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Background: Patients with secondary metastatic involvement of the musculoskeletal system due to primary cancers are a rapidly growing population with significant risks for health-related end-of-life morbidities. In particular, bone metastases or metastatic bone disease (MBD) imparts significant adversity to remaining quality of life. No rigorous review of clinical trials on the use of supportive care interventions for MBD has been conducted. The objective of this review was to examine the characteristics of supportive care interventions for MBD and critically appraise study designs, key findings, and quality of evidence of the research., Methods: We searched for published clinical trials, systematic reviews and meta-analyses in PubMED, CINAHL and Google Scholar for articles published between September 2017 and September 2022. Some examples of Medical Subject Headings terms were: 'secondary neoplasm', 'metastatic bone disease', 'palliative care' and 'supportive care intervention'. Quality of published evidence was evaluated based on treatment types and study design., Results: After reviewing 572 publications, 13 articles were included in the final review and evaluation including seven clinical trials, two trial protocols and four systematic reviews. Feasible interventions included enhanced palliative care consultation, palliative radiotherapy and alternative medicines. Interventions addressed primary endpoints of fatigue (N=4, 31%), pain (N=3, 23%) or cancer-related symptoms (N=3, 23%) with patient-reported outcome instruments. No interventions reported on fracture complications or endpoints, specifically. The quality of most studies was moderate to strong., Conclusion: Supportive care interventions for MBD are feasible and the impact is measurable via patient-reported outcome measures. While the evidence for interventions was moderate to strong, there are very few specific controlled trials for skeletal-related events and impacts of social determinants of health. Further clinical trials are needed to define supportive care interventions for MBD that demonstrate reduced risk of fracture and that mitigate the reduced quality of life when negative musculoskeletal outcomes arise., Competing Interests: Competing interests: AF is supported in part by the UC Davis Paul Calabresi Career Development Program for Clinical Oncology funded by the National Cancer Institute/National Institutes of Health (5K12-CA138464)., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to evaluate the incidence of brachial plexus birth injury (BPBI) and its associations with maternal demographic factors. Additionally, we sought to determine whether longitudinal changes in BPBI incidence differed by maternal demographics., Study Design: We conducted a retrospective cohort study of over 8 million maternal-infant pairs using California's Office of Statewide Health Planning and Development Linked Birth Files from 1991 to 2012. Descriptive statistics were used to determine BPBI incidence and the prevalence of maternal demographic factors (race, ethnicity, age). Multivariable logistic regression was used to determine associations of year, maternal race, ethnicity, and age with BPBI. Excess population-level risk associated with these characteristics was determined by calculating population attributable fractions., Results: The incidence of BPBI between 1991 and 2012 was 1.28 per 1,000 live births, with peak incidence of 1.84 per 1,000 in 1998 and low of 0.9 per 1,000 in 2008. Incidence varied by demographic group, with infants of Black (1.78 per 1,000) and Hispanic (1.34 per 1,000) mothers having higher incidences compared with White (1.25 per 1,000), Asian (0.8 per 1,000), Native American (1.29 per 1,000), other race (1.35 per 1,000), and non-Hispanic (1.15 per 1,000) mothers. After controlling for delivery method, macrosomia, shoulder dystocia, and year, infants of Black (adjusted odds ratio [AOR] = 1.88, 95% confidence interval [CI] = 1.70, 2.08), Hispanic (AOR = 1.25, 95% CI = 1.18, 1.32), and advanced-age mothers (AOR = 1.16, 95% CI = 1.09, 1.25) were at increased risk. Disparities in risk experienced by Black, Hispanic, and advanced-age mothers contributed to a 5, 10, and 2% excess risk at the population level, respectively. Longitudinal trends in incidence did not vary among demographic groups. Population-level changes in maternal demographics did not explain changes in incidence over time., Conclusion: Although BPBI incidence has decreased in California, demographic disparities exist. Infants of Black, Hispanic, and advanced-age mothers are at increased BPBI risk compared with White, non-Hispanic, and younger mothers., Key Points: · The incidence of BPBI has decreased over time.. · Demographic disparities in BPBI incidence and risk exist.. · Infants of Black, Hispanic, and advanced age mothers are at greatest risk of BPBI.., Competing Interests: None declared, (Thieme. All rights reserved.)

Background : Orthopedic oncology research is hindered by the scarcity of musculoskeletal tumors and research administrative inefficiencies. This paper introduces observational research through an innovative institution-specific methodology-termed an umbrella protocol. This protocol outlines a comprehensive standard procedure to expedite ethical approval for future aligned studies, reducing administrative barriers to research. Methods : We developed an umbrella protocol at an academic center, involving meticulous methodological identification and coordination with the institutional review board (IRB) to adhere to local guidelines. The protocol encompasses identifying investigators, research objectives, study goals, and data and safety monitoring frameworks necessary for typical standards. Results : Implementation of the umbrella protocol took 110 days to achieve exemption status, following multiple discussions with the IRB and extensive revisions. At the authors institution, this protocol significantly reduces protocol review times from an average of six-to-eight weeks to nearly instantaneous, facilitating a streamlined research process. Additionally, we established a dedicated orthopedic oncology patient registry to enhance future research endeavors. Conclusions : The adoption of umbrella protocols represents a pioneering strategy in orthopedic oncology. This approach mitigates research administrative burdens and broadens research scope in the field. It underscores the necessity of IRB collaboration, methodological precision, and stringent data management. The article also reflects on the ethical implications and potential biases introduced by emerging technologies like artificial intelligence, advocating for diligent ethical oversight. The establishment of an umbrella protocol marks a significant step towards more efficient research methodologies, ultimately aiming to improve patient care and outcomes for individuals with rare musculoskeletal conditions.

Objective: To evaluate the association of maternal delivery history with a brachial plexus birth injury risk in subsequent deliveries and to estimate the effect of subsequent delivery method on brachial plexus birth injury risk., Methods: We conducted a retrospective cohort study of all live-birth deliveries occurring in California-licensed hospitals from 1996 to 2012. The primary outcome was recurrent brachial plexus birth injury in a subsequent pregnancy. The exposure was delivery history (parity, shoulder dystocia in a previous delivery, or previously delivering a neonate with brachial plexus birth injury). Multiple logistic regression was used to model adjusted associations of delivery history with brachial plexus birth injury in a subsequent pregnancy. The adjusted risk and adjusted risk difference for brachial plexus birth injury between vaginal and cesarean deliveries in subsequent pregnancies were determined, stratified by delivery history, and the number of cesarean deliveries needed to prevent one brachial plexus birth injury was determined., Results: Of 6,286,324 neonates delivered by 4,104,825 individuals, 7,762 (0.12%) were diagnosed with a brachial plexus birth injury. Higher parity was associated with a 5.7% decrease in brachial plexus birth injury risk with each subsequent delivery (adjusted odds ratio [aOR] 0.94, 95% CI 0.92-0.97). Shoulder dystocia or brachial plexus birth injury in a previous delivery was associated with fivefold (0.58% vs 0.11%, aOR 5.39, 95% CI 4.10-7.08) and 17-fold (1.58% vs 0.11%, aOR 17.22, 95% CI 13.31-22.27) increases in brachial plexus birth injury risk, respectively. Among individuals with a history of delivering a neonate with a brachial plexus birth injury, cesarean delivery was associated with a 73.0% decrease in brachial plexus birth injury risk (0.60% vs 2.21%, aOR 0.27, 95% CI 0.13-0.55) compared with an 87.9% decrease in brachial plexus birth injury risk (0.02% vs 0.15%, aOR 0.12, 95% CI 0.10-0.15) in individuals without this history. Among individuals with a history of brachial plexus birth injury, 48.1 cesarean deliveries are needed to prevent one brachial plexus birth injury., Conclusions: Parity, previous shoulder dystocia, and previously delivering a neonate with brachial plexus birth injury are associated with future brachial plexus birth injury risk. These factors are identifiable prenatally and can inform discussions with pregnant individuals regarding brachial plexus birth injury risk and planned mode of delivery., Competing Interests: Financial Disclosure Barton L. Wise disclosed receiving payment from Novartis. Daniel J. Tancredi disclosed receiving payment from International Flavors and Fragrances. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Valley fever or coccidioidomycosis is a pulmonary infection caused by species of Coccidioides fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues, causing significant pain and restricting mobility. Manifestations of such cases are usually nonspecific, making diagnosis very challenging, especially in non-endemic areas. The lack of basic knowledge and research data on the mechanisms defining susceptibility to extrapulmonary infection, especially when it involves bones and joints, prompted us to survey available clinical and animal data to establish specific research questions that remain to be investigated. In this review, we explore published literature reviews, case reports, and case series on the dissemination of coccidioidomycosis to bones and/or joints. We highlight key differential features with other conditions and opportunities for mechanistic and basic research studies that can help develop novel diagnostic, prognostic, and treatment strategies.

