Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment.

In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (-4.1%, 95% confidence interval [CI] -6.4, -1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Pathophysiology of Vascular Calcification and Bone Loss: Linked Disorders of Ageing?

Vascular Calcification (VC), low bone mass and fragility fractures are frequently observed in ageing subjects. Although this clinical observation could be the mere coincidence of frequent age-dependent disorders, clinical and experimental data suggest that VC and bone loss could share pathophysiological mechanisms. Indeed, VC is an active process of calcium and phosphate precipitation that involves the transition of the vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Among the molecules involved in this process, parathyroid hormone (PTH) plays a key role acting through several mechanisms which includes the regulation of the RANK/RANKL/OPG system and the Wnt/ß-catenin pathway, the main pathways for bone resorption and bone formation, respectively. Furthermore, some microRNAs have been implicated as common regulators of bone metabolism, VC, left ventricle hypertrophy and myocardial fibrosis. Elucidating the common mechanisms between ageing; VC and bone loss could help to better understand the potential effects of osteoporosis drugs on the CV system.

Management of glucocorticoid-induced osteoporosis.

Long-term glucocorticoid (GC) therapy is frequently indicated to treat autoimmune and chronic inflammatory diseases in daily clinical practice. Two of the most devastating untoward effects are bone loss and fractures. Doses as low as 2.5 mg of prednisone for more than 3 months can impair bone integrity. Population at risk is defined based on the dose and duration of GC therapy and should be stratified according to FRAX (Fracture Risk Assessment Tool), major osteoporotic fracture, prior fractures, and bone mineral density values (BMD). General measures include to prescribe the lowest dose of GC to control the underlying disease for the shortest possible time, maintain adequate vitamin D levels and calcium intake, maintain mobility, and prescribe a bone acting agent in patients at high risk of fracture. These agents include oral and intravenous bisphosphonates, denosumab, and teriparatide.

Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four-Month Randomized, Double-Blind, Double-Dummy Trial.

OBJECTIVE: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.

Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study.

BACKGROUND: Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis and is associated with an estimated annual fracture rate of 5%. We aimed to assess the efficacy and safety of denosumab compared with risedronate in glucocorticoid-induced osteoporosis. METHODS: We did a 24-month, double-blind, active-controlled, double-dummy, non-inferiority study at 79 centres in Europe, Latin America, Asia, and North America. Eligible patients were aged 18 years or older and were receiving glucocorticoids (≥7·5 mg prednisone daily, or equivalent) for at least 3 months (glucocorticoid continuing) or less than 3 months (glucocorticoid initiating) before screening. Patients younger than 50 years needed to have a history of osteoporosis-related fracture; glucocorticoid-continuing patients aged 50 years or older needed a lumbar spine, total hip, or femoral neck bone mineral density T score of -2·0 or less, or -1·0 or less if they had a history of osteoporosis-related fracture. Participants were randomly assigned (1:1) to either 60 mg subcutaneous denosumab every 6 months and oral placebo daily for 24 months, or 5 mg oral risedronate daily and subcutaneous placebo every 6 months for 24 months. Randomisation was stratified by sex within each subpopulation, and was done with an interactive voice-response system. Active drugs and corresponding placebos had identical packaging, labels, and appearance. The primary outcome was non-inferiority of denosumab to risedronate in terms of percentage change from baseline in lumbar spine bone mineral density at 12 months based on non-inferiority margins (-0·7 and -1·1 percentage points for the glucocorticoid-continuing and glucocorticoid-initiating subpopulations, respectively). Superiority was also assessed as a secondary outcome. The primary efficacy set included all randomly assigned participants who had a baseline and postbaseline lumbar spine bone mineral density measurement, and was analysed according to randomised treatment assignment. The safety analysis set included all randomly assigned participants who received at least one dose of investigational product, and was analysed by actual treatment received. This study is registered with ClinicalTrials.gov (NCT01575873) and is completed. FINDINGS: Between March 28, 2012, and June 30, 2015, 795 patients, 505 of whom were glucocorticoid continuing and 290 of whom were glucocorticoid initiating, were enrolled and randomly assigned (398 to denosumab, 397 to risedronate). Denosumab was both non-inferior and superior to risedronate at 12 months for effect on bone mineral density at the lumbar spine in both glucocorticoid-continuing (4·4% [95% CI 3·8-5·0] vs 2·3% [1·7-2·9]; p<0·0001) and glucocorticoid-initiating (3·8% [3·1-4·5] vs 0·8% [0·2-1·5]; p<0·0001) subpopulations. Incidence of adverse events, serious adverse events (including infections), and fractures was similar between treatment groups. The most common adverse events were back pain (17 [4%] patients in the risedronate group and 18 [5%] in the denosumab group) and arthralgia (21 [5%] patients in the risedronate group and 17 [4%] in the denosumab group). Serious infection occurred in 15 (4%) patients in the risedronate group and 17 (4%) patients in the denosumab group. INTERPRETATION: Denosumab could be a useful treatment option for patients newly initiating or continuing glucocorticoids who are at risk of fractures. FUNDING: Amgen.

Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

OBJECTIVE: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. METHODS: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. RESULTS: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment. CONCLUSION: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

Guías Argentinas para el diagnóstico, la prevención y el tratamiento de la osteoporosis 2015 / Argentine guidelines for the diagnosis, prevention and treatment of osteoporosis, 2015

La osteoporosis es una enfermedad en constante crecimiento y que afecta a más de 200 millones de personas a nivel mundial. Nuestras recomendaciones son guías para el diagnóstico, la prevención y tratamiento, pero no normas para las decisiones clínicas en casos individuales. El médico debe adaptarlas a situaciones en la práctica clínica cotidiana, incorporando factores personales que trascienden los límites de estas guías y hacen al saber y al arte de la práctica médica. Como todo conocimiento científico, deben ser actualizadas periódicamente a medida que se adquieran nuevas, mejores y más efectivas herramientas diagnósticas y terapéuticas. (AU)

Osteoporosis is an evolving disease which affects over 200 million people worldwide. Our recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual cases. The physician must adapt them to individual special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the practice of Medicine. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available. (AU)

[Argentine guidelines for the diagnosis, prevention and treatment of osteoporosis, 2015]. / Guías argentinas para el diagnóstico, la prevención y el tratamiento de la osteoporosis 2015.

Osteoporosis is an evolving disease which affects over 200 million people worldwide. Our recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual cases. The physician must adapt them to individual special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the practice of Medicine. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available.

Guías Argentinas para el diagnóstico, la prevención y el tratamiento de la osteoporosis 2015 / Argentine guidelines for the diagnosis, prevention and treatment of osteoporosis, 2015

La osteoporosis es una enfermedad en constante crecimiento y que afecta a más de 200 millones de personas en todo el mundo. Nuestras recomendaciones son guías para el diagnóstico, la prevención y tratamiento, pero no normas para las decisiones clínicas en casos individuales. El médico debe adaptarlas a situaciones en la práctica clínica cotidiana, incorporando factores personales que trascienden los límites de estas guías y hacen al saber y al arte de la práctica médica. Como todo conocimiento científico, deben ser actualizadas periódicamente a medida que se adquieran nuevas, mejores y más efectivas herramientas diagnósticas y terapéuticas.

Osteoporosis is an evolving disease which affects over 200 million people worldwide. Our recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual cases. The physician must adapt them to individual special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the practice of Medicine. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available.

The Discriminatory Ability of the Fibromyalgia Rapid Screening Tool (FiRST): An International Study in Spain and Four Latin American Countries.

OBJECTIVE: To assess the transcultural equivalency of the Spanish version of the Fibromyalgia Rapid Screening Tool (FiRST) and its discriminatory ability in different Latin American samples. DESIGN: Validation study. SETTING: Departments of Rheumatology in general hospitals and private centers; fibromyalgia unit in a university hospital. SUBJECTS: 350 chronic pain patients from Spain, Argentina, Mexico, Peru, and Ecuador. METHODS: The cultural relevance of the Spanish version of the FiRST was evaluated. The ability of the FiRST as a screening tool for fibromyalgia was assessed by logistic regression analysis. To determine the degree to which potential confounders, such as differences in demographics, pain, affective distress, catastrophizing, and disability, might affect the discriminatory ability, the tool was reassessed by hierarchical multivariate logistic regression. RESULTS: Slightly different versions of the FiRST were recommended for use in each Latin American subsample. The FiRST showed acceptable criterion validity and was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, low specificities were observed in samples from Spain and Mexico. CONCLUSIONS: The Spanish version of the FiRST may be used as a screening tool for fibromyalgia in several Latin American subsamples, even in those patients with high scores on potential confounders. In Spain and Mexico, the low specificity of the FiRST suggests, however, that it would be best used to support a suspected diagnosis of fibromyalgia, rather than to exclude the diagnosis.

The Spanish version of the Fibromyalgia Rapid Screening Tool: translation, validity and reliability.

