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Nature Reviews. Endocrinology Sep 2023Osteoporosis is a skeletal disorder that causes impairment of bone structure and strength, leading to a progressively increased risk of fragility fractures. The global... (Review)
Review
Osteoporosis is a skeletal disorder that causes impairment of bone structure and strength, leading to a progressively increased risk of fragility fractures. The global prevalence of osteoporosis is increasing in the ageing population. Owing to the chronic character of osteoporosis, years or even decades of preventive measures or therapy are required. The long-term use of bone-specific pharmacological treatment options, including antiresorptive and/or osteoanabolic approaches, has raised concerns around adverse effects or potential rebound phenomena after treatment discontinuation. Imaging options, risk scores and the assessment of bone turnover during initiation and monitoring of such therapies could help to inform individualized treatment strategies. Combination therapies are currently used less often than 'sequential' treatments. However, all patients with osteoporosis, including those with secondary and rare causes of osteoporosis, as well as specific patient populations (for example, young adults, men and pregnant women) require new approaches for long-term therapy and disease monitoring. New pathophysiological aspects of bone metabolism might therefore help to inform and revolutionize the diagnosis and treatment of osteoporosis.
Topics: Male; Humans; Female; Pregnancy; Bone Density Conservation Agents; Osteoporosis; Fractures, Bone; Risk Factors; Bone Density
PubMed: 37464088
DOI: 10.1038/s41574-023-00866-9 -
Arthritis & Rheumatology (Hoboken, N.J.) Dec 2023The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic... (Review)
Review
OBJECTIVE
The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily.
METHODS
An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included.
CONCLUSION
This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.
Topics: Adult; Child; Humans; United States; Rheumatology; Glucocorticoids; Osteoporosis; Fractures, Bone; Bone Density
PubMed: 37845798
DOI: 10.1002/art.42646 -
International Journal of Molecular... Sep 2023Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by... (Review)
Review
Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies.
Topics: Humans; Pathology, Molecular; Osteoporosis; Osteoporotic Fractures; Bone Density; Bone and Bones
PubMed: 37834025
DOI: 10.3390/ijms241914583 -
Annals of Internal Medicine Jan 2024Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. Evidence-based screening strategies improve identification... (Review)
Review
Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. Evidence-based screening strategies improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started, choice of medication, and duration of treatment maximizes the benefits of fracture prevention while minimizing potential harms of long-term drug exposure.
Topics: Humans; Osteoporotic Fractures; Bone Density Conservation Agents; Osteoporosis; Secondary Prevention
PubMed: 38190715
DOI: 10.7326/AITC202401160 -
The New England Journal of Medicine Nov 2023
Review
Topics: Female; Humans; Bone Density; Osteoporosis, Postmenopausal
PubMed: 37991856
DOI: 10.1056/NEJMcp2307353 -
The Journal of Endocrinology Sep 2023Estrogens (estradiol, estriol, and estrone) are important hormones that directly and indirectly regulate the metabolism and function of bone and skeletal muscle via... (Review)
Review
Estrogens (estradiol, estriol, and estrone) are important hormones that directly and indirectly regulate the metabolism and function of bone and skeletal muscle via estrogen receptors. Menopause causes a dramatic reduction in the concentration of estrogen in the body. This contributes to a decline in bone and skeletal muscle function, thereby resulting in osteoporosis and sarcopenia. Menopausal women often experience osteoporosis and muscle wasting, and clinicians recognize estrogen as playing an important role in these conditions, particularly in women. Bone and muscle are closely related endocrine tissues that synthesize and produce various cytokines. These bone- and muscle-derived cytokines, including interleukin-6, irisin, β-aminoisobutyric acid, osteocalcin, fibroblast growth factor-23, and sclerostin, regulate both local and distant tissues, and they mediate the crosstalk between bone and skeletal muscle. This review examines the metabolic effects of estrogen on bone and skeletal muscle and describes cytokine-mediated bone-muscle crosstalk in conditions of estrogen deficiency.
Topics: Female; Humans; Sarcopenia; Osteoporosis, Postmenopausal; Estrogens; Muscle, Skeletal; Osteoporosis; Cytokines
PubMed: 37523234
DOI: 10.1530/JOE-23-0116 -
Journal of Translational Medicine Sep 2023Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It... (Review)
Review
Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It commonly occurs in older people, especially postmenopausal women. As global ageing increases, osteoporosis has become a global burden. There are a number of medications available for the treatment of osteoporosis, categorized as anabolic and anti-resorptive. Unfortunately, there is no drugs which have dual influence on bone, while all drugs have limitations and adverse events. Some serious adverse events include jaw osteonecrosis and atypical femoral fracture. Recently, a novel medication has appeared that challenges this pattern. Romosozumab is a novel drug monoclonal antibody to sclerostin encoded by the SOST gene. It has been used in Japan since 2019 and has achieved promising results in treating osteoporosis. However, it is also accompanied by some controversy. While it promotes rapid bone growth, it may cause serious adverse events such as cardiovascular diseases. There has been scepticism about the drug since its inception. Therefore, the present review comprehensively covered romosozumab from its inception to its clinical application, from animal studies to human studies, and from safety to cost. We hope to provide a better understanding of romosozumab for its clinical application.
