JAK-Inhibitors - A Story of Success and Adverse Events.

Rheumatoid arthritis (RA) is a systemic, chronic, immune-mediated inflammatory condition. Treatments options encompass conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) like tumor necrosis factor (TNF) inhibitors (TNFis) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) including Janus Kinase inhibitors (JAKinibs). Orally administered JAKinibs have demonstrated comparable or, in specific cases, superior efficacy compared to bDMARDs in inflammatory conditions. However, the escalating clinical utilization has been accompanied by the emergence of serious adverse effects, including major adverse cardiac events (MACE), malignancies and venous thrombotic episodes (VTE), leading to regulatory restrictions imposed by health authorities in both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Factors Associated with Objectively Measured Physical Activity in Patients with Seropositive Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which is associated with low levels of physical activity (PA). However, the factors related to low physical activity levels have rarely been studied. Methods: In this cross-sectional study, 70 seropositive RA patients were included. Physical activity was objectively assessed with an ActiGraph GT3X+ accelerometer. In addition, body mass index, smoking status, work ability, and clinical parameters (functional disabilities, disease activity, disease duration, pain, and inflammation parameters) were measured. Results: RA patients performed a mean of 215.2 (SD: 136.6) min a week of moderate physical activity and 9.1 (SD: 26.3) min of vigorous physical activity. The total amount of moderate and vigorous physical activity (MVPA) was associated with BMI, and functional disabilities. In addition, non-smokers and patients with better work ability did more MVPA. No association could be seen with disease activity, disease duration, pain, and inflammatory markers. After mutual adjusting of all the variables, only BMI showed a significant relationship with MVPA. Conclusions: RA patients perform de facto no physical activity with vigorous intensity. Factors related to low physical activity are BMI, functional disabilities, workability and smoking status, whereas due to the study design no causal and temporal link could be made.

Medication Adherence and Coping Strategies in Patients with Rheumatoid Arthritis: A Cross-Sectional Study.

OBJECTIVES: The aim of this study was to determine if strategies for coping with illnesses, demographic factors, and clinical factors were associated with medication adherence among patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study was conducted at a Viennese rheumatology outpatient clinic on RA patients. Medication adherence was assessed using the Medication Adherence Report Scale. Strategies for coping with illness were assessed using the Freiburg Questionnaire for Coping with Illness. RESULTS: Half (N=63, 52.5%) of the 120 patients included in the study were considered completely medication adherent. Female sex (odds ratio [OR]: 4.57, 95% confidence interval [CI]: 1.14 - 18.42), older age (54-65 yr vs. <45 yr OR: 9.2, CI:2.0-40.70; >65 yr vs. <45 yr OR 6.93, CI:1,17 - 40.87), middle average income (middle average income vs. lowest income class OR= 0.06, CI= 0.01-0.43), and shorter disease duration (5-10 yr vs. >10 yr OR= 3.53, CI= 1.04-11.95; 1-4 yr vs. >10 yr OR=3.71, CI= 1.02-13.52) were associated with higher medication adherence. Levels of active coping (15.57 vs. 13.47, p=0.01) or diversion and self-encouragement (16.10 vs. 14.37, p=0.04) were significantly higher among adherent as opposed to less adherent participants. However, in multivariate regression models, coping strategies were not significantly associated with adherence. CONCLUSIONS: Age, sex, monthly net income, and disease duration were found to be associated with an increased risk for medication nonadherence among patients with RA. Coping strategies such as active coping, diversion, and self-encouragement were associated with adherence in univariate models, but not when adjusted for demographic and clinical factors.

Frailty in seropositive rheumatoid arthritis patients of working age: a cross-sectional study.

