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Objective: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries., Methods: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries., Results: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA., Conclusion: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients., (Copyright © 2024 by the Journal of Rheumatology.)

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC., (Sociedad Argentina de Pediatría.)

Competing Interests: The authors declare no conflict of interest.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity, disability, and osteoporosis. We aimed to evaluate whole hand and regional BMD in RA patients compared to controls. In addition, we evaluated the BMD of dominant versus non-dominant hands in healthy subjects. We included adult female and male RA patients and control subjects matched by age, sex, and BMI. BMD (g/cm 2 ) was measured by DXA in lumbar spine (LS), whole hand, and three regions of interest: carpus, metacarpal bones, and phalanges. Results: 44 control subjects (49.5±11.8 y) and 60 with RA (52.7±12.7 y) were included. Significant lower BMD in RA patients was found in LS (-8.7%), dominant whole hand (-9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole hand (-8.7%), metacarpal bones, and phalanges compared to controls. A significant positive correlation was found between LS and whole-hand BMD (dominant r=.63, non-dominant r=.67). Finally, the whole hand, metacarpal bones, and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI. In conclusion, hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones, and phalanges) by DXA would be an easily reproducible technique to evaluate bone loss. In addition, the whole hand, metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA., (© 2023. Springer Nature Limited.)

Objective: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK)., Methods: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members., Results: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible., Conclusion: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries., Competing Interests: D.G.F.-Á. is consultant to Abbvie, Bristol Myers-Squibb, Eli Lilly, Fresenius Kabi, Janssen, Novartis, and Pfizer. M.V.S. is a speaker for and consultant to and receives research support from Abbvie, Bristol Myers-Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, and AstraZeneca. S.J.M. is a speaker for and consultant to and receives research support from Abbvie, Boehringer Ingelheim, GlaxoSmithKline, and Janssen. M.F.U.-G. receives research support and consulting fee from and is a speaker for Janssen, Pfizer, AztraZeneca, and GlaxoSmithKline. L.F.F.-S. is a speaker for Nippon Boehringer Ingelheim Co Ltd, Roche México, and Werfen Mexico. L.M.S.-R. is a speaker for and consultant to the advisory board of Novartis, Pfizer, Janssen, Bristol-Myers Squibb, Sanofi-Genzyme, Biopas, Amgen, Boehringer, Roche, and Eli Lilly. A.B. is a speaker and consultant to Abbvie, GlaxoSmithKline, Janssen, Pfizer, Boehringer Ingelheim, and Bristol-Myers Squibb. E.R.S.G. is a speaker for and consultant to and receives research support from Abbvie, Amgen, Bristol Myers-Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Roche, Sandoz, and UCB. S.U. is a consultant to and receives research support from Kiniksa, Janssen, and Genentech. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years., Methods: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%., Results: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios., Conclusions: This GIO guideline provides evidence-based guidance for health care providers treating patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted. For these reasons, the Pan American League of Associations for Rheumatology developed the first ANCA-associated vasculitis treatment guidelines tailored for Latin America. A panel of local vasculitis experts generated clinically meaningful questions related to the treatment of ANCA-associated vasculitis using the Population, Intervention, Comparator, and Outcome (PICO) format. Following the Grading of Recommendations Assessment, Development, and Evaluation methodology, a team of methodologists conducted a systematic literature review. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members. 21 recommendations and two expert opinion statements for the treatment of ANCA-associated vasculitis were developed, considering the current evidence and the socioeconomic characteristics of the region. These recommendations include guidance for the use of glucocorticoids, non-glucocorticoid immunosuppressants, and plasma exchange., Competing Interests: Declaration of interests Several authors of these guidelines, including voting members, have interacted with the pharmaceutical industry including the manufacturers of some of the drugs mentioned in these recommendations. However, none of the authors received any support or fee directly or indirectly related to or influencing the development of these guidelines. SJM reports being a speaker for, consulting for, and receiving research support from Roche, Pfizer, AbbVie, Janssen, Sandoz, and GlaxoSmithKline. MFU-G reports being a speaker for and receiving research support and consulting fees from Janssen, AstraZeneca, GlaxoSmithKline, AbbVie, and Pfizer. LFF-S reports being a speaker for and doing medical writing for the American College of Rheumatology, Sociedad Española de Reumatología, Editorial Médica Panamericana, and Elsevier. DGF-Á reports being a speaker for Amgen, Janssen, Novartis, Eli Lilly, and Pfizer; and receiving support for attending meetings from Janssen. MS reports being a speaker for, consulting for, and receiving research support from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, and AstraZeneca. EIS reports consulting for Janssen. AWSdS reports being on the advisory board of Vifor Pharma. LMS-R reports being a speaker for, consulting for, and being on the advisory board of Novartis, Pfizer, Janssen, Roche, and Eli Lilly. AMB reports being a speaker for and consulting for AbbVie, GlaxoSmithKline, Janssen, Pfizer, Boehringer-Ingelheim, and Bristol-Myers Squibb. ERSG reports being a speaker for, consulting for, and receiving research support from AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, and Sandoz. SU reports consulting for and receiving research support from Kiniksa, Janssen, Genentech, GlaxoSmithKline, and Sanofi. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction and Aim: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy., Methods: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment., Results: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range -1.6 to -2.0. The summary of findings was analyzed and put to a vote., Conclusions: With more than 80% agreement of the voting expert panel, a T-score≤-1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Purpose: To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials., Methods: Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months., Results: 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + 5.5%). A significant increase in LS BMD was found from month 6 to month 24 compared to basal in both AR-naïve, and AR-prior patients (+16.7% and +10.5%, respectively), without significant differences between the two groups. Comparable results were found in FN and TH BMD. Main conclusions . As reported in real-life clinical studies, treatment of osteoporotic postmenopausal women with TPTD induced a significant increase in bone turnover markers from month 6 onward and an increase in BMD from months 6-12 with continuous gain up to month 24. The real-life results of our study matched the results of randomized clinical trials. In addition, TPTD induced an increase in BMD, regardless of the previous use of AR., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Rodolfo Guelman et al.)

