Spanish consensus on treat to target for osteoporosis.

To reach a Spanish expert consensus on a treat-to-target strategy in osteoporosis, a Delphi Consensus Study has been developed. Most of the experts (59.8%) were rheumatologist with a mean clinical experience of 21.3 years (SD 8.5). Consensus was achieved for 70% of the items. Therapeutic objectives, patient follow-up scheme, treatment failure criteria, and appropriate treatment choice for use in T2T strategy in Spain have been defined. INTRODUCTION: The paper aims to achieve a Spanish expert consensus on a treat-to-target (T2T) strategy in osteoporosis. METHODS: A scientific committee led the project and was involved in expert panel identification and Delphi questionnaire development. Two Delphi rounds were completed. The first-round questionnaire included 24 items and assessed, using a seven-point Likert scale, the experts' wish (W) and prognosis (P) in 5 years for each topic (applicability, therapeutic objectives, patient follow-up, and possible treatment to be prescribed). Items for which there was no consensus in the first round were included in the second round. Consensus was defined as ≥75% agreement (somewhat/mostly/entirely agree) or disagreement (somewhat/mostly/entirely disagree) responses. RESULTS: Of the experts, 112 and 106 completed the first and second rounds, respectively. 59.8% were rheumatologists with a mean clinical experience of 21.3 years (SD 8.5). Consensus was achieved for 70% of the items, and was established regarding the utility of a T2T strategy to define therapeutic objectives, optimal follow-up, and therapeutic algorithm. Participants agreed on the utility of the bone mineral density (BMD) value (T-score >-2.5 SD for spine and >-2.5/-2.0 SD for femoral neck), lack of fractures, and fracture risk (FRAX) as therapeutic objectives. For measuring BMD changes, consensus was achieved on the suitability of hip and femoral neck locations. Experts agreed to consider treatment failure as when a significant BMD gain could not be achieved, or when a new fracture occurs within 2-3 years. There was consensus that all proposed therapies should achieve a therapeutic target through T2T strategy (treatments with the highest consensus scores were denosumab and teriparatide). CONCLUSION: The therapeutic objectives, patient follow-up scheme, treatment failure criteria, and appropriate treatment choice for use in T2T strategy in Spain have been established by a panel of experts. Some aspects nevertheless still require further analysis.

The global burden attributable to low bone mineral density.

INTRODUCTION: The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. OBJECTIVES: To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. METHODS: A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm(2)) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. RESULTS: Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. CONCLUSIONS: Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis.

UNLABELLED: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 µg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Impact of previous glucocorticoid therapy on diagnostic accuracy of [18F] FDG PET-CT in giant cell arteritis.

OBJECTIVE: To evaluate the impact of prior glucocorticoid (GC) treatment on the diagnostic accuracy of 18F-FDG PET-CT in giant cell arteritis (GCA). METHODS: Retrospective study of a consecutive cohort of 85 patients with proven GCA who received high-dose GC before PET-CT. RESULTS: Thirty-nine patients previously treated with methylprednisolone (MP) boluses, of whom 37% were PET-CT (uptakes grade 3 or 2) positive. The positivity rate was 80% with MP doses of 125 mg, 33% with 250 or 500 mg, and 0% with doses of 1 g.  If we also classify as positive those cases with a grade 1 uptake (with a circumferencial uptake and smooth linear or long segmental pattern, possibly indicative of "apparently inactive" vasculitis), the positivity rate increases to 62% (100%, 50-60%, and 33% for the different MP doses, respectively). In patients with new-onset GCA treated with high-dose oral GC, PET-CT positivity was 54.5% in patients treated for less than two weeks, 38.5% in those treated for 2 to 4 weeks, and 25% in those treated for 4 to 6 weeks (increasing to 91%, 77%, and 50%, respectively, if we include cases with grade 1 uptake and these characteristics). In patients with relapsing/refractory GCA, or who developed GCA having a prior history of PMR, PET-CT positivity reached 54% despite long-term treatment with low-to-moderate doses of GC (68% including cases with a grade 1 uptake). CONCLUSION: A late 18F-FDG PET-CT (beyond the first 10 days of treatment) can also be informative in a considerable percentage of cases.

Arthritis related to systemic meningococcal disease: 34 years' experience.

