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PloS One 2018We aimed to compare bone mineral density (BMD) and bone remodeling markers in chronic low back pain (cLBP) patients with and without active discopathy (Modic 1 changes). (Clinical Trial)
Clinical Trial
OBJECTIVE
We aimed to compare bone mineral density (BMD) and bone remodeling markers in chronic low back pain (cLBP) patients with and without active discopathy (Modic 1 changes).
DESIGN
We conducted a single center case-control exploratory study. For 18 months, all patients referred to a tertiary care physical medicine and rehabilitation department in France were consecutively screened. Patients fulfilling the inclusion criteria were prospectively enrolled. Cases were defined as cLBP patients with lumbar active discopathy detected on MRI and controls as cLBP patients without active discopathy. Bone mineral density (BMD) at the spine, femoral neck and total femur was assessed by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed in fasting serum samples. Overall, 37 cLBP patients (13 cases and 24 controls) fulfilled inclusion criteria and were included.
RESULTS
The median age was 42.0 years (Q1-Q3: 36.0-51.0) and mean (SD) LBP duration 72.3 (57.4) months. We found that BMD and levels of bone remodeling markers in cLBP patients did not differ with and without active discopathy.
CONCLUSION
Our results do not support the association between active discopathy and systemic bone fragility.
Topics: Absorptiometry, Photon; Adult; Bone Density; Bone Remodeling; Case-Control Studies; Chronic Pain; Female; Femur Neck; Humans; Low Back Pain; Male; Middle Aged; Spinal Diseases; Spine
PubMed: 29958270
DOI: 10.1371/journal.pone.0196536 -
Breast Cancer Research : BCR Mar 2011Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with... (Review)
Review
Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes.
Topics: Antineoplastic Agents; Aromatase Inhibitors; Arthralgia; Bone and Bones; Breast Neoplasms; Female; Humans; Musculoskeletal System; Osteoporosis; Postmenopause; Tamoxifen
PubMed: 21457526
DOI: 10.1186/bcr2818 -
In Vivo (Athens, Greece) 2017Despite affecting millions of people, chronic pain is generally treated insufficiently. A major point of focus has been the lack of translation from preclinical data to...
Despite affecting millions of people, chronic pain is generally treated insufficiently. A major point of focus has been the lack of translation from preclinical data to clinical results, with the predictive value of chronic pain models being a major concern. In contrast to current focus on stimulus-based nociceptive responses in preclinical research, development of behavioural tests designed to quantify suspension of normal behaviour is likely a more equivalent readout for human pain-assessment tests. In this study, we quantified grid-climbing behaviour as a non-stimulus-evoked behavioural test for potential use as a measure of neuropathic and cancer-induced bone pain in mice. In both models, the grid-climbing test demonstrated pain-related sparing of the affected leg during climbing. In both models, the behaviour was reversed by administration of morphine, suggesting that the observed behaviour was pain-specific.
Topics: Animals; Behavior, Animal; Bone and Bones; Disease Models, Animal; Humans; Mice; Neoplasms; Neuralgia; Nociceptive Pain; Pain Measurement
PubMed: 28652428
DOI: 10.21873/invivo.11102 -
Postepy Higieny I Medycyny... Aug 2012Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome induced by tumor produced phosphaturic factors, i.e. phosphatonins. The disorder is characterized by renal... (Review)
Review
Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome induced by tumor produced phosphaturic factors, i.e. phosphatonins. The disorder is characterized by renal tubular phosphate loss, secondary to this process hypophosphatemia and defective production of active form of vitamin D. The clinical course of oncogenic osteomalacia is characterized by bone pain, pathological fractures, muscle weakness and general fatigue. Osteomalacia-associated tumors are usually located in the upper and lower limbs, with half of the lesions primarily situated in the bones. Most of them are small, slow-growing tumors. Their insignificant size and various location coupled with rare occurrence of the disease and non-specificity of clinical symptoms lead to difficulties in reaching a diagnosis, which is often time-consuming and requires a number of additional tests. The average time between the appearance of the first symptoms and the establishment of an accurate diagnosis and the beginning of treatment is over 2.5 years. The aim of this study is to discuss the pathophysiology of disease symptoms, pathomorphology of tumors, diagnostic methods and treatment of oncogenic osteomalacia.
