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J Bone Miner Metab 2021 Mar 11. Epub 2021 Mar 11.

Eikokai Ono Hospital, Hyogo, Japan.

J Orthop Sci 2020 Dec 22. Epub 2020 Dec 22.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, Nagano, Japan.

Backgroud: Changes in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone. Read More

Sci Rep 2020 12 16;10(1):22090. Epub 2020 Dec 16.

Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. Read More

J Clin Pharmacol 2021 May 1;61(5):606-613. Epub 2020 Nov 1.

Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

The prevention of fractures is the ultimate goal of osteoporosis treatments. To achieve this objective, developing a method to predict fracture risk in the early stage of osteoporosis treatment would be clinically useful. This study aimed to develop a mathematical model quantifying the long-term fracture risk after 2 annual doses of 5 mg of once-yearly administered zoledronic acid or placebo based on the short-term measurement of bone turnover markers or bone mineral density (BMD). Read More

Aging Cell 2020 11 13;19(11):e13247. Epub 2020 Oct 13.

Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Marrow adipocytes and osteoblasts differentiate from common mesenchymal progenitors in a mutually exclusive manner, and diversion of these progenitors toward adipocytes in old age has been proposed to account for the decline in osteoblasts and the development of involutional osteoporosis. This idea has been supported by evidence that thiazolidinedione (TZD)-induced activation of PPARγ, the transcription factor required for adipocyte differentiation, increases marrow fat and causes bone loss. We functionally tested this hypothesis using C57BL/6J mice with conditional deletion of PPARγ from early mesenchymal progenitors targeted by the Prx1-Cre transgene. Read More

J Bone Miner Metab 2020 Nov 5;38(6):746-758. Epub 2020 Sep 5.

Eikokai Ono Hospital, Hyogo, Japan.

Accumulating evidence has shown that patients with lifestyle diseases such as type 2 diabetes mellitus, chronic kidney disease, and chronic obstructive pulmonary disease are at increased risk of osteoporotic fracture. Fractures deteriorate quality of life, activities of daily living, and mortality as well as a lifestyle disease. Therefore, preventing fracture is an important issue for those patients. Read More

Curr Med Res Opin 2020 11 14;36(11):1847-1859. Epub 2020 Sep 14.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, Nagano, Japan.

Aims: We conducted a head-to-head randomized trial of minodronate, a bisphosphonate, and raloxifene, a selective estrogen receptor modulator, to obtain clinical evidence and information about their efficacy and safety.

Methods: The Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04) trial is a multi-center, open-labeled, blinded endpoints, head-to-head randomized trial of minodronate and raloxifene. Ambulatory elderly women with osteoporosis (age, >60 years) were randomly allocated to the raloxifene or minodronate group by central registration. Read More

Calcif Tissue Int 2020 12 25;107(6):559-566. Epub 2020 Aug 25.

Touto Sangenjaya Rehabilitation Hospital, Tokyo, Japan.

In this post hoc analysis of the Denosumab Fracture Intervention Randomized Placebo-Controlled Trial (DIRECT) in Japanese postmenopausal women and men with osteoporosis, we evaluated the relationship between vertebral fracture risk and both bone mineral density (BMD) T-score and percent change after 24 months of denosumab treatment at total hip, femoral neck, and lumbar spine. Logistic regression analysis was performed and the proportion of treatment effect explained by BMD in vertebral fracture risk was estimated. The results demonstrate that both total hip BMD T-score and change can be strong predictors of subsequent fracture risk, and that total hip BMD change explained 73%, while T-score explained 23%, of the treatment effect. Read More

J Bone Miner Metab 2020 Nov 15;38(6):848-858. Epub 2020 Jul 15.

Touto Sangenjaya Rehabilitation Hospital, Tokyo, Japan.

Introduction: In anti-osteoporosis drug trials, vitamin D and calcium (Ca) are common supplements; however, the optimal dose of each is unclear. Using data from the randomized, double-blind, placebo-controlled DIRECT trial, we assessed whether baseline serum 25-hydroxy vitamin D (25[OH]D) level influences the efficacy of denosumab co-administered with vitamin D and Ca.

Materials And Methods: In this prespecified sub-analysis, subjects with primary osteoporosis who received denosumab or placebo, plus vitamin D (≥ 400 IU/day) and Ca (≥ 600 mg/day), were classified as 25(OH)D deficient (< 20 ng/mL), insufficient (≥ 20 to < 30 ng/mL), and sufficient (≥ 30 ng/mL). Read More

Bone 2020 08 30;137:115404. Epub 2020 Apr 30.

Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano 399-8101, Japan.

