wk GC administration with administration of vehicle during the latter 4 wk of treatment (GC group); 8-wk GC administration with administration of a low dose of ALF (0.08 Ag/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose ofALF (0.16 microg/kg) during the latter 4 wk of treatment (high-dose ALF group). The GC (methylprednisolone sodium succinate, 5.0 mg/kg) was administered subcutaneously 3 times a week, and ALF was administered orally 5 times a week. At the end of the experiment, static and dynamic bone histomorphometric analyses were performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial diaphysis. Eight-week GC administration resulted in loss of the cancellous bone volume/total tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular bone formation, increased trabecular and endocortical bone resorption, and decreased periosteal bone formation. Low-dose ALF restored the cancellous BV/TV by mildly suppressing bone resorption and restoring bone formation, whereas high-dose ALF increased it beyond the value observed in the age-matched controls by strongly suppressing bone resorption and markedly increasing bone formation. Both low- and high-dose ALF prevented the GC-induced reduction of the percent Ct Ar by increasing periosteal bone formation and suppressing endocortical bone resorption. The effects of ALF on cancellous bone mass, bone formation, and bone resorption were all dose-dependent. The present study showed the beneficial effects of ALF on cancellous and cortical bone mass in GC-treated rats.

We report on a case of muscle strain of the subscapularis muscle in a baseball player. An out-fielder (throws right-handed and bats left-handed) hurt his right shoulder while playing baseball. He complained of right-shoulder pain just after he forcefully hit his right hand against the fence in an attempt to jump and catch a flying ball with a glove on the left hand during a baseball game. Fat-suppressed T2-weighted magnetic resonance images (MRIs) of the right shoulder joint revealed muscle strain in the middle part of the subscapularis muscle, and the injury was surmised to have occurred on account of eccentric contraction of the subscapularis muscle. The case was considered to have moderate muscle strain, because he had modest muscle weakness with a negative lift-off test. Active stretching exercises were begun just after his first visit to our clinic, and throwing exercises were started 3 weeks later, by when the right-shoulder pain had completely disappeared. Repeat MRIs of the right shoulder joint obtained 4 weeks after his first visit to our clinic revealed a significant reduction of the high-intensity lesions in the subscapularis muscle. Conservative treatment was effective for managing moderate muscle strain of the subscapularis muscle. Muscle strain of the subscapularis muscle should be taken into consideration in the differential diagnosis of shoulder injuries in athletes.

Hypophysectomy (HX) arrests bone growth and induces osteopenia in the long bones of rats. The present study investigated the combined effect of vitamin K2 and risedronate on long bone mass in HX rats, in order to determine whether treatment with these two agents had an additive effect. Forty female Sprague-Dawley rats were hypophysectomized at 6 weeks of age by the supplier, and were shipped to our laboratory at three days after surgery along with ten intact rats that served as age-matched controls. The study was started on the day when the rats were received. Three HX rats were excluded from the study because of the failure of HX. Forty-seven rats (6 weeks old) were assigned to the following 5 groups by the stratified weight randomization method: intact controls, HX alone, HX + vitamin K2 (30 mg/kg, p.o., daily), HX + risedronate (2.5 μg/kg, s.c., 5 days a week), and HX + vitamin K2 + risedronate. The dosing period was 4 weeks. HX resulted in a decrease of the femoral bone area, bone mineral content (BMC) and bone mineral density (BMD), as well as a decrease in the cancellous bone mass of the proximal tibial metaphysis and the total tissue and cortical areas of the tibial diaphysis. These changes were associated with a marked reduction in the serum level of insulin like growth factor (IGF)-I and with elevation of serum alkaline phosphatase (ALP) and pyridinoline. Administration of vitamin K2 increased the serum ALP level in HX rats, but did not affect any of the other parameters. On the other hand, risedronate ameliorated the decrease of femoral BMD and cancellous bone mass at the proximal tibial metaphysis in HX rats without affecting the serum IGF-I level, as a result of not causing a significant elevation of serum pyridinoline. Vitamin K2 and risedronate combined had an additive effect on the femoral bone area, BMC and BMD, and the combined treatment group did not show any significant reduction of the total tissue and cortical areas at the tibial diaphysis, as well as a reduced serum pyridinoline level compared with untreated rats and an increased serum ALP level compared with untreated or risedronate-treated rats. These results suggest that risedronate had a positive effect on the BMD and cancellous bone mass of long bones in HX rats. Despite the lack of a significant effect of vitamin K2 on bone mass parameters, it had an additive effect with risedronate on the BMC, BMD and cortical bone mass of long bones in HX rats.

Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment.

Hypophysectomy (HX) results in cessation of bone growth and cancellous osteopenia in rats. It has been reported that prostaglandin E2 (PGE2) improves cortical and cancellous bone mass in HX rats. The purpose of the present study was to examine whether combined administration of vitamin K2 and PGE2 would have a more beneficial effect on bone than single administration of either alone in HX rats. Forty-three female Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified weight method into five groups: intact controls, HX, HX + vitamin K2 (30 mg/kg, p.o., daily), HX + PGE2 (0.83 mg/kg, i.m., 5 days a week), and HX + vitamin K2 + PGE2. The duration of the experiment was 4 weeks. There was a reduction in cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis and a reduction in total tissue area and cortical area (Ct.Ar) of the tibial diaphysis. Vitamin K2 did not affect cancellous BV/TV or Ct.Ar. On the other hand, PGE2 attenuated the loss of cancellous BV/TV in association with higher bone formation rate/bone surface (BFR/BS) and eroded surface (ES)/BS compared with intact controls. PGE2 also increased percent Ct.Ar compared with nontreated HX rats as a result of attenuation of a decrease in periosteal BFR/BS. Vitamin K2 had a synergistic effect with PGE2 on cancellous BV/TV as a result of the suppression of an increase in ES/BS observed by PGE2 treatment. These results suggested that PGE2 had an anabolic action on cancellous and cortical bone and that despite no apparent effect of vitamin K2 on bone, it had a synergistic effect with PGE2 on cancellous bone mass in young HX rats.

