Diagnosis and treatment of Paget's disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS).

INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management. METHODS: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice. RESULTS AND CONCLUSION: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released.

Refracture following vertebral fragility fracture when bone fragility is not recognized: summarizing findings from comparator arms of randomized clinical trials.

PURPOSE: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. METHODS: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. RESULTS: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9-16] and 6 (95% CI 5-8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. CONCLUSION: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures.

The integrated structure of care: evidence for the efficacy of models of clinical governance in the prevention of fragility fractures after recent sentinel fracture after the age of 50 years.

Randomized clinical trials and observational studies on the implementation of clinical governance models, in patients who had experienced a fragility fracture, were examined. Literature was systematically reviewed and summarized by a panel of experts who formulated recommendations for the Italian guideline. PURPOSE: After experiencing a fracture, several strategies may be adopted to reduce the risk of recurrent fragility fractures and associated morbidity and mortality. Clinical governance models, such as the fracture liaison service (FLS), have been introduced for the identification, treatment, and monitoring of patients with secondary fragility fractures. A systematic review was conducted to evaluate the association between multidisciplinary care systems and several outcomes in patients with a fragility fracture in the context of the development of the Italian Guidelines. METHODS: PubMed, Embase, and the Cochrane Library were investigated up to December 2020 to update the search of the Scottish Intercollegiate Guidelines Network. Randomized clinical trials (RCTs) and observational studies that analyzed clinical governance models in patients who had experienced a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random-effects models. Primary outcomes were bone mineral density values, antiosteoporotic therapy initiation, adherence to antiosteoporotic medications, subsequent fracture, and mortality risk, while secondary outcomes were quality of life and physical performance. RESULTS: Fifteen RCTs and 62 observational studies, ranging from very low to low quality for bone mineral density values, antiosteoporotic initiation, adherence to antiosteoporotic medications, subsequent fracture, mortality, met our inclusion criteria. The implementation of clinical governance models compared to their pre-implementation or standard care/non-attenders significantly improved BMD testing rate, and increased the number of patients who initiated antiosteoporotic therapy and enhanced their adherence to the medications. Moreover, the treatment by clinical governance model respect to standard care/non-attenders significantly reduced the risk of subsequent fracture and mortality. The integrated structure of care enhanced the quality of life and physical function among patients with fragility fractures. CONCLUSIONS: Based on our findings, clinicians should promote the management of patients experiencing a fragility fracture through structured and integrated models of care. The task force has formulated appropriate recommendations on the implementation of multidisciplinary care systems in patients with, or at risk of, fragility fractures.

A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS.

PURPOSE: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. METHODS: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. CONCLUSION: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

Utility of serum complement factors C3 and C4 as biomarkers during therapeutic management of giant cell arteritis.

OBJECTIVE: There is a strong unmet need for biomarkers in giant cell arteritis (GCA), as C-reactive protein (CRP) may be unreliable in patients treated with Tocilizumab (TCZ). We aimed to assess whether C3 and C4 are useful biomarkers in GCA patients, particularly in those treated with TCZ. METHOD: We retrospectively enrolled all patients who underwent C3 and C4 measurement at baseline. All patients were evaluated at 3, 6, 12, and 24 months after diagnosis, as part of routine follow-up. Two assessments after the end of the observational period, in case of further relapses, were also included. RESULTS: At baseline, mean ± sd levels (mg/dL) of C3 (133 ± 28.99) and C4 (25.9 ± 9.04) were within normal ranges. During follow-up, C3 and C4 decreased in patients attaining remission (107.07 ± 19.86, p = 0.0006; 19.86 ± 10.27, p = 0.01, respectively) and sustained remission (95.85 ± 18.04, p = 0.001; 15.61 ± 9.75, p = 0.006). In TCZ-treated patients, even stronger decreases in C3 (83.11 ± 19.66, p = 0.001) and C4 (8.26 ± 3.83, p < 0.0001) were observed, and their values were not correlated with CRP or erythrocyte sedimentation rate. CONCLUSION: C3 and C4 do not seem useful in the diagnosis of GCA, as normal values do not rule out active vasculitis. However, C3 and C4 correlate with disease activity. As the low C4 levels found in TCZ-treated patients are not correlated with CRP, C4 should be evaluated as a potential biomarker of disease activity and treatment response.