Considerable variability exists in the way that health-care providers treat patients with giant cell arteritis in Latin America, with patients commonly exposed to excessive amounts of glucocorticoids. In addition, large health disparities prevail in this region due to socioeconomic factors, which influence access to care, including biological treatments. For these reasons, the Pan American League of Associations for Rheumatology developed the first evidence-based giant cell arteritis treatment guidelines tailored for Latin America. A panel of vasculitis experts from Mexico, Colombia, Peru, Brazil, and Argentina generated clinically meaningful questions related to the treatment of giant cell arteritis in the population, intervention, comparator, and outcome (PICO) format. Following the grading of recommendations, assessment, development, and evaluation methodology, a team of methodologists did a systematic literature search, extracted and summarised the effects of the interventions, and graded the quality of the evidence. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members to be included in the guidelines. Nine recommendations and one expert opinion statement for the treatment of giant cell arteritis were developed considering the most up-to-date evidence and the socioeconomic characteristics of Latin America. These recommendations include guidance for the use of glucocorticoids, tocilizumab, methotrexate, and aspirin for patients with giant cell arteritis., Competing Interests: Declaration of interests Several authors of these guidelines, including voting members, have interacted with the pharmaceutical industry including the manufacturers of some of the drugs mentioned in these recommendations. However, none of the authors received any support or fee directly or indirectly related to or influencing the development of these guidelines. DGF-A, MLB, and ERSG are part of PANLAR committees and were involved in the critical review and editing of the manuscript. No other PANLAR committee member was involved in the writing of the manuscript. NVZ, MLAF, FV, LC, and SS received financial support from PANLAR. MS, AB, SJM, EIS, AWSdS, LMS-R, MFU-G, LFF-S, and SU did not receive financial support for this project from any entity. In addition, MS reports speaker fees from Bristol Myers Squibb, GlaxoSmithKline, Janssen, Elli Lilly, Pfizer, and Roche, and travel grants from Janssen, Pfizer, Roche, and AbbVie, all outside the submitted work. DGF-A reports consulting fees from AbbVie, speaker fees from Amgen, Janssen, Novartis, Elli Lilly, and Pfizer; travel grants from Janssen; and research grants from Pfizer, all outside the submitted work. AB reports speaker fees AbbVie, GlaxoSmithKline, Janssen, Pfizer, Boehringer Ingelheim, Bristol Myers Squibb, all outside the submitted work. SJM reports speaker fees from Roche, Janssen, and GlaxoSmithKline, and travel grants from Roche, Pfizer, AbbVie, Janssen, and Sandoz, all outside the submitted work. EIS reports consulting fees from Janssen outside the submitted work. LMS-R reports consulting fees from Roche, Novartis, and Janssen, and travel grants from Janssen and Novartis, all outside the submitted work. MFU-G reports travel grants from Pfizer and AbbVie, and research grants from Janssen, all outside the submitted work. ERSG reports consulting fees from AbbVie, Amgen, Janssen, Elli Lilly, Novartis, Pfizer, and Sandoz; speaker fees from AbbVie, Amgen, Janssen, Elli Lilly, Novartis, Pfizer, and Sandoz; travel grants from AbbVie; and research grants from Amgen, Novartis, Janssen, and Pfizer, all outside the submitted work. SU reports consulting fees from Kiniksa, Sanofi, GlaxoSmithKline, and Janssen, and research grants from Genentech and Janssen, all outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Several studies reported than vitamin D deficiency increases the risk of macrovascular and microvascular disease in patients with type 2 diabetes (T2DM). We investigated the plasma levels of 25OHD in adult patients T2DM, risk factors for 25OHD deficiency and the relationship between 25OHD, glycemic control and chronic complications of T2DM., Methods: A cross-sectional study was carried out, in which 25OHD levels were evaluated in adult patients (over 18 years) with T2DM. Correlation analyses were performed to evaluate the interdependence of the 25OHD with other continuous variables. A receiver operating characteristic analysis was also performed to identify cutoff values for diagnosing vitamin D deficiency. Logistic regression was performed to identify the independent association between vitamin D deficiency and the variables associated with lower 25OHD., Results: 208 patients were analyzed. The mean age of the patients was 62 years.  The 25OHD level was 19 ng/ml (IQR 13.28-24.43), 59.78% had vitamin D deficiency, and 10.33% had severe deficiency. Glycemia, HbA1c, and BMI were negatively correlated with 25OHD. Cutoff point for vitamin D deficiency was 33.39 kg/m2 for body mass index (BMI), 123 mg/dl for glycemia, and 6.65% for HbA1c. In multivariate logistic regression, BMI>33.39 kg/m2, glycemia >123.5 mg/dl, and albuminuria presented higher odds of vitamin D deficiency., Conclusion: Vitamin D deficiency was highly prevalent among patients with T2DM. Low levels were related to higher fasting plasma glucose, higher BMI, and diabetic nephropathy., (Universidad Nacional de Córdoba)