OBJECTIVES: The prevalence of frailty has been widely researched in the elderly population. However, data about people of working age are scarce. The aim of this paper was to assess the prevalence of prefrailty and frailty in rheumatoid arthritis (RA) patients of working age, and to assess factors associated with prefrailty/frailty. METHODS: In this monocentric cross-sectional study, 100 RA patients aged 18-65 years were included. Frailty was measured with the Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI) and disease activity with the Clinical Disease Activity Index (CDAI). In addition, disease duration (years), pain intensity (visual analogue scale) and employment status were also assessed. RESULTS: Fifty-five percent were robust, 30% prefrail and 15% were frail. Eighty-nine of the prefrail/frail individuals suffered from exhaustion. Compared to robust individuals, the prefrail/frail individuals had significantly higher median scores in disease activity [4.0 (Q25-Q75: 0-10) vs. 11 (Q25-Q75: 6-18)] and pain intensity [3.0 (Q25-Q75: 2.0-4.0) vs. 4.0 (Q25-Q75: 2.8-6.3)] and a higher rate of unemployment [31% vs. 53%]. In the multivariable analysis, higher disease activity (ß=0.444; p<0.001), unemployment (ß=0.243; p=0.005), higher pain intensity (ß=0.186; p=0.060) and longer disease duration (ß=0.181; p=0.020) were associated with a higher frailty score. CONCLUSIONS: Frailty is common in RA patients, even those of working age. As the prevalence of frailty increases with age, it is important to take this syndrome into account in younger persons and to take action to counteract frailty.

A cross-sectional study on self-reported physical and mental health-related quality of life in rheumatoid arthritis and the role of illness perception.

BACKGROUND: Psychosocial models including illness perception might explain individual differences in health-related quality of life (HRQoL) and daily functioning in chronically ill patients. The aim of this study was to assess the association of illness perception among rheumatoid arthritis (RA) patients with physical and mental HRQoL, adjusted for demographic variables, clinical variables and social support. METHODS: A cross-sectional study conducted at a Viennese rheumatology outpatient clinic on 120 RA patients. Participants completed questionnaires on demographic and clinical characteristics, HRQoL (SF-36 Questionnaire), illness beliefs (Brief Illness Perception Questionnaire) and social support (Social Support Scale-8). Analyses were performed with multivariate linear regression. RESULTS: The mean physical was lower (38.38) than the mean mental SF-36 summary score (46.94). In univariate analysis, all domains of illness perception except belief in a chronic disease course were associated with physical and mental HRQoL. In multivariate analyses, illness perception accounted for 51% of variance in physical HRQoL. A stronger belief in the consequences of RA (consequences, ß = - 0.33) and a stronger belief in repeated disease recurrence (timeline cyclical, ß = - 0 .31) were significantly associated with physical HRQoL in the fully adjusted model. Illness perception accounted for 45% of variance in mental HRQoL. Emotional representation (ß = - 0 .27) and fatigue (ß = - 0 .36) were significantly associated with mental HRQoL in the fully adjusted model. CONCLUSION: This study highlights the importance of RA patients' beliefs about their illness and symptoms in relation to HRQoL. Identification of patients' perception of RA may be a way to positively influence disease outcomes such as quality of life as illness perception is amenable to intervention.

Sleep Quality in Patients with Rheumatoid Arthritis and Associations with Pain, Disability, Disease Duration, and Activity.

We aimed to assess the subjective sleep quality in patients with rheumatoid arthritis (RA) and its correlation with disease activity, pain, inflammatory parameters, and functional disability. In a cross-sectional study, patients with confirmed RA diagnosis responded to a questionnaire (consisting of socio-demographic data, the Health Assessment Questionnaire Disability Index, and the Medical Outcome Study Sleep Scale). Disease activity was assessed with the Clinical Disease Activity Index, and pain levels using the visual analogue scale. In addition, inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor alpha) were analyzed. Ninety-five patients were analyzed, predominantly female, with an average age of 50.59 (9.61) years. Fifty-seven percent reported non-optimal sleep duration, where functional disability (92.7% vs. 69.8%; p = 0.006) and higher median pain levels (3.75 (2.3⁻6.0) vs. 2.5 (2.0⁻3.5); p = 0.003) were also more prevalent. No differences in sociodemographic variables, disease duration or activity, inflammatory parameters, or use of biological and corticosteroid therapy were observed. The multivariate regression analysis showed that more intense pain was associated with a lower likelihood of optimal sleep (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.47⁻0.98, p = 0.038). Patients with RA report a high prevalence of non-optimal sleep, which is linked to pain level. Clinicians need to be aware of this issue and the potential effects on health and functional status.

Work Ability and Employment in Rheumatoid Arthritis: A Cross-Sectional Study on the Role of Muscle Strength and Lower Extremity Function.