Purpose: This study determined whether initiation of pharmacologic treatment was delayed for newly diagnosed osteoporosis patients during the COVID-19 pandemic., Methods: 1,189 patients ≥50 years with newly diagnosed osteoporosis using dual-energy x-ray absorptiometry (DXA) screening at a single academic institution were included. Patients with previous osteoporosis were excluded. Patients diagnosed between March 1, 2018-January 31, 2020 (pre-pandemic cohort, n = 576) were compared to those diagnosed between March 1, 2020-January 31, 2022 (pandemic cohort, n = 613). Age, sex, race, ethnicity, ordering providers (primary vs specialty), and pharmacological agents were evaluated. Primary outcomes included proportion of patients prescribed therapy within 3 and 6-months of diagnosis, and mean time from diagnosis to treatment initiation., Results: The pre-pandemic cohort had more White patients (74.3 vs 68.4%, p = .02) and no differences between remaining demographic variables. Only 40.5% of newly diagnosed patients initiated pharmacologic therapy within 6 months. Patients treated at 3-months (31.8 vs 35.4%, p = 0.19) and 6-months (37.8 vs 42.9, p = 0.08) were comparable between cohorts (47.2 vs 50.2% p = 0.30). Mean time from diagnosis to treatment initiation was similar (46 vs 45 days, p = 0.72). There were no treatment differences based on gender, race, or ethnicity or between ordering providers (65.1 vs 57.4% primary care, p = 0.08). Bisphosphonates were most often prescribed in both cohorts (89% vs 82.1%)., Conclusions: This is the first study assessing COVID-19's impact on pharmacologic treatment of newly diagnosed osteoporosis. 40.5% of newly diagnosed patients were treated pharmacologically within six months of diagnosis, and the pandemic did not significantly affect treatment rates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 White et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This observational, longitudinal study's purpose was to investigate whether social network integration has a moderating effect on smoking initiation among those with attention deficit hyperactivity disorder (ADHD). Data were drawn from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative longitudinal dataset. Social network and smoking data were collected in schools, with a 6-year follow-up that included ADHD symptoms and reported smoking. Social integration was measured as peer friendship nominations (degree) and the influence of an individual on the entire social network (centrality). Multilevel logistic regression found a main effect for ADHD symptoms and low numbers of friendship nominations on smoking initiation, but social network measures were not significant moderators of the relationship between ADHD symptoms and smoking initiation among adolescents. Further investigation of the drivers of smoking initiation among those with ADHD is warranted.

Objective: The objective of this study was to review the literature on associations between chondrocalcinosis (CC) and osteoarthritis (OA) and to examine the role of colchicine, previously established as effective for calcium pyrophosphate deposition disease, in the treatment of OA., Methods: A literature search for mechanistic and clinical studies published between 1990 and 2021 listed in PubMed was performed and studies were included if they examined the associations between OA and CC or colchicine using relevant search terms., Results: Published evidence suggests significant radiographic and mechanistic associations between knee OA and knee CC, but there are only a limited number of studies demonstrating associations between OA and CC in the hips, hands, and ankles. We examined three studies testing the efficacy of colchicine on treatment of pain in OA and found insufficient evidence to definitively establish that colchicine is effective to ameliorate symptoms of OA, although differences in study methodologies and inclusion criteria may explain inconsistent study findings., Conclusion: An association between CC and OA is supported at the knee joint in both radiographic and in-vitro studies, but is less definite when the relationship is evaluated at other joints, including at the hips, hands, and ankles. Further research is required to ascertain whether CC modifies symptoms in patients with osteoarthritis or is associated with OA progression. It may be worthwhile to further evaluate colchicine or other agents for potential symptom modifying roles in OA or in OA with CC.

Background: Approximately 5% of cancer patients in the United States presented with metastatic bone disease (MBD) at diagnosis. Current study explores the disparities in survival for patients with MBD., Methods: Patients with the diagnosis of MBD at presentation for the five most common primary anatomical sites were extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset (2010-2016). Kaplan-Meier and Cox Proportional Hazard models were used to evaluate survival, and prognostic factors for each cohort. Prognostic significance of socioeconomic status (SES) and insurance status were ascertained., Results: The five most common anatomical-sites with MBD at presentation included "lung" (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal and urothelium" (n = 7718) and "colon" (n= 3068). Lower SES was an independent risk factor for worse disease-specific survival (DSS) for patients with MBD originating from lung, prostate, breast and colon. Lack of insurance was an independent risk factor for worse DSS for MBD patients with primary tumors in lung and breast., Conclusions: MBD patients from the five most common primary sites demonstrated SES and insurance-related disparities in disease-specific survival. This is the first and largest study to explore SES and insurance-related disparities among patients specifically afflicted with MBD. Our findings highlight vulnerability of patients with MBD across multiple primary sites to financial toxicity., (© 2022 Wiley Periodicals LLC.)

Objective: To determine whether the amount of physical activity (PA) is a determinant of joint space narrowing (JSN) worsening over 48 months in participants with knee osteoarthritis., Methods: Data were obtained from the Osteoarthritis Initiative. PA, measured using the Physical Activity Scale for the Elderly (PASE), was defined as the mean value of the annual measurements conducted prior to development of worsening JSN. Worsening JSN was defined as at least a partial grade increase in the Osteoarthritis Research Society International JSN score over 48 months, in comparison with baseline. Restricted cubic spline function was used to group participants based on the linear association between PA and JSN worsening. A pooled logistic regression model was used to evaluate the association between PA and JSN worsening adjusted for confounders., Results: A total of 2,167 participants were included. In total, 625 participants (28.8%) had JSN worsening over 48 months. Compared with a PASE score of 141-180, PASE scores of 101-140 and >220 were associated with an increased risk of JSN worsening in men, with odds ratios (ORs) of 1.73 (95% confidence interval [95% CI] 1.07-2.81) and 1.83 (95% CI 1.14-2.93), respectively. Similarly, in participants with Kellgren/Lawrence (K/L) grade 2, compared with a PASE score of 141-180, PASE scores of ≤100 and >220 were associated with increased risks of JSN worsening, with an OR of 1.69 (95% CI 1.13-2.54) and 1.64 (95% CI 1.05-2.56), respectively., Conclusion: Compared to moderate PA, higher or lower amounts of PA are associated with an elevated risk for JSN worsening in men and in participants with K/L grade 2 knees., (© 2021 American College of Rheumatology.)

Background: We have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD)., Methods: Patients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared., Results: The five most common anatomical sites with MBD at presentation include "lung: (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal" (n = 7718) and "colon" (n = 3068). There was an increase in incidence of MBD among cancers originating from prostate (annual percentage change [APC] 4.94), renal (APC 2.55), and colon (APC 3.21) (p < 0.05 for all). Non-Hispanic Blacks had higher incidence of MBD for prostate and breast primary sites (p < 0.001). Non-Hispanic American Indian Alaskan Native had higher incidence of MBD for cancers originating from renal (p < 0.001) and colon (p = 0.049). A higher incidence of MBD was seen in lower socioeconomic status (SES) groups for the selected sites (p < 0.001)., Conclusions: These findings suggest that there are multiple sex-related, racial/ethnic and SES disparities in the incidence of MBD from the 5 most common primary sites. Higher incidence seen among lower SES suggests delay in diagnosis and limited access to screening modalities., (© 2021 Wiley Periodicals LLC.)

