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Osteoporosis International : a Journal... Oct 2022Osteoporosis is the most common metabolic bone disease in the USA and the world. It is a subclinical condition until complicated by fracture(s). These fractures place an...
Osteoporosis is the most common metabolic bone disease in the USA and the world. It is a subclinical condition until complicated by fracture(s). These fractures place an enormous medical and personal burden on individuals who suffer from them and take a significant economic toll. Any new fracture in an adult aged 50 years or older signifies imminent elevated risk for subsequent fractures, particularly in the year following the initial fracture. What a patient perceives as an unfortunate accident may be seen as a sentinel event indicative of bone fragility and increased future fracture risk even when the result of considerable trauma. Clinical or subclinical vertebral fractures, the most common type of osteoporotic fractures, are associated with a 5-fold increased risk for additional vertebral fractures and a 2- to 3-fold increased risk for fractures at other sites. Untreated osteoporosis can lead to a vicious cycle of recurrent fracture(s), often resulting in disability and premature death. In appropriate patients, treatment with effective antifracture medication prevents fractures and improves outcomes. Primary care providers and medical specialists are critical gatekeepers who can identify fractures and initiate proven osteoporosis interventions. Osteoporosis detection, diagnosis, and treatment should be routine practice in all adult healthcare settings. The Bone Health and Osteoporosis Foundation (BHOF) - formerly the National Osteoporosis Foundation - first published the Clinician's Guide in 1999 to provide accurate information on osteoporosis prevention and treatment. Since that time, significant improvements have been made in diagnostic technologies and treatments for osteoporosis. Despite these advances, a disturbing gap persists in patient care. At-risk patients are often not screened to establish fracture probability and not educated about fracture prevention. Most concerning, the majority of highest risk women and men who have a fracture(s) are not diagnosed and do not receive effective, FDA-approved therapies. Even those prescribed appropriate therapy are unlikely to take the medication as prescribed. The Clinician's Guide offers concise recommendations regarding prevention, risk assessment, diagnosis, and treatment of osteoporosis in postmenopausal women and men aged 50 years and older. It includes indications for bone densitometry as well as fracture risk thresholds for pharmacologic intervention. Current medications build bone and/or decrease bone breakdown and dramatically reduce incident fractures. All antifracture therapeutics treat but do not cure the disease. Skeletal deterioration resumes sooner or later when a medication is discontinued-sooner for nonbisphosphonates and later for bisphosphonates. Even if normal BMD is achieved, osteoporosis and elevated risk for fracture are still present. The diagnosis of osteoporosis persists even if subsequent DXA T-scores are above - 2.5. Ongoing monitoring and strategic interventions will be necessary if fractures are to be avoided. In addition to pharmacotherapy, adequate intake of calcium and vitamin D, avoidance of smoking and excessive alcohol intake, weight-bearing and resistance-training exercise, and fall prevention are included in the fracture prevention armamentarium. Where possible, recommendations in this guide are based on evidence from RCTs; however, relevant published data and guidance from expert clinical experience provides the basis for recommendations in those areas where RCT evidence is currently deficient or not applicable to the many osteoporosis patients not considered for RCT participation due to age and morbidity.
Topics: Adult; Aged; Bone Density; Bone Density Conservation Agents; Calcium; Diphosphonates; Female; Humans; Male; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Vitamin D
PubMed: 35478046
DOI: 10.1007/s00198-021-05900-y -
Singapore Medical Journal Apr 2021Screening for osteoporosis in women can be based on age and weight, using the Osteoporosis Screening Tool for Asians and assessment for other risk factors such as early...
