Retraction Note: Forearm Bone Mineral Density in Postmenopausal Women with Rheumatoid Arthritis.

The Editors-in-Chief have retracted this article [1]. Serious concerns have been raised about the data presented [2], and after careful consideration and additional investigation the Editors-in-Chief no longer have confidence in this article.

Retraction Note: Urinary Cross-linked N-telopeptides of Type I Collagen Levels in Patients with Rheumatoid Arthritis.

The Editors-in-Chief have retracted this article [1]. Serious concerns have been raised about the data presented [2], and after careful consideration and additional investigation the Editors-in-Chief no longer have confidence in this article. All authors were contacted and did not respond to correspondence about this retraction.

Chair rising time is longer in postmenopausal women with history of nonvertebral fracture.

The objective of the present study was to clarify the relationships between physical function, bone mass, biochemical markers, renal function, and a history of nonvertebral fracture in postmenopausal women with osteoporosis. In total, 143 postmenopausal women with osteoporosis (mean age: 71.2 years) and an osteoporosis treatment-naïve status were recruited. Twenty-seven women had a history of nonvertebral fracture (nonvertebral fracture group) and 116 women did not (control group). The patients' bone mass, biochemical markers, estimated glomerular filtration rate (eGFR), unipedal standing time (index of body balance), and the five-repetition chair-rising time (index of muscle power) were compared between the two groups. Age, body mass index, bone mass, serum alkaline phosphatase, creatinine, albumin, urinary cross-linked N-terminal telopeptides of type I collagen, eGFR, and the unipedal standing time did not differ significantly between the two groups. However, the chair-rising time was significantly longer (12.3 sec vs. 9.6 sec) in the nonvertebral fracture group than in the control group. The odds ratio (95% confidence intervals) for nonvertebral fractures in subjects with a chair-rising time >10.1 sec (mean value) was 4.28 (1.78, 10.30). Thus, a significant association was found between the impairment of muscle power and a history of nonvertebral fracture in postmenopausal women with osteoporosis.

Comparison of non-vertebral fracture between minodronate and risedronate therapy in elderly female patients with Alzheimer disease.

OBJECTIVES: Minodronate is a nitrogen-containing bisphosphonate that is commercially available for the treatment of osteoporosis in Japan. Preclinical studies demonstrated that minodronate is at least 10 times more potent than alendronate in inhibiting bone resorption in vivo. A high incidence of fractures, particularly of the hip, represents an important problem in Alzheimer disease (AD) patients who are prone to falls and may have osteoporosis. METHODS: A total of 256 elderly patients with AD were assigned to daily treatment with 1.0 mg of minodronate or a daily treatment with risedronate combined with daily 1000 IU ergocalciferol and 1200 mg elemental calcium, and followed up for 12 months. RESULTS: At baseline, patients of both groups showed low 25-hydroxyvitamin D with compensatory hyperparathyroidism. Non-vertebral fractures occurred in 5 patients in the minodronate group and 7 patients in the risedronate group (5 hip fractures; one fracture each at the distal forearm and pelvis). There was no difference in risk of hip fracture between the two groups (p=.70; odds ratio=0.8). CONCLUSIONS: The study medications were well tolerated with relatively few adverse events and were equivalent in reducing the risk of a fracture in elderly patients with AD.

Sunlight exposure is important for preventing hip fractures in patients with Alzheimer's disease, Parkinson's disease, or stroke.

OBJECTIVES: Hypovitaminosis D as a result of malnutrition or sunlight deprivation, increased bone resorption, low bone mineral density (BMD), or an increased risk of falls may contribute to an increased risk of hip fractures in patients with neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. The purpose of this study was to clarify the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with such neurological diseases. METHODS: The English literature was searched using PubMed, and randomized controlled trials evaluating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke were identified. The relative risk and the 95% confidence interval were calculated for individual randomized controlled trials, and a pooled data analysis (meta-analysis) was performed. RESULTS: Three randomized controlled trials were identified. Sunlight exposure improved hypovitaminosis D and increased the BMD. The relative risk (95% confidence interval) of hip fractures was 0.22 (0.05, 1.01) for Alzheimer's disease, 0.27 (0.08, 0.96) for Parkinson's disease, and 0.17 (0.02, 1.36) for stroke. The relative risk (95% confidence interval) calculated for the pooled data analysis was 0.23 (0.10, 0.56) (P = 0.0012), suggesting a significant risk reduction rate of 77%. CONCLUSION: The present meta-analysis added additional evidence indicating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke.