Adhesive capsulitis and ultrasound diagnosis, an inseparable pair: a novel review.

PURPOSE: Adhesive Capsulitis (AC) is a musculoskeletal disorder initially described by Codman in 1934. The disease is characterized by pain-limited restriction in active and passive glenohumeral range of motion (ROM) despite the lack of a structural deficit. In the last decades, arthroscopy and magnetic resonance imaging (MRI) has been the only diagnostic tools able to highlight the characteristic alterations of the glenohumeral capsular-ligament apparatus in AC; nevertheless, both arthroscopy and MRI are burdened by intrinsic limitations. The aim of this narrative review is to summarize the most significant evidence supporting the use of ultrasound (US) for the diagnosis of AC. METHODS: We extensively searched via PubMed library the terms "frozen-shoulder" and "adhesive capsulitis" each combined with "ultrasound". RESULTS: We found 3723 papers on PubMed and selected those inherent to AC diagnosis, US imaging, correlation with arthroscopic and MRI findings. Forty papers which were strictly related to the topic of this narrative review were initially chosen, then 20 studies which described and exploited US for AC diagnosis were finally included. Coracohumeral ligament (2.65 ± 0.4 mm) and axillary pouch thickening (3.34 ± 0.8 mm), as well as an increase in vascularity at rotator interval (78/214, 36.44%), represented the commonest US signs useful for AC diagnosis and for which the most significant cut-off values were reported. CONCLUSIONS: The evidence collected in this review testify that musculoskeletal US is as reliable as MRI for AC diagnosis, therefore we believe that in this context US should be considered a first-line imaging technique.

Bone Marrow Edema: pathogenetic features.

Abstract: The term "bone marrow edema" was used for the first time in 1988 by Wilson. He noticed a high signal on fluid-sensitive sequences at MRI located in the subchondral bone. We can find bone marrow edema in many musculoskeletal diseases such as Inflammatory and Rheumatic diseases (Rheumatoid Arthritis, Spondylarthritis, etc.), Osteoarthritis (BMLs) and Bone Marrow Edema Syndromes (BMES). This classification is based on pathophysiological, histological and clinical differences despite the same imaging evidence. The distinction is useful also in terms of treatment. Bisphosphonates in association with NSAIDs or corticosteroids are the main therapy while TNF-a Inhibitors are used for the specific inflammatory origin. Bone marrow edema has become an important aspect to consider in the diagnostic path of the main musculoskeletal diseases. This paper starts from a systematic review of literature. We chose the most decisive contributions in order to develop a better description of the pathogenetic features about this "new" evidence.

Osteoarticular pain: therapeutic approach by paradigms.

Osteoarticular pain is a common condition in the adult population. It is a nociceptive pain modulated by different factors, and it is one of the major symptoms that force patients to seek medical advice. Since osteoarticular pain has a complex pathophysiology and it is not a linear condition, we propose in this paper an original approach to osteoarticular pain by paradigms, where a paradigm refers to a framework of concepts, results, and procedures within which subsequent work is structured. The paradigm presented is a conceptual tool that could help clinicians to choose the correct therapy considering both pain characteristics and clinical features.

Neridronate for transient osteoporosis of the hip in a child.

Transient osteoporosis of the hip (TOH) is usually reported in middle-aged men or during pregnancy as a benign self-limiting condition. Nevertheless, its impact on quality of life in terms of pain and disability is considerable. Also, it can lead to insufficiency fractures or, more rarely, evolve into osteonecrosis. This condition is anecdotally described in the pediatric age and very little is known about how it may affect the growing bone. We herein describe a case of TOH in a 10-year-old child treated at our pediatric rheumatology service and summarize the pediatric cases of TOH previously reported in literature. There are two points of interest in our case report, the first one being the unusual complication of TOH with a femoral physis fracture and the second the complete recovery after the off-label therapy with bisphosphonates. We suggest that interventional medical treatment could be considered in selected cases of juvenile TOH, to prevent any possible irreversible damage on the femoral physis. As far as we know, this is the first report of neridronate employment in children affected by TOH.

Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Differences in biologics for treating ankylosing spondylitis: the contribution of network meta-analysis.

OBJECTIVE: Ankylosing Spondylitis (AS) is a chronic form of arthritis of unknown origin affecting the spine. In this study, we aimed to identify clinical and safety profiles of adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and secukinumab that are biologic agents (biologics) mainly used for the treatment of AS, and to understand differences between them. MATERIALS AND METHODS: An extensive literature research was performed in MEDLINE and EMBASE in order to identify all network meta-analysis (NMA) and/or mixed treatment comparison (MTC) papers. NMA and/or MTC, with a ranking of the effectiveness of biologics in AS, were included in the analysis, and the adhesion to ISPOR guidelines was investigated. RESULTS: 60 studies were identified; after applying exclusion criteria methods, 7 studies underwent further analysis. Infliximab was the drug that exhibited the highest probability for achieving clinical efficacy by ASAS20 at 12 and 24 weeks. Considering only subcutaneous biologics, Golimumab achieved the highest probability for achieving the ASAS20 response at 12 weeks. CONCLUSIONS: Results from NMA on the use of biologics in AS indicates infliximab emerged as the drug with the highest probability of obtaining ASAS20 response both at 12 and 24 weeks of treatment.

Observations about subcalcaneal adventitial bursitis (heel fat pad inflammatory lesion) in rheumatoid arthritis. Comment on the article of Suzuki and Shirai.

Not available.

Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: a novel heterozygous mutation in SLC12A3 gene.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

A review of network meta-analysis comparing biologics in the treatment of rheumatoid arthritis.

OBJECTIVE: Even though in recent years significant improvements have been made in the management of patients with rheumatoid arthritis due to the introduction of biologic agents, it is still difficult to identify the most effective and safest available treatment. The choice and comparison between biological agents are a challenge, for only limited head-to-head clinical studies are available. The aim of this manuscript is to review the published network meta-analysis (NMA) to gain a better understanding of efficacy and safety of biological agents and small molecules in the management of RA patients. MATERIALS AND METHODS: We used MEDLINE and EMBASE to identify network meta-analyses from 2008 to June 2019 comparing efficacy and safety of licensed biological agents and tsDMARDS at the approved dosages using predefined text words related to the topic. The following scenarios have been investigated: patients not responding to csDMARD (cDMARDs - IR); csDMARD naïve patients; patients not responding to biologics (bDMARDs - IR); patients in biological monotherapy. RESULTS: On the basis of the data present in the literature, we are able to hypothesize some trends of response in terms of efficacy in different subsets of patients, for example patients in monotherapy, bDMARds unresponsive patients, and Methotrexate-naive patients. The differences of the results presented in many works are due to the different inclusion criteria used in the studies, the type of biologics agent used in each study (according to the available molecules in the different years of publication), as well as differences in the methodology of NMA and in the presentation of the data. CONCLUSIONS: We suggest that the next NMA follows the indications suggested by the Professional Society for Health Economics and Outcomes Research (ISPOR) so that the results are comparable and comprehensible.

Effects of rituximab therapy on B cell differentiation and depletion.

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell­mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/- immature B cells and IgD-CD38+/- memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127-/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.

One-year follow-up showing effects of single intra-articular injection of hyaluronic acid (1,500-2,000 kDa) in symptomatic knee osteoarthritis.