The purpose of this investigation was to assess the clinical characteristics, therapeutic aspects, and outcome of arthritis related to invasive meningococcal disease (IMD). All episodes of bacterial meningitis and IMD are recorded systematically. We selected all episodes of IMD, with or without meningitis, that presented arthritis. From 1977 to 2010, 522 episodes of IMD were treated. Thirty-nine of these (7.5 %, 26 women, mean age 33 years) presented arthritis. Of these 39, 37 (95 %) presented skin lesions and 31 (79 %) had meningitis. Twenty (51 %) had positive blood cultures and six (15 %) had shock. No differences were found in skin lesions, shock, or bacteremia compared to cases without arthritis. In contrast to other septic forms, arthritis related to IMD was cured with short antibiotic therapy and without surgical drainage. There was no mortality. All patients recovered and none presented joint sequelae; however, 13 adult patients (33 %) required long-term treatment with steroids due to persistent symptoms. Arthritis related to IMD most frequently affects the knees and ankles, and may be a cause of fever relapse. Short antibiotic therapy is enough in all cases and surgical drainage is not needed. In some adult patients, especially those over 50 years of age, evolution is torpid and steroid therapy may be required in order to achieve recovery.

Adult onset Still's disease: review of 41 cases.

OBJECTIVES: To describe the clinical, laboratory and radiological features, treatment and prognosis of patients with adult onset Still's disease (AOSD). METHODS: Specific clinical features were retrospectively recorded in 41 patients fulfilling the Yamaguchi criteria. Patients were reviewed in two academic hospitals with a referral area of 700,000-1,000,000 inhabitants. Laboratory tests including haemogram, ferritin, biochemistry and autoimmunity were reviewed. Radiological studies, treatment and ACR functional class were determined. RESULTS: Forty-one patients with AOSD were identified, 25 of whom were female. Mean age at diagnosis: 38.19 years (range 17-68). Feverish polyarthritis was the most common clinical presentation. Acute phase reactants were invariably high in all patients. Serum ferritin levels were elevated in 86% of patients. Anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) were negative in all patients except one. The course of the disease was monocyclic in 44% of the patients, polycyclic in 26%, and chronic articular in 30%. ACR class was as follows: 29 (72.5%) class I, 7 (17.5%) class II, 2 (5%) class III and 2 (5%) class IV. As for the treatment received, aspirin or NSAIDs controlled the disease in eight patients (19.5%) and high-dose corticosteroids (0.5-1 mg/kg/day) in 32 (78%). Almost half of the patients (49%) required an additional diseasemodifying agent, usually methotrexate. Finally, in seven of them (17%) a biological treatment with TNF-α or specially anti-IL-1 had to be added to control the disease. CONCLUSIONS: The clinical and laboratory findings were similar to previous studies. Anti-CCP antibodies were almost always negative. A monocyclic course was associated with a good prognosis. Most of the patients were in ACR functional class I and II. Biological agents were required in 7 patients (17%).

A prospective study of lung disease in a cohort of early rheumatoid arthritis patients.

Lung disease is common in patients with rheumatoid arthritis (RA). The onset of lung involvement in RA is not well known. The objective is to describe the features and evolution of lung involvement in early RA, its relationship with disease activity parameters, smoking and treatments. Consecutive patients with early RA without respiratory symptoms were included and tracked for 5 years. Lung assessment included clinical, radiological and pulmonary function tests at diagnosis and during follow-up. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti-citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS28-CRP, were evaluated. 40 patients were included and 32 completed the 5-year follow up. 13 patients presented lung involvement in the initial 5 years after RA diagnosis, 3 of them interstitial lung disease. Significant decrease of diffusion lung transfer capacity of carbon monoxide over time was observed in six patients, 2 of them developed interstitial lung disease. DLCO decrease was correlated with higher values of CRP and ESR at diagnosis. Methotrexate was not associated with DLCO deterioration or lung disease development. Subclinical progressive lung disease correlates with RA activity parameters. Smoking status and methotrexate were not associated with development or progression of lung disease.

Cervical spine involvement in rheumatoid arthritis: correlation between neurological manifestations and magnetic resonance imaging findings.

