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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 -
International Journal of Molecular... Dec 2022Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an... (Review)
Review
Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an inner core proteoglycan-rich nucleus pulposus (NP) and outer lamellae collagen-rich annulus fibrosus (AF) and is confined by a cartilage end plate (CEP), providing structural support and shock absorption against mechanical loads. Changes to degenerative cascades in the IVD cause dysfunction and instability in the lumbar spine. Various treatments include pharmacological, rehabilitation or surgical interventions that aim to relieve pain; however, these modalities do not halt the pathologic events of disc degeneration or promote tissue regeneration. Loss of stem and progenitor markers, imbalance of the extracellular matrix (ECM), increase of inflammation, sensory hyperinnervation and vascularization, and associated signaling pathways have been identified as the onset and progression of disc degeneration. To better understand the pain originating from IVD, our review focuses on the anatomy of IVD and the pathophysiology of disc degeneration that contribute to the development of discogenic pain. We highlight the key mechanisms and associated signaling pathways underlying disc degeneration causing discogenic back pain, current clinical treatments, clinical perspective and directions of future therapies. Our review comprehensively provides a better understanding of healthy IVD and degenerative events of the IVD associated with discogenic pain, which helps to model painful disc degeneration as a therapeutic platform and to identify signaling pathways as therapeutic targets for the future treatment of discogenic pain.
Topics: Humans; Intervertebral Disc Degeneration; Low Back Pain; Annulus Fibrosus; Cartilage; Back Pain; Intervertebral Disc
PubMed: 36613651
DOI: 10.3390/ijms24010208 -
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 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 -
Journal of Back and Musculoskeletal... 2022Low back pain is a significant spinal disorder that affects much of the population at some point during their lives. (Review)
Review
BACKGROUND
Low back pain is a significant spinal disorder that affects much of the population at some point during their lives.
OBJECTIVE
While proper diagnosis is key, diagnosing the underlying cause of low back pain may often be unclear.
METHOD
In this review article, we discuss lumbar instability as an etiology of low back pain and its treatment by prolotherapy.
RESULTS
Spinal ligaments may be an underlying culprit in the development of lumbar instability with resultant low back pain and associated disorders.
CONCLUSION
In these cases, adequate treatment consisting of non-biologic prolotherapy or cellular prolotherapy, including platelet rich plasma (PRP), can be beneficial in restoring spinal stability and resolving chronic low back pain.
Topics: Humans; Joint Instability; Low Back Pain; Lumbar Vertebrae; Platelet-Rich Plasma; Prolotherapy; Spinal Diseases
PubMed: 34957989
DOI: 10.3233/BMR-210097 -
Medicine Sep 2022The purpose of this study was to investigate the effects of resistance exercise in comparison with those of common exercise on chronic neck pain (CNP) to provide useful... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The purpose of this study was to investigate the effects of resistance exercise in comparison with those of common exercise on chronic neck pain (CNP) to provide useful clinical guidelines for reducing pain or increasing cervical range of motion (ROM), upper trapezius tone, disability level, and quality of life (QOL).
METHODS
The subjects were randomized into a cervical and scapula-focused resistance exercise group (CSREG, n = 21) or trapezius massage group (TMG, n = 20). All groups received a 4-week, five times per week CSRE or TM program for CNP. The visual analogue scale (VAS) score, cervical ROM, myotonometer measures (upper trapezius tone, stiffness, and elasticity), neck disability index (NDI), and short form-36 (SF-36) were identified as the primary outcomes.
RESULTS
Within-group changes in VAS, cervical ROM, myotonometer measures, NDI, and SF-36 were significant in the CSREG and TMG (P < .05). The between-group changes in VAS, cervical rotation, myotonometer (upper trapezius tone and stiffness), NDI, and SF-36 after intervention showed significant differences between the CSREG and TMG (P < .05).
CONCLUSION
These results suggest that the CSRE program is effective in improving pain, cervical ROM, upper trapezius tone, disability level, and QOL in patients with CNP. More comprehensive studies with longer follow-up durations are needed to better understand the potential effects of the CSRE program in patients with CNP.
Topics: Cervical Vertebrae; Chronic Pain; Humans; Massage; Neck Pain; Quality of Life; Range of Motion, Articular; Resistance Training; Scapula; Superficial Back Muscles; Treatment Outcome
PubMed: 36181044
DOI: 10.1097/MD.0000000000030887 -
International Journal of Molecular... Feb 2020Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be... (Review)
Review
Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature.
Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be associated with the pain pathway as a result of neurotization. Our goal is to perform a prospective study using radiofrequency ablation on sinuvertebral nerve and basivertebral nerve; evaluating its short and long term effect on pain score, disability score and patients' outcome. A review in literature is done on the pathoanatomy, pathophysiology and pain generation pathway in degenerative disc disease and chronic back pain. 30 patients with 38 levels of intervertebral disc presented with discogenic back pain with bulging degenerative intervertebral disc or spinal stenosis underwent Uniportal Full Endoscopic Radiofrequency Ablation application through either Transforaminal or Interlaminar Endoscopic Approaches. Their preoperative characteristics are recorded and prospective data was collected for Visualized Analogue Scale, Oswestry Disability Index and MacNab Criteria for pain were evaluated. There was statistically significant Visual Analogue Scale improvement from preoperative state at post-operative 1wk, 6 months and final follow up were 4.4 ± 1.0, 5.5 ± 1.2 and 5.7 ± 1.3, respectively, < 0.0001. Oswestery Disability Index improvement from preoperative state at 1week, 6 months and final follow up were 45.8 ± 8.7, 50.4 ± 8.2 and 52.7 ± 10.3, < 0.0001. MacNab criteria showed excellent outcomes in 17 cases, good outcomes in 11 cases and fair outcomes in 2 cases Sinuvertebral Nerve and Basivertebral Nerve Radiofrequency Ablation is effective in improving the patients' pain, disability status and patient outcome in our study.
Topics: Adolescent; Adult; Aged; Back Pain; Catheter Ablation; Chronic Pain; Female; Humans; Intervertebral Disc Degeneration; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Spinal Nerves
PubMed: 32098249
DOI: 10.3390/ijms21041483 -
Journal of Bone and Mineral Research :... Jun 2019Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the... (Review)
Review
Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years' of the literature, defining terms according to pathophysiological understanding and pointing out best practice and unmet needs related to the skeletal features of this disorder. Abnormalities of bone modeling, reduced bone density, bone infarction, and plasma cell dyscrasias accompany the displacement of healthy adipocytes in adult marrow. Exposure to excess bioactive glycosphingolipids appears to affect hematopoiesis and the balance of osteoblast and osteoclast numbers and activity. Imbalance between bone formation and breakdown induces disordered trabecular and cortical bone modeling, cortical bone thinning, fragility fractures, and osteolytic lesions. Regular assessment of bone mineral density, marrow infiltration, the axial skeleton and searching for potential malignancy are recommended. MRI is valuable for monitoring skeletal involvement: It provides semiquantitative assessment of marrow infiltration and the degree of bone infarction. When MRI is not available, monitoring of painful acute bone crises and osteonecrosis by plain X-ray has limited value. In adult patients, we recommend DXA of the lumbar spine and left and right hips, with careful protocols designed to exclude focal disease; serial follow-up should be done using the same standardized instrument. Skeletal health may be improved by common measures, including adequate calcium and vitamin D and management of pain and orthopedic complications. Prompt initiation of specific therapy for GD is crucial to optimizing outcomes and preventing irreversible skeletal complications. Investing in safe, clinically useful, and better predictive methods for determining bone integrity and fracture risk remains a need. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Topics: Bone Diseases; Bone Marrow; Bone Remodeling; Bone and Bones; Gaucher Disease; Humans; Practice Patterns, Physicians'
PubMed: 31233632
DOI: 10.1002/jbmr.3734 -
JPMA. the Journal of the Pakistan... Mar 2020To compare the effectiveness of manual therapy to the cervical spine with and without manual therapy to the upper thoracic spine in the management of non-specific neck... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of manual therapy to the cervical spine with and without manual therapy to the upper thoracic spine in the management of non-specific neck pain; a randomized controlled trial.
OBJECTIVES
To compare the effectiveness of manual therapy to the cervical spine with and without manual therapy to the upper thoracic spine in the management of non-specific neck pain.
METHODS
The randomized controlled trial was conducted at 3 different hospitals in Peshawar, Pakistan, from October 2016 to January 2017, and comprised patients suffering from non-specific neck pain aged 25-60 years. The control group received cervical manual therapy alone while the experimental group received cervical along with thoracic manual therapy for 2 weeks. Data was analysed using SPSS 20.
RESULTS
Of the 37 subjects, 20(54%) were cases and 17(46%) were controls.The overall mean age was 35.9±9.6 years. There was no significant difference between the groups at baseline in terms of the levels of pain (p=0.125) and disability (p=0.392). The experimental group showed greater reduction in pain (p=0.02) and disability (p=0.03) compared to the control group.
CONCLUSIONS
Cervical along with thoracic manual therapy reduced neck pain and associated neck disability more effectively than cervical manual therapy alone.
Topics: Adult; Cervical Vertebrae; Female; Humans; Male; Manipulation, Spinal; Middle Aged; Musculoskeletal Manipulations; Neck Pain; Pain Management; Pain Measurement; Range of Motion, Articular; Thoracic Vertebrae; Treatment Outcome
PubMed: 32207414
DOI: 10.5455/JPMA.300523 -
Endocrinology and Metabolism (Seoul,... Oct 2022Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries,...
Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.
Topics: Humans; Osteitis Deformans; Diphosphonates; Pamidronate; Bone and Bones; Bone Resorption
PubMed: 36327984
DOI: 10.3803/EnM.2022.1575