Genetic aspects of osteoporosis Hosoi, Takayuki
Journal of bone and mineral metabolism,
11/2010, Volume:
28, Issue:
6
Journal Article
Peer reviewed
The multiple factors contributing to the pathogenesis of osteoporosis include genetic and environmental factors. Because decrease in bone mineral density (BMD) is the major clinical indicator and a ...useful quantitative trait, many association and linkage studies of BMD have been conducted. Although the series of studies showed apparently significant associations, the genes have not been found that can be utilized in clinical practice. Several genes identified in robust genome-wide association studies will be the new cutting edge in genetic studies of osteoporosis. Our recent reports of functional single nucleotide polymorphism in the tissue-nonspecific alkaline phosphatase gene and gamma-carboxylase gene are presented in this review to discuss the future prospects in the genetic research of osteoporosis from the point of view of genome-nutrition interaction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese Society for Bone and Mineral Research) established the Osteoporosis Diagnostic Criteria Review Committee. Following ...discussion held at the 13th scientific meeting of the Society in 1996, the Committee, with the consensus of its members, proposed diagnostic criteria for primary osteoporosis. The Committee revised those criteria in 1998 and again in 2000. The Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society Joint Review Committee for the Revision of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining international consistency and made a revised edition based on the new findings in 2012.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs.Methods: We used data from the National Database of ...Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index.Results: We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65–74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval CI, 0.98–1.03) for bisphosphonates, 0.46 (95% CI, 0.44–0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18–0.32) for estrogens, 0.75 (95% CI, 0.71–0.79) for calcitonins, and 0.93 (95% CI, 0.84–1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14–1.22).Conclusion: The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Introduction
Older people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated ...the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis.
Materials and methods
A randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 μg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated.
Results
The Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups.
Conclusions
These results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Context:
Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian ...postmenopausal women with osteoporosis.
Objective:
The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo.
Design and Setting:
A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted.
Patients:
Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.
Intervention:
Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.
Main Outcome Measure:
The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.
Results:
Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194–0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.
Conclusion:
These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.
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 (25OHD) 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). Study endpoints included absolute serum 25(OH)D level at baseline, 12 months, and 24 months; change in serum 25(OH)D and bone mineral density (BMD) status from baseline; and incidence of new vertebral fractures at 24 months.
Results
In 475 denosumab-treated and 481 placebo-treated subjects, proportions with deficient/insufficient/sufficient 25(OH)D at baseline were 53.1%/37.1%/9.9% and 50.9%/42.0%/7.1%, respectively. Supplementation significantly increased mean serum 25(OH)D levels; at 24 months, mean levels were > 30 ng/mL (sufficient) in both treatment groups. Increase in BMD over time was higher in the denosumab group vs. placebo group in all three vitamin D status groups. At month 24, denosumab-treated subjects with deficient/insufficient baseline 25(OH)D had a significantly lower risk of new vertebral fracture vs. placebo-treated subjects.
Conclusion
Among DIRECT trial subjects supplemented with ≥ 400 IU/day of vitamin D and ≥ 600 mg/day of Ca, baseline 25(OH)D sufficiency may not influence the efficacy of denosumab in increasing BMD or preventing vertebral fractures.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
As estrogens play an important role in maintaining physiological function in various organs, the estrogen decrease after menopause is thought to cause various diseases frequently observed in ...postmenopausal or elderly women. With the aging of society and a decrease in infectious or vascular diseases, neoplasms have now become the most frequent cause of death in Japan. Cancers of the colorectum, breast, and lung have been rapidly increasing both in incidence and death, especially among postmenopausal women. Interestingly, all three of these cancers are associated with estrogens. In premenopausal women, ovarian estrogens plays major roles in the female reproductive organs through the classic estrogen receptor, ER‐α. In postmenopausal women, however, estrogens produced/activated by peripherally localized estrogen‐metabolizing enzymes such as aromatase, which converts androgen into estrogens, are thought to play physiologically and pathobiologically important roles in various organs through second ER, namely ER‐β, distributing systemically. In this article, the association of estrogens with these cancers in postmenopausal or elderly women are reviewed, especially focusing on the role of ER‐β and peripheral estrogen metabolism. The possibility of prevention or treatment of these diseases through estrogenic control is also discussed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
1. Background: Recent medical advancements, and improvements in hygiene and food supply have led to Japan having the longest life expectancy in the world. Over the past 50 years, the percentage of ...the elderly population has increased fourfold from 5.7% in 1960 to 23.1% in 2010. This change has occurred at the fastest rate in the world. Compared with France, where the percentage of the elderly population has increased just twofold in the past 100 years, Japanese society is aging at an unprecedented rate. In addition, the percentage of the very elderly (aged 75 years and over), comprising more frail people, exceeded 10% of the nation's population in 2008. In such a situation, many elderly Japanese wish to spend their later years healthy, and wish to achieve great accomplishments in their lives. To achieve that, rather than considering an aging population as a negative social phenomenon, we should create a society where elderly people can enjoy a healthy, prosperous life through social participation and contribution.
