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Physiological Reviews Jul 2021Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's... (Review)
Review
Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process: long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described, and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes, and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.
Topics: Animals; Biomarkers; Bone Density Conservation Agents; Bone Neoplasms; Bone and Bones; Denosumab; Humans
PubMed: 33356915
DOI: 10.1152/physrev.00012.2019 -
Europa Medicophysica Mar 2007Nonspecific (simple) neck pain is the commonest cause of neck symptoms and results from postural and mechanical causes. It includes pain following whiplash injury... (Review)
Review
Nonspecific (simple) neck pain is the commonest cause of neck symptoms and results from postural and mechanical causes. It includes pain following whiplash injury provided there is no bony injury or objective neurological deficit. The anatomy of the cervical spine is described, with the degenerative changes that are seen in patients with nonspecific neck pain, but also occur with ageing. The poor correlation between the degree of degeneration and presence and severity of symptoms is noted. A lack of specific pathology is also a feature of whiplash. The epidemiology, clinical presentation, investigation, and complications of nonspecific neck pain are described with a discussion of the controversial aspects of natural history, prognosis and therapy. Chronic whiplash is very common in some countries, but nonexistent in other countries and the factors which might explain this difference are considered. There is a great need for better quality studies to explore pathogenesis, natural history and factors including therapy that influence outcome.
Topics: Cervical Vertebrae; Diagnosis, Differential; Humans; Neck Pain; Whiplash Injuries
PubMed: 17369782
DOI: No ID Found -
Journal of Advanced Research Jan 2022Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific... (Review)
Review
BACKGROUND
Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected.
AIM OF REVIEW
Therefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and upcoming therapies.
KEY SCIENTIFIC CONCEPTS OF REVIEW
Notably, factors such as central sensitization, neuroinflammation, glial cell activation and an acidic environment are considered to be related to neuropathic pain in CIBP. Nonetheless, further research is needed to ascertain the mechanism of CIBP in order to develop highly effective drugs. Moreover, more attention needs to be paid to the care of patients with advanced cancer.
Topics: Bone Neoplasms; Bone and Bones; Cancer Pain; Humans; Neuroinflammatory Diseases; Quality of Life
PubMed: 35003797
DOI: 10.1016/j.jare.2021.06.006 -
Annals of the New York Academy of... Jun 2010In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain... (Review)
Review
In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain is common in patients with advanced breast, prostate, and lung cancer as these tumors have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone, they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, fractures, pain, and anemia. Currently, the factors that drive cancer pain are poorly understood. However, several recently introduced models of bone cancer pain, which closely mirror the human condition, are providing insight into the mechanisms that drive bone cancer pain and guide the development of mechanism-based therapies to treat the cancer pain. Several of these mechanism-based therapies have now entered human clinical trials. If successful, these therapies have the potential to significantly enlarge the repertoire of modalities that can be used to treat bone cancer pain and improve the quality of life, functional status, and survival of patients with bone cancer.
Topics: Acidosis; Animals; Bone Neoplasms; Bone and Bones; Breast Neoplasms; Disease Models, Animal; Female; Humans; Lung Neoplasms; Male; Mice; Neoplasm Metastasis; Osteoclasts; Pain; Prostatic Neoplasms; Sarcoma; United States
PubMed: 20536932
DOI: 10.1111/j.1749-6632.2009.05429.x -
Acta Orthopaedica Dec 2016The extent of ageing in the musculoskeletal system during the life course affects the quality and length of life. Loss of bone, degraded articular cartilage, and... (Review)
Review
The extent of ageing in the musculoskeletal system during the life course affects the quality and length of life. Loss of bone, degraded articular cartilage, and degenerate, narrowed intervertebral discs are primary features of an ageing skeleton, and together they contribute to pain and loss of mobility. This review covers the cellular constituents that make up some key components of the musculoskeletal system and summarizes discussion from the 2015 Aarhus Regenerative Orthopaedic Symposium (AROS) (Regeneration in the Ageing Population) about how each particular cell type alters within the ageing skeletal microenvironment.
Topics: Aging; Bone and Bones; Cartilage, Articular; Cellular Senescence; Chondrocytes; Humans; Intervertebral Disc; Musculoskeletal System
PubMed: 27748151
DOI: 10.1080/17453674.2016.1244750 -
Current Osteoporosis Reports Aug 2018This paper describes recent advances in understanding the mechanisms that drive fracture pain and how these findings are helping develop new therapies to treat fracture... (Review)
Review
PURPOSE OF REVIEW
This paper describes recent advances in understanding the mechanisms that drive fracture pain and how these findings are helping develop new therapies to treat fracture pain.
RECENT FINDINGS
Immediately following fracture, mechanosensitive nerve fibers that innervate bone are mechanically distorted. This results in these nerve fibers rapidly discharging and signaling the initial sharp fracture pain to the brain. Within minutes to hours, a host of neurotransmitters, cytokines, and nerve growth factor are released by cells at the fracture site. These factors stimulate, sensitize, and induce ectopic nerve sprouting of the sensory and sympathetic nerve fibers which drive the sharp pain upon movement and the dull aching pain at rest. If rapid and effective healing of the fracture occurs, these factors return to baseline and the pain subsides, but if not, these factors can drive chronic bone pain. New mechanism-based therapies have the potential to fundamentally change the way acute and chronic fracture pain is managed.
