Oxytocin and bone status in men: analysis of the MINOS cohort.

UNLABELLED: Oxytocin, a neurohypophysial hormone, regulates bone metabolism in animal studies and postmenopausal women. In men, oxytocin is not associated with bone mineral density, bone turnover markers, or prevalent fractures, but weakly negatively with incident fragility fracture requiring further studies. INTRODUCTION: We previously showed that serum oxytocin (OT) level is associated with bone mineral density (BMD) and bone turnover rate in postmenopausal women. The aim of our study was to assess the relationship between circulating OT levels and bone status in men. METHODS: In 552 men aged 50 and older from the MINOS cohort, we measured serum levels of OT. We assessed the association of serum OT levels with BMD (lumbar, femoral neck, total hip), bone turnover markers (BTM) (serum N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (bone ALP), and C-terminal telopeptide of type I collagen (CTX-I)) and fracture risk. RESULTS: In the univariate analysis, serum OT level was not associated with BMD at any site, BTM levels, or with prevalent or incident fracture. OT was significantly correlated with body mass index (BMI) (r = 0.17, p < 0.001), total or bioavalaible 17ß-estradiol (r = 0.09, p = 0.04 and r = 0.20, p < 0.001, respectively), free testosterone (r = 0.17, p < 0.001), and leptin (r = 0.16, p < 0.001). Multivariate analysis did not show significant relationship between serum OT and BMD. After adjustment for age, BMI, interaction BMI/age, history of fall in the last year, and BMD, OT and prevalent fracture were not associated. By contrast, the same analysis with additional adjustment for prevalent fracture showed a weakly significant negative association between OT and incident fracture, e.g., after adjustment for femoral neck BMD, HR = 0.73, 95 %CI 0.55-0.99, p = 0.04. CONCLUSION: In men, serum OT levels are not associated with BMD, bone turnover rate, or prevalent fractures. The weak negative relationship with fracture risk requires further studies.

Impact of systemic treatment of psoriasis on inflammatory parameters and markers of comorbidities and cardiovascular risk: results of a prospective longitudinal observational study.

BACKGROUND: Several markers of comorbidities and cardiovascular (CV) risk are disturbed in moderate to severe psoriasis (PsO). The effect of systemic treatments of psoriasis on these markers remains poorly understood. OBJECTIVES: To study the frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk associated with moderate to severe PsO and psoriatic arthritis (PsA), and to assess their evolution under systemic treatments. METHODS: Monocentric prospective study on patients with PsO and PsA starting a systemic treatment for their psoriasis. The following markers were evaluated at baseline (M0), 3 months (M3) and 6 months (M6); weight, fasting blood glucose, blood pressure, uric acid, hepatic steatosis, smoking, lipid, metabolic and inflammatory parameters. RESULTS: Forty-three patients, 31 PsO and 12 PsA, were included. Forty completed the study. Response to treatment was good, with 71% of the population obtaining a Psoriasis Area and Severity Index (PASI) of 75. All patients had at least one comorbidity, and 45% had two or more. A statistically significant decrease was observed only for inflammatory parameters (C-reactive protein [CRP], P = 0.004) and erythrocyte sedimentation rate (ESR, P = 0.002). We did not observe any correlation between the PASI and CRP (correlation coefficient 0.128, P = 0.438) or ESR (correlation coefficient 0.294, P = 0.069) for responding patients. CONCLUSIONS: We observed a high frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk in a population with moderate to severe PsO and PsA, most of which were not detected before. A significant decrease in inflammatory parameters was noted after the introduction of systemic therapy, while other parameters remained unaffected by the treatment, except the weight that increased under biologics therapies.

Prevalence of symptomatic hip and knee osteoarthritis: a two-phase population-based survey.

OBJECTIVE: Osteoarthritis (OA) epidemiologic data are scarce in Europe. To estimate the prevalence of symptomatic knee and hip OA in a multiregional sample in France. DESIGN: A two-phase population-based survey was conducted in six regions in 2007-2009. On initial phone contact using random-digit dialing, subjects 40-75 years old were screened with a validated questionnaire. Subjects screened positive were invited for ascertainment: physical examination and hip and/or knee radiography (Kellgren-Lawrence grade≥2). Multiple imputation for data missing not-at-random was used to account for refusals. RESULTS: Of 63,232 homes contacted, 27,632 were eligible, 9621 subjects screened positive, 3707 participated fully in the ascertainment phase, and 1010 had symptomatic OA: 317 hip, 756 knee. Hip OA prevalence according to age class ranged from 0.9% to 3.9% for men and 0.7-5.1% for women. Knee OA ranged from 2.1% to 10.1% for men and 1.6-14.9% for women. Both differed by geographical region. The hip and knee standardized prevalence was 1.9% and 4.7% for men and 2.5% and 6.6% for women, respectively. CONCLUSIONS: This confirmed the feasibility of using a screening questionnaire for eliciting population-based estimates of OA. In France, it increases with age and is greater among women above the age of 50. The geographical disparity of hip and knee OA parallels the distribution of obesity. Study registration ID number 906297 at http://www.clinicaltrials.gov/.