Pseudomyogenic hemangioendothelioma (PMH) can be a challenge for diagnosis and might be confused with other tumors, such as epithelioid sarcoma. Here we present a case and a systematic review of the literature to identify and discuss PMH treatment in primary bone involvement. A 25-year-old woman was referred for bone pain (10/10) in the left lower limb. Magnetic resonance imaging (MRI) showed multiple bone lesions (left femur, tibia, patella, ankle, and foot) with well-defined borders without signs of local aggressiveness. Positron Emission Tomography-Computed Tomography (PET-CT) showed multiple metabolic musculoskeletal lesions in the left lower limb. A CT scan-guided biopsy was performed. Histological and immunohistochemical findings confirmed the diagnosis of PMH. After treatment with intravenous pamidronate (90 mg/monthly), the patient had clinical improvement, mild pain 2/10 without the use of non-steroidal anti-inflammatory drugs or opiates. Follow-up was assessed by MRI and PET-CT. PET-CT showed metabolic resolution of most of the bone and muscular lesions and a significant improvement of the femoral lesion. MRI showed that the lesions in the left femur, tibia, and foot had a marked decrease in size without intravenous post-contrast enhancement and smaller lesions had disappeared. After a 3-year follow-up, PET-CT showed no metabolically active images. Literature review identified 31 records including 58 clinical cases of PMH with primary bone involvement and treatment description for qualitative analysis. Most lesions (69%) were treated by local excision or curettage. In addition, amputations were performed in a significant percentage of cases (20.7%). In the last years, mTOR inhibitors (n = 7) and anti-resorptive treatments (n = 4) were considered as alternative treatment options, especially in multifocal lesions., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues and could be genetic or non-genetic. The classic presentation of non-genetic HO is in young adults with a clear history of local trauma, surgery or prolonged immobilization after spinal cord and traumatic brain injuries. Genetic HO has a significant clinical severity compared to non-genetic causes and includes fibrodysplasia ossificans progressiva (FOP). FOP is an extremely rare genetic skeletal disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites affecting skeletal muscles, fascia, tendons, and ligaments. Previously, it has been reported an association between SARS-CoV-2 infection (COVID-19) and HO or FOP exacerbation with unclear etiopathogenesis. The possible mechanisms could be prolonged immobilization and systemic inflammation. Here, we describe the case of a 55-year-old apparently healthy man who suffered from a severe SARS-CoV-2 infection after that he experienced an extensive and progressive heterotopic ossification around the shoulders, the elbows, the hip, the knees, and the ankles. Because of the clinical severity, the painful soft-tissue swelling, the progressive HO, and the bilateral congenital hallux valgus deformity, a late-onset atypical FOP was suspected. Nevertheless, no variant of clinical significance has been identified in the coding regions and splicing sites in the ACVR1 gene and no deletions and/or duplications have been identified in exonic regions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformity and disability, as well as muscle involvement. Sarcopenia is characterized by a progressive age-related loss of muscle mass and strength., Aim: The aim of this study was to evaluate the prevalence of sarcopenia and possible contributing factors associated with sarcopenia in RA patients., Patients and Methods: Adult RA patients (n = 105) of both sexes and 100 subjects as control group (CG) matched by age, sex, and body mass index were included in this cross-sectional study. Whole-body composition was measured by dual-energy x-ray absorptiometry. