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ID PMID Title PublicationDate abstract
33168359 The amino acid variants in HLA II molecules explain the major association with adult-onset 2021 Jan Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10(-14)) and Asn in HLA-DRβ1 position 37 (p = 5.12 × 10(-11)) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10(-14)), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10(-13)), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10(-9)). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.
32011506 Fluctuations of antimitochondrial antibodies and anti-gp210 antibody in a patient with pri 2020 Jan RATIONALE: Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune disorders. However, the concurrence of PBC and Sjögren syndrome (SS) with the subsequent onset of autoimmune hemolytic anemia (AIHA) is extremely rare. PATIENT CONCERNS: This study investigated a 60-year-old woman admitted to our hospital with complaints of xerostomia for 5 years, pruritus for 3 years, and abnormal liver function for 3 months. DIAGNOSES: The patient was suffering from typical clinical PBC and SS, and developed decompensated liver cirrhosis after 32 months of ursodeoxycholic acid (UDCA) therapy. In May 2018, she was readmitted to the hospital with a high fever of 39 °C, coughing, and sever fatigue without remission after 3 days of cephalosporin antibiotic therapy. During the clinical course of PBC, her antimitochondrial antibodies (AMA) titers fluctuated from 1:1000 to negative and then to weakly positive, determined by indirect immunofluorescence (IIF), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) based on recombinant mitochondrial antigens; furthermore, her titers of anti-gp210, an antinuclear antibody (ANA), increased sharply. Laboratory tests and imaging were performed to diagnose PBC and SS in September 2015. However, she was subsequently diagnosed with AIHA after 32 months of UDCA therapy based on the identification of pancytopenia, increased reticulocyte (RET) count, and a positive result from the direct Coombs test. INTERVENTIONS: UDCA, hepatic protectant, albumin infusion, chest drainage, rational antibiotic use, diuretics, and methylprednisolone were used to treat the patient. OUTCOMES: Liver cirrhosis was complicated by the development of AIHA, which became severe at 42 months of follow-up. LESSONS: This is the first case report showing a patient with comorbid PBC and SS, as well as the sequential development of AIHA with decreased AMA and increased anti-gp210 titers; this may have been due to immunodeficiency. These findings stress the importance of the serological screening of ANA profile, as well as repeated measurement of ANA and AMA to track PBC progression and prognosis.
31345742 Disseminated cryptococcosis with granuloma formation in idiopathic CD4 lymphocytopenia. 2020 Feb Idiopathic CD4 lymphocytopenia (ICL) is a rare disease characterized by marked loss of CD4 T-cells without human immunodeficiency virus infection. CD4 T-cells play an important role in granuloma formation in cryptococcal infection. Thus far, among ICL patients, it has not been concluded definitely whether granuloma is formed or not. We report the case of a 39-year-old woman with ICL and disseminated cryptococcal infection with granuloma formation. She was referred to our department because of a lung mass, osteolytic lesion, and a subcutaneous mass identified on a computed tomography scan, and an elevated C-reactive protein level. Cryptococcus neoformans was isolated from the tissues. She also had marked CD4 lymphocytopenia (33 cells/μL), without human immunodeficiency virus infection. In a biopsy specimen of the lung mass, granulomas containing CD4 T-cells were observed. The cryptococcosis was treated with liposomal amphotericin B followed by fluconazole and she was found to be cured. The CD4 T-cell count was persistently low. This case showed that granulomas containing CD4 T-cells can be formed in ICL patients with cryptococcal infection despite very low CD4 T-cell counts.
33911815 Palisaded Neutrophilic and Granulomatous Dermatitis in a Patient with Behçet's Disease: A 2021 Feb Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an uncommon skin eruption and characterized histopathologically by the presence of granulomatous inflammation with or without leukocytoclastic vasculitis. PNGD is known to be associated with various immune-mediated connective tissue diseases such as rheumatoid arthritis and lupus erythematosus. However, to our knowledge, a case of PNGD in a patient with Behçet's disease is extremely rare and only one case has been reported in foreign literature to date. Herein, we report an unusual case of a 60-year-old female with Behçet's disease who presented multiple erythematous to flesh-colored papules on the extremities, buttocks, and ear lobes and was diagnosed with PNGD. After the treatment of systemic corticosteroids, colchicine and azathioprine, the skin lesions and oral ulcers improved. The patient is under observation without recurrence of skin lesions for 6 months.
