Osteoporosis: the evolution of a diagnosis
TL;DR: The 2001 definition of osteoporosis is still valid and useful: ‘Osteoporotic is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture’.
Abstract: The global trend towards increased longevity has resulted in ageing populations and a rise in diseases or conditions that primarily affect older persons. One such condition is osteoporosis (fragile or porous bones), which causes an increased fracture risk. Vertebral and hip fractures lead to increased morbidity and mortality and result in enormous healthcare costs. Here, we review the evolution of the diagnosis of osteoporosis. In an attempt to separate patients with normal bones from those with osteoporosis and to define the osteoporosis diagnosis, multiple factors and characteristics have been considered. These include pathology and histology of the disease, the endocrine regulation of bone metabolism, bone mineral density (BMD), fracture type or trauma severity, risk models for fracture prediction, and thresholds for pharmacological intervention. The femoral neck BMD −2.5 SDs cut-off for the diagnosis of osteoporosis is arbitrarily chosen, and there is no evidence to support the notion that fracture location (except vertebral fractures) or severity is useful to discriminate osteoporotic from normal bones. Fracture risk models (including factors unrelated to bone) dissociate bone strength from the diagnosis, and treatment thresholds are often based on health-economic considerations rather than bone properties. Vertebral fractures are a primary feature of osteoporosis, characterized by decreased bone mass, strength and quality, and a high risk of another such fracture that can be considerably reduced by treatment. We believe that the 2001 definition of osteoporosis by the National Institutes of Health Consensus Development Panel on Osteoporosis is still valid and useful: ‘Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture’.
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14 Jun 2018
TL;DR: Nonpharmacological interventions, which are recommended for all subjects, and pharmacological therapy in all postmenopausal women who have had an osteoporotic fracture or have BMD values consistent with osteopOrosis are recommended.
Abstract: Osteoporosis is a worldwide disease characterized by reduction of bone mass and alteration of bone architecture resulting in increased bone fragility and increased fracture risk. Causes of osteoporosis include increasing age, female sex, postmenopausal status, hypogonadism or premature ovarian failure, low body mass index, ethnic background, rheumatoid arthritis, low bone mineral density (BMD), vitamin D deficiency, low calcium intake, hyperkyphosis, current smoking, alcohol abuse, immobilization, and long-term use of certain medications. The diagnosis of osteoporosis is established by measurement of BMD of the hip and spine using dual energy X-ray absorptiometry. According to the World Health Organization criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviation or more below the average value for young healthy women. Bone turnover biomarker detection may be useful in monitoring osteoporosis treatment and assessing fracture risk but not for diagnosis of osteoporosis. Management of osteoporosis consists of nonpharmacological interventions, which are recommended for all subjects, and pharmacological therapy in all postmenopausal women who have had an osteoporotic fracture or have BMD values consistent with osteoporosis.
168 citations
TL;DR: The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD, and whether this affects the gut microbiome for bone metabolism in mice.
Abstract: Background: The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. Methods: In this double‐blind, placebo‐controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 1010 colony‐forming units of L. reuteri 6475 daily or placebo. The predefined primary end‐point was relative change after 12 months in tibia total volumetric BMD (vBMD). Results: Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention‐to‐treat (ITT) analysis [−0.83% (95% confidence interval [CI], −1.47 to −0.19%) vs. −1.85% (95% CI, −2.64 to −1.07%); mean difference 1.02% (95% CI, 0.02–2.03)] and per protocol analysis [−0.93% (95% CI, −1.45 to −0.40) vs. −1.86% (95% CI, −2.35 to −1.36); mean difference 0.93% (95% CI, 0.21–1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. Conclusions: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age‐associated bone loss and osteoporosis.
137 citations
Cites background from "Osteoporosis: the evolution of a di..."
...Osteoporosis is a disease characterized by loss of bone density and deteriorated bone microstructure, resulting in reduced bone strength and increased risk of fracture.[1, 2] Osteoporotic fractures are usually caused by low energy trauma and are very common, affecting every second woman and every fourth man after 50 years of age....
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TL;DR: For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD, and sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long-term fracture prevention.
Abstract: Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40-70%), nonvertebral (by 25-40%) and hip fractures (by 40-53%) in postmenopausal women with osteoporosis. Due to the risk of rare side-effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well-proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk-based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long-term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone-building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long-term fracture prevention and should be the golden standard of future osteoporosis treatment.
88 citations
TL;DR: Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporeosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis.
Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis. Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD. COPD-associated osteoporosis is however extremely undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients. Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described. It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks. Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis.
87 citations
Cites background from "Osteoporosis: the evolution of a di..."
