Impact of COVID-19 pandemic on social isolation and loneliness among minority populations.

BACKGROUND: The impact of social isolation and loneliness (SIL) was heightened during the COVID-19 pandemic. Although the pandemic disproportionately affected racial/ ethnic minorities, no studies have investigated the ramifications of the pandemic on SIL among these populations. This study aimed to determine the prevalence and pervasiveness of SIL during the COVID-19 pandemic on minority communities. MATERIALS AND METHODS: This was a single center, cross sectional study conducted by scientists from the University of Rochester Medical Center (URMC) working in collaboration with members of the Rochester community. Adult patients presenting to the emergency department at URMC who identified themselves as belonging to minority communities were asked to complete a survey that comprised questions from the Lubben Social Network Scale-6 and questions from the Campaign to End Loneliness Measurement Tool. We analyzed the percentage of SIL and conducted linear regression models to study the association between these outcomes and race/ ethnicity, age, gender, chronic disease status and the frequency of hospitalizations. RESULTS: A total of 1,029 subjects completed the survey. Social isolation was reported by 375 (37%) persons. Those of Latinx ethnicity had higher prevalence of social isolation (41%) compared to those of Black/African American race (36%) and also had higher degrees of isolation (14.8%) (15.42; p = 0.07). Loneliness was documented by 215 (21%) for the cohort with no differences based on race or ethnicity. CONCLUSIONS: Social isolation was common among minority communities during the pandemic but loneliness was less pervasive. The study highlights the need to address the specific needs of these populations.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

A Provider-Based Approach to Address Racial Disparities in Lupus Clinical Trial Participation.

OBJECTIVE: Substantial disparities exist in clinical trial participation, which is problematic in diseases such as lupus that disproportionately affect racial/ethnic minority populations. Our objective was to examine the effectiveness of an online educational course aiming to train medical providers to refer Black and Latino patients to lupus clinical trials (LCTs). METHODS: The American College of Rheumatology's Materials to Increase Minority Involvement in Clinical Trials (MIMICT) study used an online, randomized, 2-group, pretest/posttest design with medical and nursing providers of multiple specialties. We exposed intervention group participants to an education course, while the control group participants received no intervention. Controlling for the effects of participant characteristics, including specialty, and professional experience with lupus, we modeled relationships among exposure to the education course and changes in knowledge, attitudes, self-efficacy, and intentions to refer Black and Latino patients to LCTs. We also examined education course satisfaction. RESULTS: Compared to the control group, the intervention group had significantly higher posttest scores for knowledge, self-efficacy, and intentions to refer Black and Latino patients to LCTs. Both medical and nursing trained intervention group participants had significantly higher mean posttest scores for knowledge and intentions to refer compared to the medical and nursing trained control group participants. Attitude was insignificant in analysis. The online education course, which received a favorable summary score, indicated that satisfaction and intentions to refer were strongly and positively correlated. CONCLUSION: The MIMICT education course is an effective method to educate medical providers about LCTs and to improve their intentions to refer Black and Latino patients.

Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis.

Objective: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is essential for the formation of fully functional multinucleated osteoclasts. DC-STAMP deficient mice, under physiological conditions, exhibit osteopetrosis and develop systemic autoimmunity with age. However, the function of DC-STAMP in inflammation is currently unknown. We examined whether genetic ablation of DC-STAMP attenuates synovitis and bone erosion in TNF transgenic (Tg) and K/BxN serum-induced murine rheumatoid arthritis. Methods: We evaluated arthritis onset in Tg(hTNF) mice lacking DC-STAMP and 50:50 chimeric mice by visual examination, measurement of ankle width, micro-CT-scan analysis and quantitation of the area occupied by osteoclasts in bone sections. To further investigate the cellular and molecular events modulated by DC-STAMP, we measured serum cytokines, determined changes in cytokine mRNA expression by monocytes activated with IL4 or LPS/IFNγ and enumerated immune cells in inflamed mouse joints. Results: Synovitis, bone loss and matrix destruction are markedly reduced in Dcstamp-/-;Tg(hTNF) mice. These mice had significantly lower CCL2 and murine TNF serum levels and exhibited impaired monocyte joint migration compared to Tg(hTNF) mice. The reduced arthritic severity in Dcstamp deficient mice was associated with compromised monocyte chemotaxis, cytokine production, and M2 polarization. Conclusion: These results reveal that DC-STAMP modulates both bone resorption and inflammation and may serve as an activity biomarker and therapeutic target in inflammatory arthritis and metabolic bone disease.