Background: Osteoarthritis (OA) is a leading cause of musculoskeletal pain and disability among Americans. Physical therapy (PT) is recommended per the 2019 ACR /Arthritis Foundation Guideline for Treatment of OA of the Hand, Hip, and Knee. During COVID-19, access to healthcare has been altered in a variety of clinical settings, with the pandemic creating delays in healthcare, with an unknown impact on access to PT care for OA., Objectives: We sought to determine whether referrals to PT for OA were reduced in 2020 during the COVID-19 pandemic compared to 2019., Methods: A retrospective analysis was done of 3586 PT referrals placed by the University of California, Davis for 206 OA ICD-10 codes from January to November 2019 and from January to November 2020. The numbers of PT referrals per month of each year were compared using both descriptive statistics and Poisson Regression analysis., Results: A total of 1972 PT referrals for OA were placed from January to November 2019. Only 1614 referrals for OA were placed from January to November 2020, representing a significant decrease (p = 0.001). Month-by-month analysis of 2020 compared to 2019 revealed statistically significant drops in PT referrals for OA in April (p = 0.001), May (p = 0.001), and August (p = 0.001)., Conclusions: These findings reveal a significant reduction in the number of referrals for PT for OA placed in 2020 during the first year of the COVID-19 pandemic. These reductions were particularly evident in the months following state-mandated actions and closures. Factors associated with this outcome may include decreased access to primary care providers, perceptions of PT availability by health care providers, decreased mobility limiting access to both clinic and PT appointments, and/or willingness to engage in PT by patients during the pandemic., Competing Interests: The authors have declared that no competing interests exist.

Supplemental feeding of wildlife is a common practice often undertaken for recreational or management purposes, but it may have unintended consequences for animal health. Understanding cryptic effects of diet supplementation on the gut microbiomes of wild mammals is important to inform conservation and management strategies. Multiple laboratory studies have demonstrated the importance of the gut microbiome for extracting and synthesizing nutrients, modulating host immunity, and many other vital host functions, but these relationships can be disrupted by dietary perturbation. The well-described interplay between diet, the microbiome, and host health in laboratory and human systems highlights the need to understand the consequences of supplemental feeding on the microbiomes of free-ranging animal populations. This study describes changes to the gut microbiomes of wild elk under different supplemental feeding regimes. We demonstrated significant cross-sectional variation between elk at different feeding locations and identified several relatively low-abundance bacterial genera that differed between fed versus unfed groups. In addition, we followed four of these populations through mid-season changes in supplemental feeding regimes and demonstrated a significant shift in microbiome composition in a single population that changed from natural forage to supplementation with alfalfa pellets. Some of the taxonomic shifts in this population mirrored changes associated with ruminal acidosis in domestic livestock. We discerned no significant changes in the population that shifted from natural forage to hay supplementation, or in the populations that changed from one type of hay to another. Our results suggest that supplementation with alfalfa pellets alters the native gut microbiome of elk, with potential implications for population health., Competing Interests: The authors have declared that no competing interests exist.

Background: Postpartum women are at increased risk for lower limb musculoskeletal disorders. Foot arch collapse following pregnancy has been reported as a mechanism for this increased risk. However, dynamic changes during gait in postpartum women have not been reported. Therefore, we assessed the association between parity and dynamic foot pronation during gait., Objective: To determine (1) if there is an association between parity and dynamic foot pronation (center of pressure excursion index, CPEI) during gait; and (2) the extent to which there is a dose-effect of parity on foot pronation., Design: The Multicenter Osteoarthritis Study (MOST) Study is a longitudinal cohort study of adults with or at risk for knee osteoarthritis (OA)., Setting: Two communities in the United States, Birmingham, Alabama and Iowa City, Iowa., Interventions: Not applicable PARTICIPANTS: A population-based sample of 1177 MOST participants who were female, had complete CPEI and parity data and completed the baseline, 30- and 60-month visits., Main Outcome Measures: Odds of a one quintile decrease in CPEI by parity group and mean CPEI by parity group., Results: In 1177 women, mean age was 67.7 years and mean body mass index (BMI) was 30.6 kg/m 2 . As parity increased, there was significantly greater foot pronation, lower mean CPEI: 19.1 (18.2-20.1), 18.9 (18.4-19.4), 18 (17.5-18.6) to 17.5 (16.4-18.6) in the 0 to 4 and >5 children groups, respectively; (P = .002), which remained significant after adjusting for race and clinic site (P = .005). There was a positive linear trend (β = 1.08, 1.03-1.14) in odds ratios of a one quintile decrease in CPEI (greater pronation) with increasing parity level (P = .004), which remained significant after adjusting for race and clinic site (P = .01). After adjusting for age and BMI, these two associations were no longer statistically significant., Conclusions: This study indicates a positive correlation between parity and greater dynamic pronation of the feet., (© 2020 American Academy of Physical Medicine and Rehabilitation.)

Nerve growth factor (NGF) is a neurotrophin that activates nociceptive neurons to transmit pain signals from the peripheral to the central nervous system and that exerts its effects on neurons by signalling through tyrosine kinase receptors. Antibodies that inhibit the function of NGF and small molecule inhibitors of NGF receptors have been developed and tested in clinical studies to evaluate the efficacy of NGF inhibition as a form of analgesia in chronic pain states including osteoarthritis and chronic low back pain. Clinical studies in individuals with painful knee and hip osteoarthritis have revealed that NGF inhibitors substantially reduce joint pain and improve function compared with NSAIDs for a duration of up to 8 weeks. However, the higher tested doses of NGF inhibitors also increased the risk of rapidly progressive osteoarthritis in a small percentage of those treated. This Review recaps the biology of NGF and the studies that have been performed to evaluate the efficacy of NGF inhibition for chronic musculoskeletal pain states. The adverse events associated with NGF inhibition and the current state of knowledge about the mechanisms involved in rapidly progressive osteoarthritis are also discussed and future studies proposed to improve understanding of this rare but serious adverse event.

Background: Progesterone receptor (PR) affects immunomodulation, and lack of PR in osteoprogenitor cells primarily affects pathways associated with immunomodulation, especially in males. In this study, we selectively deleted PR from osteoprogenitor cells using Prx1-Cre to evaluate the tissue-specific effects of PR on the pathegenesis of inflammatary arthritis (IA)., Methods: Collagen-induced arthritis (CIA) was used as an IA animal model. Both male and female PR ΔPrx1 mice and their wild-type (WT) littermates were immunized with collagen II (CII) emulsified complete Freund's adjuvant (CFA). Joint erosion, inflammation, and cartilage damage were assessed using a semiquantitative histologic scoring system. Bone volume and erosions in knee and ankle joints were quantitated using microCT and histology., Results: Bone erosions developed in both paw joints in 37.5% and 41.7% of the WT and PR ΔPrx1 female mice and in 45.4 and 83.3% of the WT and PR ΔPrx1 male mice, respectively. Also, both joint damage and subchondral bone erosions were significantly more severe in male PRcKO-CIA mice than in male WT-CIA mice. Female PR ΔPrx1 mice also developed higher bone loss in the knee joints than the KO-normal or WT-CIA females although with less severity compared to the male mice., Conclusions: The presence of PR in osteoprogenitor cells decreased the development of collagen-induced arthritis and might help to explain the sex differences observed in human inflammatory arthritis.