Whole body vibration exercise improves body balance and walking velocity in postmenopausal osteoporotic women treated with alendronate: Galileo and Alendronate Intervention Trail (GAIT).

A randomized controlled trial was conducted to determine the effect of 6 months of whole body vibration (WBV) exercise on physical function in postmenopausal osteoporotic women treated with alendronate. Fifty-two ambulatory postmenopausal women with osteoporosis (mean age: 74.2 years, range: 51-91 years) were randomly divided into two groups: an exercise group and a control group. A four-minute WBV exercise was performed two days per week only in the exercise group. No exercise was performed in the control group. All the women were treated with alendronate. After 6 months of the WBV exercise, the indices for flexibility, body balance, and walking velocity were significantly improved in the exercise group compared with the control group. The exercise was safe and well tolerated. The reductions in serum alkaline phosphatase and urinary cross-linked N-terminal telopeptides of type I collagen during the 6-month period were comparable between the two groups. The present study showed the benefit and safety of WBV exercise for improving physical function in postmenopausal osteoporotic women treated with alendronate.

Chair rising exercise is more effective than one-leg standing exercise in improving dynamic body balance: a randomized controlled trial.

A randomized controlled trial was conducted to compare the effect of a one-leg standing exercise and a chair-rising exercise on body balance in patients with locomotive disorders. Thirty ambulatory patients (mean age: 66.6 years) were randomly divided into two groups (n=15 in each group): a one-leg standing exercise group and a chair-rising exercise group. All the participants performed calisthenics of the major muscles, a tandem gait exercise, and a stepping exercise. The exercises were performed 3 days per week, and the study period was 5 months. Physical function was evaluated at baseline and at one-month intervals. No significant differences in the baseline characteristics were observed between the two groups. After the 5-month exercise program, the timed up and go, one-leg standing time, and tandem gait time improved significantly in the one-leg standing exercise group, while the walking time and chair-rising time in addition to above parameters improved significantly in the chair-rising exercise group. The improvements in the walking time, chair-rising time, and tandem gait time were significantly greater in the chair-rising exercise group than in the one-leg standing exercise group. The present study showed that the chair-rising exercise was more effective than the one-leg standing exercise for improving walking velocity and dynamic body balance.

Alendronate is more effective than elcatonin in improving pain and quality of life in postmenopausal women with osteoporosis.

UNLABELLED: A randomized controlled trial was performed to compare the short-term effects of alendronate (ALN) and ECT on pain and quality of life (QOL) in postmenopausal women with osteoporosis. Back pain and QOL [Short-Form Health Survey (SF-8)] significantly improved at 1, 3, and 6 months in both groups, with greater improvements in the ALN group than in the ECT group. These results suggested that ALN reduced back pain and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain. INTRODUCTION: Intramuscular ECT is known to reduce pain via the central nervous system. A multicenter randomized controlled trial was performed to compare the short-term effects of ALN and ECT on pain and QOL in postmenopausal women with osteoporosis. METHODS: One hundred and 94 postmenopausal osteoporotic women with back pain (mean age 79.8 years, range 60-96 years) were randomly divided into two groups: the ALN group (35 mg weekly) and the ECT group (intramuscular 20 units a week). The duration of the study was 6 months. The trial was completed in 97 (100%) women of the ALN group and 96 (99.0%) women of the ECT group. Urinary levels of cross-linked N-terminal telopeptide of type I collagen (NTX), serum alkaline phosphatase (ALP), face scale score (FSS, back pain), and SF-8 (QOL) were monitored. RESULTS: Urinary NTX levels significantly decreased at 3 months in the ALN group, but not in the ECT group. Serum ALP levels significantly decreased at 6 months in the both groups, with a greater reduction in the ALN group. The FSS and SF-8 significantly improved at 1, 3, and 6 months in both groups, with greater improvements in the ALN group than in the ECT group. CONCLUSIONS: ALN suppressed bone turnover, reduced back pain, and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain.