OBJECTIVE: To evaluate the correlation between neurological deficits indicative of compressive myelopathy and MRI findings in a series of patients with RA and symptomatic involvement of the cervical spine. METHODS: Forty-one consecutive patients with RA were studied using cervical spine MRI. Unconditional logistic regression analysis was used to identify MRI parameters of cervical spine involvement associated with the development of neurological dysfunction. RESULTS: The mean age of the 41 patients (33 women and 8 men) was 59 yrs (range 23-82 yrs), while the median disease duration was 18 +/- 9 yrs (range 4-40 yrs). According to Ranawat's classification, 17 (42%) patients were in Class I, 21 (51%) in Class II and 3 (7%) in Class III. Thus, patients with clinical manifestations of compressive myelopathy (Ranawat's Class II + III) represented 58% (24/41) of all cases. Among the different MRI parameters of cervical spine involvement analysed, only the presence of atlantoaxial spinal canal stenosis [odds ratio (OR) 4.55; 95% CI 1.14-18.15], atlantoaxial cervical cord compression (OR 9.6; 95% CI 1.08-85.16) and subaxial myelopathy changes (OR 11.43; 95% CI 1.3-100.81) were associated with a significantly increased risk for neurological dysfunction (Ranawat's Class II or III). CONCLUSION: In RA patients with symptomatic cervical spine involvement, there is a strong correlation between the development of neurological dysfunction and MRI identification of atlantoaxial spinal canal stenosis, especially in those cases with evidence of upper cervical cord or brainstem compression and subaxial myelopathy changes.

High HDL-cholesterol in women with rheumatoid arthritis on low-dose glucocorticoid therapy.

BACKGROUND: Dyslipidaemia has been described in non-treated rheumatoid arthritis (RA), and improves after therapy with disease modifying anti-rheumatic drugs or glucocorticoids; however, it has generally been perceived that glucocorticoids adversely affect lipid metabolism. The association of low dose glucocorticoid therapy with plasma lipid levels was evaluated in female RA patients. MATERIALS AND METHODS: A cross-sectional study was conducted in 78 female RA patients [mean age: 60 (12) years; mean disease duration: 13 (9) years]. Sixty-five (83%) were on glucocorticoid therapy [total equivalent mean prednisone dose: 5.1 (1.7) mg d(-1)]. Each patient was assessed through a self-reported questionnaire, structured interview and physical examination. Blood samples were obtained for routine biochemistry, lipid profile and haematological tests. Lipid profiles of RA patients who were and were not on glucocorticoid therapy were compared. RESULTS: Clinical and laboratory features of the two groups of patients were similar, except for the Health Assessment Questionnaire and body mass index, which were significantly higher in the patients on glucocorticoid therapy. These patients had 14.7% higher serum high-density lipoprotein cholesterol (HDL-c) levels than untreated patients (P = 0.043), mainly at the expense of HDL2 subfraction, which was 24.4% higher (P < 0.039), whereas HDL3-c was only 7.4% higher (P = 0.219). Serum levels of glucose and total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL -c), very low-density lipoprotein cholesterol, apolipoproteins A-I and B were not increased in patients on glucocorticoid therapy. CONCLUSIONS: Low dose glucocorticoid therapy in RA patients is associated with an increase in HDL-c, without increasing LDL-c or triglyceride. These lipid changes may overall be considered favourable.

Impact of antiplatelet therapy in the development of severe ischemic complications and in the outcome of patients with giant cell arteritis.

OBJECTIVE: To evaluate whether concomitant treatment with low-dose aspirin or other antiplatelet agents have an impact on the risk of severe ischemic complications and in the outcome of patients with giant cell arteritis (GCA). METHODS: A retrospective follow-up study of an unselected population of 121 patients with GCA. RESULTS: Thirty-seven patients (30.5%) received antiplatelet therapy before the onset of GCA symptoms and continued taking it during the corticosteroid treatment (30 received aspirin and 7 other antiplatelet agents). No statistically significant reduction in the incidence of ischemic manifestations (including jaw claudication, visual manifestations, cerebrovascular accidents, ischemic heart disease, and limb claudication due to large artery stenosis) was observed in this group compared with the remaining patients. When we analyzed follow-up data, we found no significant differences between groups in terms of frequency of relapses and percentage of patients recovered from GCA. Corticosteroid requirements among patients in long-lasting remission were lower in those under antiplatelet therapy, but this reduction was fairly modest, statistically non significant and thus of uncertain clinical significance. Similar results were found when only aspirin exposed patients (n=30) were compared to non-exposed patients. Logistic regression analysis showed that antiplatelet therapy (p=0.54, OR 1.31; 95% CI: 0.54-3.19) had not an independent protective effect against ischemic events when adjusted for age, sex, and the presence of atherosclerotic risk factors. CONCLUSION: We did not observe a significant benefit derived from the use of antiplatelet therapy in either the incidence of severe ischemic events or the disease outcome. Although our results do not discard a potential therapeutic effect of high-dose aspirin, they do not confirm its suggested protective effect in preventing ischemic complications when used at antiplatelet doses.

Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: Fasciitis with myositis syndrome as a new complication of immunotherapy.

OBJECTIVE: To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors. METHODS: This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018. RESULTS: During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease. In this period, a total of 220 patients were treated with PD1 inhibitors in our center; therefore, the estimated minimum prevalence of rheumatic IRAEs related to these therapies in our population was 5%. The rheumatic IRAEs evaluated included 5 cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome, 2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented symptomatic inflammatory myositis with fasciitis in lower extremities, and 1 patient with a paraneoplastic acral vascular syndrome. The median time to IRAE after anti-PD1 exposure was 8 weeks (range: 2-24). In 5 patients, immunotherapy was discontinued (due to the adverse effect in three and cancer progression in two). In general terms the symptoms resolved completely with symptomatic treatment. Disease-modifying antirheumatic drugs were needed for 2 patients. CONCLUSION: Rheumatic IRAEs should be kept in mind during the follow-up and evaluation of patients treated with PD-1 inhibitors. The concomitant development of symptomatic inflammatory myositis with fasciitis in lower extremities appears to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are needed to determine how to adequately control and manage these complications.

Pyarthrosis in patients with rheumatoid arthritis: a detailed analysis of 10 cases and literature review.

OBJECTIVES: 1) To analyze the clinical features and outcome of patients with rheumatoid arthritis and pyarthrosis seen in a rheumatology department during a 9-year period; 2) To review the available literature about this association in the last decade. METHODS: From the database of our department, we collected all hospitalized cases of infectious arthritis in native joints between January 1990 and December 1998. In 10 cases (27%), pyarthrosis occurred in patients with rheumatoid arthritis. A detailed analysis of each patient was performed. The literature was reviewed by using MEDLINE from 1990 to 1999. RESULTS: The mean age of patients was 63.2 years; six were female. Most patients had long-standing disease and poor functional class, and all received glucocorticoid treatment. Mean diagnostic delay was 7.3 days. Causative organisms were Staphylococcus aureus (4 cases), gram-negative bacilli (3 cases), anaerobic bacteria (2 cases), and Streptococcus pneumoniae (n = 1). Two patients died. In all but two patients who survived, joint function worsened. CONCLUSIONS: Rheumatoid arthritis is a relevant host-related risk factor for septic arthritis. Pyarthrosis in these patients is associated with considerable morbidity and mortality.

The association of dehydroepiandrosterone sulphate levels with bone mineral density in systemic lupus erythematosus.

OBJECTIVES: To evaluate, in premenopausal systemic lupus erythematosus (SLE) patients, the possible protective role of androgens on bone mass. METHODS: Bone mineral density (BMD) was measured in the lumbar spine and femoral neck in 37 women with SLE (mean age 31.1 years) without disturbances or therapy that could interfere with bone metabolism except glucocorticoid therapy. We measured serum intact parathyroid hormone (iPTH): 2.5 +/- 1.3 pmol/L, serum testosterone: 1.6 +/- 1.1 nmol/L, salivary testosterone: 0.09 +/- 0.1 nmol/L, and serum dehydroepiandrosterone sulphate (DHEAS): 2.2 +/- 2.2 umol/L. RESULTS: BMD in the spine (L2-L4) was 0.94 +/- 0.1 g/cm2 and in the femoral neck 0.77 +/- 0.1 g/cm2. Four patients (10.8%) had osteoporosis. We found a significant positive relationship between DHEAS and BMD, a negative relationship between DHEAS and the glucocorticoid dose at the time of study, and a negative correlation between iPTH and DHEAS. CONCLUSIONS: Bone loss in corticosteroid-treated premenopausal patients with SLE may be modulated through down-regulation of the endogenous production of DHEAS.