Identification and Characterization of a High-Need, High-Cost Group Among Hospitalized Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To identify a high-need, high-cost (HNHC) group among hospitalized lupus patients and to compare clinical and social factors of the HNHC group with those of other patients with lupus. METHODS: All hospitalizations for lupus in a tertiary care center over a 3-year period were recorded. The number of admissions, 30-day readmissions, length of stay (LOS), and cost of admissions were compared for high-risk patients with those of all other hospitalized lupus patients (OHLP) during this period. We then compared clinical measures (double-stranded DNA [dsDNA] levels, complement proteins, body mass index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] scores, and Case Mix Index [CMI] scores) for the HNHC cohort with those of the OHLP group. We additionally differentiated social factors (age, race and ethnicity, poverty, and medication adherence) between the 2 groups. RESULTS: A total of 202 patients with lupus accounted for 467 hospitalizations over the study period. The total cost of admissions was $13,192,346. Forty-four patients had significantly higher admissions, 30-day readmissions, and LOS. Furthermore, the cost for this group was 6-fold that for the OHLP group, confirming the presence of an HNHC cohort. The HNHC group had significantly higher dsDNA levels, SDI scores, and CMI scores compared with the OHLP group. Infections were the most common cause of admission for both groups. Patients in the HNHC group were more likely to be African American, younger, diagnosed with lupus at an earlier age, to have lower medication adherence, and to be significantly more likely to live in areas of poverty. CONCLUSION: A small group of patients with lupus (the HNHC group) accounts for most of the hospitalizations and cost. The HNHC group has both social and clinical factors significantly different from other patients with lupus.

Designing an Intervention to Improve Management of High-Risk Lupus Patients Through Care Coordination.

Health care disparities are a major cause for large discrepancies in health outcomes between different populations with systemic lupus erythematosus in the United States.A team-based model that incorporates a care coordination strategy in the management of high-risk lupus patients can provide an effective method to overcome the obstacles posed by health care disparities.Access, behavioral modification, community outreach programs, depression, and education are key aspects that need to be addressed when designing interventions to improve the quality of care for high-risk lupus patients.

Adopting the Quadruple Aim: The University of Rochester Medical Center Experience: Moving from Physician Burnout to Physician Resilience.

BACKGROUND: The high rates of burnout among medical professionals in the United States are well documented. The reasons for burnout and the factors that contribute to physician resilience among health care providers in academic centers, however, are less well studied. METHODS: Health care providers at a large academic center were surveyed to measure their degree of burnout and callousness and identify associated factors. Additional questions evaluated features linked to resilience. The survey assessed demographic variables, work characteristics, qualifications, experience, and citizenship. RESULTS: A total of 528 surveys were sent out; 469 providers responded, and 444 (84%) completed the survey. High burnout was reported by 214 providers (45.6%), and callousness was noted among 163 (34.8%). Rates of burnout and callousness were higher among advanced practice providers than physicians. Lack of support, lack of respect, and problems with work-life balance were themes significantly associated with a risk for burnout. Rates of burnout (P < .05) and callousness (P < .001) were also significantly higher among those who spent more than 80% of their time in patient care. Participation in patient care was the most sustaining factor, followed by teamwork, scholarly activities, autonomy, and medicine as a calling. CONCLUSIONS: Academic physicians enjoy patient care and value scholarly activities, but lack of support, lack of respect, workload, and problems with work-life balance prevent them from finding a sense of meaning in their professional work. Changes at the organizational level are needed to overcome these impediments and recreate joy in the practice of medicine.