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass [ASM] index by dual-energy x-ray absorptiometry). The association between sarcopenia and associated factors was evaluated using logistic regression analyses., Results: Significantly lower percentage of lean mass and ASM were found in the whole RA group compared with controls. However, lower lean parameters (total lean mass, percentage of lean mass, and ASM) were observed only in female subjects. The ASM index was significantly lower in female subjects with RA (RA 31.0% vs CG 11.9%) without differences in male subjects. On the other hand, fat mass and most adipose indices were significantly higher in both female and male subjects with RA. Female RA patients had higher prevalence of sarcopenia and sarcopenic obesity. Through univariate logistic regression analysis, the time of corticosteroids use, cumulative corticosteroid dose, previous fragility fractures, total lean mass, and ASM were associated with sarcopenia., Conclusions: Higher prevalence of sarcopenia and sarcopenic obesity were found in female RA patients. Sarcopenia was found in younger female subjects with RA compared with healthy control subjects. Sarcopenia was associated with previous fragility fractures in female patients with RA., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Rheumatoid arthritis (RA) patients had a higher risk of developing low bone mineral density (BMD) or osteoporosis. RA patients on classic disease-modifying antirheumatic drug (c-DMARD) therapy showed significantly lower BMD than controls, while no significant differences in most parameters were found between RA patients receiving biological disease-modifying antirheumatic drugs (b-DMARDs) and controls. The 3D analysis allowed us to find changes in the trabecular and cortical compartments., Introduction: To evaluate cortical and trabecular bone involvement of the hip in RA patients by dual-energy X-ray absorptiometry (DXA) and 3D analysis. The secondary end-point was to evaluate bone involvement in patients treated with classic (c-DMARD) or biological (b-DMARD) disease-modifying antirheumatic drug therapies and the effect of the duration of the disease and corticosteroid therapy on 3D parameters., Methods: A cross-sectional study of 105 RA patients and 100 subjects as a control group (CG) matched by age, sex, and BMI was carried out. BMD was measured by DXA of the bilateral femoral neck (FN) and total hip (TH). The 3D analyses including trabecular and cortical BMD were performed on hip scans with the 3D-Shaper software., Results: FN and TH BMD and trabecular and cortical vBMD were significantly lower in RA patients. The c-DMARD (n = 75) group showed significantly lower trabecular and cortical vBMD than the CG. Despite the lower values, the b-DMARD group (n = 30) showed no significant differences in most parameters compared with the CG. The trabecular and cortical 3D parameters were significantly lower in the group with an RA disease duration of 1 to 5 years than in the CG, and the trabecular vBMD was significantly lower in the group with a duration of corticosteroid therapy of 1 to 5 years than in the CG, while no significant differences were found by standard DXA in the same period., Conclusions: RA patients had a higher risk of developing low BMD or osteoporosis than controls. RA patients receiving c-DMARD therapy showed significantly lower BMD than controls, while no significant differences in most parameters were found between RA patients receiving b-DMARDs and controls. 3D-DXA allowed us to find changes in trabecular and cortical bone compartments in RA patients.