Increasing the number of steps walked each day improves physical fitness in Japanese community-dwelling adults.

We aimed to investigate the effects of increasing the number of steps each day on physical fitness, and the change in physical fitness according to the angiotensin-converting enzyme (ACE) genotype. A total of 174 participants were randomly assigned to two groups. Subjects in group A were instructed for 24-week trial to increase the number of steps walked each day, while subjects in group B were instructed to engage in brisk walking, at a target heart rate, for 20 min or more a day on two or more days a week. The values of the 3-min shuttle stamina walk test (SSWT) and the 30-s chair-stand test (CS-30) significantly increased, but no differences in increase were found between the groups. A significant relationship was found between the percentage increase in SSWT values and the increase in the number of steps walked by 1 500 steps or more per day over their baseline values. Our results suggest that increasing the number of steps walked daily improves physical fitness. No significant relationships were observed between the change in physical fitness and ACE genotypes.

Preventative effect of exercise against falls in the elderly: a randomized controlled trial.

SUMMARY: The present study was conducted to determine the effect of 5-month exercise program on the prevention of falls in the elderly. The exercise training, which consisted of calisthenics, body balance training, muscle power training, and walking ability training 3 days/week improved the indices of the flexibility, body balance, muscle power, and walking ability and reduced the incidence of falls compared with non-exercise controls. The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly. INTRODUCTION: The present study was conducted to determine the effect of exercise on the prevention of falls in the elderly. METHODS: Sixty-eight elderly ambulatory volunteers were randomly divided into two groups: the exercise and control groups. The daily exercise, which consisted of calisthenics, body balance training (tandem standing, tandem gait, and unipedal standing), muscle power training (chair-rising training), and walking ability training (stepping), were performed 3 days/week only in the exercise group. No exercise was performed in the control group. RESULTS: After the 5-month exercise program, the indices of the flexibility, body balance, muscle power, and walking ability significantly improved in the exercise group compared with the control group. The incidence of falls was significantly lower in the exercise group than in the control group (0.0% vs. 12.1%, P = 0.0363). The exercise program was safe and well tolerated in the elderly. CONCLUSIONS: The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.

Effects of exercise on bone mineral density in mature osteopenic rats.

Dual-energy X-ray absorptiometry (DXA) was used to examine the effects of quantitative application of treadmill running exercise on bone mineral density (BMD) of the tibia and the fourth and fifth lumbar (L4 + L5) vertebrae in mature osteopenic rats. Twenty 37-week-old rats with bone loss, resulting from feeding a relatively low calcium diet for 14 weeks after ovariectomy at the age of 23 weeks, were divided into four groups of five rats each according to the intensity and duration of the exercise: 12 m/minute, 1 h/day in group EX1; 18 m/minute, 1 h/day in group EX2; 12 m/minute, 2 h/day in group EX3; and sedentary control in group CON. With a standard calcium diet, the exercise was performed 5 days a week for 12 weeks, and the BMD of both the right tibia and the L4 + L5 vertebrae was measured using DXA at weeks 0, 4, 8, and 12. At the end of 12 weeks of exercise, the right femur and the L5 vertebra were dissected and the mechanical strength was measured using a three-point bending test and a compression test, respectively. After 12 weeks of exercise, a significant increase in the tibial BMD was observed in only group EX1 compared with that in group CON (p = 0.0039, by two-way analysis of variance). However, any significant increase in the L4 + L5 vertebral BMD was not observed in any exercise groups compared with that in the control group. While a maximum breaking force of the femoral shaft in group EX1 was significantly greater than that in group CON (p < 0.05, by Mann-Whitney's U-test), that in groups EX2 and EX3 did not significantly differ from that in group CON. However, there was no significant difference in a maximum breaking force of the L5 vertebral body among all the exercise and control groups. These results indicated that the beneficial effects of treadmill running exercise under a standard calcium diet were recognized only in the weight-bearing bones of the mature osteopenic rats resulting from estrogen deficiency and inadequate calcium intake only when an optimal level of exercise was applied.