Topics: Biopsy; Bone and Bones; Cholecalciferol; Diagnostic Imaging; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fractures, Spontaneous; Humans; Hypophosphatemia; Neoplasms, Connective Tissue; Osteomalacia; Pain; Paraneoplastic Syndromes; Somatostatin
PubMed: 22922156
DOI: 10.5604/17322693.1006413 -
Kidney International. Supplement Dec 1999Survival rates of patients on dialysis have increased with improved dialytic therapy. However, the resultant increased duration of dialysis has led to a rise in renal... (Review)
Review
Survival rates of patients on dialysis have increased with improved dialytic therapy. However, the resultant increased duration of dialysis has led to a rise in renal osteodystrophy (ROD). Because this metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Types of ROD include predominant hyperparathyroid bone disease, low turnover bone disease (including osteomalacia and adynamic bone disease), and mixed uremic osteodystrophy. Serum PTH levels are commonly used to assess bone turnover in dialyzed patients. However, a recent study in our laboratory found that serum PTH levels between 65 and 450 pg/ml seen in the majority of dialysis patients are not predictive of the underlying bone disease. To date, bone biopsy is the most powerful and informative diagnostic tool to provide important information on precisely the type of renal osteodystrophy affecting patients, the degree of severity of the lesions, and the presence and amount of aluminum deposition in bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of new therapies on bone. The methods of in situ hybridization histochemistry (ISHH) and immunohistochemistry (IHC) are providing the means to study local biomolecules that play a role in bone metabolism. As these research tools become more refined, they will become increasingly valuable in the study of bone. Alternatives to the bone biopsy continue to be pursued, but they have not been proven to have the same specificity or sensitivity to effectively determine the potential value of a specific therapeutic regimen.
Topics: Animals; Biopsy; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hyperparathyroidism; Immunohistochemistry; In Situ Hybridization
PubMed: 10633459
DOI: 10.1046/j.1523-1755.1999.07313.x -
Annals of the Rheumatic Diseases Nov 2016Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon...
OBJECTIVE
Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis.
METHODS
OA was induced in wild-type (WT) and PAR2-deficient (PAR2) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain.
RESULTS
Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone.
CONCLUSIONS
This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.
Topics: Animals; Arthralgia; Arthritis, Experimental; Bone and Bones; Cartilage, Articular; Chondrocytes; Disease Models, Animal; Humans; Mice; Osteoarthritis; Osteocytes; Receptor, PAR-2
PubMed: 26698846
DOI: 10.1136/annrheumdis-2015-208268 -
The International Journal of... 2004Pain treatment due to cancer is a large fraction of the care in a radiotherapy department. While radiation treatment is very effective in reducing pain, the... (Review)
Review
Pain treatment due to cancer is a large fraction of the care in a radiotherapy department. While radiation treatment is very effective in reducing pain, the pathophysiology of bone metastases remains very complex. Reducing the number of tumour cells by radiation will reduce the pressure in bone marrow, but the very rapid response to radiation treatment seen in some patients is probably related to the presence of highly radiosensitive inflammatory cells. In this review we give an overview of the pathophysiological mechanisms which lead to pain associated with bone metastasis and the impact of radiation treatment and other treatments on this mechanism.
Topics: Analgesia; Bone Neoplasms; Bone and Bones; Clinical Trials as Topic; Humans; Models, Biological; Neoplasm Metastasis; Pain; Palliative Care; Radiation, Ionizing
PubMed: 15349834
DOI: 10.1387/ijdb.041817lv -
The Journal of Neuroscience : the... May 2018Pain associated with skeletal pathology or disease is a significant clinical problem, but the mechanisms that generate and/or maintain it remain poorly understood. In...
Pain associated with skeletal pathology or disease is a significant clinical problem, but the mechanisms that generate and/or maintain it remain poorly understood. In this study, we explored roles for GDNF, neurturin, and artemin signaling in bone pain using male Sprague Dawley rats. We have shown that inflammatory bone pain involves activation and sensitization of peptidergic, NGF-sensitive neurons via artemin/GDNF family receptor α-3 (GFRα3) signaling pathways, and that sequestering artemin might be useful to prevent inflammatory bone pain derived from activation of NGF-sensitive bone afferent neurons. In addition, we have shown that inflammatory bone pain also involves activation and sensitization of nonpeptidergic neurons via GDNF/GFRα1 and neurturin/GFRα2 signaling pathways, and that sequestration of neurturin, but not GDNF, might be useful to treat inflammatory bone pain derived from activation of nonpeptidergic bone afferent neurons. Our findings suggest that GDNF family ligand signaling pathways are involved in the pathogenesis of bone pain and could be targets for pharmacological manipulations to treat it. Pain associated with skeletal pathology, including bone cancer, bone marrow edema syndromes, osteomyelitis, osteoarthritis, and fractures causes a major burden (both in terms of quality of life and cost) on individuals and health care systems worldwide. We have shown the first evidence of a role for GDNF, neurturin, and artemin in the activation and sensitization of bone afferent neurons, and that sequestering these ligands reduces pain behavior in a model of inflammatory bone pain. Thus, GDNF family ligand signaling pathways are involved in the pathogenesis of bone pain and could be targets for pharmacological manipulations to treat it.