OBJECTIVE: Despite showing acceptable psychometric properties, the criterion validity of the original Fibromyalgia Rapid Screening Tool (FiRST) has been called into question for including insufficiently challenging comparison groups. Consequently our objective was to validate a Spanish version of the FiRST including pain disorders more analogous to fibromyalgia. METHODS: The FiRST was translated following international standards. Internal consistency and temporal stability were assessed. The ability of the FiRST global score as a screening tool for fibromyalgia (criterion validity) was assessed by logistic regression analysis. To determine the degree to which potential confounders might affect the criterion validity of the FiRST (divergent validity), it was reassessed by hierarchical multivariate logistic regression, entering demographics in a first step, followed by pain, anxiety and depression, catastrophizing, disability and the FiRST global score in a last step. RESULTS: The final sample comprised 257 patients (67% cases of fibromyalgia). The Spanish version of the FiRST showed acceptable internal consistency, reliability and criterion validity. The FiRST was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, both criterion and divergent validity were challenged by a moderate specificity. CONCLUSION: The Spanish version of the FiRST may be used as a screening tool for fibromyalgia even in those patients whose cognitive style is characterized by catastrophizing about pain and high levels of functional disability, anxiety and depression. The clinical consequences of the moderate specificity shown by this Spanish version of the FiRST are discussed.

Rheumatoid arthritis in Latin Americans enriched for Amerindian ancestry is associated with loci in chromosomes 1, 12, and 13, and the HLA class II region.

OBJECTIVE: To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. METHODS: Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. RESULTS: A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies. CONCLUSION: Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.

Guías 2012 para el diagnóstico, la prevención y el tratamiento de la osteoporosis / [Guidelines for the diagnosis, prevention and treatment of osteoporosis, 2012].

Osteoporosis is a constantly growing disease which affects over 200 million people worldwide. The present recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual patients. The physician must adapt them to individual patients and special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the physician. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available.

[Guidelines for the diagnosis, prevention and treatment of osteoporosis, 2012]. / Guías 2012 para el diagnóstico, la prevención y el tratamiento de la osteoporosis.

Osteoporosis is a constantly growing disease which affects over 200 million people worldwide. The present recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual patients. The physician must adapt them to individual patients and special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the physician. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available.

Guías 2012 para el diagnóstico, la prevención y el tratamiento de la osteoporosis. / [Guidelines for the diagnosis, prevention and treatment of osteoporosis, 2012].

Osteoporosis is a constantly growing disease which affects over 200 million people worldwide. The present recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual patients. The physician must adapt them to individual patients and special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the physician. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available.

The prevalence of rheumatoid arthritis in Argentina: a capture-recapture study in a city of Buenos Aires province.

OBJECTIVE: The objective of this study was to assess the prevalence of rheumatoid arthritis (RA) in the population of a city of 70,000 inhabitants located in Buenos Aires, Argentina. METHODS: Based on the hypothesis that RA is an underdiagnosed disease in Argentina, a capture-recapture method was applied. A local registry of RA patients of Luján City was taken as the primary source; a telephone survey was specifically carried out as a secondary source of information. Patients suspected of having RA were referred to a local hospital to be examined by a team of 12 rheumatologists. Anamnesis and physical examination were followed by hand and foot radiography and erythrocyte sedimentation rate and rheumatoid factor measurements. RESULTS: According to the American College of Rheumatology criteria, a prevalence rate of 0.94% (95% confidence interval [CI], 0.86%-1.02%) was found in the surveyed population; in agreement with other studies, this prevalence was higher in women when compared with men (for female, 1.54% [95% CI, 1.40%-1.69%]; for male, 0.40% [95% CI, 0.32%-0.49%]). CONCLUSION: The prevalence of RA in a representative sample of the population of a city from the central region of Argentina seems to be close to 1%.

[FRAX: a new instrument for calculating 10-year absolute fracture risk]. / FRAX: un nuevo instrumento para calcular el riesgo absoluto de fracturas a 10 años.

The efficacy of new pharmacological agents for the prevention of osteoporotic fractures and the clinical decision to intervene with that purpose in daily medical practice have been guided by the evaluation of bone mineral density (BMD). However, given the multifactorial nature of the proposed endpoint, a new calculator has been proposed: Fracture Risk Assessment Tool FRAX, which follows the same objectives of previous models, but integrates and combines several of those factors according to their relative weight. It can estimate absolute risk of hip fracture (or a combination of osteoporotic fractures) for the following 10 years. The calculator could be adapted for use in any country by the incorporation of hip fracture incidence and age- and sex-adjusted life expectancy in the same country. This instrument has been presented as a new paradigm to assist in clinical and therapeutic decision-making. In the present review some of its characteristics are discussed, such as: the purported applicability to different populations, the convenience of using 10-year absolute fracture risk for the whole age range under consideration, and whether the efficacy of pharmacological treatment for the prevention of bone fractures in osteoporotic patients can be expected to be equally effective among patients selected for treatment on the basis of this model. Finally, we would like to call attention to the fact that risk thresholds for intervention are not yet clearly defined; those thresholds can obviously be expected to have a profound impact on the number of patients amenable to treatment.