Immune changes in post-menopausal osteoporosis: the Immunos study.

UNLABELLED: The phenotypic and functional characteristics of immune cells of osteoporotic women compared to healthy controls similar for age and estrogen level showed for the first time significant changes in several B lymphocytes populations in postmenopausal osteoporosis, related to bone mineral density (BMD) and fractures, and a significant lower basal secretion of interferon-gamma (IFN-gamma) by CD4(+). INTRODUCTION: To investigate the interactions between bone and immune system, we studied the phenotypic and functional characteristics of immune cells of 26 postmenopausal women with osteoporotic (OP) fractures compared to 24 healthy controls. METHODS: We analyzed surface markers of peripheral B, CD4(+) and CD8(+) lymphocytes and cytokine secretion in supernatants of these cells cultured with or without stimulation. Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: The two groups were similar for age and estrogen level. OP women had a significantly lower body mass index, fat mass, and lean mass. The number of CD19(+), CD19(+)/CD27(+), CD19(+)/CD27(+)/CD5(-)/CD38(+) and CD19(+)/CD27(+)/RANK(+), CD4(+)/CD27(+)/CD45RA(-)/RANK(+), and CD4(+)/CD27(+)/CD45RA(-)/CD28(+) was lower in OP women and positively correlated to BMD. In OP women, under basal conditions, CD4(+) secreted less IFN-gamma and B lymphocytes more granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF was positively correlated to fracture rate and negatively to BMD. CONCLUSIONS: Our results suggest that, regardless of age and estrogen status, postmenopausal OP is associated with immune changes, highlighting a possible role of IFN-gamma in the pathophysiology of OP and reporting, for the first time, changes in several B lymphocyte populations. These alterations may reflect the frailty observed after fracture, providing new insight into the mechanisms of morbidity and mortality associated with OP fractures.

Prospective, multi-centre, randomised evaluation of the safety and efficacy of five dosing regimens of viscosupplementation with hylan G-F 20 in patients with symptomatic tibio-femoral osteoarthritis: a pilot study.

INTRODUCTION: Viscosupplementation by repeated intra-articular injections of hyaluronic acid (HA) is used widely in the treatment of symptomatic knee osteoarthritis (OA). The number of injections required can limit the availability of treatment and affect patient compliance. The aim of this study was to assess different dosing regimens of hylan G-F 20, a high molecular-weight cross-linked derivative of HA, in the treatment of pain due to knee OA. MATERIALS AND METHODS: Pilot, prospective, multi-centre, open-label, randomised trial in 100 patients with unilateral, symptomatic, tibio-femoral OA (Kellgren-Lawrence grade II or III), aged > or =40 years. Patients were randomised to receive varying dosing regimens of hylan G-F 20 (1 x 6 mL, 1 x 4 mL, 2 x 4 mL 2 weeks apart, 3 x 4 mL 1 week apart, or 3 x 2 mL 1 week apart). Adverse events (AE's) were monitored throughout the study. The primary efficacy endpoint was the change from baseline in the patient-rated knee OA pain assessment (100 mm visual analogue scale (VAS)) at 24 weeks. The secondary efficacy criteria included the WOMAC index, patient and physician global assessments using a 100 mm VAS, and knee OA pain assessment at all other visits. Concomitant use of permitted rescue medications (paracetamol) was also assessed. RESULTS: The treatment was well tolerated overall. Patients in the 3 x 4 mL group reported the highest percentage of device-related local AE's (30%) while patients in the 1 x 6 mL and 3 x 2 mL groups reported only 10%. There were no serious device-related AEs. There was a statistically significant improvement from baseline at week 24 in all efficacy endpoints for all treatment regimens. The 1 x 6 and 3 x 4 and 3 x 2 mL treatment groups showed the greatest mean improvements (-34.9, -32.6 and -36.7 mm respectively) in the patient-rated knee OA pain assessment VAS. CONCLUSION: This study suggests that a single 6 mL injection of hylan G-F 20 may be as efficacious, and as well tolerated, as 3 x 2 mL one week apart. A double-blind, controlled trial is needed to confirm these data.