Screening for osteoporosis in women can be based on age and weight, using the Osteoporosis Screening Tool for Asians and assessment for other risk factors such as early menopause, Chinese ethnicity and other secondary factors. Based on the resulting risk profile, women can be triaged to dual-energy X-ray absorptiometry (DEXA) scanning for definite diagnosis of osteoporosis. Treatment should be considered in women with previous fragility fractures, DEXA-diagnosed osteoporosis and high risk of fracture. Exercise improves muscle function, can help prevent falls and has moderate effects on improvements in bone mass. Women should ensure adequate calcium intake and vitamin D. Menopausal hormone therapy (MHT) effectively prevents osteoporosis and fractures, and should be encouraged in those aged < 50 years. For women aged < 60 years, MHT or tibolone can be considered, especially if they have vasomotor or genitourinary symptoms. Risedronate or bisphosphonates may then be reserved for those aged over 60 years.
Topics: Bone Density; Diphosphonates; Female; Humans; Menopause; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 33948669
DOI: 10.11622/smedj.2021036 -
Annals of Internal Medicine Feb 2023The prevalence of osteoporosis is increasing in the United States. (Meta-Analysis)
Meta-Analysis Review
Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.
BACKGROUND
The prevalence of osteoporosis is increasing in the United States.
PURPOSE
To evaluate low bone mass and osteoporosis treatments to prevent fractures.
DATA SOURCES
Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022.
STUDY SELECTION
Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies ( ≥1000) for harms.
DATA EXTRACTION
Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE).
DATA SYNTHESIS
We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE).
LIMITATION
Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years.
CONCLUSION
Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42021236220).
Topics: Male; Adult; Female; Humans; Aged; Bone Density Conservation Agents; Teriparatide; Alendronate; Osteoporosis, Postmenopausal; Denosumab; Network Meta-Analysis; Fractures, Bone; Osteoporosis; Diphosphonates; Spinal Fractures; Physicians
PubMed: 36592455
DOI: 10.7326/M22-0684 -
Periodontology 2000 Jun 2022Periodontitis and osteoporosis are prevalent inflammation-associated skeletal disorders that pose significant public health challenges to our aging population. Both... (Review)
Review
Periodontitis and osteoporosis are prevalent inflammation-associated skeletal disorders that pose significant public health challenges to our aging population. Both periodontitis and osteoporosis are bone disorders closely associated with inflammation and aging. There has been consistent intrigue on whether a systemic skeletal disease such as osteoporosis will amplify the alveolar bone loss in periodontitis. A survey of the literature published in the past 25 years indicates that systemic low bone mineral density (BMD) is associated with alveolar bone loss, while recent evidence also suggests a correlation between clinical attachment loss and other parameters of periodontitis. Inflammation and its influence on bone remodeling play critical roles in the pathogenesis of both osteoporosis and periodontitis and could serve as the central mechanistic link between these disorders. Enhanced cytokine production and elevated inflammatory response exacerbate osteoclastic bone resorption while inhibiting osteoblastic bone formation, resulting in a net bone loss. With aging, accumulation of oxidative stress and cellular senescence drive the progression of osteoporosis and exacerbation of periodontitis. Vitamin D deficiency and smoking are shared risk factors and may mediate the connection between osteoporosis and periodontitis, through increasing oxidative stress and impairing host response to inflammation. With the connection between systemic and localized bone loss in mind, routine dental exams and intraoral radiographs may serve as a low-cost screening tool for low systemic BMD and increased fracture risk. Conversely, patients with fracture risk beyond the intervention threshold are at greater risk for developing severe periodontitis and undergo tooth loss. Various Food and Drug Administration-approved therapies for osteoporosis have shown promising results for treating periodontitis. Understanding the molecular mechanisms underlying their connection sheds light on potential therapeutic strategies that may facilitate co-management of systemic and localized bone loss.
Topics: Aged; Alveolar Bone Loss; Bone Density; Female; Humans; Inflammation; Osteoporosis; Osteoporosis, Postmenopausal; Periodontal Diseases; Periodontitis
PubMed: 35244945
DOI: 10.1111/prd.12422 -
Frontiers in Immunology 2021Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled... (Review)
Review
Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause - the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.