Wnt/β-catenin signaling is important for skeletal development and health. Eleven heterozygous gain-of-function missense mutations within the first β-propeller of low-density lipoprotein receptor-related protein 5 (LRP5) are known to cause the autosomal dominant disorder called high bone mass (HBM). In 2019, different heterozygous LRP6 missense mutations were identified in two American families with the HBM phenotype but including absent lateral maxillary and mandibular incisors. We report a 19-year-old Argentinian man referred for "osteopetrosis" and nine years of generalized, medium-intensity bone pain and arthralgias of both knees. His jaw and nasal bridge were broad and several teeth were missing. Routine biochemical testing, including of mineral homeostasis, was normal. Urinary deoxypyridinoline and serum CTX were slightly increased. Radiographic skeletal survey showed diffusely increased radiodensity. DXA revealed substantially elevated BMD Z-scores. Digital orthopantomography confirmed agenesis of his maxillary and mandibular lateral incisors and his second left superior premolar. Cranial magnetic resonance imaging showed diffuse thickening of the calvarium and skull base, dilation of the sheath of the optic nerves containing increased fluid and associated with subtle stenosis of the optic canal, and narrow internal auditory canals. Mutation analyses identified a heterozygous indel mutation in exon 4 of LRP6 involving a single nucleotide change and 6-nucleotide deletion (c.678T>Adel679-684, p.His226Gln-del227-228ProPhe) leading to a missense change and 2-amino acid deletion that would compromise the first β-propeller of LRP6. Experience to date indicates LRP6 HBM is indistinguishable from LRP5 HBM without mutation analysis, although in LRP6 HBM absence of adult lateral incisors may prove to be a unique feature., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Community-acquired pneumonia (CAP) is the infectious disease with the highest number of deaths worldwide. Several studies have shown an association between vitamin D deficiency and increases susceptibility to respiratory tract infections., Objective: The aim of this study was to evaluate the serum 25-hydroxyvitamin D (25OHD) levels in hospitalized adults in general room with CAP., Materials and Methods: An observational study was carried out in 207 hospitalized adults of both sex with CAP (>18 years) from Rosario city, Argentina (32° 52' 18″S) between July 2015 and June 2016., Results: In total, 167 patients were included in the data analysis [59% women (57.4 ± 19.6 years), body mass index 27.2 ± 7.8 kg/m 2 ]. In brief, 63% showed unilobar infiltrate and 37% were multilobar. The CURB-65 index was 66.5% low risk, 16.0% intermediate risk and 17.5% high risk. According to Charlson comorbidity index (CCI) 53.5% had not comorbidity (CCI = 0) and 46.5% showed CCI ≥ 1. The 25OHD level was: 11.92 ± 7.6 ng/mL (51.5%: <10 ng/mL, 33.5%: 10-20 ng/mL, 13.2%: 20-30 ng/mL and 1.8%: >30 ng/mL). Higher 25OHD were found in male (female: 10.8 ± 6.7 ng/mL, male: 13.5 ± 8.5 ng/mL, P = .02) and 25OHD correlated with age (r = -.17; P = .02). 25-Hydroxyvitamin D was also correlated with CURB65 index (r = -.13; P = .049), CCI (r = -.20, P = .007) and with the 10 years of life expectative (%) (r = .19; P = .008). In addition, higher 25OHD were found with lower CCI (CCI 0 = 13.0 ± 8.2 ng/mL, CCI ≥ 1= 10.5 ± 6.7 ng/mL; P = .0093)., Conclusions: Hospitalized adults with CAP have lower 25OHD levels and would be associated with the severity of CAP., (© 2018 John Wiley & Sons Ltd.)