Screening for hip and knee osteoarthritis in the general population: predictive value of a questionnaire and prevalence estimates.

OBJECTIVE: To study the feasibility and validity of a two-step telephone screening procedure for symptomatic knee and hip osteoarthritis (OA) in the general population. METHOD: The screening questionnaire was based on signs and symptoms, previous diagnosis of OA and validated OA criteria. A random sample of telephone numbers was obtained and, at each number, one person aged 40-75 years was included. A physical examination and knee or hip radiographs were offered when the screen was positive. A sample of subjects with negative screens was also examined. The diagnosis of hip/knee OA was based on the American College of Rheumatology criteria for signs and symptoms and Kellgren-Lawrence radiographic stage 2 or greater. Prevalence rates were estimated with correction for the performance of the screening procedure. RESULTS: Of 1380 subjects, 479 had positive screens, among whom 109 were evaluated; symptomatic radiographic OA was found in 50 subjects, at the knee (n = 35) or hip (n = 20). Corrected prevalence estimates of symptomatic OA were 7.6% (6.4%-8.8%) for the knee and 5% (3.9%-6.1%) for the hip. The screening procedure had 87% (95% CI 79% to 95%) sensitivity and 92% (95% CI 91% to 93%) specificity for detecting knee OA and respectively 93% (95% CI 86% to 100%) and 93% (95% CI 92% to 94%) for hip OA. CONCLUSION: This study establishes the feasibility of telephone screening for symptomatic knee/hip OA, which could be used for a nationwide prevalence study. Pain and previous OA diagnosis were the best items for detecting symptomatic OA.

[Uveitis treated with biotherapy and/or DMARD: Analysis from the French Pharmacovigilance Study Base]. / Uvéites sous biothérapies et/ou DMARDs en rhumatologie : analyse de la base de données déclarative de la pharmacovigilance nationale française.

PURPOSE: To report the characteristics of uveitis cases occurring while on biologic therapy or disease-modifying antirheumatic drugs (DMARDs) reported to the French national pharmacovigilance database. METHODS: All the uveitis cases occurring in patients with chronic rheumatologic diseases, chronic inflammatory intestinal diseases or connective tissue diseases, while treated with DMARDs and/or biologic therapies between 2000 and 2015 and reported to the French National Pharmacovigilance Database were collected. RESULTS: During the study period, 32 cases of uveitis were reported (15 men, 17 women). Two patients were treated with one DMARD alone, 24 with biologic therapy alone, and six with both treatments. Anterior uveitis was diagnosed in 19 patients (8 cases were bilateral); intermediate uveitis was found (unilaterally) in one patient; posterior and diffuse uveitis occurred in 5 and 2 cases respectively. Five cases were inconclusive with regard to the anatomical type of uveitis. The uveitis was of infectious origin in 5 cases: 2 toxoplasmosis, 2 herpes virus and 1 tuberculosis. In the 27 other cases, it was not possible to state whether the uveitis was associated with the underlying disease (uncontrolled) or a side effect of the biologic/DMARD treatments. The occurrence of the uveitis led to 9 switches in biologic therapy and 13 discontinuations of treatment (8 complete discontinuations, 5 discontinuations only until uveitis remission was obtained). In 4 cases, the treatments were not modified. The database does not specify the ultimate course or rheumatologic disease activity at the time of the uveitis. CONCLUSIONS: The presence of uveitis while on biologic therapy must not be taken to indicate a therapeutic failure, especially if the ocular manifestation is isolated. In the case of uveitis occurring in patients treated with biologic therapies and/or DMARDs, infectious complications should be ruled out.

Evaluation of the expectations osteoarthritis patients have concerning healthcare, and their implications for practitioners.