Although associations among obesity, adipocytokines, and bone mineral density have been reported, the influence of adipocytokines on osteoporotic fractures remains unclear. This study aimed to assess the impact of the adipocytokines leptin and adiponectin on the risk of incident vertebral and long-bone fractures in postmenopausal women. Clinical data were obtained from the retrospective Nagano Cohort Study of outpatients followed at a single primary care institute in Nagano Prefecture, Japan, between 1993 and 2018. Read More

Menopause 2019 11;26(11):1277-1283

Touto Sangenjaya Rehabilitation Hospital, Tokyo, Japan.

Objective: This randomized, clinical trial investigated whether zoledronic acid combined with oral health maintenance can improve periodontal disease associated with osteoporosis, thus reducing the risk of tooth loss.

Methods: Participants were those of the ZONE (ZOledroNate treatment in efficacy to osteoporosis) study. None of the participants had symptomatic periodontal disease at baseline. Read More

IEEE Trans Med Imaging 2020 05 23;39(5):1359-1368. Epub 2019 Oct 23.

Osteoporosis is an age-associated disease characterised by low bone mineral density (BMD) and micro-architectural deterioration leading to enhanced fracture risk. Conventional dual-energy X-ray absorptiometry (DXA) analysis has facilitated our understanding of BMD reduction in specific regions of interest (ROIs) within the femur, but cannot resolve spatial BMD patterns nor reflect age-related changes in bone microarchitecture due to its inherent averaging of pixel BMD values into large ROIs. To address these limitations and develop a comprehensive model of involutional bone loss, this paper presents a fully automatic pipeline to build a spatio-temporal atlas of ageing bone in the proximal femur. Read More

Clin Chim Acta 2019 Nov 16;498:101-107. Epub 2019 Aug 16.

Women's Medical Center, Sanno Medical Center, 8-5-35 Akasaka, Minato-ku, Tokyo 107-0052, Japan.

With the aging of society, the number of osteoporosis-related fractures is increasing. Prevention of osteoporosis and maintenance of the quality of life of osteoporosis patients require early diagnosis, effective treatment, and highly precise treatment monitoring. Although bone biopsy is clinically one of the essential techniques for diagnosis of osteoporosis, it is invasive and difficult to perform in general clinical practice. Read More

J Bone Miner Metab 2020 Jan 16;38(1):86-98. Epub 2019 Aug 16.

Internal Medicine 1, Shimane University, Faculty of Medicine, Izumo, Shimane, Japan.

Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with involutional osteoporosis. Patients received 2. Read More

Osteoporos Int 2019 Nov 8;30(11):2321-2331. Epub 2019 Aug 8.

Toto Sangenjaya Rehabilitation Hospital, 1-24-3 Sangenjaya, Setagaya-ku, Tokyo, 154-0024, Japan.

A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen of teriparatide, while also improving safety. Read More

J Bone Miner Metab 2019 Nov 18;37(6):1067-1074. Epub 2019 Jun 18.

Department of Orthopedic Surger, Jikei University School of Medicine, Tokyo, Japan.

To evaluate whether or not the urinary pentosidine level has clinical value in the assessment of the osteoporotic fracture risk, a novel ELISA for pentosidine was used in clinical samples. This study employed a cross-sectional design to analyze a subset of postmenopausal women in the Nagano Cohort Study. A total of 517 urine samples were analyzed using an ELISA system, which can measure urinary pentosidine without hydrolysis. Read More

J Bone Miner Metab 2019 Sep 4;37(5):886-892. Epub 2019 Feb 4.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.

Osteonecrosis of the jaw (ONJ) associated with bisphosphonate therapy is a rare but severe side effect in osteoporosis patients. Recently, the number of osteoporosis patients with ONJ has dramatically increased in Japan. This has contributed to an increase in the number of patients avoiding extractions. Read More

Osteoporos Int 2019 Mar 27;30(3):593-599. Epub 2018 Nov 27.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.

The associations of multiple vitamin deficiencies on incident fractures were uncertain, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. The number of deficiencies was additively associated with incident fracture after adjustment for possible confounding factors including the treatment of osteoporosis.

Introduction: To evaluate the associations of multiple vitamin deficiencies on incident fractures, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. Read More

Osteoporos Int 2018 Dec 30;29(12):2677-2683. Epub 2018 Aug 30.

Kenézy Gyula University Hospital, University of Debrecen, Bartók Béla 2-26, Debrecen, H-4031, Hungary.

BMD changes in patients under tight control (monitored at 3-month intervals with adjustment of therapy guided by bone turnover markers) and routine management (controlled once a year) were compared. After 1 year, the femoral neck BMD increased significantly in the tight control compared to the routine management group.