Background: Knee osteoarthritis (OA) is more common in females than in males; however, the biological mechanisms for the difference in sex in patients with knee OA are not well understood. Knee shape is associated with OA and with sex, but the patterns of change in the bone's shape over time and their relation to sex and OA are unknown and may help inform how sex is associated with shape and OA and whether the effect is exerted early or later in life.Questions/purposes (1) Does knee shape segregate stably into different groups of trajectories of change (groups of knees that share similar patterns of changes in bone shape over time)? (2) Do females and males have different trajectories of bone shape changes? (3) Is radiographic OA at baseline associated with trajectories of bone shape changes?, Methods: We used data collected from the NIH-funded Osteoarthritis Initiative (OAI) to evaluate a cohort of people aged 45 to 79 years at baseline who had either symptomatic knee OA or were at high risk of having it. The OAI cohort included 4796 participants (58% females; n = 2804) at baseline who either had symptomatic knee OA (defined as having radiographic tibiofemoral knee OA and answering positively to the question "have you had pain, aching or stiffness around the knee on most days for at least one month during the past 12 months") or were at high risk of symptomatic knee OA (defined as having knee symptoms during the prior 12 months along with any of the following: overweight; knee injury; knee surgery other than replacement; family history of total knee replacement for OA; presence of Heberden's nodes; daily knee bending activity) or were part of a small nonexposed subcohort. From these participants, we limited the eligible group to those with radiographs available and read at baseline, 2 years, and 4 years, and randomly selected participants from each OAI subcohort in a manner to enrich representation in the study of the progression and nonexposed subcohorts, which were smaller in number than the OA incidence subcohort. From these patients, we randomly sampled 473 knees with radiographs available at baseline, 2 years, and 4 years. We outlined the shape of the distal femur and proximal tibia on radiographs at all three timepoints using statistical shape modelling. Five modes (each mode represents a particular type of knee bone shape variation) were derived for the proximal tibia and distal femur's shape, accounting for 78% of the total variance in shape. Group-based trajectory modelling (a statistical approach to identify the clusters of participants following a similar progression of change of bone shape over time, that is, trajectory group) was used to identify distinctive patterns of change in the bone shape for each mode. We examined the association of sex and radiographic OA at baseline with the trajectories of each bone shape mode using a multivariable polytomous regression model while adjusting for age, BMI, and race., Results: Knee bone shape change trajectories segregated stably into different groups. In all modes, three distinct trajectory groups were derived, with the mean posterior probabilities (a measure of an individual's probability of being in a particular group and often used to characterize how well the trajectory model is working to describe the population) ranging from 84% to 99%, indicating excellent model fitting. For most of the modes of both the femur and tibia, the intercepts for the three trajectory groups were different; however, the rates of change were generally similar in each mode. Females and males had different trajectories of bone shape change. For Mode 1 in the femur, females were more likely to be in trajectory Groups 3 (odds ratio 30.2 [95% CI 12.2 to 75.0]; p < 0.001) and 2 than males (OR 4.1 [95% CI 2.3 to 7.1]; p < 0.001); thus, females had increased depth of the intercondylar fossa and broader shaft width relative to epicondylar width compared with males. For Mode 1 in the tibia, females were less likely to be in trajectory Group 2 (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.01) than males (that is, knees of females were less likely to display superior elevation of tibial plateau or decreased shaft width relative to head width). Radiographic OA at baseline was associated with specific shape-change trajectory groups. For Mode 1 in the femur, knees with OA were less likely to be in trajectory Groups 3 (OR 0.4 [95% CI 0.2 to 0.8]; p = 0.008) and 2 (OR 0.6 [95% CI 0.3 to 1.0]; p = 0.03) than knees without OA; thus, knees with OA had decreased depth of the intercondylar fossa and narrower shaft width relative to epicondylar width compared with knees without OA. For Mode 1 in the tibia, knees with OA were not associated with trajectory., Conclusions: The shapes of the distal femur and proximal tibia did not change much over time. Sex and baseline knee radiographic OA status are associated with the trajectory of change in the bone's shape, suggesting that both may contribute earlier in life to the associations among trajectories observed in older individuals. Future studies might explore sex-related bone shape change earlier in life to help determine when the sex-specific shapes arise and also the degree to which these sex-related shapes are alterable by injury or other events., Level of Evidence: Level III, prognostic study.

Objective: The presence or relative proportion of progesterone nuclear receptors (PR) in different tissues may contribute to sexual dimorphism in these tissues. PR is expressed in chondrocytes, but its function is mostly unknown. We hypothesized that the PR may regulate chondrocyte metabolism and affect subchondral bone structure., Methods: We utilized genetic fate mapping and immunohistochemistry to elucidate PR expression in and effect on cartilage. To define sex-dependent and chondrocyte-specific effects of the PR on subchondral bone, we selectively deleted PR in osteochondrogenic progenitor cells marked by Prx1 (Prx1; PRcKO) and Collagen 2 (Col2; PRcKO), or in matured chondrocytes marked by aggrecan (Acan; PRcKO) and evaluated subchondral bone structure at 4 months of age. Chondrocyte aging was monitored by anti-senescence marker p16INK4a, and MMP13, one of the Senescence-Associated Secretary Phenotype (SASP) components., Results: Compared to wild-type (WT) mice, the female Prx1; PRcKO and the Col2; PRcKO mice had greater total subchondral bone volume and greater subchondral cortical bone thickness, with increased estimated subchondral bone stiffness and failure load in both female and male Col2; PRcKO mice. Moreover, Col2; PRcKO mice from both sexes had greater bone formation and bone strength at the femurs. In contrast, we did not observe any subchondral bone changes in Acan; PRcKO mice other than higher work-to-failure observed in the male Acan; PRcKO mice. Despite no detected difference in articular cartilage between the WT and the PR; chondrocyte conditional deletion mice, there were greater numbers of senescent chondrocytes and increased MMP13 expression, especially in the male mutant mice., Conclusion: These findings suggest that selective inhibition of PR in osteoprogenitor cells, but not in terminally differentiated chondrocytes, induced an increased subchondral bone phenotype and high estimated subchondral bone strength, which might be associated with the development of osteoarthritis in older age., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Knee bone shape differs between men and women and the incidence of knee osteoarthritis (OA) is higher in women than in men. Therefore, the purpose of the present study was to determine whether the observed difference in the incidence of knee radiographic OA (ROA) between men and women is mediated by bone shape., Methods: We randomly sampled 304 knees from the OAI with incident ROA (i.e., development of Kellgren/Lawrence grade ≥ 2 by month 48) and 304 knees without incident ROA. We characterized distal femur and proximal tibia shape on baseline radiographs using Statistical Shape Modeling. If a specific bone shape was associated with the risk of incident ROA, marginal structural models were generated to assess the mediation effect of that bone shape on the relation of sex and risk of incident knee ROA adjusting for baseline covariates., Results: Case and control participants were similar by age, sex and race, but case knees were from higher body mass index (BMI) participants (29.4 vs. 27.0; p < 0.001). Women had 49% increased odds of incident knee ROA compared with men (adjusted odds ratio (OR) = 1.49, 95% Confidence Interval (C.I.): 1.04, 2.12). There was an inconsistent mediation effect for tibial mode 2 between sex and incident knee ROA, with an indirect effect OR of 0.96 (95% C.I.: 0.91-1.00) and a direct effect OR of 1.56 (95% C.I.: 1.08-2.27), suggesting a protective effect for this mode. Similar findings were also observed for the mediation effect of tibia mode 10 and femur mode 4. These shape modes primarily involved differences in the angular relation of the heads to the shafts of the femur and tibia., Conclusions: Distal femur and proximal tibia bone shapes partially and inconsistently mediated the relationship between sex and incident knee OA. Women had a higher risk of incident ROA, and specific bone shapes modestly protected them from even higher risk of ROA. The clinical significance of these findings warrant further investigation.

