Effects of gender and employment situation on weight loss and lifestyle modification were assessed in a 3-month intervention study done for overweight and obesity. A total of 384 individuals in Izumo City Japan, participated from 2000 to 2006. Lifestyle modifications were quantitatively evaluated by calculating calories of energy intake and expenditure. Eleven men and 15 women failed to complete the intervention; they were significantly younger in both genders, and the women had a higher rate of employment than the completing group (91 men and 267 women). Intervention induced a weight loss of 1.9 kg for men and 1.6 kg for women, with no significant differences by gender. Significant differences were found in changes in energy intake and expenditure in both genders, but these disappeared after adjusting for weight. There were significant decreases in weight (1.6 kg in unemployed, 2.5 kg in employed) in men. Increases in walking and exercise for the employed were smaller than those for the unemployed. The relationship between changes in weight and energy balance by employment status was independently significant using multiple regression analysis. Employment is associated with difficulty in losing weight due to limited exercise time in behavioral intervention.

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p< 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p< 0.05 and R2=0.103, p< 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p< 0.001), serum ALP level, and urinary NTX level (R2=0.074, p< 0.05 and R2=0.160, p< 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.
Aged ; Aged, 80 and over ; Alendronate/*administration & dosage ; Alkaline Phosphatase/blood ; Bone Density/*drug effects ; Calcium/blood ; Collagen/urine ; Densitometry, X-Ray ; Female ; Humans ; Incidence ; Japan ; *Lumbar Vertebrae/radiography ; Middle Aged ; Osteoporosis, Postmenopausal/*drug therapy/epidemiology/radiography ; Peptides/urine ; Phosphorus/blood ; Spinal Fractures/epidemiology/prevention & control

Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects.
Administration, Oral ; Bone Diseases/*drug therapy ; Etidronic Acid/*administration & dosage ; Humans ; Japan

The purpose of the present study was to discuss the effects of risedronate on osteoarthritis (OA) of the knee by reviewing the existing literature. The literature was searched with PubMed, with respect to prospective, double-blind, randomized placebo-controlled trials (RCTs), using the following search terms: risedronate, knee, and osteoarthritis. Two RCTs met the criteria. A RCT (n = 231) showed that risedronate treatment (15 mg/day) for 1 year improved symptoms. A larger RCT (n = 1,896) showed that risedronate treatment (5 mg/day, 15 mg/day, 35 mg/week, and 50 mg/week) for 2 years did not improve signs or symptoms, nor did it alter radiological progression. However, a subanalysis study (n = 477) revealed that patients with marked cartilage loss preserved the structural integrity of subchondral bone by risedronate treatment (15 mg/day and 50 mg/week). Another subanalysis study (n = 1,885) revealed that C-terminal crosslinking telopeptide of type II collagen (CTX-II) decreased with risedronate treatment in a dose-dependent manner, and levels reached after 6 months were associated with radiological progression at 2 years. The results of these RCTs show that risedronate reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone. The review of the literature suggests that higher doses of risedronate (15 mg/day) strongly reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone.
Animals ; Calcium Channel Blockers/pharmacology/*therapeutic use ; Cartilage/drug effects ; Diphosphonates/therapeutic use ; Etidronic Acid/*analogs & derivatives/pharmacology/therapeutic use ; Humans ; Osteoarthritis, Knee/*drug therapy

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.
Vitamin K 2/chemistry/metabolism/*pharmacology ; Tomography, X-Ray Computed ; Tibia/pathology ; Rats ; Osteoporosis/*drug therapy/*prevention & control ; Male ; Magnesium Deficiency/diagnosis ; Magnesium/metabolism ; Homeostasis ; Female ; *Disease Models, Animal ; Diphosphonates ; Calcium/metabolism ; Bone and Bones/*drug effects/metabolism ; Bone Resorption ; Bone Diseases, Metabolic/*metabolism ; Animals

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.
Spinal Fractures/prevention & control/radiography ; Osteoporosis, Postmenopausal/*drug therapy ; Middle Aged ; Lumbar Vertebrae/*drug effects ; Humans ; Female ; Etidronic Acid/adverse effects/*therapeutic use ; Bone Density Conservation Agents/adverse effects/*therapeutic use ; Bone Density/*drug effects ; Biological Markers/blood/urine ; Back Pain/drug therapy ; Alendronate/adverse effects/*therapeutic use ; Aged, 80 and over ; Aged