33437177 CCR6 blockade on regulatory T cells ameliorates experimental model of multiple sclerosis. 2020 Regulatory T cells (Tregs) play a significant role in limiting damage of tissue affected by autoimmune process, which has been demonstrated in various experimental models for multiple sclerosis (MS) (mostly experimental autoimmune encephalomyelitis - EAE), rheumatoid arthritis, and type 1 diabetes. In this study, we demonstrated that Tregs increasingly migrate to central nervous system (CNS) during subsequent phases of EAE (preclinical, initial attack, and remission). In contrast, in peripheral tissues (blood, lymph nodes, and spleen), a significant accumulation of Tregs is mostly present during EAE remission. Moreover, an increased expression of CCR6 on Tregs in the CNS, blood, lymph nodes, and spleen in all phases of EAE was observed. The highest expression of CCR6 on Tregs from the CNS, lymph nodes, and spleen was noted during the initial attack of EAE, whereas in the blood, the peak expression of CCR6 was detected during the preclinical phase. The presence of Tregs in the CNS during EAE was confirmed by immunohistochemistry. To analyze additional functional significance of CCR6 expression on Tregs for EAE pathology, we modulated the clinical course of this MS model using Tregs with blocked CCR6. EAE mice, which received CCR6-deficient Tregs showed significant amelioration of disease severity. This observation suggests that CCR6 on Tregs may be a potential target for future therapeutic interventions in MS.
33425432 Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines. 2020 Dec Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties. Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis. Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma. In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.
33262991 Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Der 2020 Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is a myositis-specific marker detected in clinically amyopathic dermatomyositis (DM). DM with anti-MDA5 antibody can be accompanied by rapidly progressive interstitial lung disease (RP-ILD) and other autoimmune disorders. Until now, only one case of neuromyelitis optica (NMO) with anti-MDA5-positive DM has been reported worldwide, in which the patient achieved a favorable outcome with intensive immunotherapy. We report a case of NMO in a patient with anti-MDA5-positive DM complicated by ILD and rheumatoid arthritis. Our patient experienced a fulminant course of NMO, rather than RP-ILD, in the presence of hyperferritinemia, which resulted in profound neurological sequelae despite immunotherapy including rituximab.
33261260 Effects of NGF and BDNF on chondrocytes: a microarray analysis. 2020 Jul Osteoarthritis (OA) represents an inflammation-driven injury of articular tissues, progressively leading to structural and functional joint impairment. The main symptom of OA is pain. Although it has been well established that OA represents a whole joint disease, the source of pain remains to be clarified. Nowadays, it has been well established that neurotrophines expression is evident in joints affected by OA. In addition, elevated NGF levels are found in the synovial fluid of patients with inflammatory or degenerative rheumatic diseases, including OA, rheumatoid arthritis and spondylarthritis. Growing evidences indicate that blocking NGF signaling using an anti NGF agent (i.e. tanezumab) provides effective pain relief. This study analyzed the effects of NGF and BDNF on cultured human chondrocytes by evaluating and their effects on chondrogenesis, chondrocyte differentiation and cartilage degeneration through a microarray analysis. The whole transcriptome analysis performed in this study highlighted how NGF and BDNF could be able to induce a proinflammatory response in human chondrocytes. Moreover, NGF and BDNF treatments seems to be able to induce the activation of several genes involved in the OA pathogenesis as IL17AR, HLA-DRB1, GDF-15, NR1D1, MCF2L and TGF-Beta.
33193597 JS-MA: A Jensen-Shannon Divergence Based Method for Mapping Genome-Wide Associations on Mu 2020 Taking advantage of the high-throughput genotyping technology of Single Nucleotide Polymorphism (SNP), Genome-Wide Association Studies (GWASs) have been successfully implemented for defining the relative role of genes and the environment in disease risk, assisting in enabling preventative and precision medicine. However, current multi-locus-based methods are insufficient in terms of computational cost and discrimination power to detect statistically significant interactions with different genetic effects on multifarious diseases. Statistical tests for multi-locus interactions (≥2 SNPs) raise huge analytical challenges because computational cost increases exponentially as the growth of the cardinality of SNPs in an interaction module. In this paper, we develop a simple, fast, and powerful method, named JS-MA, based on Jensen-Shannon divergence and agglomerative hierarchical clustering, to detect the genome-wide multi-locus interactions associated with multiple diseases. From the systematical simulation, JS-MA is more powerful and efficient compared with the state-of-the-art association mapping tools. JS-MA was applied to the real GWAS datasets for two common diseases, i.e., Rheumatoid Arthritis and Type 1 Diabetes. The results showed that JS-MA not only confirmed recently reported, biologically meaningful associations, but also identified novel multi-locus interactions. Therefore, we believe that JS-MA is suitable and efficient for a full-scale analysis of multi-disease-related interactions in the large GWASs.