Topics: Acute Pain; Analgesics, Opioid; Animals; Bone and Bones; Central Nervous System Sensitization; Chronic Pain; Disease Models, Animal; Fracture Healing; Fractures, Bone; Humans; Neuralgia; Nociceptive Pain; Nociceptors; Pain Management; Peripheral Nerve Injuries; Sensory Receptor Cells
PubMed: 29948820
DOI: 10.1007/s11914-018-0446-8 -
Orthopaedic Surgery Sep 2023Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint... (Review)
Review
Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint mobility difficulties and pain, severe cases can lead to limb paralysis, which poses major pressure to the quality of life and mental health of patients, but also brings serious economic burden to society. The occurrence and development of KOA is influenced by many factors, including systemic factors and local factors. The joint biomechanical changes caused by aging, trauma and obesity, abnormal bone metabolism caused by metabolic syndrome, the effects of cytokines and related enzymes, genetic and biochemical abnormalities caused by plasma adiponectin, etc. all directly or indirectly lead to the occurrence of KOA. However, there is little literature that systematically and comprehensively integrates macro- and microscopic KOA pathogenesis. Therefore, it is necessary to comprehensively and systematically summarize the pathogenesis of KOA in order to provide a better theoretical basis for clinical treatment.
Topics: Humans; Osteoarthritis, Knee; Quality of Life; Bone and Bones; Pain; Knee Joint
PubMed: 37435789
DOI: 10.1111/os.13809 -
Annals of the Rheumatic Diseases Apr 2021Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation of subchondral bone in the pathogenesis of OA has attracted increasing attention. This review summarises the microstructural and histopathological changes in subchondral bone during OA progression that are due, at the cellular level, to changes in the interactions among osteocytes, osteoblasts, osteoclasts (OCs), endothelial cells and sensory neurons. Therefore, we focus on how pathological cellular interactions in the subchondral bone microenvironment promote subchondral bone destruction at different stages of OA progression. In addition, the limited amount of research on the communication between OCs in subchondral bone and chondrocytes (CCs) in articular cartilage during OA progression is reviewed. We propose the concept of 'OC-CC crosstalk' and describe the various pathways by which the two cell types might interact. Based on the 'OC-CC crosstalk', we elaborate potential therapeutic strategies for the treatment of OA, including restoring abnormal subchondral bone remodelling and blocking the bridge-subchondral type H vessels. Finally, the review summarises the current understanding of how the subchondral bone microenvironment is related to OA pain and describes potential interventions to reduce OA pain by targeting the subchondral bone microenvironment.
Topics: Aged; Bone and Bones; Cartilage, Articular; Endothelial Cells; Humans; Osteoarthritis; Pain
PubMed: 33158879
DOI: 10.1136/annrheumdis-2020-218089 -
European Spine Journal : Official... Nov 2016Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic... (Review)
Review
PURPOSE
Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic changes on MRI have a high specificity for discogenic LBP. This review summarizes the pathobiology of Modic changes and suggests a disease model.
METHODS
Non-systematic literature review.
RESULTS
Chemical and mechanical stimulation of nociceptors adjacent to damaged endplates are likely a source of pain. Modic changes are adjacent to a degenerated intervertebral disc and have three generally interconvertible types suggesting that the different Modic change types represent different stages of the same pathological process, which is characterized by inflammation, high bone turnover, and fibrosis. A disease model is suggested where disc/endplate damage and the persistence of an inflammatory stimulus (i.e., occult discitis or autoimmune response against disc material) create predisposing conditions. The risk to develop Modic changes likely depends on the inflammatory potential of the disc and the capacity of the bone marrow to respond to it. Bone marrow lesions in osteoarthritic knee joints share many characteristics with Modic changes adjacent to degenerated discs and suggest that damage-associated molecular patterns and marrow fat metabolism are important pathogenetic factors. There is no consensus on the ideal therapy. Non-surgical treatment approaches including intradiscal steroid injections, anti-TNF-α antibody, antibiotics, and bisphosphonates have some demonstrated efficacy in mostly non-replicated clinical studies in reducing Modic changes in the short term, but with unknown long-term benefits. New diagnostic tools and animal models are required to improve painful Modic change identification and classification, and to clarify the pathogenesis.
CONCLUSION
Modic changes are likely to be more than just a coincidental imaging finding in LBP patients and rather represent an underlying pathology that should be a target for therapy.
Topics: Bone Marrow; Humans; Intervertebral Disc; Low Back Pain; Lumbar Vertebrae; Magnetic Resonance Imaging; Models, Biological
PubMed: 26914098
DOI: 10.1007/s00586-016-4459-7 -
Osteoarthritis and Cartilage Jan 2013Osteoarthritis (OA) has long been considered a "wear and tear" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading... (Review)
Review
Osteoarthritis (OA) has long been considered a "wear and tear" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an "inflammatory" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review.
Topics: Animals; Bone and Bones; Cartilage, Articular; Chondrocytes; Humans; Immunity, Innate; Inflammation Mediators; Mice; Osteoarthritis; Synovitis
PubMed: 23194896
DOI: 10.1016/j.joca.2012.11.012