OBJECTIVE: The aim of the present study was to assess the association between muscle strength, lower extremity function, employment status, and work ability in RA patients. METHODS: One hundred seropositive RA outpatients of working age were included in this cross-sectional study. Employment status was assessed by interview and work ability by the Work Ability Index-Single Item Scale (WAS). Muscle strength was determined using dynamometer measurement of isometric hand grip and knee extensor strength. Lower extremity function was measured using the short physical performance battery (SPPB). Regression models estimate the association between unemployment, work ability and muscle strength, and lower extremity function, controlling for sociodemographic and disease-related factors. RESULTS: Forty-one percent of the RA patients were not gainfully employed, and their median work ability had a good WAS value (7.00 [4.00-7.00]). Patients with better knee extensor strength (OR=1.07, 95% CI [1.02-1.12) and better physical performance (OR=1.71, 95% CI [1.18-2.49]) had a significantly better chance of gainful employment. The odds for hand grip strength remained significant when adjusted for sociodemographic (OR=1.5, 95% CI [1.00-1.09]), but not for disease-specific variables. Better hand grip strength (ß=0.25, p=0.039) and better knee extensor strength (ß=0.45, p=0.001) as well as better lower extremity function (SPPB) (ß=0.51, p<0.001) remained significantly associated with work ability following adjustment for sociodemographic and disease-specific variables. CONCLUSIONS: The association of employment status and work ability with parameters of physical fitness suggests that improvement in muscle strength and lower extremity function may positively influence work ability and employment in individuals with RA.

Sexual health in patients with rheumatoid arthritis and the association between physical fitness and sexual function: a cross-sectional study.

The aim of this study was to examine sexual health in patients with rheumatoid arthritis (RA), and to analyse factors associated with sexual health with a focus on physical fitness. One hundred RA patients aged between 18 and 65 years were included in a cross-sectional study. Handgrip strength and knee extensor strength were measured with a dynamometer, and physical performance with the Short Physical Performance Battery (SPPB). Fifty-four patients, mean age 47.8 (SD 10.6) years, 61% female, answered a questionnaire about sexual health. Fifty-seven percent reported, at least, sometimes having difficulty with sexual intercourse (27.8% due to joint stiffness, 24.1% due to fatigue, 18.5% due to pain). Handgrip strength and knee extensor strength significantly correlated with the desire to engage in sexual intercourse, frequency of sexual contact and satisfaction with overall sex life. The SPPB total score correlated with satisfaction with overall sex life, and the SPPB repeated chair stands test with the desire to have sexual intercourse and satisfaction with overall sex life. After adjusting for age, gender, disease activity, comorbidity, co-medication and pain intensity, the repeated chair stands test remained significantly associated with the frequency of sexual contact (0.53; 0.01-1.05) and with satisfaction with overall sex life (1.39; 0.28-2.51). The results of this study show that problems with sexual health are highly prevalent in patients with RA. The ability to rise from a chair is associated with sexual function, independent of disease activity and pain intensity.

Workability and Muscle Strength in Patients With Seropositive Rheumatoid Arthritis: Survey Study Protocol.

BACKGROUND: Rheumatoid arthritis (RA) and other rheumatic conditions not only fundamentally affect patients' quality of life and physiological needs but are also negatively associated with work ability. The costs of poor work ability, which, in sum, are more than treatment costs, pose an economic burden to society and patients. Work ability in RA appears to be multifactorial; symptoms such as pain, swelling, and stiffness play a major role, as these directly affect functional disability. Also, RA patients typically suffer from reduced muscle strength. Lower extremity function and grip strengths especially impair their quality of life. However, the role of muscle strength and disease activity as determinants of work ability have not yet been studied. OBJECTIVE: The primary objective of this study is to compare work ability in working-age participants with seropositive RA and with high and low disease activity; the secondary objective is to evaluate the association of muscle strength, functional ability, and frailty with work ability. METHODS: This monocentric cross-sectional study will be conducted at a rheumatologic outpatient clinic and day hospital with approximately 100 seropositive RA patients aged <65 years. A clinical disease activity index as a measure for rheumatoid disease activity will be assessed during the patients' routine visits at the clinic. Work ability, frailty, and functional disability will be evaluated with (self-reported) questionnaires as well as with physical tests (Work Ability Index/Score; Health Assessment Questionnaire Disability Index; Survey of Health, Ageing, and Retirement in Europe Frailty Instrument; Short Physical Performance Battery). Muscle strength will be determined with dynamometer measurements of isometric hand grip strength and quadriceps femoris muscle contraction strength. Sleep quality (Medical Outcomes Study Sleep Scale) and sexual functioning as physiological needs will additionally be determined with self-reported questionnaires. RESULTS: For this study funding has already been awarded and enrollment has been completed. Data are currently being evaluated. CONCLUSIONS: This study will evaluate the association of work ability with modifiable parameters such as muscle strength and functional ability. It will provide further insights into work ability in RA and its associated risk factors. Any evidence of association will motivate further research, and the findings might encourage interventions focused specifically on improving muscle strength and lower extremity function to positively affect work ability. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02581852); https://clinicaltrials.gov/ct2/show/NCT02581852 (Archived by WebCite at http://www.webcitation.org/6oNcelHtQ).