Osteoporosis is one of the most serious complications of corticosteroid treatment. Loss of bone mineral density (BMD) and fractures occur early in the course of corticosteroid treatment, and thus early recognition of fracture risk and effective intervention based on evidence-based-medicine (EBM) are needed. A study of meta-analysis representing the highest level in a hierarchy of evidence showed that when the outcome measure of interest was limited to changes in lumbar spine BMD, bisphosphonates were the most effective of the agents studied in comparison with no therapy or treatment with calcium, and were also more efficacious than either vitamin D or calcitonin; the efficacy of bisphosphonates was enhanced when used in combination with vitamin D. Randomized controlled trials (RCTs) representing the second level in a hierarchy of evidence showed that bisphosphonates stabilized BMD not only in the lumbar spine, but also in the hip, and that parathyroid hormone (PTH) markedly increased lumbar spine BMD. According to the EBM, bisphosphonates and possibly PTH are suggested to be the most efficacious for preserving BMD. The efficacy of these agents in reducing the incidence of vertebral fractures in patients exposed to corticosteroids remains to be established in meta-analysis studies, although some RCTs have demonstrated the anti-fracture effects of etidronate, alendronate, and risedronate in the spine. Further RCTs of fracture prevention conducted on a large number of patients and their meta-analysis are needed to confirm the efficacy of bisphosphonates, PTH, or other agents in preventing vertebral and nonvertebral fractures.
Adrenal Cortex Hormones/*adverse effects ; Bone Density ; Diphosphonates/therapeutic use ; Estrogens/therapeutic use ; Humans ; Osteoporosis/*chemically induced/*drug therapy/prevention & control ; Parathyroid Hormone/therapeutic use ; Vitamin K 2/therapeutic use

PURPOSE: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. MATERIALS AND METHODS: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. RESULTS: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. CONCLUSION: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.
Alkaline Phosphatase/blood ; Animals ; *Bone Density ; Collagen Type I/urine ; Female ; Femur Neck/metabolism ; Lumbar Vertebrae/metabolism ; Macaca fascicularis/*physiology ; Ovariectomy/*adverse effects ; Radius/metabolism ; Random Allocation

PURPOSE: To compare the effect of vitamin K2 and risedronate on trabecular bone in glucocorticoid (GC)-treated rats. MATERIALS AND METHODS: Forty-eight Sprague-Dawley female rats, 3 months of age, were randomized by the stratified weight method into 5 groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K2, risedronate, or vitamin K2 + risedronate. GC (methylprednisolone sodium succinate, 5.0 mg/kg) and risedronate (10 microgram/kg) were administered subcutaneously three and five times a week, respectively. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally three times a week. At the end of the 8-week experiment, bone histomorphometric analysis was performed on trabecular bone of the tibial proximal metaphysis. RESULTS: GC administration decreased trabecular bone mass compared with age-matched controls because of decreased bone formation (mineralizing surface, mineral apposition rate, and bone formation rate) and increased bone erosion. Vitamin K2 attenuated GC-induced trabecular bone loss by preventing GC-induced decrease in bone formation (mineralizing surface) and subsequently reducing GC-induced increase in bone erosion. Risedronate prevented GC-induced trabecular bone loss by preventing GC-induced increase in bone erosion although it also suppressed bone formation (mineralizing surface, mineral apposition rate, and bone formation rate). Vitamin K2 mildly attenuated suppression of bone formation (mineralizing surface) and bone erosion caused by risedronate without affecting trabecular bone mass when administered in combination. CONCLUSION: The present study showed differential effect of vitamin K2 and risedronate on trabecular bone in GC-treated rats.
Animals ; Bone Density/drug effects ; Bone and Bones/anatomy & histology/*drug effects/metabolism ; Etidronic Acid/*analogs & derivatives/pharmacology ; Female ; Glucocorticoids/*pharmacology ; Random Allocation ; Rats ; Vitamin K/*pharmacology ; Vitamins/*pharmacology

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25microgram/100 g, food intake), or vitamin K + vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.
Age Factors ; Animals ; Antifibrinolytic Agents/*pharmacology ; Bone Density/*drug effects ; Bone Development/*drug effects ; Calcium, Dietary/*pharmacology ; Dietary Supplements ; Female ; Rats ; Rats, Sprague-Dawley ; Vitamin D/*pharmacology ; Vitamin K/*pharmacology