32844516 To dispense or not to dispense: Lessons to be learnt from ethical challenges faced by phar 2021 Dec The year 2020 is facing one of the worst public health situations in decades. The world is experiencing a pandemic that has triggered significant challenges to healthcare systems in both high and low-middle income countries (LMICs). Government policymakers and healthcare personnel are experiencing real-life ethical dilemmas and are pressed to respond to these situations. Many possible treatments are being investigated, one of which is the use of hydroxychloroquine or chloroquine. These drugs are approved for use by patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and malaria. The demand for these products has increased, and the stocks are depleting for the patient population for whom the drugs are intended initially. Although both innovator and generic pharmaceutical manufacturers are making plans for increased production, there are challenges with global supply chains disruption and the retention of supplies for local markets. This may cause countries that rely on the importation of pharmaceuticals to be out of stock of supplies for an extended period. There are allegations of off-label prescribing and hoarding. Pharmacists are the custodians and dispensers of medications and are faced with the task of assessing prescriptions and making decisions about the allocation of these products. This paper seeks to 1) highlight some of the ethical challenges of dispensing hydroxychloroquine by pharmacists during the COVID-19 pandemic, 2) identify some of the responses to these issues from various regulatory authorities in the USA, and 3) recommend approaches to assist pharmacists in their decision-making process, especially in LMICs.
32605400 Necrobiosis Lipoidica in a Patient with β-Thalassemia Major: A Case Report and Review of 2020 May Necrobiosis lipoidica (NL) is a rare granulomatous disease that predominantly affects middle-aged women and is often associated with diabetes mellitus (DM), rheumatoid arthritis (RA) and other metabolic disorders. Thalassemias are the most common hereditary hemoglobin (Hb) disorders worldwide. A few studies investigated dermatologic problems that coexist with β-thalassemia major (β-TM). The most common skin disorders in patients with β-TM are xerosis, urticaria, pseudoxanthoma, hyperpigmentation, leg ulcers and small-vessel vasculitis. Necrobiosis lipoidica has only been occasionally reported in patients with β-TM. Herein, we present a female with β-TM and NL. Furthermore, a brief review of the literature was performed.
32526864 Porphyromonas gingivalis, a Long-Range Pathogen: Systemic Impact and Therapeutic Implicati 2020 Jun 9 Periodontitis is an inflammatory disease associated with a dysbiosis of the oral flora characterized by a chronic sustained inflammation leading to destruction of tooth-supporting tissues. Over the last decade, an association between periodontitis and systemic disorders such as cardiovascular diseases, rheumatoid arthritis and obesity has been demonstrated. The role of periodontal pathogens, notably Porphyromonas gingivalis (P. gingivalis), in the onset or exacerbation of systemic diseases has been proposed. P. gingivalis expresses several virulence factors that promote its survival, spreading, and sustaining systemic inflammation. Recently, the impact of periodontitis on gut dysbiosis has also been suggested as a potential mechanism underlying the systemic influence of periodontitis. New therapeutic strategies for periodontitis and other dysbiotic conditions, including the use of beneficial microbes to restore healthy microbial flora, may pave the way to improved therapeutic outcomes and more thorough patient management.
32412958 Refractive surgery for the patient with autoimmune diseases. 2020 Jul PURPOSE OF REVIEW: Autoimmune and immune-mediated diseases are considered contraindications for laser refractive surgeries according to the US Food and Drug Administration's guideline. This guideline, however, is based on limited case reports or complications reported during other intraocular procedures. There have been only a handful of new clinical studies that evaluate the efficacy and safety of refractive surgery in this specific patient population. The aim of this article is to review currently available research and offer updated recommendations for the evaluation and management of laser refractive surgery (LRS) in patients with autoimmune diseases. RECENT FINDINGS: More recent retrospective studies have reported good refractive outcomes in patients with well controlled autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, seronegative spondyloarthropathy, among others. No severe sight-threatening complications have been reported in these reports. Although postoperative complications occur, the risk of refractive surgery is comparable with those without autoimmune diseases. SUMMARY: With the exception of primary Sjogren's syndrome, patients with autoimmune diseases may be good candidates for LRS if diseases are well controlled and have minimal ophthalmic manifestation. Patients should be made aware of the potential surgical complications and be informed of the currently available data. More multicenter and larger prospective studies are needed to compare the refractive outcomes and surgical complications in patients with and without autoimmune diseases. This will help patients make better informed medical decisions.