Objective: To determine the association between quadriceps rate of force development (RFD) and decline in self-reported physical function and objective measures of physical performance., Design: Longitudinal cohort study., Setting: Community-based sample from 4 urban areas., Participants: Osteoarthritis Initiative participants with or at risk for knee osteoarthritis, who had no history of knee/hip replacement, knee injury, or rheumatoid arthritis (N=2630)., Interventions: Not applicable., Main Outcome Measures: Quadriceps RFD (N/s) was measured during isometric strength testing. Worsening physical function was defined as the minimal clinically important difference for worsening self-reported Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscale score, 20-m walk time, and repeated chair stand time over 36 months., Results: Compared with the slowest tertile of RFD, the fastest tertile had a lower risk for worsening of WOMAC physical function subscale score at 36-month follow-up, with an odds ratio (OR) of .68 (95% confidence interval [CI], .51-.92) after adjustment for age, sex, body mass index, depression, history of chronic diseases, and knee pain. In women, in comparison with the slowest tertile of RFD, the fastest tertile had a lower risk for worsening of WOMAC physical function subscale score at 36-month follow-up, with an adjusted OR of .57 (95% CI, .38-.86). This decreased risk did not reach statistical significance in men (OR, 0.81; 95% CI, 0.52-1.27). No statistically significant associations were detected between baseline RFD and walk or chair stand times., Conclusions: Our results indicate that higher RFD is associated with decreased risk for worsening self-reported physical function but not with decreased risk for worsening of physical performance., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate whether knee alignment explains the higher prevalence of lateral compartment tibiofemoral radiographic osteoarthritis (TFROA) among rural Chinese compared with that among Whites., Methods: The Wuchuan OA Study is a population-based longitudinal study of risk factors for knee OA. At baseline 1030 participants had home interviews, clinical examinations and weight-bearing posteroanterior semi-flexed radiographs of the tibiofemoral joints. Anatomic knee alignment was measured using an e-film workstation and divided into three categories: normal (182°-184°), valgus (> 184°), and varus (< 182°) alignment. A knee was defined as having medial or lateral compartmental ROA if its Kellgren and Lawrence grade was ≥ 2 and joint space narrowing ≥ 1 in the medial or lateral compartment, respectively. We examined the association between knee alignment with prevalent medial or lateral knee ROA separately using multiple logistic regression., Results: Among 1030 participants, the proportions of knees with normal, valgus and varus alignment were 29.9%, 56.5% and 13.7%, respectively. The prevalence of medial and lateral ROA was 16.0% and 4.3%, respectively. Valgus alignment was associated with prevalence of lateral compartment ROA (odds ratio [OR] = 5.0, 95% CI: 2.4-10.5), while varus alignment was associated with medial compartment ROA (OR = 6.1, 95% CI: 4.4-8.6). The ratio of prevalence of lateral versus medial compartment TFROA was greater in Wuchuan than that in the Framingham OA Study and valgus malalignment was more common in Wuchuan than in the Rotterdam study., Conclusions: The prevalence of compartment-specific TFROA differs between rural Chinese and Whites. This difference is likely due to relatively high prevalence of valgus malalignment in rural Chinese compared with that in Whites., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To examine the longitudinal relationship of knee pain, radiographic osteoarthritis (OA), symptomatic knee OA, and knee pain severity to incident widespread pain., Methods: The Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. Participants were characterized as having consistent frequent knee pain, radiographic OA (Kellgren/Lawrence scale grade ≥2), symptomatic OA, and knee pain severity at the 60-month visit (baseline). Widespread pain was categorized as pain above and below the waist, on both sides of the body and axially, using a standard homunculus, excluding knee pain. Incident widespread pain was defined as the presence of widespread pain at 84 months in those who were free of widespread pain at baseline. We assessed the relationship of baseline radiographic OA, symptomatic OA, consistent frequent knee pain, and knee pain severity, respectively, with incident widespread pain using logistic regression, adjusting for potential confounders, including models with and without pain severity., Results: At baseline, 1,129 subjects were eligible for analysis (mean ± SD age 66.7 ± 7.8 years; mean ± SD body mass index 30.1 ± 5.8 kg/m 2 ; 52% women). Radiographic OA in either knee (adjusted odds ratio [OR adj ] 0.90 [95% confidence interval (95% CI) 0.63-1.30]; P = 0.587) was not associated with incident widespread pain. Baseline bilateral consistent frequent knee pain (OR adj 2.35 [95% CI 1.37-4.03]), bilateral symptomatic OA (OR adj 2.11 [95% CI 1.04-4.24]), and knee pain severity (worst knee) (OR adj 1.11 [95% CI 1.05-1.17]; P < 0.001) were significantly associated with incident widespread pain., Conclusion: Consistent frequent knee pain, symptomatic OA, and knee pain severity increased the risk of developing widespread pain, independently of structural pathology. These results suggest that knee pain, and not structural pathology, contributes to the onset of widespread pain., (© 2016, American College of Rheumatology.)

Both epidemiologic and clinical research continues to be performed in osteoarthritis (OA). While epidemiologic studies identify risk factors for incident and progressive disease, clinical studies explore the role of both non-pharmacologic and pharmacologic treatments, including oral and intra-articular therapies. We performed a systematic review of the literature using PubMed for the time period between April 1, 2015 to February 22, 2016. Selected publications in the areas of both epidemiology and treatment are reviewed in this article., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: Isolated lateral compartment tibiofemoral radiographic osteoarthritis (IL-ROA) is an understudied form of knee osteoarthritis (OA). The objective of the present study was to characterize Magnetic Resonance Imaging (MRI) abnormalities and MR-T2 relaxation time measurements associated with IL-ROA and with isolated medial compartment ROA (IM-ROA) compared with knees without OA., Method: 200 case subjects with IL-ROA (Kellgren/Lawrence (K/L) grade≥2 and joint space narrowing (JSN) > 0 in the lateral compartment but JSN = 0 in the medial compartment) were randomly selected from the Osteoarthritis Initiative baseline visit. 200 cases with IM-ROA and 200 controls were frequency matched to the IL-ROA cases. Cases and controls were analyzed for odds of having a subregion with >10% cartilage area affected, with ≥25% bone marrow lesions (BML), with meniscal tear or maceration, and for association with cartilage T2 values., Results: IL-ROA was more strongly associated with ipsilateral MRI knee pathologies than IM-ROA (IL-ROA: OR = 135.2 for size of cartilage lesion, 95% CI 42.7-427.4; OR = 145.4 for large size BML, 95% CI 41.5-509.5; OR = 176 for meniscal tears, 95% CI 59.8-517.7; IM-ROA: OR = 28.4 for size of cartilage lesion, 95% CI 14.7-54.7; OR = 38.1 for size of BML, 95% CI 12.7-114; OR = 37.0 for meniscal tears, 95% CI 12-113.6). Cartilage T2 values were higher in both tibial and medial femoral compartments in IL-ROA, but in IM-ROA were only significantly different from controls in the medial femur., Conclusion: IL-ROA knees show a greater prevalence and severity of MRI lesions and higher cartilage T2 values than IM-ROA knees compared with controls., Competing Interests: BLW has had a contract with Pfizer, Inc., for unrelated work in the last 5 years. AG is the President of the Boston Imaging Core Lab, LLC, and is a consultant to TissueGene, Genzyme, OrthoTrophix and Merck Serono. Other authors had no competing interests. COMPETING INTEREST STATEMENT BLW has had a contract with Pfizer, Inc., for unrelated work in the last 5 years. AG is the President of the Boston Imaging Core Lab, LLC, and is a consultant to TissueGene, Genzyme, OrthoTrophix and Merck Serono. Other authors had no competing interests., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: We examined rheumatologists' approaches to and perceptions of depression in everyday practice., Methods: A questionnaire was mailed to 470 practicing rheumatologists in California; 226 were included in the final analyses. Respondents provided information on demographics, practice characteristics, and attitudes, perceptions, and practices related to depression. Logistic regression models were constructed to assess the relationship of rheumatologists' personal and practice characteristics with their depression-related practices., Results: Fifty-one percent of respondents reported that at least half of their patients had depression. Nearly all providers (99%) reported addressing mental health issues during some visits. Rheumatologists were about equally likely to prescribe antidepressants, refer to a psychiatrist, or return the patient to the primary care physician, with roughly 60% often applying each of the 3 strategies. Respondents identified access to services and patients' resistance to mental health diagnoses as major barriers to effective depression management. In logistic regression models, greater number of patient visits per week, greater percentage of patients with fibromyalgia, and private practice setting were associated with more prescription of antidepressants (P < 0.05)., Conclusions: Depression is common in rheumatologic practice, yet systems for identification, treatment, and referral of depressed patients are not universal. Rheumatologists' awareness of the need for mental health services is high, but they may lack the confidence, time, and/or referral networks to provide consistently effective care for depressed patients. Improving depression care in rheumatology may require a combination of clinician-level interventions (e.g., enhanced behavioral health training) and practice-level reforms (e.g., collaborative care).