OBJECTIVE The purpose of this study was to clarify the efficacy of conservative treatment in athletes with symptomatic lumbar disc herniation, especially in terms of their ability to return to their original sporting activities. DESIGN A total of 71 consecutive athletes (53 men and 18 women), who consulted our sports medicine clinic during the 10-yr period between September 1993 and October 2003 because of severe low back pain or leg pain/numbness due to lumbar disc herniation (confirmed on magnetic resonance images), were studied. The mean age of the subjects was 21 yrs. All of them were conservatively treated by advising them to discontinue their sporting activities, with or without short-term medication. After the subjective symptoms had reduced by >80%, individual training was started to allow the athletes to return to their original sporting activities. RESULTS A total of 56 athletes (78.9%) could return to their original sporting activities at an average of 4.7 mos (range, 1-12 mos) after the start of treatment and were able to sustain the activities for > or =6 mos, the minimum duration of follow-up in this study. The outcome of the conservative treatment was not influenced by the intensity of the sporting activity. Multiple logistic regression analyses showed that the only factor influencing the ability of the athletes to return to their original sporting activities was the severity of the symptoms before the start of treatment. CONCLUSION The results of this study suggest that the short-term outcome of conservative treatment in athletes with symptomatic lumbar disc herniation may be satisfactory in terms of control of the symptoms and the ability of the athletes to return to their original sporting activities and that the subjective symptoms before treatment may be a key factor influencing the success of the conservative management. Randomized controlled trials, or even comparative follow-up studies, are needed to confirm our results.

This paper discusses the efficacy and safety of alendronate and risedronate in the treatment of postmenopausal osteoporosis.The literature was searched with the PubMed from 1996 to the present, with respect to strictly conducted systematic reviews with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with narrow Confidence Interval.According to the results of large randomized controlled trials (RCTs), bisphosphonates (alendronate, risedronate, and ibandronate), raloxifene, calcitonin, parathyroid hormone (PTH), and strontium ranelate effectively prevent vertebral fractures in postmenopausal women with osteoporosis. Because raloxifene has been shown to be effective in preventing the initial vertebral fracture in postmenopausal osteoporotic women without prevalent vertebral fractures, it is considered in the treatment of postmenopausal women with mild osteoporosis or osteopenia with some risk factors for fractures. RCTs have also demonstrated that alendronate, risedronate, PTH, and strontium are useful to prevent non-vertebral fractures and that alendronate and risedronate prevent hip fractures, thus alendronate or risedronate are primarily considered as the first-line drugs in the treatment of elderly women with osteoporosis having some risk factors for falls. While it has been suggested that PTH may be considered in patients with severe osteoporosis, the use of PTH in the treatment for osteoporosis is limited to 2 years or less, and it may be appropriate to use other anti-resorptive drugs after the completion of PTH treatment to maintain the skeletal effects gained during the treatment. RCTs have demonstrated that the incidence of gastrointestinal tract adverse events in postmenopausal osteoporotic women treated with bisphosphonates and placebo are similar, and also the long-term efficacy and safety of alendronate and risedronate.The evidence derived from the literature, based on strict evidence-based medicine guidelines, suggests that there is long-term efficacy and safety with alendronate and risedronate in the treatment of osteoporosis in postmenopausal women.

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis.

Objectives: To compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous bone in rats with glucocorticoid (GC)-induced osteopenia. Materials and Methods: Thirty female Sprague-Dawley rats, 4 mo of age, were randomly divided by the stratified weight method into three groups of 10 rats each according to the following treatment schedule: 8-wk GC administration with 4-wk vehicle (control), Ris, and Cal as therapeutic treatment initiated after 4-wk GC administration. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 μg/kg, s.c.), and Cal (0.1 μg/kg, p.o.) were administered 3 times a week. At the end of the 8-wk treatment period, two-dimensional (2D) bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis, 3D micro-computed tomographic analysis was performed for the distal femoral metaphysis, and the mechanical strength of the distal femoral metaphysis was evaluated by a compression test. Results: Ris and Cal treatment increased both 2D and 3D cancellous bone mass. However, Ris treatment exhibited more pronounced effects on 2D and 3D cancellous bone mass than Cal treatment, and the effects of both Ris and Cal treatment were greater on 3D cancellous bone mass than on 2D cancellous bone mass. The response of 2D and 3D cancellous bone mass to Ris treatment was characterized by its effect on trabecular number and thickness, which was associated with markedly suppressed bone resorption and bone formation in terms of suppressed bone turnover. On the other hand, the response of 2D cancellous bone mass to Cal treatment was attributed to the effect of Cal on 2D trabecular thickness, and the response of 3D cancellous bone mass to Cal treatment might be characterized by the effect of Cal on 3D trabecular number and thickness, with a more marked effect of trabecular thickness. These effects were primarily due to mildly suppressed bone resorption and maintained or even increased bone formation. Despite the differential effect of Ris and Cal treatment on the cancellous bone structure and bone metabolism, both treatment increased the maximum load and braking energy of the distal femoral metaphysis to a similar extent, suggesting different mechanisms for improving bone strength. Conclusions: This study showed the differential effects of Ris and Cal on cancellous bone in rats with GC-induced osteopenia.

Vitamin K2, raloxifene, and bisphosphonates, such as etidronate, alendronate, and risedronate, are widely used in the treatment of postmenopausal osteoporosis in Japan. A meta-analysis study has demonstrated the efficacy of anti-resorptive agents: raloxifene and etidronate have been shown to reduce the incidence of vertebral fractures, and alendronate and risedronate have been shown to reduce the incidence of both vertebral and hip fractures. Furthermore, a report of the World Health Organization (WHO) has provided evidence from a randomized controlled trial suggesting that vitamin K2, which may stimulate bone formation via gamma-carboxylation of osteocalcin and/or steroid and xenobiotic receptors (SXRs), reduces the incidence of vertebral fractures, despite having only modest effects on the bone mineral density (BMD). Based on the weight of the currently available evidence, it is recommended that alendronate and risedronate, rather than vitamin K2, should be chosen initially for the treatment of postmenopausal osteoporosis, because these agents have been shown to be the most efficacious for reducing the incidence of both vertebral and hip fractures among the current range of commercially available agents. However, the more potent anti-fracture efficacy of combined treatment with the anti-resorptive and commercially available anabolic agents may need to be established. Some studies have shown that combined treatment with a bisphosphonate and vitamin K2 may be more effective than treatment with a bisphosphonate alone in preventing vertebral fractures. On the other hand, the results of a preclinical study do suggest the possible efficacy of combined treatment with vitamin K2 and raloxifene in the prevention of vertebral and hip fractures in postmenopausal women, although no clinical studies have reported on the effects of combined treatment with vitamin K2 and raloxifene in postmenopausal women with osteoporosis. Vitamin K deficiency, as indicated by high serum levels of undercarboxylated osteocalcin, has been shown to contribute to the occurrence of hip fractures in elderly women. Thus, we propose that the important role of vitamin K2 used in combination with bisphosphonates or raloxifene should not be underestimated in the prevention of fractures in postmenopausal women with osteoporosis with vitamin K deficiency.

