Retraction: Paper “Efficacy of Oral Etidronate for Skeletal Diseases in Japan” by Iwamoto J, et al. [Yonsei Med J 2005 Jun;46(3):313-320]

Jun Iwamoto,Tsuyoshi Takeda,Yoshihiro Sato 연세대학교의과대학 2023 Yonsei medical journal Vol.64 No.5

We have decided to retract the paper entitled “Efficacy of Oral Etidronate for Skeletal Diseases in Japan” [Yonsei Med J 2005 Jun;46(3):313-320.] by Iwamoto J, Takeda T, Sato Y. From information obtained after publication, we have recently become aware of a number of issues related to scientific misconduct.

Retraction: Paper “Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures” by Iwamoto J, et al. [Yonsei Med J 20

Jun Iwamoto,Yoshihiro Sato,Mitsuyoshi Uzawa,Tsuyoshi Takeda,Hideo Matsumoto 연세대학교의과대학 2023 Yonsei medical journal Vol.64 No.3

We have decided to retract the paper entitled “Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures” [Yonsei Med J 2009 Aug;50(4):474-481] by Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. From information obtained after publication, we have recently become aware of a number of issues related to scientific misconduct.

Comparative effect of alendronate and teriparatide on bone mineral density and bone turnover among Japanese postmenopausal women with history of fragility fractures: A clinical practice-based observational study

Jun Iwamoto,Hitoshi Kono,Mitsuyoshi Uzawa 대한골다공증학회 2015 Osteoporosis and Sarcopenia Vol.1 No.1

A clinical practice-based observational study was performed to compare the outcome of alendronate (ALN) and teriparatide (TPTD) treatment among Japanese postmenopausal women with a history of fragility fractures. Sixty-one Japanese postmenopausal women with a history of fragility fractures were treated with ALN (35 mg weekly, n ¼ 32) or TPTD (20 mg daily, n ¼ 29) for 2 years in our outpatient clinic. Alfacalcidol (1 mg daily) was combined with ALN. The lumbar spine or total hip bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and bone turnover markers were monitored. ALN decreased the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) (38.3% after 3 months) and the serum levels of alkaline phosphatase (ALP) (25.7% at 24 months), whereas TPTD increased the serum levels of intact procollagen type 1 N-terminal propeptide (P1NP) and ALP (79% and 14.1%, respectively at 24 months). Both ALN and TPTD increased the lumbar spine BMD (8.8% and 15.9%, respectively) and sustained the total hip BMD at 24 months. One patient treated with ALN experienced vertebral fractures, and one patient treated with TPTD experienced a nonvertebral fracture. These results confirmed the differential effects of ALN and TPTD on bone turnover and the greater effect of TPTD on the BMD among Japanese postmenopausal women with a history of fragility fractures.

Comparison of Effects of Alendronate and Raloxifene on Lumbar Bone Mineral Density, Bone Turnover, and Lipid Metabolism in Elderly Women with Osteoporosis

Jun Iwamoto,Yoshihiro Sato,Mitsuyoshi Uzawa,Tsuyoshi Takeda,Hideo Matsumoto 연세대학교의과대학 2008 Yonsei medical journal Vol.49 No.1

Purpose: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. Subjects and Methods: One hundred twenty- two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. Results: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. Conclusion: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.

Efficacy of Oral Etidronate for Skeletal Disease in Japan

Jun Iwamoto,Tsuyoshi Takeda,Yoshihiro Sato 연세대학교의과대학 2005 Yonsei medical journal Vol.46 No.3

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.

Comparison of the Effect of Vitamin K2 and Risedronate on Trabecular Bone in Glucocorticoid-Treated Rats: A Bone Histomorphometry Study

Jun Iwamoto,Hideo Matsumoto,Tsuyoshi Tadeda,Yoshihiro Sato,James K. Yeh 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.2

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 μg/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. 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 μg/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.

Influence of Ovariectomy on Bone Turnover and Trabecular Bone Mass in Mature Cynomolgus Monkeys

Jun Iwamoto,Azusa Seki,Masao Matsuura,Yoshihiro Sato,Tsuyoshi Takeda,Hideo Matsumoto,James K. Yeh 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.3

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 bonespecific 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. 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 bonespecific 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.

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

Jun Iwamoto,Tsuyoshi Takeda,Yoshihiro Sato 연세대학교의과대학 2006 Yonsei medical journal Vol.47 No.2

Differential Effect of Vitamin K and Vitamin D Supplementation on Bone Mass in Young Rats Fed Normal or Low Calcium Diet

Jun Iwamoto,Tsuyoshi Takeda,Shoichi Ichimura,Yoshihiro Sato,James K. Yeh 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.2

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 (25μg/100g, 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.

Effects of Risedronate on Osteoarthritis of the Knee

Jun Iwamoto,Tsuyoshi Takeda,Yoshihiro Sato,Hideo Matsumoto 연세대학교의과대학 2010 Yonsei medical journal Vol.51 No.2

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 50mg/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.