Introduction: We intended to ascertain whether tight control (i. Read More

J Bone Miner Metab 2019 May 17;37(3):491-495. Epub 2018 Jul 17.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, Nagano, Japan.

We planned to conduct multi-center, open-labeled, blinded-endpoints, head-to-head randomized trial of minodronate and raloxifene to compare incidences of vertebral and non-vertebral fractures. The study is the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-4). Here, we present the pre-fixed study design. Read More

Curr Med Res Opin 2019 03 7;35(3):447-454. Epub 2018 Aug 7.

l Japan Osteoporosis Foundation , Tokyo , Japan.

Objective: Very few reports have described changes in bone mineral density (BMD) with long-term, once weekly administration of elcatonin, and its effects in reducing incident fractures remain unverified. Therefore, the efficacy and safety of once weekly elcatonin were examined over a 3 year period.

Methods: This was a multicenter, double-blinded, randomized, placebo-controlled study. Read More

Osteoporos Int 2018 05;29(5):1225

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.

There were two errors in this article. 1. In the section "Ethical considerations", the registration number of the study was incorrectly given as UMIN000024492. Read More

Osteoporos Int 2018 05 8;29(5):1155-1163. Epub 2018 Feb 8.

Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Annual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients.

Introduction: The measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. Read More

Bone Joint Res 2018 Jan;7(1):58-68

Bone and Joint Research Unit, The Institution of Health Research (IIS)-Fundación Jiménez Díaz, UAM, Madrid, Spain.

Objectives: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. Read More

Osteoporos Int 2018 03 23;29(3):723-732. Epub 2017 Dec 23.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.

Intestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH)D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine. Read More

J Bone Miner Metab 2018 Nov 13;36(6):734-740. Epub 2017 Dec 13.

Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bumkyo-ku, Tokyo, Japan.

Decline of body weight with aging is a major risk factor for frailty, osteoporosis and fracture, suggesting that treatment for osteoporosis may affect body composition. Recently, we have shown that 5-year treatment with raloxifene prevented age-related weight loss, suggesting some other drugs for osteoporosis may also prevent a decrease in body weight with aging. The present study aimed to identify the relationship between bisphosphonate treatment and body composition markers. Read More

Osteoporos Int 2018 03 7;29(3):625-633. Epub 2017 Dec 7.

Third Department of Medicine, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara-shi, Chiba, 299-0111, Japan.

Association between lung function and bone metabolism remains controversial. We found that impaired lung function was associated with vertebral fractures and bone loss in Japanese postmenopausal women. While vertebral deformities would impair lung function, respiratory dysfunction might in turn increase fracture risk, suggesting a complex bidirectional interaction. Read More

J Bone Miner Metab 2018 Sep 9;36(5):620-625. Epub 2017 Nov 9.

Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.

Populations of East Asian countries have been known to have low calcium intakes and low serum 25(OH)D concentrations, suggesting that Ca and vitamin D (VitD)-deficiencies are commonly observed. These nutritional imbalances may lead to low peak bone mass (PBM). The low PBM seen in Ca/VitD-deficient individuals may lead to osteoporosis, as well as an increased risk of fracture. Read More

Bone 2018 Jan 12;106:179-186. Epub 2017 Oct 12.

Japan Osteoporosis Foundation, 2-14 Odenma-cho, Nihonbashi Chuo-ku, Tokyo, Japan.

The effects of zoledronic acid on hip structural and biomechanical properties were evaluated in Japanese patients with osteoporosis by computed tomography (CT). The subjects included in this study were a subset of female subjects (zoledronic acid group, 49 subjects; placebo group, 53 subjects) in the phase 3 trial (ZONE study) who were available for multi-detector row CT (MDCT) scanning. Eligible subjects were those diagnosed with primary osteoporosis based on the Diagnostic Criteria for Primary Osteoporosis (2000) by the Japanese Society for Bone and Mineral Research and who had between one and four fractured vertebrae located between the fourth thoracic vertebra and the fourth lumbar vertebra. Read More

JCI Insight 2017 09 7;2(17). Epub 2017 Sep 7.

Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.

Decreased cortical thickness and increased cortical porosity are the key anatomic changes responsible for osteoporotic fractures in elderly women and men. The cellular basis of these changes is unbalanced endosteal and intracortical osteonal remodeling by the osteoclasts and osteoblasts that comprise the basic multicellular units (BMUs). Like humans, mice lose cortical bone with age, but unlike humans, this loss occurs in the face of sex steroid sufficiency. Read More