Weak androgen levels, glucocorticoid therapy, and bone mineral density in postmenopausal women with rheumatoid arthritis.

OBJECTIVE: To study dehydroepiandrosterone sulfate (DHEAS) and androstenedione (AND) status in postmenopausal women with rheumatoid arthritis (RA), the effects of glucocorticoid therapy on DHEAS and AND levels, and their relationship with bone mineral density (BMD). METHODS: Forty-six postmenopausal women with RA were separated into two groups based on whether they had a negative history for glucocorticoid therapy (n = 24) or were currently on glucocorticoid therapy (n = 22). The control group was composed of 39 postmenopausal women who had never received hormone replacement therapy. Serum DHEAS and AND levels were measured using a radioimmunoassay. BMD was determined at the lumbar spine (L2-L4) and femoral neck using a DEXA Hologic QDR-1000 densitometer. Results. RA patients and controls were similar in age, weight, body mass index, and years since menopause. DHEAS and AND levels were lower in the glucocorticoid-treated RA group than in the other two groups. The glucocorticoid-treated RA group also had a significantly lower femoral BMD value than the nonglucocorticoid-treated RA group. Lumbar BMD was similar in the two RA groups and in the controls. CONCLUSION: Decreases in DHEAS and AND levels in postmenopausal women with RA are probably related to glucocorticoid therapy rather than to the disease itself.

Bone mineral density in patients with type 1 diabetes mellitus.

Although osteopenia is often reported as a complication of type 1 diabetes mellitus, its frequency and severity remain unclear, and studies of bone mineral density in type 1 diabetics have yielded conflicting results. We measured bone mineral density at the lumbar spine and femoral neck in 88 Spanish adults with type 1 diabetes mellitus responsible for moderately severe complications. Mean age (+/- SD) was 28.9 +/- 8.8 years, and mean disease duration was 11.2 +/- 6.4 years. As compared to normal Spanish adults, bone mineral density was decreased in the patients at the lumbar spine (Z-score, -0.32 +/- 1.08; P < 0.001) but not at the femoral neck (Z-score, -0.21 +/- 1.03; P non-significant). The magnitude of bone loss in the diabetics was small (T-score, -0.38 +/- 1.13 at the lumbar spine and -0.37 +/- 1.08 at the femoral neck). Only three patients met WHO criteria for osteoporosis at one or both measurement sites. Patients with retinopathy (n = 37) had lower lumbar spine bone mineral density values than patients without retinopathy; however, this difference was no longer present after adjustment for age and disease duration. Bone mineral density values were similar in patients with (n = 13) and without microalbuminuria. Our findings suggest that bone loss is not a major problem in younger type 1 diabetics with short disease durations and no severe diabetic complications.

Nutritional status in patients with rheumatoid arthritis.

BACKGROUND: Some chronic diseases have been associated to an impairment of nutritional status. OBJECTIVE: To analyze nutritional status and its relation to dietary intake, disease activity and treatment in rheumatoid arthritis. PATIENTS AND METHODS: We have included 93 patients (43 men and 50 women) and 93 age- and sex-matched healthy controls. The assessment of nutritional status included anthropometric (body mass index, tricipital skin fold and midarm muscular circumference) and biochemical (serum albumin, prealbumin and retinol binding protein) parameters. Dietary intake was calculated from a food frequency questionnaire. As a measure of disease activity, we used the Health Assessment Questionnaire, Ritchie index, tender and swollen joint count and C-reactive protein. Statistical analysis was performed in the whole series and in every functional class. RESULTS: In the whole series, midarm muscular circumference and serum albumin were significantly lower in patients than in controls. All anthropometric parameters and serum albumin were significantly lower in patients in functional class IV than in their respective controls. The dietary intake of energy, carbohydrates, vegetal proteins and lipids was higher in patients than in controls. Midarm muscular circumference and serum albumin had a significant inverse relation with disease activity parameters; body mass index, midarm muscular circumference and serum albumin correlated inversely with the cumulative dose of glucocorticoids. CONCLUSIONS: Patients with rheumatoid arthritis in functional class IV have an impairment of nutritional status without a deficient dietary intake. The differences found in other functional classes are explained by rheumatoid arthritis itself. Nutritional parameters are related to disease activity and glucocorticoid treatment.