Adult-onset Still's disease is a systemic inflammatory disorder of unknown etiology, characterized by skin rash, spiking fever, arthralgias or arthritis, and leukocytosis. The typical skin rash is evanescent, salmon-pink, nonpruritic and maculopapular, predominantly on the extremities. It is considered one of the major Yamaguchi's criteria in adult-onset Still's disease. However, atypical skin lesions are also described. Here, a 61-year-old woman with sore throat, spiking fever, polyarthritis and evanescent salmon-pink nonpruritic maculopapular skin rash on the extremities was diagnosed with adult-onset Still's disease. In addition, atypical brown macules on oral mucosa, localized on the inner lips and tongue were also observed. Biopsy revealed a neutrophilic infiltrate. Despite treatment and improvement of the adult-onset Still's disease, the atypical oral mucosal lesions persisted.

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

Yerba mate (Ilex paraguariensis) is a xanthine-containing beverage, which is also rich in caffeine. Because caffeine has a negative impact on bone mineral density (BMD) mainly associated with low calcium (Ca) diets, there would be expected a negative effect of yerba mate on bone. In this study, Sprague-Dawley rats were used and randomly assigned into four groups (n = 6/group): Control + Ca 0.2 g %; Control + Ca 0.9 g %; Yerba + Ca 0.2 g %; Yerba + Ca 0.9 g %. At the end of the experiment, tibias and femurs were obtained for BMD, morphometric, histomorphometric, and biomechanical analyses. While there was no difference in bone parameters between rats with and without yerba mate consumption, a negative effect of low Ca diet was observed in BMD, morphometric, histomorphometric, and biomechanical results. Interaction between Ca content in the diet and yerba mate was only found in trabecular bone volume, which would indicate that the negative effect of low Ca intake on bone volume is reversed in part by yerba mate infusion. However, yerba mate was not able to reverse the negative effect of low Ca content on biomechanical properties and trabecular connectivity. In summary, at least in our study, yerba mate would not have a negative effect on bone and would be safe for the bone health of consumers.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease with high prevalence of osteoporosis. Previous evidence indicates an association between vitamin D deficiency and autoimmune diseases. The aim of this study was to evaluate serum 25 hydroxyvitamin D [25(OH)D] levels, bone mineral density (BMD) and disease activity in RA patients living in Argentina. We studied 34 RA women and 41 healthy women as a control group. RA patients had lower 25(OH)D levels (20.4 ± 0.9 ng/ml) than controls (26.3 ± 1.9 ng/ml; p < 0.05). No significant differences were found in lumbar spine BMD between premenopausal (preM) or postmenopausal (postM) patients, but femoral neck BMD was significantly lower in postM RA patients (T score -2.5 ± 0.4) than in postM control subjects (T score -0.9 ± 0.3, p = 0.014). Although no linear correlation between 25(OH)D levels and disease activity (DAS-28) was found, patients with moderate-high disease activity had lower 25(OH)D levels than those with low disease activity: DAS-28 >3.2: 19.5 ± 0.88 ng/ml; DAS-28 ≤3.2: 23.7 ± 2.8 ng/ml (p = 0.047). After 1 year of vitamin D treatment 25(OH)D levels were increased while DAS-28 were decreased (n = 25; p < 0.05). We conclude that patients with RA had lower 25(OH)D levels than the control group. Low levels of 25(OH)D were associated with moderate-high disease activity suggesting the importance of optimal 25(OH)D levels in RA patients. Femoral neck BMD was lower in postM RA patients. No differences in lumbar BMD were found between preM and postM RA patients, suggesting that bone mass evaluation in RA patients should include femoral neck BMD regardless of age.

This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date.

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of SrR in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 482 postmenopausal women treated with SrR (2 g/day) for 1 year in ten Argentine centers; 41 patients were excluded due to insufficient data, while 441 were included. Participants were divided according to previous bisphosphonate treatment in two groups: BP-naïve (n = 87) and BP-prior (n = 350). Data are expressed as mean ± SEM. After 1 year of treatment with SrR the bone formation markers total alkaline phosphatase and osteocalcin were increased (p < 0.0001), while the bone resorption marker s-CTX was decreased (p = 0.0579). Also increases in BMD at the lumbar spine (LS, 3.73%), femoral neck (FN, 2.00%) and total hip (TH, 1.54%) [p < 0.0001] were observed. These increments were significant (p < 0.0001) both among BP-naïve and BP-prior patients. Interestingly, the change in BMD after 1 year of SrR treatment was higher in BP-naïve patients: LS: BP-naïve = 4.58 ± 0.62%; BP-prior = 3.45 ± 0.28% (p = 0.078). FN: BP-naïve = 2.79 ± 0.56%; BP-prior = 2.13 ± 0.29% (p = 0.161). TH: BP-naïve = 3.01 ± 0.55%; BP-prior = 1.22 ± 0.27% (p = 0.0006). SrR treatment increased BMD and bone formation markers and decreased a bone resorption marker in the whole group, with better response in BP-naïve patients.