An overview of psoriatic arthritis - epidemiology, clinical features, pathophysiology and novel treatment targets.

Psoriatic arthritis is a chronic inflammatory joint disease occurring in a subgroup of patients suffering from psoriasis. This article gives an overview of the complexity of psoriatic arthritis, looking at several aspects of this heterogeneous disease, such as epidemiology, important clinical features and comorbidities as well as current concepts of the pathophysiology and subsequent insights in novel treatment targets.

A randomized, double-blind, parallel, single-site pilot trial to compare two different starting doses of methotrexate in methotrexate-naïve adult patients with rheumatoid arthritis.

BACKGROUND: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis. Despite its widespread use, expert opinions differ about the optimal MTX starting dosage to achieve rapid onset of action while averting increased occurrence of adverse effects. Plasma concentrations have not been assessed in previous studies that monitored clinical efficacy. OBJECTIVE: This study was performed to compare the pharmacokinetic parameters and clinical response of a standard (15 mg) and an accelerated (25 mg) dosing regimen, each administered orally once a week. METHODS: This randomized, controlled, double-blind, parallel, single-site study included 19 MTX-naïve patients older than 18 years with rheumatoid arthritis. Patients participated for 16 weeks. Disease activity was assessed using the Disease Activity Score in 28 joints (DAS-28) as the primary outcome parameter. Plasma MTX concentrations were measured using HPLC at weeks 1, 5, 10, and 16. Tolerability was assessed via routine blood analysis (hematology and clinical chemistry) and a patient questionnaire to monitor adverse events. Reported or observed adverse events were recorded along with information about their severity and causal relationship to the study medication. RESULTS: Nineteen white patients (13 women and 6 men; mean age, 56 years; and mean weight, 74 kg) participated. At study entry, mean (SD) DAS-28-4v (erythrocyte sedimentation rate) was 4.73 (1.02). Health Assessment Questionnaire scores were 1.45 (0.85); for C-reactive protein, 11.45 (10.04) mg/dL; for alkaline phosphatase, 73.58 (19.91) U/L; for aspartate aminotransferase, 23.32 (7.13) U/L; and for creatinine, 0.87 (0.22) mg/dL. Although pharmacokinetic parameters such as AUC and C(max) were significantly higher after the accelerated dosing regimen, clinical activity scores (DAS-28) and inflammation parameters (C-reactive protein) did not indicate a significant benefit of an accelerated starting regimen. Considering toxicity, no elevation in liver function enzymes and no decrease in renal function were observed using the accelerated dosing (statistical significance set at P ≤ 0.05). No serious adverse events were noted. All observed adverse events were classified as study related. Overall, adverse events were noted in 58% of patients. Comparison of the two doses revealed that 60% of patients receiving the standard dosing regimen and 56% of patients receiving the accelerated dosing regimen reported adverse events, the most frequent being gastrointestinal. These events were generally self-limiting. CONCLUSIONS: Differences in clinical response between these two small selected patient groups who received an initial oral dose of either 15 or 25 mg MTX per week did not reach the level of statistical significance. The overall incidence of adverse effects, all classified as study related, was 58%, with 60% of patients receiving the standard dosage and 56% of patients receiving the accelerated dosing regimen reporting adverse effects. However, because of the small sample size, this study was not powered to detect differences in the incidence of adverse events between the two dosing groups. ClinicalTrials.gov identifier: NCT00695188.

A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate.