Patients with rheumatoid arthritis in clinical remission manifest persistent joint inflammation on histology and imaging studies.

OBJECTIVE: The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology. METHODS: We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined. RESULTS: Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US. CONCLUSION: Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.

Imaging in psoriatic arthritis.

Psoriatic arthritis (PsA), a chronic inflammatory arthritis associated with psoriasis, is often associated with significant inflammation and joint damage leading to a decrease in quality of life measures. Plain radiographs have traditionally been used to detect and estimate the extent of joint damage. Newer imaging modalities such as ultrasound and MRI however, have provided the ability to detect joint damage earlier and measure the extent of joint damage more accurately, than with radiographs. These imaging modalities also provide a sensitive means of assessing for the presence of and quantifying the amount of inflammation. Furthermore, these imaging modalities can help with the identification of enthesitis, tendonitis, and dactylitis, features that can help make a diagnosis of PsA. Additionally, MRI and scintigraphy can help in the early detection and assessment of sacroiliitis and axial disease. In addition to benefits with diagnosis and prognosis, recent advances in imaging techniques have led to their increased use in the assessment of efficacy of novel therapies for psoriatic arthritis. Imaging modalities therefore allow for early detection, assessment of joint inflammation and joint damage as well as in the estimation of disease activity of PsA and thereby enable the clinician to treat PsA early, adequately, and safely.

Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor.

INTRODUCTION: As a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy. METHODS: Peripheral blood samples were obtained from RA patients, including a subset treated with anti-TNF, and from healthy controls to examine influenza-specific responses following seasonal influenza vaccination. Serum antibody was measured by hemagglutination inhibition assay. The frequency of influenza vaccine-specific antibody secreting cells and memory B cells was measured by EliSpot. Plasmablast (CD19+IgD-CD27hiCD38hi) induction was measured by flow cytometry. RESULTS: Compared with healthy controls, RA patients treated with anti-TNF exhibited significantly decreased influenza-specific serum antibody and memory B cell responses throughout multiple years of the study. The short-term influenza-specific effector B cell response was also significantly decreased in RA patients treated with anti-TNF as compared with healthy controls, and correlated with decreased influenza-specific memory B cells and serum antibody present at one month following vaccination. CONCLUSIONS: RA patients treated with anti-TNF exhibit a compromised immune response to influenza vaccine, consisting of impaired effector and consequently memory B cell and antibody responses. The results suggest that the increased incidence and severity of infection observed in this patient population could be a consequence of diminished antigen-responsiveness. Therefore, this patient population would likely benefit from repeat vaccination and from vaccines with enhanced immunogenicity.

Update on research and future directions of the OMERACT MRI inflammatory arthritis group.

The OMERACT Magnetic Resonance Imaging (MRI) Task Force has developed and evolved the psoriatic arthritis MRI score (PsAMRIS) over the last few years, and at OMERACT 10, presented longitudinal evaluation by multiple readers, using PsA datasets obtained from extremity MRI magnets. Further evaluation of this score will require more PsA imaging datasets. As well, due to improved image resolution since the development of the original rheumatoid arthritis MRI scoring system (RAMRIS), the Task Force has worked on semiquantitative assessment of joint space narrowing, and developed a reliable method as a potential RAMRIS addendum, although responsiveness will need to be evaluated. One of the strengths of MRI is the ability to detect subclinical synovitis, so the group worked on obtaining low disease activity/clinical remission datasets from a number of international centers and presented cross-sectional findings. Subsequent longitudinal evaluation of this unique resource will be a major continuing focus for the group.

Development and preliminary validation of a magnetic resonance imaging joint space narrowing score for use in rheumatoid arthritis: potential adjunct to the OMERACT RA MRI scoring system.