The purpose of the present study was to examine the effect of pretreatment with risedronate and/or vitamin K2 and treatment continuation with reduced dosing frequency of the drugs on the early cancellous bone loss induced by ovariectomy (OVX) in rats. Eighty female Sprague-Dawley rats, 4 mo of age, were randomized by the stratified weight method into eight groups (n=10 in each group); rats subjected to OVX, but not sham-operated rats, were treated with vehicle, risedronate, vitamin K2 (menatetrenone), or risedronate+vitamin K2 for 4 wk before the surgery, and the treatment was either discontinued (pretreatment groups) or continued after the surgery (treatment continuation groups) for 2 wk. Sham-operated rats (controls) were treated with the vehicle throughout the experimental period. During the 4 wk prior to the surgery (pretreatment), risedronate and vitamin K2 were administered five times a week either subcutaneously at a dose of 2.5 μg/kg body weight (risedronate) or orally at the dose of 30 mg/kg body weight (vitamin K2). During the 2 wk after the surgery (treatment continuation), the dosing frequency of the drugs was reduced to twice a week. Risedronate and vitamin K2 had an anti-resorptive effect on the bone. Pretreatment with risedronate alone, but not vitamin K2 alone, prevented the loss of the cancellous bone volume/total volume (BV/TV) of the proximal tibial metaphysis after OVX. Treatment continuation with vitamin K2 alone prevented the loss of the cancellous BV/TV after OVX, while treatment continuation with risedronate alone increased the cancellous BV/TV to beyond the values in controls. Pretreatment with risedronate+vitamin K2 had a more beneficial effect in increasing the cancellous bone mass than pretreatment with risedronate alone. Treatment continuation with risedronate and/or vitamin K2 appeared to have a more beneficial effect in increasing the cancellous bone mass than the respective pretreatment. Neither the total tissue area nor the cortical area of the tibial diaphysis was affected by any treatment. The present study demonstrated that pretreatment with risedronate had a beneficial effect on the early cancellous bone loss after OVX in rats, with a more beneficial effect when combined with vitamin K2. Moreover, even though the dosing frequency of the drugs was reduced after OVX, treatment continuation appeared to be more beneficial than pretreatment for increasing the cancellous bone mass.

The purpose of the present study was to compare the effects of risedronate (RIS) and alfacalcidol (ALF) on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats in a head-to-head fashion. Forty female Sprague-Dawley rats, 7 mo of age, were randomized into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 μg/kg, p.o., daily). At the end of the 8-wk experimental period, bone histomorphometric analyses of the cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial disphysis was performed, and the mechanical properties of the bone were evaluated at the femoral distal metaphysis (FDM) and femoral diaphysis (FD). RIS prevented the decrease in the cancellous bone volume/total tissue volume (BV/TV) noted in ovariectomized rats in a dose-dependent manner, by suppressing increases in cancellous bone formation and resorption, without any apparent effect on the Ct Ar or maximum load of the FDM or FD. On the other hand, ALF increased the cancellous BV/TV, Ct Ar, and maximum load of the FDM or FD, by mildly decreasing cancellous bone formation and resorption, increasing periosteal and endocortical bone formation, and preventing an increase in endocortical bone resorption. Thus, the present study clearly showed that RIS and ALF had differential effects on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the therapeutic effects of alendronate and alfacalcidol on the cancellous and cortical bone mass and mechanical properties in ovariectomized osteopenic rats in a head-to-head fashion. Twenty-five female Sprague-Dawley rats, 7 mo of age, were randomly divided by the stratified weight method into four groups: the sham-operated control (Sham) group and three ovariectomized groups treated with vehicle, alendronate (2.5 mg/kg, p.o., daily), or alfacalcidol (0.5 microg/kg, p.o., daily). Treatment was started 6 wk after the surgery and continued for 6 wk. At the end of the experiment, urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels were evaluated, and cancellous and cortical bone histomorphometric analyses were performed for the proximal tibial metaphysis and tibial diaphysis, respectively. Alendronate prevented the elevation of the urinary DPD level induced by ovariectomy (OVX), and markedly decreased the serum OC level to below the value observed in the Sham group, while alfacalcidol prevented the elevation of the urinary DPD and serum OC levels induced by OVX. Alendronate increased the cancellous bone volume/total tissue volume (BV/TV) relative to the values observed in the OVX-Vehicle group by preventing the increases in the eroded surface/bone surface (ES/BS), osteoclast surface (OcS)/BS, and bone formation rate (BFR)/BS induced by OVX. However, it decreased the mineral apposition rate (MAR) in the ovariectomized osteopenic rats to below the value observed in the Sham group. It also prevented the increase in the marrow area (Ma Ar) caused by OVX. Alfacalcidol increased the BV/TV relative to the values observed in the OVX-Vehicle group by decreasing the ES/BS and OcS/BS, but maintaining the BFR/BS. The effect of alfacalcidol on the BV/TV was more pronounced than that of alendronate, despite the less pronounced suppression of OcS/BS by this drug in the ovariectomized osteopenic rats. In addition, this drug increased the cortical area (Ct Ar) and prevented the increase in the Ma Ar in the ovariectomized osteopenic rats by decreasing the endocortical ES/BS, and even increasing the endocortical BFR/BS. Furthermore, it also prevented the reduction in the maximum load of the femoral distal metaphysis in the ovariectomized osteopenic rats. Thus, the present study clearly showed that alendronate and alfacalcidol had differential therapeutic effects on the cancellous and cortical bone mass and mechanical properties in ovariectomized osteopenic rats.

The starting technique is one of the most important factors for sprint performance in competitive swimming. Take-off velocity and take-off angle determine the horizontal take-off velocity and flight distance in the aerial phase. The most appropriate take-off angle for start performance has not been investigated, although the importance of take-off velocity is well known. The purpose of this study was to clarify the effects of take-off angle on take-off velocity, flight distance and block time during swim-start. Twelve elite competitive swimmers performed three different types of start trial. In the experimental starting trials, swimmers were instructed to take off from the starting block higher (High) and lower (Low) than the usual grab start trial (Normal). The starting motions of subjects were recorded by a high-speed camera (Photron FAST-CAM PCI, 250 fps) and the 2D-DLT method was used for calculating the kinematic variables. The starting movement was modeled by a pendulum model, and the take-off velocity was resolved to the rotational component and the extensional component. A decrement of the take-off angle resulted in an increment of rotational component, extensional component of take-off velocity. Therefore, the decrement of flight distance with decrement of the take-off angle resulted in fewer disadvantages for start performance. In addition, there was no correlation between take-off angle and the block time in Normal trials. Considering the importance of horizontal take-off velocity, which is in the direction of swimming, take-off angle should be approximately 0 degree in the aerial phase.