...Vertebral fractures are often asymptomatic, and only one-third are recognized as clinical fractures with symptoms.(21,22) Furthermore, as discussed earlier, fractures can occur even with BMD above the threshold of osteoporosis, ie, T-score ....
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...Nonhip, nonvertebral fractures such as wrist fractures can occur throughout all ages, beginning from 50s.(16,21,25)...
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California Pacific Medical Center1, Beth Israel Deaconess Medical Center2, University of Florida3, Brigham and Women's Hospital4, United States Department of Agriculture5, University of Maryland, Baltimore6, University of Pittsburgh7, Johns Hopkins University8, National Institutes of Health9, University of Alberta10, Washington University in St. Louis11, Boston University12, Oregon Health & Science University13, The Catholic University of America14, VU University Amsterdam15, University of Sydney16, The Chinese University of Hong Kong17, Novartis18, Astellas Pharma19, Foundation for the National Institutes of Health20
TL;DR: The attendees of a meeting of SDOC and other experts to discuss strategic considerations in the development of evidence-based sarcopenia definition recommended the establishment of an International Expert panel to review a series of position statements on sarc Openia definition that are informed by the findings of the SDOC analyses and synthesis of literature.
Abstract: BACKGROUND Lack of consensus on how to diagnose sarcopenia has limited the ability to diagnose this condition and hindered drug development. The Sarcopenia Definitions and Outcomes Consortium (SDOC) was formed to develop evidence-based diagnostic cut points for lean mass and/or muscle strength that identify people at increased risk of mobility disability. We describe here the proceedings of a meeting of SDOC and other experts to discuss strategic considerations in the development of evidence-based sarcopenia definition. METHODS Presentations and panel discussions reviewed the usefulness of sarcopenia as a biomarker, the analytical approach used by SDOC to establish cut points, and preliminary findings, and provided strategic direction to develop an evidence-based definition of sarcopenia. RESULTS The SDOC assembled data from eight epidemiological cohorts consisting of 18,831 participants, clinical populations from 10 randomized trials and observational studies, and 2 nationally representative cohorts. In preliminary assessments, grip strength or grip strength divided by body mass index was identified as discriminators of risk for mobility disability (walking speed <0.8 m/s), whereas dual-energy X-ray absorptiometry-derived lean mass measures were not good discriminators of mobility disability. Candidate definitions based on grip strength variables were associated with increased risk of mortality, falls, mobility disability, and instrumental activities of daily living disability. The prevalence of low grip strength increased with age. The attendees recommended the establishment of an International Expert Panel to review a series of position statements on sarcopenia definition that are informed by the findings of the SDOC analyses and synthesis of literature. CONCLUSIONS International consensus on an evidence-based definition of sarcopenia is needed. Grip strength-absolute or adjusted for body mass index-is an important discriminator of mobility disability and other endpoints. Additional research is needed to develop a predictive risk model that takes into account sarcopenia components as well as age, sex, race, and comorbidities.
81 citations
References
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TL;DR: Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences.
Abstract: OBJECTIVES
To clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas.
PARTICIPANTS
From March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research.
EVIDENCE
MEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience.
CONSENSUS PROCESS
The panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks.
CONCLUSIONS
Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.
4,623 citations
TL;DR: Among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebra fractures, as well as other clinical fractures.
3,730 citations
TL;DR: Women with multiple risk factors and low bone density have an especially high risk of hip fracture and maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk.
Abstract: Background Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study. Methods We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films. Results During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one's arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age. Conclusions Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk.
3,587 citations
TL;DR: Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture, and a programme of screening menopausal women for osteoporosis by measuring bone density cannot be recommended.
Abstract: Objective: To determine the ability of measurements of bone density in women to predict later fractures. Design: Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Subjects: Eleven separate study populations with about 90000 person years of observation time and over 2000 fractures. Main outcome measures: Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. Results: All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Conclusions: Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density. Key messages Measuring bone mineral density has been suggested as a method of identifying individuals at high risk of fracture in a preventive context Our meta-analysis of prospective studies showed that all studies measuring bone density at any site had similar predictive ability for a decrease of 1 SD in bone density except for measurements at hip and spine, which have better predictive ability for fractures in hip and spine respectively Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease Although bone mineral density measurements can predict fracture risk, they cannot identify individuals who will have a fracture, and a screening programme for osteoporosis cannot be recommended
3,466 citations
TL;DR: In this paper, epidemiological research was done and used to identify individuals at high risk of disabling fractures, thereby allowing careful allocation of expensive treatments to individuals most in need, which could potentially be as expensive as medical treatment of fractures.
3,103 citations