33048480 2020 Jan 21 Sjögren’s syndrome is an autoimmune disease most frequently affecting women between 30 and 50 years of age. Sjögren’s syndrome is often under-diagnosed but may affect up to 430,000 Canadians. The cause of Sjögren’s syndrome is currently unknown, however, one prevalent theory is that certain genetic factors coupled with an environmental stimulus (i.e., a virus) triggers the disease.(,) There are two main classifications of Sjögren’s syndrome: primary and secondary. Patients are classified as having primary Sjögren’s syndrome when there is no other autoimmune disease present. Patients are classified as having secondary Sjögren’s syndrome when another autoimmune disorder, such as rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis, is also present. Both types of Sjögren’s syndrome are characterized by damage to exocrine glands such as the salivary, tear and mucous-secreting glands, which can result in dry eyes and dry mouth.(,) Dry eyes can cause discomfort via a scratchy and gritty sensation. In rare, severe cases, vision impairment may occur due to damage to the corneal surface. Dry mouth occurs secondary to a diminished saliva production and can cause difficulty chewing and swallowing, Candida infections, tooth decay and sialolithiasis. Both dry eyes and dry mouth can be managed with a variety of non-pharmacological and non-prescription therapies. Pharmacological therapy with muscarinic agonists (i.e., pilocarpine, cevimeline) which stimulate exocrine glands, can also be used to alleviate the symptoms of dry eyes and dry mouth. Other symptoms of Sjögren’s syndrome may include extraglandular manifestations such as lymphadenopathy, Raynaud phenomenon, and vasculitis. This report aims to summarize the evidence regarding the clinical effectiveness, cost-effectiveness and evidence-based guidelines’ recommendations for the use of pilocarpine in the treatment of Sjögren’s syndrome-induced dry eyes and dry mouth.
34277118 Identification and quantification of the bioactive components in Osmanthus fragrans roots 2021 Jun The roots of O. fragrans are also a valuable resource in addition to its flowers and fruits. In this study, the HPLC-MS/MS method used for analyzing the chemical constituents in O. fragrans roots extract was developed, which showed high sensitivity for both qualitative and quantitative analyses. Thirty-two compounds were first discovered in O. fragrans roots, one compound of which was reported for the first time. The simultaneous determination method for acteoside, isoacteoside, oleuropein and phillyrin was validated to be sensitive and accurate. Then it was applied to determine the content of bioactive components in O. fragrans roots from different cultivars. The content of oleuropein and phillyrin in the twelve batches was relatively stable, while the content of acteoside and isoacteoside varied greatly. Moreover, the therapeutic material basis and mechanism of O. fragrans roots exerting its traditional pharmacodynamics were analyzed by network pharmacology. The results showed that O. fragrans roots might be effective for the treatment of inflammation, cardiovascular diseases, cancer, and rheumatoid arthritis, which is consistent with the traditional pharmacodynamics of O. fragrans roots. This work can provide an analytical method for the comprehensive development of O. fragrans roots.
32314799 Acute hypertriglyceridemia in patients with COVID-19 receiving tocilizumab. 2020 Oct Tocilizumab is an interleukin‐6 (IL‐6) receptor antibody and is progressing as a viable and promising treatment option in patients with severe coronavirus disease 2019 (COVID‐19). IL‐6 is known to have both immunomodulatory and metabolic actions. In this letter we outline two cases of acute hypertriglyceridemia in patients with COVID‐19 treated with tocilizumab: one with elevated biomarkers consistent with acute pancreatitis the other without. Given the paucity of robust clinical trial data for most COVID‐19 pharmacotherapies at this time, clinicians should continue to remain steadfast in recognition of interventions that improve clinical outcomes and vigilant in monitoring for acute adverse effects that are difficult to detect in clinical trials with small sample sizes. The observations from our two cases highlight the complex, not fully elucidated interrelationship between elevated IL‐6 and pharmacologic interventions impacting this pathway. Clinicians should consider monitoring for hypertriglyceridemia and acute pancreatitis as described with chronic tocilizumab use for rheumatoid arthritis in those receiving it for COVID‐19. This article is protected by copyright. All rights reserved.