The purpose of this open-labeled prospective study was to compare the treatment effects of cyclical etidronate and alendronate on the lumbar bone mineral density (BMD), bone resorption, and back pain in elderly women with osteoporosis. Fifty postmenopausal women with osteoporosis, age ranging from 55 to 86 years (mean: 70.7 years), were randomly divided into two groups with 25 patients in each group: the cyclical etidronate group (etidronate 200 mg daily for 2 weeks every 3 months) and the alendronate group (5 mg daily). The BMD of the lumbar spine (L1-L4) measured by DXA, the urinary cross-linked N-terminal telopeptides of type I collagen (NTX) level measured by the enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Etidronate treatment sustained the lumbar BMD following a reduction in the urinary NTX level and improved back pain, while alendronate treatment reduced the urinary NTX level more significantly, resulting in an increase in the lumbar BMD, and similarly improved back pain. No serious adverse events were observed in either group. This study confirmed that alendronate treatment had a greater efficacy than etidronate treatment in increasing the lumbar BMD through the reduction of bone resorption in elderly women with osteoporosis.

Immobilization induces a rapid loss of bone density and bone strength in rats. The purpose of the present study was to examine the effects of risedronate (Ris) on the femoral bone density and bone strength of sciatic neurectomized young rats. Forty male Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified weight method into the following four treatment groups of 10 rats each: sham-operation, bilateral sciatic neurectomy (NX), NX + low-dose Ris (0.25 mg/kg/day, orally), and NX + high-dose Ris (0.5 mg/kg/day, orally). After 8 weeks of feeding, the volumetric bone mineral density (vBMD) and stress strain index (SSI) of the femoral distal metaphysis and middiaphysis of the rats were measured by peripheral quantitative computed tomography. The mechanical properties of the femoral distal metaphysis and middiaphysis were measured by the compression and three-point bending tests, respectively. The femoral length was also measured. As compared with the findings in the sham-operated controls, NX resulted in a loss of femoral length, cancellous vBMD, SSI, maximum load, stiffness, and breaking energy of the femoral distal metaphysis; there was also loss of cortical thickness, SSI, maximum load, and stiffness of the femoral middiaphysis, with no significant effects on the cortical vBMD or breaking energy of the femoral middiaphysis. High-dose Ris increased the vBMD to values higher than those in the sham-operated controls, and prevented the loss of SSI, maximum load, and stiffness of the femoral distal metaphysis, while low-dose Ris prevented the loss of cancellous vBMD of the femoral distal metaphysis. Neither high- nor low-dose Ris affected any of the cortical bone parameters of the femoral middiaphysis, except for cortical thickness, or the femoral length. These findings suggest that Ris may prevent immobilization-induced loss of cancellous bone density and bone strength in a dose-dependent manner without interfering with bone growth, but has no apparent effects on the cortical bone in sciatic neurectomized young rats. The results of the present preclinical study should be taken into consideration prior to the commencement of Ris treatment for disabled children.

We evaluated the skeletal effects of two osteoporosis therapies in an ovariectomized rat model, raloxifene and vitamin K2, as well as the vitamin K2 plus raloxifene (K + Ral) combination. In two studies, 6-month-old rats were ovariectomized, except for sham-ovariectomy controls (Sham), and dosed orally with vehicle, 30 mg/kg vitamin K2, 1 mg/kg raloxifene, or the combination of K + Ral for 6 weeks following surgery. Vitamin K2 had no effect on serum estrogen, low-density lipoprotein cholesterol (LDL-C), or urinary deoxypyridinoline levels, but slightly increased osteocalcin levels compared to Ovx. Raloxifene lowered total cholesterol, LDL-C, osteocalcin, and urinary deoxypyridinoline levels to below Ovx levels, while having no effect on estrogen levels. Raloxifene, but not vitamin K2, prevented ovariectomy-induced loss of bone in the distal femoral metaphysis and proximal tibial metaphysis, as did the K + Ral combination. Raloxifene, but not vitamin K2, partially prevented, loss of vertebral bone mineral density (BMD), whereas K + Ral had BMD greater than that of Ovx. Vitamin K2 increased bone formation rate to above Ovx, whereas raloxifene and K + Ral reduced bone formation rate to Sham levels. Vitamin K2 had no effect on eroded surface compared to Ovx, while raloxifene and K + Ral reduced eroded surface to Sham levels. Groups were not different in the BMD of femoral midshaft; however vitamin K2 was observed to increase periosteal mineralizing surface of the tibial shaft to above Ovx, while raloxifene reduced periosteal mineralizing surface toward Sham levels. Femoral neck strength was not different between groups, indicating no significant beneficial effect of either raloxifene or vitamin K2 at this site. However, K + Ral had reproducibly greater femoral neck strength than Ovx or Sham. Raloxifene, but not vitamin K2, partially prevented loss of lumbar vertebra strength; but K + Ral was not different from Sham or Ovx. Therefore, raloxifene and vitamin K2 had complementary effects on bone resorption and formation activities, respectively, resulting in a reproducible, significant improvement of femoral neck strength. These rat data suggest interesting therapeutic possibilities that may require clinical verification.

A phase-space distribution of a weak electron-beam injected into a cold plasma is experimentally investigated in electron time scales. It is shown that electron-beam holes in phase-space evolve dynamically from appearance to collapse, as synchronized with a wave packet dominated by a beam mode. The dependence of the hole velocity radii on the packet crest amplitudes indicates that the holes are induced by self-trapping of the beam. It is found that the beam is well trapped while the packet grows linearly, but easy to be detrapped after that.