Effect of deconditioning on cortical and cancellous bone growth in the exercise trained young rats.

Exercise enhances bone growth and increases peak bone mass. The aim of this study was to determine whether or not 4 weeks of deconditioning after 8 weeks of exercise in growing rats would result in a decrease in bone gain or reverse the benefits of exercise. Fifty 4-week-old female Sprague-Dawley rats were randomized by a stratified weight method into 5 groups with 10 rats in each group: 8 weeks exercise (8EX), 8 weeks sedentary control (8S), 12 weeks exercise (12EX), 8 weeks exercise followed by 4 weeks sedentary (8EX4S), and 12 weeks sedentary control (12S). The exercise consisted of running on a treadmill with a 5 degrees slope at 24 m/minute for 1 h/day and 5 days/week. After each period of exercise, cancellous and cortical bone histomorphometry were performed on double fluorescent labeled 5-microm-thick sections of the proximal tibia and 40-microm-thick sections of the tibial shaft, respectively. Eight and 12 weeks of exercise resulted in a significant increase in the body weight and gastrocnemius muscle weight by two-way analysis of variance (ANOVA). The femoral wet weight (mg; mean +/- SD; 8EX, 781 +/- 45.1 vs. 8S, 713 +/- 40.5; p < 0.05; 12EX, 892 +/- 41.6 vs. 12S, 807 +/- 19.8; p < 0.05) was significantly higher in the exercise group than that in the respective control groups. The femoral wet weight and bone volume (BV) of the 8EX4S group (818 +/- 46.2 mg and 531 +/- 31.2 microl, respectively) were significantly lower than those of the 12EX group (p < 0.05) and did not differ significantly from those of the 12S groups. The cancellous BV was significantly higher in the 8EX and 12EX groups than that in the respective sedentary groups (p < 0.05). The cortical bone area of the tibial shaft was also significantly higher in the 12EX than that in the 12S group (p < 0.05). The increase in the cancellous BV or cortical bone area was caused by an increase in the mineral apposition rate (MAR), without a significant effect in the labeled perimeter. The bone formation rate (BFR; microm3/microm2 per day) in the cancellous bone (12EX, 27.9 +/- 7.74 vs. 12S, 15.4 +/- 4.56; p < 0.05) or periosteal surface (12EX, 127.6 +/- 27.7 vs. 12S, 79.5 +/- 18.6; p < 0.05) was significantly higher in the exercised groups than that in the respective control group (p < 0.05). Again, deconditioning resulted in a decrease in the cancellous BFR, BV, periosteal BFR, and cortical bone area to levels not significantly different from the 12S group. In conclusion, our findings showed that exercised growing rats, when deconditioned, lost the benefits gained through exercise and their bone parameters were reduced to levels not different from the sedentary control. Thus, continued exercise is required to maintain high bone mass.

Differential effect of treadmill exercise on three cancellous bone sites in the young growing rat.

The aim of the present study was to examine cancellous bone changes induced by exercise on three different skeletal sites, the lumbar vertebra, the proximal, and the distal tibia, in the young growing rat. Forty 4-week-old female Sprague-Dawley rats were randomized into 4 groups of 10 animals each; 8 weeks exercise (8EX), 8 weeks sedentary control (8CON), 12 weeks exercise (12EX), and 12 weeks sedentary control (12CON). The exercise regimen consisted of treadmill running at 24 m/min 1 hr per day 5 days a week. After each period of exercise, the proximal and distal tibial metaphyses (PTM and DTM, respectively) and the fifth lumbar (L5) vertebral body were processed for histomorphometry of the cancellous bone (secondary spongiosa) and cortical periosteum. Eight and twelve weeks of exercise significantly increased the mineral apposition rate and bone formation rate in the PTM and DTM, and 12 weeks of exercise significantly increased the labeled perimeter in the DTM, compared with the age-matched controls. Eight and twelve weeks of exercise significantly increased cancellous bone volume in the PTM (mean +/- standard deviation, 8EX; 19.1 +/- 2.9% vs 8CON; 14.3 +/- 3.1%, P < 0.05 and 12EX; 18.8 +/- 3.5% vs 12CON; 15.2 +/- 3.3%, P < 0.05), and 12 weeks exercise significantly increased cancellous bone volume in the DTM, compared with age-matched control (12EX; 32.5 +/- 7.7%, 12CON; 22.2 +/- 4.8%, P < 0.05). The increase in cancellous bone volume by 12 weeks exercise was higher in the DTM than that in the PTM (43.4% and 24.0%, respectively). On the other hand, the exercise did not significantly affect cancellous bone volume and bone formation in the L5 vertebral body, although the cortical periosteal bone formation rate and the L5 vertebral bone mass were increased. These findings suggest that cancellous bone adaptation to treadmill exercise is site specific, and the effect may be influenced by factors such as mechanical loading and metaphyseal bone architecture in the young growing rat.