Objectives: Risk of knee osteoarthritis (OA) is much higher in women than in men. Previous studies have shown that bone shape is a risk factor for knee OA. However, few studies have examined whether knee bone shape differs between men and women. The purpose of the present study was to determine whether there are differences between men and women in knee bone shape., Methods: We used information from the NIH-funded Osteoarthritis Initiative (OAI), a cohort of persons aged 45-79 at baseline who either had symptomatic knee OA or were at high risk of it. Among participants aged between 45 and 60 years, we randomly sampled 340 knees without radiographic OA (i.e., Kellgren/Lawrence grade of 0 in central readings on baseline radiograph). We characterized distal femur and proximal tibia shape of these selected radiographs using statistical shape modeling (SSM). We performed linear regression analysis to examine the association between sex and each knee shape mode (proximal tibia and distal femur), adjusting for age, race, body mass index (BMI), and clinic site., Results: The mean age was 52.7 years (±4.3 SD) for both men and women. There were 192 female and 147 male knees for the distal femur analysis. Thirteen modes were derived for femoral shape, accounting for 95.5% of the total variance. Distal femur mode 1 had the greatest difference in standardized score of knee shape between females and males (1.04, p < 0.01); modes 3, 5, 6, 8, and 12 were also significantly associated with sex. For tibial shape, 191 female knees and 149 male knees were used for the analysis. Overall, 10 modes explained 95.5% of shape variance. Of the significantly associated modes in the proximal tibia, mode 2 had the greatest difference in standardized score of bone shape between males and females (-0.30, p = 0.01); modes 3 and 4 were also significantly associated., Conclusion: The shapes of the distal femur and proximal tibia that form the knee joint differ by sex. Additional analyses are warranted to assess whether the difference in risk of OA between the sexes arises from bone shape differences., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate associations between lower levels of muscle strength, physical performance and physical activity and the risk of knee replacement (KR) in older adults with frequent knee pain., Method: Participants from the Multicenter Osteoarthritis Study (MOST) with knee pain on most of the past 30 days at baseline were included (n = 1257; mean (SD) age of 62.2 (8.2)). We examined the association between (1) baseline peak isokinetic knee extensor strength, (60°/sec, maximum out of four trials), (2) best time to stand in timed chair stand (2 trials of five repetitions), and (3) baseline Physical Activity Scale for the Elderly score (PASE) with incident KR between baseline and the 84-month follow-up., Results: 1252 (99.6%) participants (1682 knees) completed the follow-up visits. 331 participants (394 knees) underwent a KR during the 84 months (229 women and 102 men). The crude analysis demonstrated a decreased risk of KR in women (P < 0.0001) with higher knee extensor strength (Hazard Ratio (HR; 95% CI) 0.99 (0.98-0.99)). The risk remained significant (P = 0.03) when adjusting for age, BMI, race, clinic site, education, occupation, previous knee injury, previous knee surgery, and WOMAC pain (HR (95% CI) 0.99 (0.99-1.00)), but not when adjusting for Kellgren-Lawrence grade (P = 0.97)., Conclusion: Lower levels of chair stand performance and self-reported physical activity are not associated with an increased risk of KR within 7 years, while the independent effect of knee extensor strength on risk for KR in women is non-significant after adjusting for radiographic severity., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Debilitating pain associated with knee osteoarthritis (OA) often leads patients to seek and complete total knee arthroplasty (TKA). To date, few studies have evaluated the relation of functional impairment to the risk of TKA, despite the fact that OA is associated with functional impairment., Questions/purposes: The purpose of our study was to (1) evaluate whether function as measured by WOMAC physical function subscale was associated with undergoing TKA; and (2) whether any such association varied by sex., Methods: The National Institutes of Health-funded Multicenter Osteoarthritis Study (MOST) is an observational cohort study of persons aged 50 to 79 years with or at high risk of symptomatic knee OA who were recruited from the community. All eligible subjects with complete data were included in this analysis. Our study population sample consisted of 2946 patients with 5796 knees; 1776 (60%) of patients were women. We performed a repeated-measures analysis using baseline WOMAC physical function score to predict the risk of TKA from baseline to 30 months and WOMAC score at 30 months to predict risk of incident TKA from 30 months to 60 months. We used generalized estimating equations to account for the correlation between two knees within an individual and across the two periods. We calculated relative risk (RR) of TKA over 30 months by WOMAC function using a score of 0 to 5 as the referent in multiple binomial regressions with log link., Results: Those with the greatest functional impairment (WOMAC scores 40-68; 62 TKAs in 462 knee periods) had 15.5 times (95% confidence interval [CI], 7.6-31.8; p<0.001) the risk of undergoing TKA over 30 months compared with the referent group (12 TKAs in 3604 knee periods), adjusting for basic covariates, and 5.9 times (95% CI, 2.8-12.5; p<0.001) the risk after further adjusting for knee pain severity. At every level of functional limitation, the RR for TKA for women was higher than for men, but interaction with sex did not reach significance after adjustment for covariates including ipsilateral pain (p=0.138)., Conclusions: Baseline physical function appears to be an important element in patients considering TKA. Future studies should examine whether interventions to improve function can reduce the need for TKA., Level of Evidence: Level III, observational cohort study.

Objective: This study examined the association of proximal femur shape with ipsilateral medial and lateral compartment knee osteoarthritis (OA)., Design: Radiographs were obtained from the NIH-funded Osteoarthritis Initiative (OAI). Cases of isolated radiographic lateral compartment knee OA were defined on baseline radiographs as Kellgren/Lawrence (K/L) Grade ≥ 2 and joint space narrowing (JSN) > 0 in the lateral compartment and JSN = 0 in the medial compartment; isolated medial compartment knee OA had K/L ≥ 2 and JSN > 0 medially with JSN = 0 in the lateral compartment. Controls had K/L < 2 and JSN = 0 in both compartments. Controls were frequency matched to cases by sex and 10-year age intervals. We characterized the shape of the proximal femurs on radiographs using Active Shape Modeling (ASM) and determined the association of proximal femur shape with knee OA using logistic regression., Results: There were 168 lateral compartment knee OA cases (mean body mass index (BMI) 29.72 ± 5.26), 169 medial compartment knee OA cases (mean BMI 29.68 ± 4.83) and 168 controls (mean BMI 26.87 ± 4.2). Thirteen modes were derived for femur shape which described 95.5% of the total variance in proximal femur shape in the population. Modes 6, 8 and 12 were associated with prevalent lateral compartment knee OA. Medial compartment knee OA was associated with proximal femur modes 1, 5, 8, and 12., Conclusions: Prevalent lateral and medial compartment knee OA are associated with different ipsilateral proximal femur shapes. Additional studies are needed to better define how the shape of the proximal femur influences compartment-specific knee OA., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Lateral tibiofemoral osteoarthritis (OA) is overall less common than medial tibiofemoral OA, but it is more prevalent in women. This may be explained by sex differences in hip and pelvic geometry. The aim of this study is to explore sex differences in hip and pelvic geometry and determine if such parameters are associated with the presence of compartment-specific knee OA., Methods: This case-control study reports on 1,328 hips/knees from 664 participants and is an ancillary to the Multicenter Osteoarthritis Study (MOST). Of the 1,328 knees, 219 had lateral OA, 260 medial OA, and 849 no OA. Hip and pelvic measurements were taken from full-limb radiographs on the ipsilateral side of the knee of interest. After adjusting for covariates, means were compared between sexes and also between knees with medial and lateral OA vs no OA using separate regression models., Results: Women were shown to have a reduced femoral offset (FO) (mean 40.9 mm vs 45.9 mm; P = 0.001) and more valgus neck-shaft angle (mean 128.4° vs 125.9°; P < 0.001) compared to men. Compared to those with no OA, knees with lateral OA were associated with a reduced FO (P = 0.012), increased height of hip centre (HHC) (P = 0.003), more valgus neck-shaft angle (P = 0.042), and increased abductor angle (P = 0.031). Knees with medial OA were associated with a more varus neck-shaft angle (P = 0.043) and a decreased abductor angle (P = 0.003)., Conclusion: These data suggest anatomical variations at the hip and pelvis are associated with compartment-specific knee OA and may help to explain sex differences in patterns of knee OA., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD., (© 2014 American Society for Bone and Mineral Research.)