BACKGROUND: The expectations of patients with osteoarthritis are essential for health care provision and may be used to improve the patient-doctor relationship. METHODS: A total of 96 osteoarthritis patients aged 42-89 years (mean=65; 81% female) were recruited among customers of 10 pharmacies in 10 towns in 10 regions (selected at random from the 22 French regions). Ten focus groups were organized looking at three categories of expectation: 1) Information about and understanding of osteoarthritis; its impact on lifestyle, and its treatment, consequences, and outlook; 2) Communication skills, attitudes of practitioners and communication between health professionals; 3) Support available from doctors, family circle and society. RESULTS: The patient-practitioner relationship begins with a dialogue, the quality of which, the participants could be improved by: developing greater trust: patients expect communication skills and expressions of sympathy that practitioners seem ill-prepared to provide. Strengthening involvement: general practitioners in particular should act as mediators and facilitators to improve recognition and understanding of osteoarthritis by employers and public decision-makers. CONCLUSION: The present study enabled patients to express their expectations. Meeting those expectations could markedly improve the therapeutic process, but the question arises of whether practitioners are ready to agree that there is a need to reconsider and modify the care they provide for their patients.

Pleural amyloidosis as the first sign of IgD multiple myeloma.

We describe a case of IgD myeloma with amyloid and plasmocytic pleural localisations. At the onset of the disease it mimicked rheumatoid arthritis, which can be the first presentation of both AL amyloidosis and multiple myeloma. Pleural effusion can happen first in IgD myeloma, but our observation is of interest in that it confirms the very rare possibility of pleural amyloid and plasmocytic localisations devoid of pleural effusion.

Occipitocervical fixation using hooks and screws for upper cervical instability.

OBJECTIVES: Occipitocervical fixation is used for the treatment of nontraumatic upper cervical instabilities. To date, plates have been fixed with screws or wires. However, these devices are not indicated in the treatment of patients with severe osteoporosis or in instances of significant thinning of the occipital bone. We performed a clinical trial of a new type of fixation that uses cervical interlaminar hooks and occipital claws with hooks or with screws (CCD type; Sofamor-Danek, Roissy, France) for the treatment of nontraumatic upper cervical instabilities. METHODS: Five women and one man ranging in age from 28 to 72 years (average age, 54 yr) were thus treated. The CCD type material had two rod plates and hooks allowing the proper placement of interlaminar and occipital claws. The occipital plate can also be directly screwed to the bone. Occipital hooks were used in four patients. The other two patients, who had occipitocervical congenital abnormalities that required an occipitocervical opening and an additional dural enlargement, underwent occipital screw fixation because of the previous opening of the foramen magnum. A cancellous iliac autograft allowed the usual fusion. RESULTS: No postoperative complications were observed, and all patients experienced significant improvement of their neck pain. Four patients had neurological symptoms. The condition of two patients improved, and the condition of the other two stabilized. CONCLUSION: This report confirms the interest of the CCD method to correct all types of upper cervical instabilities, even in cases of unusual thinning of the occipital bone or in osteoporotic states.

Intravertebral vacuum phenomenon in multiple myeloma.

Authors report one case of intravertebral vacuum phenomenon associated with a multiple myeloma. Initially, there occurred a collapse and a lysis of the L4 vertebral body. Two months later, after chemotherapy and cobalt-therapy, X-ray examination showed a vacuum cleft phenomenon within the body of L4 and a backward displacement of the L4 posterior wall. At the same time the patient complained of a cruralgia. Recovery occurred after decompression surgery. Histologic sampling of the L4 vertebral body revealed bone necrosis without any abnormal plasmocytosis. Authors draw attention to the neurological complications occurring in the course of the vertebral necrosis and to the fact that, even in case of multiple myeloma, the occurrence of a transverse vacuum cleft may result from osteonecrosis.

Gonadal dysgenesis and bone metabolism.

Gonadal dysgenesis is defined as congenital hypogonadism related to abnormalities of the sex chromosomes. Because sex steroids play a central role in the acquisition and maintenance of bone mass, studies have been done to investigate bone status in patients with gonadal dysgenesis, particularly Turner's syndrome and Klinefelter's syndrome, which are the two most common types. The severe estrogen deficiency characteristic of Turner's syndrome (44, X0) is associated with a significant bone mass decrease ascribable to increased bone turnover, as shown by histological studies and assays of bone turnover markers. Estrogen therapy is followed by a significant bone mass gain and a return to normal of bone turnover markers, suggesting that it is the estrogen deficiency rather than the chromosomal abnormality that causes the bone mass deficiency, although abnormalities in the renal metabolism of vitamin D have been reported. Combined therapy with estrogens and growth hormone seems beneficial during the prepubertal period. In Klinefelter's syndrome (47XXY), serum testosterone levels are at the lower end of the normal range and dihydrotestosterone levels are low. Histological studies show depressed osteoblast function and a decrease in 5-alpha-reductase activity responsible for partial tissue resistance to androgens. Assays of bone turnover markers show evidence of increased bone turnover. The bone deficiency is most marked at the femoral neck and seems correlated with serum testosterone and estradiol levels. Androgen therapy has favorable effects on the bone only if it is started before puberty. Recent data suggest that estrogens may contribute to the development of demineralization in KS and that bisphosphonate therapy may be beneficial.