RETRACTED: Comparative effects of vitamin K and vitamin D supplementation on prevention of osteopenia in calcium-deficient young rats.

The aim of this study was to clarify the difference in the effects of vitamin K and vitamin D supplementation on the development of osteopenia in young rats under mild calcium deficiency. Sixty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into six groups with 10 rats in each group: baseline control, 0.5% (normal) calcium diet, 0.1% (low) calcium diet, 0.1% calcium diet + vitamin K (30 mg/100 g, food intake), 0.1% calcium diet + vitamin D (25 microg/100 g, food intake), and 0.1% calcium diet + K + D. After 10 weeks of feeding, serum calcium, 25-hydroxyvitamin D(3) [25 (OH) D(3)], 1,25-dihydroxyvitamin D(3) [1,25 (OH)(2) D(3)], and parathyroid hormone (PTH) levels were measured, and intestinal calcium absorption and renal calcium reabsorption were evaluated. Bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Calcium deficiency induced hypocalcemia, increased serum PTH and 1,25 (OH)(2) D(3) levels with decreased serum 25 (OH) D(3) level, stimulated intestinal calcium absorption and renal calcium reabsorption, and reduced maturation-related cortical bone gain as a result of decreased periosteal bone gain and enlarged marrow cavity but did not significantly influence maturation-related cancellous bone gain. Vitamin K supplementation in calcium-deficient rats stimulated renal calcium reabsorption, retarded the abnormal elevation of serum PTH level, increased maturation-related cancellous bone gain, and retarded the reduction in maturation-related cortical bone gain. On the other hand, vitamin D supplementation in calcium-deficient rats stimulated intestinal calcium absorption via increased serum 1,25 (OH)(2) D(3) level with prevention of the abnormal elevation of serum PTH level, prevented hypocalcemia, reduced the maturation-related cancellous bone gain, and prevented the reduction in periosteal bone gain and enhanced enlargement of the marrow cavity with no significant effect on the reduction in maturation-related cortical bone gain. However, no synergistic effect of vitamin K and vitamin D on intestinal calcium absorption, renal calcium reabsorption, and cancellous and cortical bone mass was found. This study shows the differential effects of vitamin K and vitamin D supplementation on the development of osteopenia in young rats under mild calcium deficiency. Vitamin K supplementation stimulates renal calcium reabsorption, increases maturation-related cancellous bone gain, and retards the reduction in maturation-related cortical bone gain, whereas vitamin D supplementation stimulates intestinal calcium absorption and prevents the reduction in maturation-related periosteal bone gain by inducing accumulation of calcium from cancellous and endocortical bone.

Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats.

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.

Effects of moderate intensity exercise on tibial bone mass in mature ovariectomized rats: bone histomorphometry study.

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.

Effect of increased physical activity on bone mineral density in postmenopausal osteoporotic women.