Topics: Animals; Female; Humans; Aged; Osteoporosis; Antibodies, Monoclonal; Aging; Bone Development
PubMed: 37759285
DOI: 10.1186/s12967-023-04563-z -
CMAJ : Canadian Medical Association... Oct 2023In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased...
BACKGROUND
In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older.
METHODS
This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework.
RECOMMENDATIONS
The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized.
INTERPRETATION
The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.
Topics: Aged; Female; Humans; Male; Middle Aged; Canada; Fractures, Bone; Nutritional Status; Osteoporosis; Quality of Life
PubMed: 37816527
DOI: 10.1503/cmaj.221647 -
Endocrine Practice : Official Journal... May 2024Osteoporosis is a chronic progressive disease that requires lifelong monitoring and treatment. Sequencing from one treatment to another at different ages and stages of... (Review)
Review
BACKGROUND
Osteoporosis is a chronic progressive disease that requires lifelong monitoring and treatment. Sequencing from one treatment to another at different ages and stages of disease is an approach that can maximize benefits and avoid potential risks from long-term treatment with a single agent.
OBJECTIVE
This article reviews clinical trial data in postmenopausal women that evaluate the effects of antiresorptive agents followed by other antiresorptives, osteoanabolic agents followed by antiresorptives, and antiresorptives followed by osteoanabolic medications.
METHODS
Literature review and discussion.
RESULTS
When medications are discontinued, in the absence of sequential therapy, bone turnover rates return to baseline or above baseline, and bone loss occurs. The rate of bone loss differs for different treatments, with a very slow decline after stopping bisphosphonates and a particularly rapid decline after stopping denosumab. Careful attention to osteoporosis medication transitions can mitigate bone density loss and its consequences. For women who remain at high risk, switching from bisphosphonates to the more potent antiresorptive, denosumab, will result in further improvement in bone mineral density (BMD). When indicated, stopping denosumab can be accomplished safely by transition to an adequate bisphosphonate regimen. For high- and very-high-risk patients, treating with osteoanabolic agents first, followed by antiresorptive agents, produces substantially larger BMD gains than the reverse treatment sequence, with the biggest differences seen for BMD of the hip.
CONCLUSION
Awareness of the importance of treatment sequences can help improve osteoporosis care across the postmenopausal lifespan.
Topics: Humans; Bone Density Conservation Agents; Female; Diphosphonates; Osteoporosis, Postmenopausal; Denosumab; Bone Density; Osteoporosis
PubMed: 38311211
DOI: 10.1016/j.eprac.2024.01.014 -
The Journal of Clinical Endocrinology... Jan 2024Osteoporosis is a chronic condition characterized by decreased bone mass, loss of skeletal integrity, and increased susceptibility to fracture. Drugs used to treat... (Review)
Review
Osteoporosis is a chronic condition characterized by decreased bone mass, loss of skeletal integrity, and increased susceptibility to fracture. Drugs used to treat osteoporosis can be classified as those that block bone resorption (antiresorptive), stimulate bone formation (anabolic), or do both. While all currently approved medications reduce the risk of fragility fractures in high-risk populations, they are generally unable to fully restore bone strength in most patients with established disease. Thus, the majority of patients require disease management over many years. Unfortunately, the continuous use of a single drug has limitations, both in terms of efficacy and safety, and so sequential therapy is commonly required. Given the expanding list of pharmacological agents currently available, careful consideration needs to be given as to which drugs to use and in what sequence. This review will evaluate the differential effects of antiresorptive, bone-forming, and dual-acting drugs when used in specific sequences and will explore the current evidence favoring the initial use of bone-forming/dual-acting drugs followed by antiresorptive medications. This review will also examine the notion that long-term treatment with an antiresorptive drug may diminish the efficacy of subsequent treatment with a bone-forming/dual-acting drug. Finally, this review will explore the current evidence pertaining to the specific issue of how to best prevent the clinical ramifications of denosumab cessation.
Topics: Female; Humans; Osteoporosis, Postmenopausal; Bone Density; Osteoporosis; Bone Density Conservation Agents; Fractures, Bone
PubMed: 37610985
DOI: 10.1210/clinem/dgad496