The purpose of this study was to determine whether early changes in the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) during alendronate treatment would be correlated with the 1-year response of lumbar bone mineral density (BMD) in postmenopausal Japanese women with osteoporosis. One hundred five postmenopausal women with osteoporosis, aged 54-88 years, were treated with alendronate (5 mg daily) for 12 months. The urinary NTX levels were measured by enzyme-linked immunosorbent assay at the baseline and at 3, 6, and 12 months, and lumbar (L1-L4) BMD was measured by dual-energy X-ray absorptiometry using the Hologic QDR 1500W equipment at the baseline and at 12 months. The mean percent reduction in urinary NTX level at 3, 6, and 12 months was 36.8%, 49.5%, and 49.0%, respectively, the extent of reduction at 6 and 12 months being greater than that at 3 months, and the mean percent increase of the lumbar BMD at 12 months was 8.2%. Single regression analysis showed a significant correlation between the percent reductions in the urinary NTX level at 3, 6, and 12 months of treatment and the percent increase of the lumbar BMD at 12 months (r = 0.200, P < 0.05; r = 0.341, P < 0.001; and r = 0.338, P < 0.001, respectively). Thirty percent of the patients were labeled as poor responders at 3 months, with the reduction in the urinary NTX level being less than the minimum significant change (MSC); 61% of these patients showed a greater reduction in the urinary NTX level, exceeding the MSC, at 6 months. These results suggest that the changes in the urinary NTX levels at 3 and 6 months after the start of alendronate treatment at the dose of 5 mg daily may be correlated with the 1-year response of the lumbar BMD in postmenopausal Japanese women with osteoporosis. In other words, the greater the reduction of the urinary NTX level at 3 and 6 months after the start of alendronate treatment, the greater can be the expected increase of the lumbar BMD after 12 months of treatment. In this study, 70% of the patients were good responders, who showed a reduction of the urinary NTX level exceeding the MSC at 3 months. Among the remaining 30% poor responders, about 60% showed satisfactory reduction of the urinary NTX level, exceeding the MSC, at 6 months after the start of treatment with alendronate.

Exercise may enhance the effect of alendronate on bone mineral density (BMD) and reduce chronic back pain in elderly women with osteoporosis. The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover, and reduce chronic back pain in postmenopausal women with osteoporosis.Fifty post-menopausal women with osteoporosis, 55-88 years of age, were randomly divided into two groups of 25 patients each: one taking alendronate (5 mg daily, ALN) and one taking alendronate plus exercise (ALN+EX). Exercise consisted of whole-body vibration using a Galileo machine (Novotec, Pforzheim, Germany), at an intensity of 20 Hz, frequency once a week, and duration of exercise 4 minutes. The study lasted 12 months. Lumbar BMD was measured by dual energy X-ray absorptiometry (Hologic QDR 1500W). Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels were measured by enzyme-linked immunosorbent assay and standard laboratory techniques, respectively. Chronic back pain was evaluated by face scale score at baseline and every 6 months.There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, lumbar BMD, urinary NTX and serum ALP levels, or face scale score between the two groups. The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups. However, the reduction in chronic back pain was greater in the ALN+EX group than in the ALN group.The results of this study suggest that whole-body vibration exercise using a Galileo machine appears to be useful in reducing chronic back pain, probably by relaxing the back muscles in post-menopausal osteoporotic women treated with alendronate.

This paper reviews the interventions to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight. Weightlessness during space flight results in calcium, vitamin D, and vitamin K deficiency, increases urinary calcium excretion, decreases intestinal calcium absorption, and increases serum calcium level, with decreased levels of serum parathyroid hormone and calcitriol. Bone resorption is increased, whereas bone formation is decreased. The loss of bone mineral density (BMD) in the spine, femoral neck and trochanter, and pelvis is 1.0-1.6% per month. High calcium intake and vitamin D supplementation during space flight does not affect bone metabolism, but prevents an elevation of serum calcium level through increased calcitriol level, while vitamin K counteracts the reduction in bone formation. However, there are no data to show the efficacy of pharmaceutical agents for prevention of development of osteoporosis in astronauts during flight, although the preventative effect of bisphosphonates, testosterone, and vitamin K2 on cancellous bone loss in the tibia or BMD loss in the hindlimb was reported in tail-suspended mature rats. It still remains uncertain whether these agents can prevent cortical bone loss caused by weightlessness in tail-suspended rats. Therefore, in addition to calcium, vitamin D, and vitamin K supplementation, agents that have both potent anti-resorptive and anabolic effects on cancellous and cortical bone may be needed to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight.

We examined the effect of vitamin K and vitamin D supplementation on calcium balance in young rats fed a normal or low calcium diet. Eighty female Sprague-Dawley rats, 6 wk of age, were randomized by the stratified weight method into eight groups with 10 rats in each group: 0.5% (normal) or 0.1% (low) calcium diet, 0.5% or 0.1% calcium diet+vitamin K (vitamin K2, menatetrenone, 30 mg/100 g, food intake), 0.5% or 0.1% calcium diet+vitamin D (25 microg/100 g, food intake), and 0.5% or 0.1% calcium diet+vitamin K+vitamin D. The duration of the study was 10 wk. Vitamin K supplementation promoted the reduction in urinary calcium excretion and retarded the abnormal elevation of serum PTH level in rats fed a low calcium diet, and stimulated intestinal calcium absorption in rats fed a normal calcium diet. Vitamin D supplementation stimulated intestinal calcium absorption with prevention of the abnormal elevation of serum PTH levels and prevented hypocalcemia in rats fed a low calcium diet, and stimulated intestinal calcium absorption in rats fed a normal calcium diet. The stimulation of intestinal calcium absorption was associated with increased serum 1,25-dihydroxyvitamin D levels. An additive effect of vitamin K and vitamin D on intestinal calcium absorption was found only in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on calcium balance in young rats fed a normal or low calcium diet.

It is observed that electron-beam holes in phase-space evolve dynamically from arising to collapsing in electron time scales in an electron-beam-plasma system. The holes are synchronized with a wave packet dominated by a beam mode of the two-stream instability, and their velocity radii depend on the amplitudes of the packet crests. This shows that the holes are induced by the self-trapping of the beam. The observed images indicate that the holes keep alive due to the hard detrapping of the beam during the packet linear growth, but begin to collapse due to the easy detrapping in the packet saturation.