OBJECTIVE: To develop and validate a magnetic resonance imaging (MRI) method of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA). METHODS: Phase A: JSN was scored 0-4 on MR images of 5 RA patients and 3 controls at 15 wrist sites and 2nd-5th metacarpophalangeal (MCP) joints by 8 readers (7 once, one twice), using a preliminary scoring system. Phase B: Image review, discussion, and consensus on JSN definition, and revised scoring system. Phase C: MR images of 15 RA patients and 4 controls were scored using revised system by 5 readers (4 once, one twice), and results compared with radiographs [Sharp-van der Heijde (SvdH) method]. RESULTS: Phase A: Intraobserver agreement: intraclass correlation coefficient (ICC) = 0.99; smallest detectable difference (SDD, for mean of readings) = 2.8 JSN units (4.9% of observed maximal score). Interobserver agreement: ICC = 0.93; SDD = 6.4 JSN units (9.9%). Phase B: Agreement was reached on JSN definition (reduced joint space width compared to normal, as assessed in a slice perpendicular to the joint surface), and revised scoring system (0-4 at 17 wrist sites and 2nd-5th MCP; 0: none; 1: 1-33%; 2: 34-66%; 3: 67-99%; 4: ankylosis). Phase C: Intraobserver agreement: ICC = 0.90; SDD = 6.8 JSN units (11.0%). Interobserver agreement: ICC = 0.92 and SDD = 6.2 JSN units (8.7%). The correlation (ICC) with the SvdH radiographic JSN score of the wrist/hand was 0.77. Simplified approaches evaluating fewer joint spaces demonstrated similar reliability and correlation with radiographic scores. CONCLUSION: An MRI scoring system of JSN in RA wrist and MCP joints was developed and showed construct validity and good intra- and interreader agreements. The system may, after further validation in longitudinal data sets, be useful as an outcome measure in RA.

Comparative analysis of disease activity measures, use of biologic agents, body mass index, radiographic features, and bone density in psoriatic arthritis and rheumatoid arthritis patients followed in a large U.S. disease registry.

OBJECTIVE: To compare disease activity, radiographic features, and bone density in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) matched cohorts. METHODS: Disease activity and radiographic data in the Consortium of Rheumatology Researchers of North America database from 2001 to 2008 were compared for 2481 patients with PsA and 17,107 patients with RA subsequently matched for age, gender, and disease duration. Radiographic outcomes included presence of erosions, and joint deformity. In addition, bone mineral density (BMD) scores for lumbar spine (L-spine) and femoral neck were compared using the same matching criteria plus weight and smoking status. RESULTS: Tender (4.5 vs 3.4, p < 0.001) and swollen (4.4 vs 2.9, p < 0.012) joint counts, and modified Health Assessment Questionnaire scores were significantly higher (0.4 vs 0.3, p < 0.001) in patients with RA compared with patients with PsA. Patient general health and pain scores were also higher in patients with RA vs patients with PsA. Joint erosions (47.4% vs 37.6%, p = 0.020) and deformity (25.2% vs 21.6%, p = 0.021) were more prevalent in RA than PsA. In multivariate analysis, a reduced prevalence of erosions in PsA vs RA was noted (OR 0.609, p < 0.001). After matching, T-scores for L-spine (-0.54 vs -0.36, p = 0.077) and femoral neck (-0.88 vs -0.93, p = 0.643) were similar in patients with RA and patients with PsA, although body weight was a major confounder. CONCLUSION: The level of disease activity and radiographic damage was significantly higher for RA vs PsA subjects, although the magnitude of differences was relatively small. BMD levels were comparable between cohorts. Outcomes in patients with PsA and patients with RA may be more similar than previously reported.

Erosive osteoarthritis.

Erosive osteoarthritis (EOA) represents a subset of symptomatic osteoarthritis of hand, characterized by intermittent and often frequent inflammatory episodes and progressive joint damage. A greater degree of inflammation and the presence of subchondral bone erosions on plain radiographs help distinguish EOA from generalized osteoarthritis of hand. High resolution ultrasound and magnetic resonance imaging (MRI) have demonstrated the presence of synovitis and MRI has additionally highlighted the role of inflammation in bone, tendons, and ligaments in EOA. Further evidence for the crucial role of inflammation comes from recent studies that have unraveled the roles for several cytokines in the pathogenesis of EOA. Despite these advances, treatment options for EOA to date have been of modest benefit. Additional research is therefore needed to better understand the pathogenesis of EOA and lead to the development of novel therapeutic agents for this disabling form of arthritis.