Background: Frailty has been associated in previous studies with increased mortality and morbidity, but little has been published on its association with arthritis. This study examined the association of hip osteoarthritis to frailty status in a longitudinal observational cohort of older men in the Osteoporotic Fractures in Men Study., Methods: Participants (N = 4,130) were men aged 65 years and older with complete frailty status and hip radiographs. We defined frailty as three or more of the following components: unintentional weight loss, weakness, self-reported exhaustion, low activity level, and slow walking speed. Men with intermediate stage status met one or two criteria while robust men had none. We defined radiographic hip osteoarthritis (RHOA) as a modified Croft score greater than or equal to 2 on hip radiograph. The relation of RHOA or total hip replacement (THR) to frailty status was examined in cross-sectional and incident analyses using logistic regression., Results: Prevalence of robust, intermediate, and frail status was 50%, 42%, and 8%, respectively. RHOA or THR was associated with increased odds of being frail or intermediate compared with robust (adjusted odds ratio = 1.45, 95% confidence interval [CI] 1.18, 1.78). Men with RHOA or THR were 1.27 times more likely to have incident frail or intermediate status compared with robust (95% CI: 1.19, 1.38)., Conclusions: RHOA and THR are associated with greater frailty status in older men, suggesting that interventions to reduce frailty should be evaluated in older men with either RHOA or THR.

We present a method based on spectral theory for the shape analysis of carpal bones of the human wrist. We represent the cortical surface of the carpal bone in a coordinate system based on the eigensystem of the two-dimensional Helmholtz equation. We employ a metric--global point signature (GPS)--that exploits the scale and isometric invariance of eigenfunctions to quantify overall bone shape. We use a fast finite-element-method to compute the GPS metric. We capitalize upon the properties of GPS representation--such as stability, a standard Euclidean (ℓ(2)) metric definition, and invariance to scaling, translation and rotation--to perform shape analysis of the carpal bones of ten women and ten men from a publicly-available database. We demonstrate the utility of the proposed GPS representation to provide a means for comparing shapes of the carpal bones across populations.

Objective: We evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA)., Design: The NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50-79 years with either symptomatic knee OA or at elevated risk of disease. Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence (K/L) grade ≥2 or KR. Women were grouped based by number of births: 0; 1 (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to the incidence over 30 months of ROA and KR using a Poisson regression model. Generalized estimating equations (GEE) were used to control for correlation between two knees within a subject. We adjusted for age, BMI, race, education, occupation, baseline estrogen use, clinical site, injury, and for KR analyses WOMAC pain and use of pain medication., Results: Among 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m(2), mean WOMAC pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high (95% CI: 1.2, 5.3) among women with five to 12 children compared with those with one birth., Conclusion: Parity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than four children., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Participation is an important, yet seldom studied, outcome after total knee replacement (TKR)., Objective: The purpose of this study was to investigate the extent and predictors of participation and participation restriction among people after TKR., Materials and Methods: This study investigated the changes in pain, function, and participation scores (measured using a subscale of the Late-Life Function and Disability Instrument) from pre-TKR to ≥1 year post-TKR among a subsample of participants from the Multicenter Osteoarthritis Study (MOST) longitudinal cohort (MOST is funded by the National Institutes of Health). The proportions of individuals with participation restriction pre-TKR and ≥1 and ≥2 years post-TKR were calculated for all participants and for important demographic subgroups. The association between demographic and clinical factors and participation was estimated using linear regression. The association between demographic and clinical factors and participation restriction was estimated using logistic regression., Results: There were 292 individuals with outcome data ≥1 year post-TKR. Of these, 218 (75%) had data pre-TKR and ≥1 year post-TKR and 160 (55%) had data ≥2 years post-TKR. There were mean improvements in pain, function, and participation at ≥1 and 2 years. However, approximately 30% of the study sample had participation restriction pre-TKR and post-TKR, and the proportion decreased significantly only for those <65 years old. Non-whites had a higher proportion of participation restriction than any other subgroup (41% ≥1 year, 48% ≥2 years). Female sex and non-white race were associated with a worse participation score, and several demographic and modifiable factors were associated with participation restriction following TKR., Limitations: The time between pre-TKR and post-TKR assessment varied across study participants, and data were not available on their rehabilitation utilization., Conclusions: Although there was a mean increase in participation ≥1 year following TKR, participation restriction was common. The likelihood of low participation was increased among women, non-whites, and those with depressive symptoms, severe pain in either knee, or worse pre-TKR function.

Objective: Nerve growth factor (NGF) is a key regulator of nociceptive pain and thus appears to be an interesting target molecule for an innovative class of analgesic medication. We set out to review the principles of neurogenic inflammation and results of anti-NGF regimens in animal studies as well as clinical trials with patients with back pain and osteoarthritis (OA)., Design: We searched using Google Scholar Search and Pubmed as well as through conference reports for articles and abstracts related to NGF and clinical trials using anti-NGF regimens. We report on efficacy findings and adverse events (AEs) related to these agents in this review., Results: We identified five full articles and eight abstract reports relating to anti-NGF agents studied for use in back pain and in OA., Conclusions: Anti-NGF agents either alone or in combination with non-steroidal anti-inflammatory agents (NSAIDs) were more efficacious for the treatment of pain in a number of trials of knee and hip pain compared to NSAIDs alone. However, adverse effects that included rapidly progressive OA and joint replacement were more common in patients treated with anti-NGF and NSAIDs than either treatment alone. Anti-NGF treatment related neurologic symptoms including paresthesias, and potentially other types of adverse effects were usually transient but warrant additional investigation., (Copyright © 2013. Published by Elsevier Ltd.)

Background: Quinolone antibiotics are associated with increased risk of tendinopathy. Identifying at-risk individuals has important clinical implications. We examined whether age, sex, glucocorticoid use, obesity, diabetes, and renal failure/dialysis predispose individuals to the adverse effects of quinolones., Methods: Among 6.4 million patients in The Health Improvement Network (THIN) database, 28,907 cases of Achilles tendonitis and 7685 cases of tendon rupture were identified in a case-crossover study. For each participant, we ascertained whether there was a prescription of a quinolone and comparison antibiotic within 30 days before the diagnosis of tendon disorder (case period) and a prescription of the same medications within 30 days 1 year before disease diagnosis (control period)., Results: Use of quinolones was strongly associated with an increased risk of Achilles tendonitis (odds ratio [OR], 4.3; 95% confidence interval [CI], 3.2-5.7) and tendon rupture (OR, 2.0; 95% CI, 1.2-3.3). No association was found between the use of other antibiotics and either outcome. The association with Achilles tendonitis was stronger among participants who were aged more than 60 years (OR, 8.3 vs 1.6), who were nonobese (OR, 7.7 vs 2.4), and who used oral glucocorticoids (OR, 9.1 vs 3.2). The association was nonsignificantly stronger in women (OR, 5.0 vs 3.6), diabetic persons (OR, 7.0 vs 4.1), and those in renal failure or receiving dialysis (OR, 20.0 vs 3.9). The effect for tendon rupture was stronger in women, with borderline significance in glucocorticoid users and nonobese persons., Conclusion: Quinolone-associated tendinopathy is more pronounced among elderly persons, nonobese persons, and individuals with concurrent use of glucocorticoids., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: We conducted a cross-sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by sex and ethnic groups, and, if it does, to what extent such a difference is accounted for by knee malalignment., Methods: The Multicenter Osteoarthritis Study is an observational study of persons ages 50-79 years with either symptomatic knee osteoarthritis or high risk of disease. Knee radiographs were assessed for JSN in each tibiofemoral compartment. Mechanical axis angle was measured using full-extremity films. We compared the proportion of knees with medial compartment JSN and with lateral JSN between men and women, as well as between whites and African Americans, using a logistic regression model adjusting for covariates (race or sex and body mass index, age, education, and clinic site). We used generalized estimating equations to account for correlation between 2 knees within a person., Results: Of 5,202 knees (2,652 subjects), 1,532 (29.5%) had medial JSN and 427 (8.2%) had lateral JSN. Lateral JSN was more prevalent in the knees of women than in men (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.5-2.4) and was also higher in the knees of African Americans than in whites (OR 2.4, 95% CI 1.7-3.3). Further adjustment for malalignment attenuated the OR for sex but not the OR for race., Conclusion: Women and African Americans are more likely to have lateral JSN than men and whites, respectively. Valgus malalignment may contribute to the higher prevalence in women., (Copyright © 2012 by the American College of Rheumatology.)