32242478 Characterization, Pathogenesis, and Clinical Implications of Inflammation-Related Atrial M 2020 Apr 7 Historically, atrial fibrillation has been observed in clinical settings of prolonged hemodynamic stress, eg, hypertension and valvular heart disease. However, recently, the most prominent precedents to atrial fibrillation are metabolic diseases that are associated with adipose tissue inflammation (ie, obesity and diabetes mellitus) and systemic inflammatory disorders (ie, rheumatoid arthritis and psoriasis). These patients typically have little evidence of left ventricular hypertrophy or dilatation; instead, imaging reveals abnormalities of the structure or function of the atria, particularly the left atrium, indicative of an atrial myopathy. The left atrium is enlarged, fibrotic and noncompliant, potentially because the predisposing disorder leads to an expansion of epicardial adipose tissue, which transmits proinflammatory mediators to the underlying left atrium. The development of an atrial myopathy not only leads to atrial fibrillation, but also contributes to pulmonary venous hypertension and systemic thromboembolism. These mechanisms explain why disorders of systemic or adipose tissue inflammation are accompanied an increased risk of atrial fibrillation, abnormalities of left atrium geometry and an enhanced risk of stroke. The risk of stroke exceeds that predicted by conventional cardiovascular risk factors or thromboembolism risk scores used to guide the use of anticoagulation, but it is strongly linked to clinical evidence and biomarkers of systemic inflammation.
32031236 Importance of osteocyte-mediated regulation of bone remodelling in inflammatory bone disea 2020 Jan 27 Although the impact of osteoblast-osteoclast crosstalk in bone remodelling has been intensively studied, the importance of osteocytes, descendants of osteoblasts, in this process has for a long time been neglected. During their embedding phase, osteocytes undergo considerable phenotypic transformation, from a cuboidal, highly metabolically active osteoblast secreting extracellular matrix to a small, stellate, quiescent osteocyte with numerous long dendrites. Osteocytes are encysted in cavities (lacunae) and their dendritic extensions are located in tunnels (canaliculi) forming a remarkable, highly branched, lacunar-canalicular signalling network that spans the entire bone matrix. Osteocytes and their dendrites can communicate directly with each other and through the release of effector proteins such as sclerostin and nuclear factor κB ligand (RANKL), influence osteoblast and osteoclast formation. This allows osteocytes embedded within the bone matrix to communicate and coordinate activity of cells on the bone surface to adapt to mechanical needs and hormonal changes. Besides their importance in sustaining physiological bone homeostasis, accumulating evidence suggests that dysregulated osteocyte function and alterations in the osteocyte lacunar-canalicular network structure are characteristics of skeletal diseases. This review highlights some aspects of osteocyte communication with osteoclasts and mesenchymal stromal cells, the importance of blood vessel-osteocyte interaction and describes central functions of these cells in rheumatoid arthritis, osteoarthritis, osteomyelitis and osteoporosis. Within the last decade new technologies and tools have facilitated the study of osteocyte biology and the search for therapeutic targets to address bone fragility in the near future.
31998129 Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteocla 2019 Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis-related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL-induced osteoclastogenesis by suppressing NF-kB, Ca2(+), PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.
31954740 A review on osteoclast diseases and osteoclastogenesis inhibitors recently developed from 2020 Apr Natural products have been investigated as potential candidates of novel therapeutics and play a crucial role in advanced medicinal drugs. Natural resources, including local medicinal plants (especially folk medicinal plants), animals, bacteria, and fungi have been used for more than a century, and are precious gifts from nature, providing potential medicines with high safety. Osteoclast-related diseases, such as osteoporosis, rheumatoid arthritis, Paget's disease, osteoclastoma, and periprosthetic osteolysis, are currently the most common reasons for bone inflammation, pain and fractures, resulting in low quality of life. However, the curative effects of current therapeutic drugs for these osteoclast-related diseases are limited, and long-term treatment is needed. Further, in severe cases, surgical treatments are necessary, which may cause unaffordable expenses and subsequent influences such as neuralgia, mental stress, and even development of cancer. Thus, safer inhibitors and potential drugs with enhanced curative effects and quick relief are needed to treat patients with osteoclast diseases. This review aims to introduce the main osteoclast-related diseases and some of the recently developed naturally sourced inhibitors against osteoclastogenesis, also it is desired to attract people's attention on using widely available natural resources for the evolution of new types of osteoclast inhibitors with minimal or no side-effects upon long-term treatments.