Objective: Osteoporosis is the consequence of an imbalance in bone remodeling caused by excessive resorption or inappropriate bone formation. This paper proposes a sequential treatment with monofluorophosphate (MFP) and zoledronic acid (Z), together with changes in the calcium content in the diet., Method: Seven-week-old female Sprague Dawley rats were divided into five groups (n = 21 per group): (1) sham-operated rats (Sham); (2) ovariectomized (OVX) rats fed with a normal calcium diet (OVX); (3) OVX rats fed with a normal calcium diet and treated sequentially with monofluorophosphate and zoledronic acid (OVX.G1); (4) OVX rats sequentially fed with a low calcium diet and then a high calcium diet, without treatment (OVX.G2); (5): OVX rats fed with a low calcium diet and then a high calcium diet, treated sequentially with monofluorophosphate and zoledronic acid (OVX.G3)., Results: After 150 days, the OVX.G3 group showed a similar bone volume to that of the Sham group due to an increase in trabecular number. Dual X-ray absorptiometry bone analysis showed an increase of 9.8% compared with OVX rats. Additionally, an increase in the fracture load at the cortical bone and higher fracture load, ultimate load and stiffness in the compression test were found., Conclusion: The sequential treatment with monofluorophosphate and zoledronic acid increases trabecular bone mass, bone mineral density and bone strength.

Scope: Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption., Methods and Results: We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells., Conclusion: Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggests an involvement in the uptake of nutrients, but its role has not yet been defined. IAP expression parallels that of other proteins involved in Ca absorption under vitamin D stimulation. Experiments carried out in vitro with purified IAP have demonstrated an interaction between Ca and IAP. The gut is prepared to face different levels of Ca intake over time, but high Ca intake in a situation of a low-Ca diet over time would cause excessive entry of Ca into the enterocytes. The presence of a mechanism to block Ca entry and to avoid possible adverse effects is thus predictable. Thus, in the present study, Sprague-Dawley rats were fed with different amounts of Ca in the diet (0.2, 1 and 2 g%), and the percentage of Ca absorption (%Ca) in the presence and absence of L-phenylalanine (Phe) was calculated. The presence of Phe caused a significant increase in %Ca (52.3 (SEM 6.5) % in the presence of Phe v. 31.1 (sem 8.9) % in the absence of Phe, regardless of the amount of Ca intake; paired t test, P = 0.02). When data were analysed with respect to Ca intake, a significant difference was found only in the group with low Ca intake (paired t test, P = 0.03). Additionally, IAP activity increased significantly (ANOVA, P < 0.05) as Ca concentrations increased in the duodenal lumen. The present study provides in vivo evidence that luminal Ca concentration increases the activity of IAP and simultaneously decreases %Ca, acting as a minute-to-minute regulatory mechanism of Ca entry.

Two fractions of rat intestinal alkaline phosphatase (IAP) were detected by Western blot: 168 +/- 6 and 475 +/- 45 kDa. The low molecular weight fraction constitutes 43% of the isolated proteins exhibiting 82% of the enzymatic activity, and a heavier fraction constitutes 57% of the isolated proteins and has 18% of the enzymatic activity. Calcium produced an increase of the 475-kDa form to the detriment of the 168-kDa form. This work also describes the kinetic and structural changes of IAP as a function of calcium concentration. With [Ca2+] < 10 mmole/L, the Ca(2+)-IAP interaction fitted a binding model with 7.8 +/- 4.4 moles of Ca2+ /mole of protein, affinity constant = 19.1 +/- 8.4 L/mmole, and enzymatic activity increased as a linear function of [Ca2+] (r = 0.946 p < 0.01). On the other hand, with [Ca2+] > 10 mmole/L the data did not fit this model and, the enzymatic activity decreased as a function of [Ca2+] (r = - 0.703 p < 0.05).