Background: The number of total shoulder arthroplasties performed in the United States increased slightly between 1990 and 2000. However, the incidence of shoulder arthroplasty in recent years has not been well described. The purpose of the present study was to examine recent trends in shoulder hemiarthroplasty and total shoulder arthroplasty along with the common reasons for these surgical procedures in the United States., Methods: We modeled the incidence of shoulder arthroplasty from 1993 to 2008 with use of the Nationwide Inpatient Sample. On the basis of hemiarthroplasty and total shoulder arthroplasty cases that were identified with use of surgical procedure codes, we conducted a design-based analysis to calculate national estimates., Results: While the annual number of hemiarthroplasties grew steadily, the number of total shoulder arthroplasties showed a discontinuous jump (p < 0.01) in 2004 and increased with a steeper linear slope (p < 0.01) since then. As a result, more total shoulder arthroplasties than hemiarthroplasties have been performed annually since 2006. Approximately 27,000 total shoulder arthroplasties and 20,000 hemiarthroplasties were performed in 2008. More than two-thirds of total shoulder arthroplasties were performed in adults with an age of sixty-five years or more. Osteoarthritis was the primary diagnosis for 43% of hemiarthroplasties and 77% of total shoulder arthroplasties in 2008, with fracture of the humerus as the next most common primary diagnosis leading to hemiarthroplasty., Conclusions: The number of shoulder arthroplasties, particularly total shoulder arthroplasties, is growing faster than ever. The use of reverse total arthroplasty, which was approved by the United States Food and Drug Administration in November 2003, may be part of the reason for the greater increase in the number of total shoulder arthroplasties. A long-term follow-up study is warranted to evaluate total shoulder arthroplasty in terms of patient outcomes, safety, and implant longevity.

From October 2009 through July 2010, five captive, 3-yr-old, female Rocky Mountain elk (Cervus elaphus) and nine free-ranging elk (one male, eight female) were immobilized with 0.1 mg/kg sufentanil plus 0.5 mg/kg xylazine which was antagonized with 1 mg/kg naltrexone and 2 mg/kg tolazoline. Induction and recovery times averaged 4.9 ± 0.3 min and 3.9 ± 0.4 min, respectively. Physiologic and blood gas parameters as well as bispectral index (BIS) were measured on the captive elk every 10 min for 30 min. Immobilization induced profound hypoxemia via hypoventilation and ventilation-perfusion mismatching as demonstrated by depressed partial pressure of arterial oxygen (P(a)O(2)) and increased partial pressure of arterial carbon dioxide (P(a)CO(2)). The only values to significantly (P<0.05) change over time were base excess (BE), bicarbonate (HCO(3)), and lactate. Bispectral index is a measure of anesthetic depth. The average BIS value over the 30 min period (59.1 ± 2.4) was higher than the BIS value at the approximate point where elk lose consciousness, which indicated that this drug combination produced neuroleptanalgesia but not general anesthesia. Sufentanil and xylazine provided effective remote immobilization in elk and could be substituted for carfentanil or thiafentanil and xylazine should the need arise.

Objective: To examine whether the consistency or persistence of knee pain, in addition to its severity, predicts incident total knee replacement (TKR)., Methods: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of persons aged 50 to 79 years with symptomatic knee osteoarthritis or at high risk of disease. Subjects were queried about the presence of knee pain on most days of the previous 30 days (i.e., frequent knee pain; FKP) at 2 timepoints: a telephone screen followed by a clinic visit (median separation 4 weeks). We defined a knee as having "consistent pain" if the subject answered positively to the FKP question at both timepoints, "inconsistent pain" if FKP was positive at only one timepoint, or as "no FKP" if negative at both. We examined the association between consistent FKP and risk of TKR using multiple binomial regression with generalized estimating equations., Results: In 3026 persons (mean age 63 yrs, mean body mass index 30.4), 2979 knees (50%) had no FKP at baseline, 1279 knees (21.5%) had inconsistent FKP, and 1696 knees (28.5%) had consistent FKP. Risk of TKR over 30 months was 0.8%, 2.6%, and 8.8% for knees with no, inconsistent, and consistent FKP, respectively. Relative risks of TKR over 30 months were 1.2 (95% CI 0.6-2.3) and 2.3 (95% CI 1.2-4.4) for knees with inconsistent and consistent FKP, compared with those without FKP. This association was consistent across each level of pain severity on the Western Ontario and McMaster Universities Osteoarthritis Index., Conclusion: Consistency of frequent knee pain is associated with an increased risk of TKR independently of knee pain severity.

Objective: We assessed associations between mental health and osteoarthritis (OA) pain., Methods: Two hundred and sixty-six subjects with hip and/or knee OA from the Longitudinal Examination of Arthritis Pain (LEAP) study were interviewed weekly for 12 weeks, measuring Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale and 5-item Mental Health Inventory (MHI-5). We examined associations between MHI-5 and its change, divided into quartiles, to WOMAC pain and its change (occurring 1 week later) using linear regression, adjusting for age, sex, body mass index (BMI), medication use. Generalized estimating equations were used to account for repeated measurements correlation. We also assessed the relation of MHI-5 to the risk of pain flare using conditional logistic regression in a case-crossover study., Results: Seventy-five men and 191 women were included. Mean age was 65.0, mean BMI 31.5. 82% had knee as their primary site. The mean WOMAC score was 2.93 in the quartile with the highest MHI-5 as compared with a mean WOMAC of 4.57 in the quartile with the lowest MHI-5 (P for trend across quartiles <0.001). In the case-crossover analysis (91 subjects), periods with the worst MHI-5 quartile had 2.1 times the odds of a pain flare the subsequent week as compared to periods with the best MHI-5 quartile (P<0.001)., Conclusion: We demonstrate an association between worsened measures of mental health and OA pain and risk of pain flares. General mental health is a modifiable component of health and may represent a new avenue for prevention of OA pain flares., (Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: We examined reported associations between radiographic hand osteoarthritis (OA) and single-nucleotide polymorphisms (SNP) in 2 candidate genes associated with OA in other joints: estrogen receptor alpha (ESR1) and beta (ESR2)., Methods: In 539 Framingham Offspring Study participants (49% men; mean age 61 +/- 9 yrs) joint-specific radiographic hand OA was defined as Kellgren/Lawrence (K/L) scores >or= 2 in the first carpometacarpal joint (CMC), distal interphalangeal joints (DIP), first-digit interphalangeal joint (IP), or proximal interphalangeal joints (PIP). Four SNP were genotyped for ESR1 (PvuII-rs2234693, XbaI-rs9340799, rs2077647, and rs1801132) and 4 for ESR2 (rs1256031, rs1256034, rs1256059, rs944460). Logistic regression analyses were performed to evaluate the relationships between genotypes and hand OA, adjusting for age, sex, height, and weight., Results: Radiographic hand OA was identified in at least one investigated joint of DIP (39%), PIP (33%), and first CMC (40%). There was no evidence of association between OA and genotype at any polymorphism. We found no significant association between our OA phenotypes or generalized or severe generalized OA as defined by Ushiyama and heterozygosity for rs2234693 and rs9340799, although in metaanalysis with the former study this heterozygosity remained significantly associated with generalized or severe generalized OA., Conclusion: We found no significant association between hand OA and the investigated polymorphisms of ESR1 or ESR2 despite published reports of association and a priori hypotheses implicating their potential roles. However, we could not absolutely exclude associations with rs2234693, rs9340799, or rs944460.

Certain levels of empathy are vital to health professionals for understanding their patients. The Level I clinical practicum experienced by Ohio State University juniors did not have the anticipated impact upon their empathy scores, but a group process course, where it was possible to teach and evaluate empathy levels, might have positively affected the empathy levels of students.