OBJECTIVES: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA). Although in general MTX is very effective, the major drawback is the large inter-patient variability in clinical response. The circulating levels of MTX polyglutamates (MTXPGs) are supposed to correlate with clinical efficacy, therefore having a potential role in drug monitoring. However, there is a controversial discussion about the importance of methotrexate polyglutamates as outcome parameters in the therapy of rheumatoid arthritis. The aim of the present study was to investigate the formation and pharmacokinetics of MTXPGs and to correlate their concentration with clinical response in MTX-naïve patients. METHODS: The pharmacokinetics of erythrocyte MTXPGs was determined in samples of nineteen MTX-naïve patients by high pressure liquid chromatography (HPLC) using post-column photo-oxidation and fluorimetric detection. The relationship between erythrocyte concentrations of MTXPGs and the primary outcome parameter DAS-28 was assessed using the Spearman's correlation coefficient. RESULTS: The short-chain polyglutamate MTXPG2 revealed to be a potential marker for clinical outcome in rheumatoid arthritis with a statistically significant positive correlation of MTXPG2 Cmax levels and improvement in DAS-28 (+0.518, p=0.023) over 16 weeks. Furthermore, Cmax levels of MTXPG2 negatively correlated with basophils (-0.478, p=0.038) and eosinophils (-0.531, p=0.019), both pro-inflammatory cells involved in the disease. CONCLUSIONS: MTXPG2 seems to be a potential indicator for clinical response and may serve as a marker for drug monitoring.

The influence of methotrexate on the gene expression of the pro-inflammatory cytokine IL-12A in the therapy of rheumatoid arthritis.

OBJECTIVES: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA). Among its anti-proliferative activity, the anti-inflammatory mechanisms of MTX seem to play a major role in the treatment of RA. MTX reduces the production of pro-inflammatory cytokines such as interleukin (IL)-1, IL-2, IL-6 and interferon (INF)-γ, while the gene expression of anti-inflammatory Th2 cytokines like IL-4 and IL-10 is increased - altogether resulting in the anti-inflammatory effect. As little is known about the impact of MTX on other cytokines involved in the pathogenesis of RA, the present trial investigated the effect of MTX on IL-12A and IL-18 gene expression by peripheral blood mononuclear cells (PBMCs). For comparison, the effect on IL-6 and tumour necrosis factor (TNF) was analysed. METHODS: Using real-time PCR, mRNA concentrations of pro-inflammatory cytokines were determined in PBMCs from 17 patients before and during MTX therapy. Furthermore, gene expression was correlated with clinical and pharmacokinetic parameters such as methotrexate polyglutamate concentrations (Spearman's correlation coefficient). To eliminate concomitant corticosteroids as confounding factor, a subgroup analysis for methotrexate without corticosteroids was performed in 6 patients. RESULTS: MTX statistically significantly reduced the mRNA expression of IL-12A by PBMCs in rheumatoid arthritis patients (Wilcoxon-test for paired samples, p<0.046). Consistent with other reports, IL-6 was reduced under MTX treatment. Although the combination of MTX and corticosteroids significantly reduced the gene expression of IL-18, this key molecule was unaffected by MTX without corticosteroids. Our results were further supported by a negative correlation of methotrexate polyglutamate concentrations and the mRNA expression of the pro-inflammatory cytokines IL-6 and IL-12A. CONCLUSIONS: We describe a novel effect of MTX reducing the gene expression of IL-12A independently of corticosteroid application in patients. This impact was further enhanced by a reduction of IL-12A-producing lymphocytes and neutrophils under MTX treatment. These results expand the understanding of the mechanism of action of the most widely used drug in RA.

Analysing cell-free plasma DNA and SLE disease activity.

BACKGROUND: Over the years, the demonstration and confirmation of cell-free DNA in the circulation has increasingly been recognized as a valuable diagnostic tool. Likewise, it has been known for some time that DNA structures that are targeted by auto-antibodies play a central role in systemic lupus erythematosis (SLE) and that DNA-antibody complexes in the circulation are one of the hallmarks of SLE. Investigating whether and to what degree fluctuations in free plasma DNA levels in patients with SLE might correspond to disease severity was therefore the goal of this investigation. METHODS: Blood from 13 patients with SLE and from 13 healthy controls was taken and analysed for the presence of anti-dsDNA, anti-ssDNA, anti-nucleosome, anti-histone antibodies as well as for cell-free DNA concentrations. For each patient, the SLE disease activity index (SLEDAI) was calculated. RESULTS: As demonstrated herein, compared to healthy subjects, cell-free DNA plasma levels in patients with SLE were significantly increased and so were anti-dsDNA, anti-ssDNA, anti-histone and anti-nucleosome antibodies. Furthermore, a statistically significant correlation was noted between cell-free DNA and anti-histone antibodies in patients with SLE. However, no correlation was noted between disease activity and anti-dsDNA, anti-ssDNA and anti-nucleosome antibody concentrations. Surprisingly, and more important in the context of this study, there was no correlation between cell-free DNA levels and SLEDAI scores. CONCLUSIONS: The presented data seem to exclude measuring free plasma DNA as an inexpensive, simple and quick tool to assess disease activity in patients with SLE. Further studies on a larger patient population would be needed to confirm our results.