[Correlation between the serum level of soluble CD16 and the staging of myeloma: study of 214 serums]. / Corrélation entre le taux sérique du CD16 soluble et le stade du myélome: étude de 214 sérums.

Soluble CD16 (sCD16) are soluble part of Fc receptor for IgG which control in mice, proliferation of hybridoma B cells and IgG production. The levels of sCD16 in 165 myeloma patients and 29 patients with MGUS appear significantly different:25a.u./ml versus 144a.u./ml and values of stage I are significantly higher than those of stages II + III.sCD16 might be a prognosis factor in myeloma.

[Fracture of the sacrum caused by bone insufficiency in a pregnant woman]. / Fracture du sacrum par insuffisance osseuse chez une femme enceinte.

Sacral insufficiency fractures are not rare. They are well known in female patients over age 50 with osteopenia. One case occurring in a young pregnant woman is described. We did not find another case in the literature.

[Etanercept--infliximab switch in rheumatoid arthritis 14 out of 131 patients treated with anti TNFalpha]. / Switch étanercept--infliximab dans la polyarthrite rhumatoïde. 14 patients sur 132 traités par anti-TNFalpha.

OBJECTIVE: Patients with severe rheumatoid arthritis and resistant to at least three DMARDS can benefit from anti-TNFalpha (tumor necrosis factor) therapy. In some patients, because of inefficacy or adverse events, treatment with one of the two available TNFalpha drugs (etanercept and infliximab) must be stopped. In this study, we explored the results in efficacy and tolerance of switching from one anti-TNFalpha to the other. PATIENTS: Between August 1999 and January 2002, we administered one of the two anti TNFalpha drugs to 131 patients: 67 patients received infiximab and 64 etanercept. RESULTS: Among the 67 patients treated with infliximab, 17 patients had to stop treatment. In 8 of them (4 allergies, 2 infections and 2 non responders) the switch from infliximab to etanercept was beneficial for 5 patients, 2 patients did not respond and 1 patient withdrew for personal reasons. Among the 64 patients treated with etanercept, 13 had to stop treatment. In 6 of them (2 adverse events, 4 failures) the switch from etanercept to infliximab was beneficial for 3 patients, 2 did not respond and 1 withdrew because of adverse events. CONCLUSION: In all, 14 patients with severe rheumatoid arthritis and treated by one of the two TNFalpha drugs (and in whom treatment was stopped because of adverse events or inefficacy) benefited from the switch to the other anti- TNFalpha, with excellent response in 8 out of 14 patients.

[Femoral neck fracture complicating algodystrophy in pregnancy]. / Fracture du col fémoral compliquant une algodystrophie au cours de la grossesse.

BACKGROUND: Sympathetic reflex dystrophy is an uncommon cause of pelvic pain not to be overlooked in pregnant women. CASE REPORT: At 8 months pregnancy, a 27-year-old woman complained of invalidating pain of the left hip. Magnetic resonance imaging of the pelvis performed the day after delivery evidenced a non-displaced fracture of the femoral neck and a typical aspect of sympathetic reflex dystrophy. DISCUSSION: The true frequency of sympathetic reflex dystrophy during pregnancy is probably underestimated. Approximately one hundred cases have been reported. The hip joint is involved in 9 out of 10 cases. Such localizations are uncommon outside pregnancy, accounting for 14 to 17% of all cases.

[Treatment of systemic scleroderma with factor XIII in 86 patients, with long-term follow-up]. / Traitement de la sclérodermie systémique par le facteur XIII chez 86 malades suivis à long terme.

Eighty-six patients with progressive systemic sclerosis were given coagulation factor XIII intravenously in different dosage regimens. The mean duration of treatment was 19 +/- 18 months and patients were followed up for 22.9 +/- 18.8 months. Improvement or stabilization of the lesions was obtained in 44/86 patients and exclusively concerned skin lesions; there was no improvement in visceral lesions. The drug was well tolerated in short-and long-term treatment. It is concluded that factor XIII demonstrated lasting effectiveness in one-half of the patients treated.