Topics: Anabolic Agents; Animals; Anti-Inflammatory Agents; Bone Density Conservation Agents; Bone Remodeling; Bone and Bones; Estrogens; Female; Humans; Inflammation; Inflammation Mediators; Osteoporosis, Postmenopausal; Signal Transduction; T-Lymphocytes
PubMed: 34276675
DOI: 10.3389/fimmu.2021.687551 -
International Journal of Molecular... Aug 2022Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting... (Review)
Review
Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting mainly postmenopausal women and older adults. Osteoporosis is characterized by an imbalance between bone resorption and bone production. It is diagnosed through different methods such as bone densitometry and dual X-rays. The treatment of this pathology focuses on different aspects. On the one hand, pharmacological treatments are characterized by the use of anti-resorptive drugs, as well as emerging regenerative medicine treatments such as cell therapies and the use of bioactive hydrogels. On the other hand, non-pharmacological treatments are associated with lifestyle habits that should be incorporated, such as physical activity, diet and the cessation of harmful habits such as a high consumption of alcohol or smoking. This review seeks to provide an overview of the theoretical basis in relation to bone biology, the existing methods for diagnosis and the treatments of osteoporosis, including the development of new strategies.
Topics: Aged; Bone Density; Bone Resorption; Exercise; Female; Health Behavior; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Smoking
PubMed: 36012730
DOI: 10.3390/ijms23169465 -
Endocrinology and Metabolism (Seoul,... Jun 2021Osteoporosis is an incurable chronic condition, like heart disease, diabetes, or hypertension. A large gap currently exists in the primary prevention of fractures, and...
Osteoporosis is an incurable chronic condition, like heart disease, diabetes, or hypertension. A large gap currently exists in the primary prevention of fractures, and studies show that an estimated 80% to 90% of adults do not receive appropriate osteoporosis management even in the secondary prevention setting. Case finding strategies have been developed and effective pharmacological interventions are available. This publication addresses how best to use the pharmacological options available for postmenopausal osteoporosis to provide lifelong fracture protection in patients at high and very high risk of fracture. The benefit of osteoporosis therapies far outweighs the rare risks.
Topics: Bone Density Conservation Agents; Diphosphonates; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 34154042
DOI: 10.3803/EnM.2021.301 -
Osteoporosis International : a Journal... Jan 2022The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral,... (Meta-Analysis)
Meta-Analysis Review
The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral, and clinical fractures significantly. In addition, decreased incidence of falls and increased bone mineral density at lumbar spine, total hip, and femoral neck was observed. Romosozumab is a monoclonal antibody that acts against the sclerostin pathway leading to enhanced bone formation and reduced bone resorption in patients with osteoporosis. Electronic search was performed on Medline (via PubMed), The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, till May 2020, for RCTs evaluating the effectiveness of Romosozumab in postmenopausal osteoporosis. RCTs evaluating the effect of Romosozumab on fractures and bone mineral density in postmenopausal osteoporosis patients. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. Cochrane risk of bias 2.0 tool and GRADE pro-GDT were applied for methodological quality and overall evidence quality, respectively. One hundred seventy-nine studies were screened, and 10 eligible studies were included in the analysis, with a total of 6137 patients in romosozumab group and 5732 patients in control group. Romosozumab significantly reduced the incidence of vertebral fractures [OR = 0.43 (95%CI = 0.35-0.52), High-quality evidence], nonvertebral fractures [OR = 0.78 (95%CI = 0.66-0.92), High quality], and clinical fractures [OR = 0.70 (95%CI = 0.60-0.82), High quality] at 24 months. Significant reduction in incidence risk of falls [OR = 0.87 (95%CI = 0.78-0.96), High quality] was observed with romosozumab. Bone mineral density was significantly increased in the romosozumab treated groups at lumbar spine [MD = 12.66 (95%CI = 12.66-12.67), High quality], total hip [MD = 5.69 (95%CI = 5.68 - 5.69), Moderate quality], and femoral neck [MD = 5.18 (95%CI = 5.18-5.19), Moderate quality] at 12 months. The total adverse events [RR = 0.98(95%CI = 0.96-1.01), Moderate quality] and serious adverse events [RR = 0.98(95%CI = 0.88-1.08), Moderate quality] with romosozumab were comparable to the control group. The current analysis with evidence on efficacy and safety of Romosozumab, authors opine to recommend the use of Romosozumab treatment for post-menopausal osteoporosis.Systematic review registration: PROSPERO registration number: CRD42019112196.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal
PubMed: 34432115
DOI: 10.1007/s00198-021-06095-y -
BMJ (Clinical Research Ed.) May 2023To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures... (Meta-Analysis)
Meta-Analysis
Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
OBJECTIVE
To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors.