The diagnosis and treatment of early psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disorder associated with a heterogeneous disease presentation, varied disease expression and an unpredictable but often chronically destructive clinical course. Joint damage can occur early in the disease; indeed, several imaging modalities have demonstrated subclinical joint involvement in psoriasis patients without musculoskeletal signs or symptoms. Efforts are underway to validate questionnaires that will enable dermatologists to screen patients with psoriasis for the presence of musculoskeletal disease. To date, the use of therapies in patients with early PsA has not been reported in randomized controlled trials. Moreover, conventional agents are partially effective in established PsA but, in general, trials with DMARDS have not included validated outcome measures for the different manifestations of PsA. Tumor necrosis factor antagonists can alleviate the signs and symptoms of established psoriatic arthritis and inhibit radiographic progression, but the therapeutic impact of early intervention with these agents requires further study. The extent of disease and the presence of comorbidities should be used to guide treatment decisions and to minimize adverse events.

Bone loss in the spondyloarthropathies: role of osteoclast, RANKL, RANK and OPG in the spondyloarthropathies.

Bone loss is a common finding in the spondyloarthropathies. It may be localized and present as erosions or be generalized and cause osteoporosis. The pathogenesis of bone loss in the spondyloarthropathies is yet to be fully understood. There is however increasing evidence to support a role for the osteoclasts in bone erosions. Similarly a balance between the receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) levels is thought to regulate osteoclastic activity and therefore bone loss in the inflammatory arthritides. In this chapter we will review the recent literature on the role of osteoclasts and the RANKL/OPG system in the various spondyloarthropathies and try to formulate a hypothesis for the possible mechanism of bone loss in this group of inflammatory rheumatic disease.

The OMERACT MRI inflammatory arthritis group: advances and future research priorities.

The OMERACT magnetic resonance imaging (MRI) in inflammatory arthritis group previously developed the rheumatoid arthritis MRI score (RAMRIS) for use in clinical studies, evaluated the use of extremity MRI, and initiated development of a psoriatic arthritis MRI score (PsAMRIS). At OMERACT 9 the group looked at clarifications of applying the RAMRIS, and presented data from a study examining how the contrast agent gadolinium affects RAMRIS outcomes. Much of the group's effort has been aimed at the iterative development of its PsA score, and reported exercises examining this score demonstrated encouraging results, allowing subsequent presentation of a preliminary PsAMRIS. The large amount of data presented were followed by discussions with the wider audience highlighting constructive suggestions for future research priorities, including further feasibility studies, understanding imaging remission, and further improvements to PsAMRIS.

Role of RANKL in bone diseases.

Bone remodeling is a tightly regulated process of osteoclast-mediated bone resorption, balanced by osteoblast-mediated bone formation. Disruption of this balance can lead to increased bone turnover, resulting in excessive bone loss or extra bone formation and consequent skeletal disease. The receptor activator of nuclear factor kappaB ligand (RANKL) (along with its receptor), the receptor activator of nuclear factor kappaB and its natural decoy receptor, osteoprotegerin, are the final effector proteins of osteoclastic bone resorption. Here, I provide an overview of recent studies that highlight the key role of RANKL in the pathophysiology of several bone diseases and discuss the novel therapeutic approaches afforded by the modulation of RANKL.

Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications.

Focal bone loss around inflamed joints in patients with autoimmune disease, such as rheumatoid arthritis, remains a serious clinical problem. The recent elucidation of the RANK/RANK-ligand/OPG pathway and its role as the final effector of osteoclastogenesis and bone resorption has brought a tremendous understanding of the pathophysiology of inflammatory bone loss, and has heightened expectation of a novel intervention. Here, we review the etiology of inflammatory bone loss, the RANK/RANK-ligand/OPG pathway, and the clinical development of anti-RANK-ligand therapy.