Factors that hamper the elderly from leading a healthy life include various psychological and social problems occurring in older age, as well as a high incidence of diseases. Therefore, gerontology, which focuses on health promotion of the elderly by encompassing the study of social welfare, psychology, environment and social systems; and geriatrics, which focuses on health care of elderly people and carried out research, education and practices to promote health in the elderly, are becoming more important. Furthermore, along with a need for multidisciplinary care to support geriatric medicine, the development of a comprehensive education system for aged‐care professionals is awaited. Thus, we should now recognize the importance of gerontology and geriatrics, and a reform of medical‐care services should be made in order to cope with the coming aged society.
Population aging is a global phenomenon. The actions being taken by Japan, the world's most aged society, have been closely watched by the rest of the world. Japan's aged society has been posing not only medical, nursing and welfare problems, but also complex problems closely associated with economy, industry and culture. Therefore, to solve these problems, a macroscopic integration and cooperation among industries, education institutions, administration and community through an interdisciplinary approach including medical science, nursing science, nursing care, study of social welfare, social science, engineering, psychology, economics, religion and ethics should be made. Regarding the promotion of gerontology, the “Committee for Establishing a Scientific Community for Sustainable Aged Society” of the Science Council of Japan also prepared a proposal and this was announced on 20 April 2011.
2. Current situation and problems (1) Promotion of social participation and contribution of elderly people
In Japan, the overall labor force rate is expected to decrease in the near future as a result of the low birth rate and high life expectancy. In contrast, many elderly people, particularly the young‐old, have sufficient physical strength to fulfil their job duties and make a social contribution. For these people, a social structure where elderly people can work should be developed through re‐educating the elderly and providing various job types. Promotion of social participation and contribution of the elderly is expected to cause a substantial increase in the labor force. Furthermore, it is also expected to contribute to not only the upturn of national economic activity through an increase in total consumption, but also a decrease in the number of elderly people who are likely to be in need of care. Therefore, in order for elderly people to be engaged in various social activities, strategies for developing a social structure for re‐education, various employment statuses and employment opportunities should be prepared. However, as the total number of jobs is fixed, consideration should also be given to young workers.
(2) Fostering medical specialists for aging
Older people often suffer from many diseases, together with geriatric syndromes with multiple etiologies. Signs and symptoms vary according to each individual, and are often atypical; therefore, the patients visit different hospitals and receive many screening tests and prescriptions at the same time. To solve this problem, an effective screening system carried out by a primary‐care doctor, and privacy‐preserving medical data sharing among hospitals and clinics are needed. In a geriatric clinical setting, health‐care professionals should be aware of the physical traits of older people who often develop not only dementia, but also geriatric syndromes, such as depression, falls and urinary incontinence, so that a holistic approach with consideration of nursing care is required. However, the existing Japanese medical education system is not prepared for medical professionals enabled to respond to the aforementioned requirements. Thus, the fostering of medical professionals who can provide comprehensive care – especially for the oldest‐old – such as geriatric specialists and medical professionals who understand the principles of elderly care, is urgently needed.
(3) Diagnosis of elderly‐specific diseases and reform of medical‐care services
In Japan, the diagnostic system for elderly‐specific diseases, including dementia, and reform of medical care services are markedly delayed. The current status concerning diagnosis, care and nursing should be investigated to collect academic data. In order to accumulate evidence for providing safe elderly care and nursing, the promotion of clinical research and a marked expansion of geriatric medical centers with high‐level medical services are eagerly awaited.
(4) Promotion of home‐based care and multidisciplinary care
To reduce the length of stay in acute hospitals, to reduce the physical burden of health‐care professionals working at acute hospitals and to meet the demand of older people who prefer to remain in their own homes, further promotion of home‐based care is needed. In addition, “multidisciplinary care” is increasingly needed to meet various demands in the medical care and welfare of the elderly. It is considered important to share countermeasures against the problems of disease prevention, medicine, care and welfare among health‐care professionals in medicine, care and welfare, and cooperate by making the best use of health‐care professionals' specialties.
3. Contents of the proposal The subcommittee for aging, thus, provided the following proposal:
1 Development and promotion of systems that enable elderly people to participate socially and make a contribution using an interdisciplinary approach among the various areas, including nursing science, nursing care, study of social welfare, social science, psychology, economics, religion and ethics, as well as medical sciences;
2 Promotion of gerontology, reform and enhancement of geriatrics in undergraduate, postgraduate and lifelong education;
3 Building geriatric medical centers in each area, and accumulating large‐scale evidence of geriatric diseases and geriatrics; and
4 Structural development and promotion of home‐based care and multidisciplinary care.
Through implementation of the above measures, Japan is expected to function as a successful example for the rest of the world. Geriatr Gerontol Int 2012; 12: 16–22.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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