The article entitled “Effects of Vitamin K2 on Osteoporosis, published in Curr Pharm Des 2004; 10(21): 2557-76, by Iwamoto J, Takeda T and Sato Y.” has been retracted by the Editorial office of the journal Current Pharmaceutical Design, as the text, data and some figures used/referred in this review article are from sources which have been retracted or under investigation on the basis of data fabrication and falsification, authorship misconduct, duplicate publication, unethical research practices, text recycling/self-plagiarism, and unresolved concerns about data integrity and research conduct. The authors were informed of this complaint and were requested to give justification on the matter in their defense. However, no reply was received from their side in this regard. Some sources that have been retracted are as follows:1. Iwamoto J, Takeda T, Ichimura S. Combined treatment with vitamin K2 and bisphosphonate in postmenopausal women with osteoporosis. Yonsei Med J 2003; 44: 751-6. Available at: https://eymj.org/DOIx.php?id=10.3349/ymj.2019.60.1.115.2. Sato Y, Honda Y, Kuno H, Oizumi K. Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. Bone 1998; 23: 291-6. Available at: https://www.sciencedirect.com/science/article/pii/S8756328298001082.3. Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, et al. Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency. Bone 2002; 31: 114-8. Available at: https://pubmed.ncbi.nlm.nih.gov/ 12110423/.Bentham Science apologizes to its readers for any inconvenience this may have caused. The Bentham Editorial Policy on Article. Retraction can be found at https://benthamscience.com/editorial-policies-main.phpIt is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

The purpose of this study was to investigate the effect of alendronate on metacarpal and lumbar bone mineral density (BMD), bone resorption, and chronic back pain in postmenopausal women with osteoporosis. Eighty postmenopausal women with osteoporosis, 59–88 years of age, were divided into two groups of 40 each according to the site of BMD measurement: the metacarpus (M) and the lumbar spine (L). All of them were treated with alendronate (5 mg/day) for 12 months. Metacarpal or lumbar BMD was measured by computed X-ray densitometry or dual-energy X-ray absorptiometry in the M or the L group, respectively, at baseline and every 6 months. Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) were measured by enzyme-linked immunosorbent assay, and chronic back pain was evaluated by face scale score at baseline and every 6 months in both groups. There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, urinary NTX level, face scale score, or number of prevalent vertebral fractures per patient between the two groups. Urinary NTX level was reduced and chronic back pain was improved similarly in both groups. Whereas metacarpal BMD did not significantly change in the M group (0.20% increase), lumbar BMD increased by 8.15% in the L group. These results suggest that although alendronate increases BMD of the lumbar spine, which is rich in cancellous bone, and improves chronic back pain, with suppression of bone resorption in postmenopausal women with osteoporosis, it may fail to increase cortical BMD of the metacarpus, a distal site of the upper extremity.

The aim of the present study was to examine the effects of exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. Twenty 6-week-old female Wistar rats were randomized into the following four groups with 5 animals each: 7 weeks of exercise, 7 weeks of sedentary control, 11 weeks of exercise, and 11 weeks of sedentary control. The exercise regimen consisted of running on a treadmill at 25 m/min for 1 h each day on 5 days a week. After each period of exercise, the bone mineral content (BMC) of the tibia and fifth lumbar spine was measured by dual-energy X-ray absorptiometry, using a Lunar DPX-L instrument. The femoral length and levels of bone markers and calciotropic hormones were also assessed. Seven and 11 weeks of exercise increased the serum osteocalcin and 1,25-dihydroxyvitamin D(3) levels, and decreased the serum parathyroid level. Seven weeks of exercise decreased the urinary deoxypyridinoline level, and 11 weeks of exercise increased the serum alkaline phosphatase level and decreased the serum tartrate-resistant acid phosphatase level. As a result, 7 and 11 weeks of exercise increased the femoral length and tibial BMC, but did not alter the lumbar BMC. The present study demonstrates that treadmill exercise stimulates bone formation and suppresses bone resorption, increases the serum 1,25-dihydroxyvitamin D(3) level, and decreases the serum parathyroid hormone level, resulting in an increase in bone mass with stimulation of longitudinal bone growth, especially at weight-bearing sites, in young growing rats. Further studies with long-term exercise may be needed to obtain a positive effect on the lumbar BMC.

The aim of the present study was to analyze the effects of short-term treatment with the antiresorptive agent, etidronate, on orchidectomized adult rats, via comparison of three cancellous bone sites, the lumbar vertebral body (LVB), proximal tibial metaphysis (PTM), and distal tibial metaphysis (DTM). Thirty-five male Wistar rats, aged 10 months, were randomly divided into four groups: baseline control (BLC, nF10), age-matched sham-operated control (AMC, nF9), orchidectomy (ORX, nF9), and ORXBetidronate treatment (nF7). Etidronate treatment (10 mg/kg, daily subcutaneous injection) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, the 5th LVB, PTM, and DTM were processed for histomorphometric analysis of cancellous bone (secondary spongiosa). ORX resulted in a decrease in body weight. No significant difference in cancellous bone volume (BV/TV) was found between the BLC and AMC groups at any skeletal site. The cancellous BV/TV loss was attributable to increased eroded surface (ES/BS) with no significant alteration in the mineral apposition rate (MAR), at all skeletal sites and etidronate treatment in ORX rats significantly decreased ES/BS to a level not significantly different from that in the AMC group, resulting in complete prevention of ORX-induced cancellous BV/TV loss. The MAR was markedly decreased in the PTM and LVB, but maintained in the DTM by etidronate treatment. The present study showed that etidronate treatment could completely prevent ORX-induced cancellous bone loss regardless skeletal sites by suppressing bone resorption. In particular, suppression of bone formation in terms of osteoblastic activity by etidronate treatment was not evident only in the DTM

The purpose of the present study was to clarify the differences in the alterations of cellular activities of osteoblasts and osteoclasts, mineralization, and bone mass in cortical and cancellous bones of young growing rats with mild calcium deficiency. Twenty female Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified method into two groups with 10 rats in each group: 0.5% (normal) calcium diet group and 0.1% (low) calcium diet group. After 10 weeks of feeding, bone histomorphometric analysis was performed on cancellous bone of the proximal tibia as well as cortical bone of the tibial shaft. Calcium deficiency increased eroded surface (ES/bone surface [BS]) and the number of osteoclast (N.Oc/BS) with an increase in osteoblast surface (ObS/BS), but decreased bone formation rate (BFR/BS) in cancellous bone. However, cancellous bone volume was preserved, while cortical bone area was decreased as a result of decreased periosteal bone gain and enlargement of the marrow cavity. These results suggest that short-term mild calcium deficiency in young growing female rats increased bone resorption by increasing osteoclastic recruitment, and suppressed mineralization followed by increased osteoblastic recruitment in cancellous bone, but cancellous bone loss was counteracted through redistribution of calcium from cortical bone to cancellous bone.