Clinical evidence on knee osteoarthritis suggests that intra-articular administration of hyaluronic acid may be useful in the management of patients with persistent pain. This study assesses the duration of effectiveness of a single intra-articular hyaluronic acid injection in a large population of patients with knee osteoarthritis. This retrospective post-marketing cohort study collected data from the ANTIAGE Registry (http://www.antiagefbf.it/registro), selecting patients of age ≥ 40 years, with symptomatic knee osteoarthritis (Kellgren-Lawrence grade I-III) of ≥ 12 months duration, and ≥12 months of follow-up. Patients had received a single intra-articular injection of high molecular weight hyaluronic acid (1,500-2,000 kDa) at baseline. WOMAC Osteoarthritis Index total scores measured using the LK 3.1 scale and 10 cm VAS pain scores were evaluated before IA Injection and at 6, 9, 10, 11 and 12 months. Blood cell counts, uricemia, erythrocyte sedimentation rates and levels of C-reactive protein were measured at baseline and 12 months. Time from initial treatment to second injection up to 12 months was recorded to assess event-free survival. Included patients (n=187) were 53.5% female and had a mean (±SD) age at baseline of 62 (±16.6) years and mean (±SD) body mass index of 26.2 (±2.5) kg/m2. Mean (±SD) WOMAC index total score and VAS pain scores were 60.9 (±7.1) and 5.9 cm (±1.8), respectively. There were statistically significant reductions compared to baseline in mean WOMAC index total score and VAS pain score at all time points (p less than0.01 at 6 and 9 months; p less than 0.05 at 10, 11 and 12 months for both parameters). These results support the clinical effectiveness and safety of hyaluronic acid for up to 12 months for pain relief and function improvement in patients with knee osteoarthritis, confirming previous data on intra-articular administration of hyaluronic acid as chronic therapy in the management of knee osteoarthritis.

Spasmophilia and entrapment nerve syndrome comorbidities in fibromyalgic patients: a possible neuromuscular pain generator.

This paper is aimed at investigating whether peripheral dysfunction at the neuromuscular level may represent a pain generator in fibromyalgia. We studied the prevalence of spasmophilia (SP), carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a group of 40 subjects suffering from fibromyalgia. Clinical and electrophysiological data were obtained to ascertain whether comorbid conditions were present. For subjective evaluation of symptoms severity, validated questionnaires for CTS and UNE were completed by patients. Twenty subjects were positive for SP (50%); CTS was diagnosed in 12 subjects (30%); no patient suffered from UNE; 6 subjects were affected at the same time by SP and CTS (15%); 14 subjects (35%) were affected by SP alone. The prevalence of CTS and SP was higher in fibromyalgia subjects than in the general population. The scores of the questionnaires related to CTS were significantly higher in fibromyalgia subjects positive for CTS, with respect to the other subjects. In fibromyalgia, CTS and SP may be considered clinical entities in themselves, the importance of which lies in their acting as peripheral pain generators that enhance or initiate central sensitization, thereby contributing to chronic widespread pain. The amplification of pain is indeed a correctable/misguided message that occurs inside the brain of fibromyalgia subjects and identification and local treatment of pain generators would lessen the total pain burden. The magnitude of the overlap in symptoms between fibromyalgia and CTS/SP necessitates careful investigation of these conditions.

The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study.

PURPOSE: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. METHODS: This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥ 50 and older in different areas of Italy in the period 2012-2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. RESULTS: The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. CONCLUSIONS: Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

HyalOne® in the treatment of symptomatic hip OA - data from the ANTIAGE register: seven years of observation.

OBJECTIVE: Several studies on knee osteoarthritis suggest that the intra-articular administration of hyaluronic acid products may be a relevant option in the management of patients with persistent pain. The aim of this study is to report the data of efficacy of US-guided HyalOne®/Hyalubrix® 60 injections in a large population of patients with hip osteoarthritis, repeated at least 2 times per year for up to seven years. PATIENTS AND METHODS: This is a prospective, post-marketing, cohort study. Data were collected from the ANTIAGE registry. Values of Lequesne index, pain VAS, NSAIDs intake, global medical and patients assessments were evaluated every six months from the baseline to the end of the follow-up, seven years later. The inclusion criteria were: age ≥18 years, symptomatic hip osteoarthritis of at least 1-year duration, and up to 84 months of follow-up. All the patients received hyaluronic acid injections at least every six months, using ultrasound guidance to ensure accurate placement. RESULTS: 1022 patients were included in the study. The patients were categorized by age classes, gender, and body mass index (BMI). All the groups show a statistically significant reduction at all time points compared to baseline values of Lequesne index, pain VAS, NSAIDs intake, global medical and patients assessments. There are slight differences in the subgroups of overweighted, obese and over 70 years patients. CONCLUSIONS: Our study supports the clinical efficacy and safety of HyalOne®/Hyalubrix®60 in patients affected by osteoarthritis. This is the first study, reporting on a large cohort of patients in different categories with a long follow-up on seven years. The data confirm the proper use of ultrasound-guided viscosupplementation (VS) as background therapy in the management of hip osteoarthritis.