Health-related quality of life in patients with osteopenia or osteoporosis with and without fractures in a geriatric rehabilitation department.

BACKGROUND: Health-related quality of life (HRQOL) is an important aspect in the management of patients with osteoporosis. The objective of this study was to estimate differences in HRQOL in women and men with osteopenia and osteoporosis with and without a fracture history and to assess HRQOL with a generic and disease-specific instrument. METHODS: Women and men were recruited from a geriatric rehabilitation department. Osteopenia or osteoporosis was diagnosed by Dual X-Ray Energy Absorptiometry (DXA). HRQOL was evaluated with the generic SF-36 questionnaire and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO-41). All subjects were instructed to complete these questionnaires. The level of pain was documented with a VAS (Visual Analogue Scale). RESULTS: 173 women and 49 men at a mean age of 79.3 +/- 8.5 years were enrolled. 85 participants reported a history of vertebral or hip fractures. The QUALEFFO score was 49.8 +/- 19.2 in patients with osteopenia, but significantly higher in osteoporotic patients without fractures (mean 58.1 +/- 13.3; p < 0.05). In osteoporotic patients with a fracture history the mean QUALEFFO score was significantly higher still, i.e. 63.8 +/- 13.6 (p < 0.05). The mean SF-36 summation scores of osteopenic patients and osteoporotic patients without fractures were similar (314 +/- 117 and 312 +/- 99, respectively). Osteoporotic patients with a fracture history showed lower mean scores (276 +/- 88; p < 0.05). VAS scores did not differ significantly. CONCLUSIONS: Osteoporosis has a considerably greater impact on HRQOL than osteopenia. Patients with a history of vertebral or hip fractures have a significantly poorer quality of life. These differences should be taken into account when prioritizing health care management.

BMP-6-induced osteogenic differentiation of mesenchymal cell lines is not modulated by sex steroids and resveratrol.

Bone morphogenetic protein-6 (BMP-6) is a potent inducer of osteogenic differentiation and its expression is stimulated by 17beta-estradiol. The existence of a regulatory loop between sex steroids and BMP-6 is therefore reasonable to hypothesize. Here we determined whether the sex steroids 17beta-estradiol and dihydrotestosterone, and the phytoestrogen resveratrol can modulate BMP-6-induced alkaline phosphatase activity and osteocalcin expression. Mesenchymal cells of murine (osteoblastic MC3T3-E1 cells, preadipogenic ST2 cells, prechondrogenic ATDC5 cell) and human origin (osteosarcoma SaOS and HOS cells, primary bone marrow stromal cells) were cultured in the presence of recombinant BMP-6 under serum-free conditions. BMP-6 dose-, and time-dependently increased alkaline phosphatase activity in murine cell lines, but not in human cells. Osteocalcin expression was also increased upon stimulation with BMP-6. The presence of 17beta-estradiol, dihydrotestosterone, and resveratrol had no effect on BMP-6-induced alkaline phosphatase activity and osteocalcin expression. These data suggest that osteogenic differentiation in response to BMP-6 occurs independent of steroid hormones and resveratrol in mesenchymal cells that express basal receptor levels.

Joint protection and home hand exercises improve hand function in patients with hand osteoarthritis: a randomized controlled trial.

OBJECTIVE: To determine the effect of joint protection and home exercises on hand function of patients with hand osteoarthritis (OA). METHODS: Randomized, controlled, 3-month trial with a blinded assessor. Primary outcome parameter was grip strength; secondary parameters were Health Assessment Questionnaire and visual analog scales (VAS) for pain and global hand function. Forty patients with hand OA were randomly assigned to 2 groups: One group received instruction for joint protection and home hand exercises (JPE group), the control group received an information session about hand OA. RESULTS: Grip strength improved by 25% in the JPE group (right hand, P < 0.0001; left hand, P = 0.0005), but not in the control group. Global hand function (by VAS) improved in a larger proportion (65%) of patients in the JPE group (P < 0.05). CONCLUSIONS: Joint protection and hand home exercises, easily administered and readily acceptable interventions, were found to increase grip strength and global hand function.