DESIGN
Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
DATA SOURCES
Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events.
RESULTS
The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision.
CONCLUSIONS
The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019128391.
Topics: Humans; Female; Bone Density Conservation Agents; Network Meta-Analysis; Postmenopause; Denosumab; Receptor, Parathyroid Hormone, Type 1; Osteoporosis; Osteoporotic Fractures; Diphosphonates; Spinal Fractures; Risk Reduction Behavior; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 37130601
DOI: 10.1136/bmj-2021-068033 -
Seminars in Cell & Developmental Biology Mar 2022Postmenopausal osteoporosis is a systemic disease characterized by the loss of bone mass and increased bone fracture risk largely resulting from significantly reduced... (Review)
Review
Postmenopausal osteoporosis is a systemic disease characterized by the loss of bone mass and increased bone fracture risk largely resulting from significantly reduced levels of the hormone estrogen after menopause. Besides the direct negative effects of estrogen-deficiency on bone, indirect effects of altered immune status in postmenopausal women might contribute to ongoing bone destruction, as postmenopausal women often display a chronic low-grade inflammatory phenotype with altered cytokine expression and immune cell profile. In this context, it was previously shown that various immune cells interact with osteoblasts and osteoclasts either via direct cell-cell contact, or more likely via paracrine mechanisms. For example, specific subtypes of T lymphocytes express TNFα, which was shown to increase osteoblast apoptosis and to indirectly stimulate osteoclastogenesis via B cell-produced receptor-activator of NF-κB ligand (RANKL), thereby triggering bone loss during postmenopausal osteoporosis. T17 cells release interleukin-17 (IL-17), which directs mesenchymal stem cell differentiation towards the osteogenic lineage, but also indirectly increases osteoclast differentiation. B lymphocytes are a major regulator of osteoclast formation via granulocyte colony-stimulating factor secretion and the RANKL/osteoprotegerin system under estrogen-deficient conditions. Macrophages might act differently on bone cells dependent on their polarization profile and their secreted paracrine factors, which might have implications for the development of postmenopausal osteoporosis, because macrophage polarization is altered during disease progression. Likewise, neutrophils play an important role during bone homeostasis, but their over-activation under estrogen-deficient conditions contributes to osteoblast apoptosis via the release of reactive oxygen species and increased osteoclastogenesis via RANKL signaling. Furthermore, mast cells might be involved in the development of postmenopausal osteoporosis, because they store high levels of osteoclastic mediators, including IL-6 and RANKL, in their granules and their numbers are greatly increased in osteoporotic bone. Additionally, bone fracture healing is altered under estrogen-deficient conditions with the increased presence of pro-inflammatory cytokines, including IL-6 and Midkine, which might contribute to healing disturbances. Consequently, in addition to the direct negative influence of estrogen-deficiency on bone, immune cell alterations contribute to the pathogenesis of postmenopausal osteoporosis.
Topics: Bone Resorption; Bone and Bones; Cell Differentiation; Estrogens; Female; Humans; Osteoblasts; Osteoclasts; Osteoporosis, Postmenopausal
PubMed: 34024716
DOI: 10.1016/j.semcdb.2021.05.014