The sternoclavicular joint is a diarthrodial joint that can be involved in rheumatoid arthritis (RA), and is detectable by ultrasound (US) examination in 15% of patients with RA1. Methotrexate-related lymphoproliferative disorder (MTX-LPD) occurs in extranodal sites in about 40%–50% of the affected patients2; however, intraarticular MTX-LPD is a very rare manifestation with only 1 case report occurring in the knee joint3 …

The purpose of the present open-labeled, randomized, prospective study was to compare the effects of cyclical etidronate combined with alfacalcidol with those of cyclical etidronate alone on lumbar bone mineral density (BMD), bone resorption, and back pain in postmenopausal women with osteoporosis. Forty postmenopausal women with osteoporosis, 60-86 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group. One group was treated with cyclical etidronate (oral etidronate 200 mg daily for 2 weeks every 3 months) and the other was given cyclical etidronate combined with alfacalcidol (cyclical etidronate plus alfacalcidol 1 Ig daily continuously). The BMD of the lumbar spine (L1-L4) measured by dual-energy X-ray absorptiometry, urinary crosslinked N-terminal telopeptides of type I collagen (NTX) measured by an enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Both treatments significantly reduced the urinary NTX level and back pain. Cyclical etidronate combined with alfacalcidol significantly increased the lumbar BMD with a more significant reduction in the urinary NTX level than cyclical etidronate alone, but cyclical etidronate alone did not significantly increase the lumbar BMD. Alleviation of back pain was similar in the two groups. These results suggest that cyclical etidronate combined with alfacalcidol appears to be more useful than cyclical etidronate alone for increasing the lumbar BMD by more markedly suppressing bone resorption in postmenopausal women with osteoporosis.

The purpose of this study was to investigate the association of stress fractures with age, sex, sport level, sporting activity, and skeletal site in athletes seen at our sports medicine clinic between September 1991 and May 2001. During these 10 years, 10 726 patients (6415 males, 3861 females) visited our clinic because of sport-related injuries, and 196 patients [125 males (1.9%), 71 females (1.8%)] sustained stress fractures. The average age of the patients with stress fractures was 20.1 years (range 10-46 years); 84 patients (42.6%) were 15-19 years of age, and 68 (34.7%) were 20-24 years of age. Altogether, 74 patients (37.8%) were active at the high recreational level and 122 (62.2%) at the competitive level. The sites of the stress fractures varied from sport to sport. The ulnar olecranon was the most common stress fracture site among baseball athletes and the rib among the rowing athletes. Classical ballet, aerobics, tennis, and volleyball athletes predominantly sustained stress fractures of the tibial shaft. Basketball athletes predominantly sustained stress fractures of the tibial shaft and medial malleolus and the metatarsal bone, whereas track and field and soccer athletes predominantly sustained stress fractures of the tibial shaft and pubic bone. Our results show that stress fractures are seen even in high-level adolescent athletes, with similar proportions for males and females, and that particular sports are associated with specific sites for stress fractures.

Osteoclastic activation rather than suppression of bone formation has been suggested to be the dominant process leading to bone loss in rheumatoid arthritis (RA). Although many studies have already shown the correlation of urinary pyridinoline (PYD) and deoxypyridinoline (DPD) levels with RA-related bone loss, urinary cross-linked N-telopeptides of type I collagen (NTx), a more specific marker of bone-derived type I collagen fragments in urine than urinary PYD and DPD in RA, has not been adequately studied. The purpose of the present study was to determine clinical factors that are associated with an increase in urinary NTx levels in patients with RA. One hundred and eighty-four patients with RA and 185 sex- and age-matched controls were enrolled in the study: 71 men, 37-68 years of age (RA: 31, controls: 40); 129 premenopausal women, 30-48 years of age (RA: 67, controls: 62), and 169 postmenopausal women, 48-69 years of age (RA: 86, controls: 83). The correlations of urinary NTx levels, measured by enzyme-linked immunosorbent assay with anatomic grade in the wrist, functional class, duration of disease, steroid use, modified health assessment questionnaire (HAQ) score for the upper and lower extremities, the levels of serum c-reactive protein and rheumatoid factor (RF), erythrocyte sedimentation rate, and/or years since menopause were examined by multiple regression analysis. Urinary NTx levels (nmol BCE/mmol Cr) did not differ significantly between men with RA and controls (53.2 +/- 29.6 vs 41.0 +/- 19.6, respectively), whereas urinary NTx levels were significantly higher in pre- and postmenopausal women with RA than in respective controls (premenopausal women: 57.1 +/- 36.6 vs 42.3 +/- 21.3, P

The purpose of the present study was to examine the early response of lumbar bone min- eral density (BMD), bone resorption, and back pain to alendronate after treatment with cyclical etidronate in postmenopausal women with osteoporosis. Forty postmenopausal women with osteopo- rosis, 60-83 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group: 18 months of cyclical etidronate (200 mg daily for 2 weeks every 3 months) group and 12 months of cyclical etidronate followed by 6 months of alendronate (5 mg daily) group. BMD of the lumbar spine (L1-L4) measured by DXA, urinary cross-linked N- terminal telopeptides of type I collagen (NTX) level measured by enzyme-linked immunosorbent assay, and back pain evaluated by face scale score were assessed at baseline and every 6 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two groups. Cyclical etidronate significantly reduced urinary NTx level and face scale score over 12 months, but did not significantly increase lumbar BMD. After 12 months of treatment, the switch to alendronate sig- nificantly reduced urinary NTX level and face scale score, and significantly increased lumbar BMD, while continued cyclical etidronate did not significantly alter these parameters. These results suggest that switching to alendronate after treatment with cyclical etidronate produces a greater response of lumbar BMD, bone resorption, and back pain than continued cyclical etidronate in postmenopausal women with osteoporosis. (Keio J Med 52 (2): 113-119, June 2003)

Previously we have shown that a modified Warthin-Starry (mWS) method, to which was added a minor change to prevent fading, is useful and convenient to detect chemically induced chromatin condensation during thymic apoptosis in rats treated with dexamethasone. In this study, we investigated the relationship between mWS-positive cells and programmed cell death in the interdigital spaces of the developing limb in fetal SD rats. The limbs were removed from fetuses at day 15 of gestation, and routinely processed for both hematoxylin and eosin (H&E) staining and the mWS method. The results clearly showed that the distribution pattern of mWS-positive cells coincided well with that for the programmed cell death observed by H&E staining in the mesenchyme of interdigital notches and at the areas corresponding to the interphalangeal joints. These results confirm that the mWS method might be useful and convenient to detect condensed chromatin during apoptosis in embryonic organogenesis as well as by chemical induction.