The effect of increased physical activity on bone mineral density (BMD) of the lumbar vertebrae was examined in postmenopausal osteoporotic women. Thirty-five postmenopausal women, aged 53-77 years, whose BMD in the lumbar vertebrae (L2-L4) measured by dual energy x-ray absorptiometry (Norland XR-26) was below (> 30%) the young adult mean, were divided into two groups: a control group of 20 women and an exercise group of 15 women. The physical exercise consisted of daily outdoor walking and gymnastic training performed for 12 months. During the study period, all subjects were treated with calcium lactate, 2.0 g, and 1 alpha-hydroxyvitamin D3, 1 microgram, daily. Initial L2-L4 BMD was 0.611 +/- 0.045 (mean +/- SEM) g/cm2 in the control group and 0.606 +/- 0.066 g/cm2 in the exercise group (NS). In the control group, the BMD changes were -0.54 +/- 0.58% (mean +/- SEM) at 6 months and +1.00 +/- 1.29% at 12 months, compared to the baseline (P = 0.3424, by oneway ANOVA). In the exercise group, however, the changes were +1.78 +/- 0.90% and +4.48 +/- 0.93%, respectively (P = 0.0305, by two-way ANOVA). These data suggest that increased physical activity consisting of daily outdoor walking and gymnastic training can be useful in increasing lumbar BMD in postmenopausal osteoporotic women on calcium and vitamin D3 supplementation.

The cytoprotective role of lipopolysaccharide-induced nitric oxide against liver damage during early phase of endotoxemia in rats.

Lipopolysaccharide (LPS)-induced endotoxemia produces nitric oxide (NO); however, the role of the NO during endotoxemia is still controversial. The aim of this study was to investigate a role of LPS-induced NO during the early phase of endotoxemia. Wistar rats were intraperitoneally injected with saline or LPS at various doses (0.001, 0.01, or 5 mg/kg), and intra-abdominal NO concentration was determined by chemiluminescence before and after LPS administration at indicated times (1, 2, 6, 10, and 18 h). Serum aspartate aminotransferase and alanine aminotransferase levels were determined and histological examination was performed 10 h after LPS administration to assess liver damage. N(G)-nitro-L-arginine-methyl ester (L-NAME), a nonselective inhibitor of NO synthase, was used to investigate the possible roles of NO during LPS-induced endotoxemia. The intra-abdominal NO concentration was elevated within 2 h and reached a maximal level at 10 h after low doses of LPS injection (0.001 and 0.01 mg/kg) while liver damage was not observed. After high-dose LPS (5 mg/kg) administration, liver damage was observed and intra-abdominal NO was elevated continuously until 18 h. A time course study revealed very similar patterns of intra-abdominal NO increase after the three different dose of LPS at each times points during the first 10 h. Pretreatment of L-NAME inhibited the intra-abdominal NO release and aggravated the liver damage caused by low doses (0.001 and 0.01 mg/kg) of LPS as well as high dose (5 mg/kg) of LPS. Therefore, NO, released during the first 10 h after LPS injection, may play a cytoprotective role in the liver.

Nitric oxide inhibition varies with hemoglobin saturation.

Endothelium-derived nitric oxide (NO) appears to be involved in the regulation of pulmonary vascular tone by O2. We hypothesized that the ability of blood to inhibit the vasodilation caused by NO would vary inversely with the saturation of hemoglobin by O2. To test this hypothesis, we used the pulmonary circulation of the unanesthetized fetal lamb as a bioassay for NO-induced vasodilation. Two to 3 days before the experiment, the main pulmonary artery, left atrium, carotid artery, and trachea of the fetus were catheterized and an ultrasonic blood flow transducer was placed around the proximal portion of the left pulmonary artery. On the day of the experiment, NO solution was prepared by bubbling 10% NO-90% N2 gas mixture in saline. This solution was injected into the fluid-filled potential air spaces of the fetal lungs via the trachea. At the highest dose (0.8 mumol), NO increased pulmonary blood flow fourfold and decreased pulmonary vascular resistance similarly. The dose-response curve for NO was similar to those obtained from isolated pulmonary blood vessels and gas-ventilated animals. Mixing NO solution with maternal arterial blood before injection decreased the effect of NO, and mixing it with venous blood virtually eliminated the effect. The decrease in fetal pulmonary vascular resistance caused by NO was inhibited by blood in inverse proportion to the saturation of hemoglobin with O2 in the blood (R2 = 0.93, P < or = 0.0001), confirming our hypothesis.