Topics: Animals; Bone Diseases; Bone Marrow; Bone and Bones; Glial Cell Line-Derived Neurotrophic Factor; Inflammation; Male; Nerve Tissue Proteins; Neurons, Afferent; Neurturin; Pain; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 29712778
DOI: 10.1523/JNEUROSCI.0421-18.2018 -
ELife Mar 2021Osteoarthritis, a highly prevalent degenerative joint disorder, is characterized by joint pain and disability. Available treatments fail to modify osteoarthritis...
Osteoarthritis, a highly prevalent degenerative joint disorder, is characterized by joint pain and disability. Available treatments fail to modify osteoarthritis progression and decrease joint pain effectively. Here, we show that intermittent parathyroid hormone (iPTH) attenuates osteoarthritis pain by inhibiting subchondral sensory innervation, subchondral bone deterioration, and articular cartilage degeneration in a destabilized medial meniscus (DMM) mouse model. We found that subchondral sensory innervation for osteoarthritis pain was significantly decreased in PTH-treated DMM mice compared with vehicle-treated DMM mice. In parallel, deterioration of subchondral bone microarchitecture in DMM mice was attenuated by iPTH treatment. Increased level of prostaglandin E2 in subchondral bone of DMM mice was reduced by iPTH treatment. Furthermore, uncoupled subchondral bone remodeling caused by increased transforming growth factor β signaling was regulated by PTH-induced endocytosis of the PTH type 1 receptor-transforming growth factor β type 2 receptor complex. Notably, iPTH improved subchondral bone microarchitecture and decreased level of prostaglandin E2 and sensory innervation of subchondral bone in DMM mice by acting specifically through PTH type 1 receptor in Nestin mesenchymal stromal cells. Thus, iPTH could be a potential disease-modifying therapy for osteoarthritis.
Topics: Animals; Bone Remodeling; Bone and Bones; Dinoprostone; Disease Models, Animal; Hindlimb; Male; Meniscus; Mice, Inbred C57BL; Mice, Transgenic; Osteoarthritis; Pain; Parathyroid Hormone; Mice
PubMed: 33646122
DOI: 10.7554/eLife.66532 -
European Spine Journal : Official... Jul 2022The composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient... (Observational Study)
Observational Study
PURPOSE
The composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient diffusion. However, the relative contributions of these factors to disc degeneration in patients with chronic low back pain (cLBP) have not been quantified. The goal of this study was to use compositional biomarkers derived from quantitative MRI to establish how CEP composition (surrogate for permeability) and vertebral bone marrow fat fraction (BMFF, surrogate for perfusion) relate to disc degeneration.
METHODS
MRI data from 60 patients with cLBP were included in this prospective observational study (28 female, 32 male; age = 40.0 ± 11.9 years, 19-65 [mean ± SD, min-max]). Ultra-short echo-time MRI was used to calculate CEP T2* relaxation times (reflecting biochemical composition), water-fat MRI was used to calculate vertebral BMFF, and T1ρ MRI was used to calculate T1ρ relaxation times in the nucleus pulposus (NP T1ρ, reflecting proteoglycan content and degenerative grade). Univariate linear regression was used to assess the independent effects of CEP T2* and vertebral BMFF on NP T1ρ. Mixed effects multivariable linear regression accounting for age, sex, and BMI was used to assess the combined relationship between variables.
RESULTS
CEP T2* and vertebral BMFF were independently associated with NP T1ρ (p = 0.003 and 0.0001, respectively). After adjusting for age, sex, and BMI, NP T1ρ remained significantly associated with CEP T2* (p = 0.0001) but not vertebral BMFF (p = 0.43).
CONCLUSION
Poor CEP composition plays a significant role in disc degeneration severity and can affect disc health both with and without deficits in vertebral perfusion.
Topics: Adult; Bone Marrow; Cartilage; Female; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Low Back Pain; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Middle Aged
PubMed: 35441890
DOI: 10.1007/s00586-022-07206-x