The purpose of the present study was to compare the therapeutic effects of risedronate (RIS) and alfacalcidol (ALF) on cancellous and cortical bone in ovariectomized osteopenic rats. Forty-two female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 microg/kg, p.o., daily). Treatment was started 6 weeks after surgery and continued for 6 weeks. Evaluation at 12 weeks after surgery revealed that ovariectomy (OVX) decreased the cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis as a result of an increase of the bone formation rate/bone surface (BFR/BS), BFR/BV, and eroded surface (ES/BS), while having no effect on the cortical area (Ct Ar) of the tibial diaphysis. OVX also decreased the maximum load of the femoral distal metaphysis, while having no effect on any mechanical property parameters of the femoral diaphysis. RIS (at all the doses) increased the BV/TV relative to the value in the OVX-Vehicle group, but the value was not restored to that observed in the Sham group. The effects of RIS (1.0 mg/kg and 2.5 mg/kg) were similar, and greater than those of RIS (0.1 mg/kg). ALF also increased the BV/TV relative to the OVX-Vehicle group, but the value was not restored to that observed in the Sham group, similar to the results of RIS (1.0 mg/kg and 2.5 mg/kg) treatment. The alterations of the structural parameters induced by RIS (at the doses) were attributable to suppression of the increase of ES/BS, BFR/BS, and BFR/BV. The alterations of the structural parameters induced by ALF were attributable to suppression of the increase of ES/BS and attenuation of the increase of BFR/BV, while the BFR/BS was maintained. ALF also increased the Ct Ar to beyond the value observed in the Sham group. RIS (at all the doses) had no effect on the mechanical properties of the femoral distal metaphysis, whereas ALF prevented the loss of the maximum load of the femoral distal metaphysis. Thus, the results of the present study show differential effects of RIS and ALF on cancellous and cortical bone in ovariectomized osteopenic rats.

The following articles have been retracted by the Editorial Board of Experimental Animals, because some parts of their contents were published elsewhere.

The purpose of this retrospective study was to compare the effects of long-term treatment (5 years) with elcatonin and alfacalcidol on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Fifty-six osteoporotic women, more than 5 years after menopause and 58-79 years of age, were enrolled in the study and allocated to an elcatonin treatment group (20 units IM, weekly; n = 30) or an alfacalcidol treatment group (1 micro g/day, daily; n = 26). BMD of the lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry at baseline and every year for 5 years. There were no significant differences in age, body mass index, years since menopause, BMD, or number of prevalent vertebral fractures at baseline between the two groups. One-way analysis of variance with repeated measurements showed no significant longitudinal changes in BMD in either group, suggesting that both treatments sustained the BMD over 5 years. Two-way analysis of variance with repeated measurements also showed no significant differences in longitudinal changes in BMD between the two groups, suggesting that the effects of the two treatments on BMD were similar. However, the number of incident vertebral fractures per patient was significantly lower in the alfacalcidol treatment group than in the elcatonin treatment group (0.80 +/- 1.19 and 2.08 +/- 2.73, respectively; P0.05). These findings indicate that both treatments appeared to sustain lumbar BMD similarly over a 5-year period in postmenopausal women with osteoporosis, but alfacalcidol treatment may be superior to elcatonin treatment regarding the incidence of vertebral fractures. Further study with prospective observations are needed to confirm the results of the present study.

The aims of the present study were to determine whether patients with painful bone metastases from primary cancer sites showed a higher level of a bone resorption marker than those with no evidence of skeletal-related events, and to clarify the efficacy of oral administration of etidronate for pain due to bone metastases and bone resorption. Thirty outpatients with cancer were recruited: 10 with pain due to bone metastasis from the primary cancer site; lung (4), prostate (3), and breast (3) (M group), and 20 with primary cancer of the stomach (11), colon (4), breast (3), lung (1), and bladder (1) with no such evidence of skeletal-related events (non-M group). None of the patients in the M group either needed morphine for pain relief or had hypercalcemia, although all of them had been taking nonsteroidal anti-inflammatory drugs (NSAIDs). During the study, they continued taking NSAIDs, as they had before the study. The level of urinary cross-linked N-telopeptides of type I collagen (NTx) at baseline was significantly higher in the M group than in the non-M group ( P < 0.01). Oral administration of etidronate (400 mg/day for 2 weeks) to patients in the M group significantly reduced bone pain 2 and 12 weeks after the start of treatment; however, the pain relief effect was diminished 12 weeks after the start of treatment, despite a significant decrease in urinary NTx level ( P < 0.05 by one-way analysis of variance [ANOVA] with repeated measurements). The present study provides evidence suggesting that patients with painful bone metastases from primary cancer sites may have a higher level of urinary NTx than those with no evidence of skeletal-related events, and that oral administration of etidronate at the dose we used may have the potential to transiently relieve their bone pain by decreasing abnormally raised bone resorption. Although the present study had a small sample size, and had no placebo controls, the results may be useful, especially as they raise additional questions that could stimulate further research in Japan.

The purpose of the present study was to determine whether etidronate treatment could prevent bone loss caused by orchidectomy (ORX) and unilateral sciatic neurectomy (NX) in adult male rats. Seventy-four male Wistar rats, aged 10 months, were randomly divided into eight groups: baseline controls (n = 10); age-matched sham-operated controls (AMC; n = 9); ORX (n = 9); NX (n = 10); ORX + NX (n = 9); ORX + etidronate treatment (ORX + E; n = 7); NX + E (n = 10); and ORX + NX + E (n = 10). Etidronate treatment (10 mg/kg per day subcutaneously) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, bone mineral density (BMD) of the proximal and middle tibia (PT and MT, respectively), distal and middle femur (DF and MF, respectively), and fourth lumbar vertebral body (LVB) was measured by dual-energy X-ray absorptiometry (Model DCS-600, Aloka, Tokyo, Japan). The mechanical properties of the MF and third LVB were measured by three-point bending and compression tests, respectively. Levels of urinary deoxypyridinoline (Dpd) and serum osteocalcin (Oc) were also measured by enzyme-linked immunosorbent assay. Four weeks of aging had no significant effects on BMD, bone mechanical properties, or bone markers. ORX significantly increased the levels of urinary Dpd and serum Oc, which resulted in significant decreases in BMD of the PT, MT, DF, MF, and fourth LVB, as well as the mechanical strength (maximum load) of the MF and third LVB. NX significantly increased levels of urinary Dpd and decreased levels of serum Oc, resulting in a significant decrease in BMD of the PT, DF, and fourth LVB. The ORX-induced decrease in BMD of the PT was more pronounced when combined with NX. Etidronate treatment for NX, ORX, and ORX + NX rats significantly decreased levels of urinary Dpd and serum Oc, resulting in complete prevention of loss of BMD and/or bone mechanical strength. The present study demonstrates the efficacy of etidronate treatment for prevention of bone loss caused by testosterone deficiency and immobilization in adult male rats.