Generating evidence and understanding the treatment of osteoarthritis in Brazil: a study through Delphi methodology

OBJECTIVES: This study aimed to provide evidence for understanding how to treat osteoarthritis (OA) in our country. Therefore, it was necessary to match information and investigations related to the treatment of the disease from the three main types of specialists involved: physiatrists, orthopedists and rheumatologists. METHODS: The authors acted as a scientific advisory committee. From the initial discussions, a structured questionnaire was developed for use with a group of specialists on OA using the Delphi technique. The questionnaire was sent to 21 experts appointed by the authors, and the results obtained were critically analyzed and validated. RESULTS: The prevalence of OA was 33% in Brazil, corresponding to one-third of the individuals in the reference population, which included individuals over 25 years of age. Another significant finding was that most patients did not receive any form of treatment in the early stages of OA. CONCLUSION: The committee pointed to the need for early intervention and that the available medicinal resources can fulfil this important role, as is the case with SYSADOA treatments. Glucosamine-based medicinal products with or without chondroitin could also fulfill this need for early treatment. The other generated evidence and included investigations were then grouped together and are the subject of this publication

Association between Bone Mass Index (BMI) and Hand Osteoarthritis (OA)

OBJECTIVE: To evaluate the incidence of hand osteoarthritis (OA) among patients that were referred to the Rheumatology Unit at State University of Campinas and to verify the association between hand OA and bone mass index (BMI). METHODS: We evaluated 515 outpatients, calculating the BMI and registering the age at diagnosis, sex, ethnicity and diagnosis. Logistic regression was also performed. RESULTS: Hands OA was present in 15.8%. There was no relation between BMI and hands OA in the univariated analysis. However, when multivariated logistic regression was performed, we observed 5.4% increase in the risk to develop hands OA per each 1 kg/m² of enhance in the BMI. We also observed that overweight patients showed 2,16 fold more risk than normal subjects to present hands OA. The obese patients showed 2.04 fold more risk than the normal ones. CONCLUSIONS: We concluded that despite the lack of direct association between BMI and the hands OA prevalence, patients with BMI > 25 kg/m² are at higher risk to develop hands OA.OBJETIVO: avaliar a incidência de osteoartrite de mãos nos pacientes encaminhados aos ambulatórios de reumatologia do Hospital das Clínicas da Universidade Estadual de Campinas e analisar a possível associação entre osteoartrite (OA) de mãos e o índice de massa corpórea (IMC). MÉTODOS: foram analisados 515 pacientes, calculando-se o IMC e também a idade no momento do diagnóstico (20-80 anos), sexo, cor e o diagnóstico através de regressão logística. RESULTADOS: OA de mãos esteve presente em 15,8% dos diagnósticos reumatológicos, incluindo-se, entre outras, as doenças do tecido conjuntivo e as doenças auto-imunes. Não houve relação estatisticamente significativa entre IMC e OA de mãos na regressão univariada. Entretanto, quando realizado estudo de regressão logística multivariada, verificou-se que a cada 1 kg/m² de aumento do IMC, o risco de OA de mãos aumenta em 5,4%. Observou-se, ainda, que pacientes com sobrepeso apresentam 2,16 vezes mais risco de ter OA de mãos que os com peso considerado normal. Os obesos apresentam esse risco 2,04 vezes maior. CONCLUSÕES: a despeito de a associação entre o IMC e a prevalência da OA de mãos não ter sido significativa, pacientes com IMC > 25 apresentam maior risco de desenvolverem OA de mãos.20621

Factors associated with the history of falls of elderly assisted by the Family Health Program

This study aims at identifying the sociodemographic, clinical-functional and psycho-cognitive factors associated with the history of falls of community-dwelling elderly individuals assisted by Programa Saúde da Família (PSF - Family Health Program). The sample comprised 96 elderly subjects equally divided into three groups according to the report of falls that occurred during the past year, as follows: without falls, one fall or recurrent falls. There were no significant differences between groups in relation to sociodemographic data. The non-faller group presented less complaints about pain (p=0.012) and dizziness (p=0.003), and less near-falls reports (p=0.003) when compared to the faller groups. Besides, it presented better mobility (p<0.001) and functional capacity (p<0.001) in comparison with the same groups. In the psycho-cognitive assessment, recurrent fallers showed higher depressed mood score (p=0.009) and higher cognitive impairment score (p=0.040) compared to non-fallers. The occurrence of falls must be considered a significant agent that negatively affects elders' life. This is why its causative as well as impeditive factors must be accurately identified, so that professionals can effectively prevent falls or their debilitating consequences.Este estudo tem como objetivo identificar os fatores sociodemográficos, clínico-funcionais e psicocognitivos associados ao histórico de quedas de idosos saudáveis. A amostra foi constituída por 96 idosos divididos igualmente em três grupos de acordo com o histórico de quedas ocorrido no último ano (sem queda, uma queda e quedas recorrentes). Não houve diferença entre os grupos quanto aos dados sociodemográficos. Os idosos do grupo sem quedas apresentaram menor queixa de dor (p = 0,012) e de tontura (p = 0,003), melhor mobilidade (p < 0,001), capacidade funcional (p < 0,001) e menor relato de quase quedas (p = 0,003) quando comparados aos idosos dos grupos com histórico de quedas. Na avaliação psicocognitiva os idosos com quedas recorrentes revelaram maior escore para humor deprimido (p = 0,009) e maior déficit cognitivo (p = 0,040) do que os sem quedas. As quedas interferem de forma negativa na vida do idoso, motivo da importância de identificação dos fatores protetores e potencializadores deste evento. Com o reconhecimento desses fatores é possível que os profissionais possam prevenir as quedas ou as consequências debilitantes causadas por sua ocorrência.Universidade Federal de São Paulo (UNIFESP) Departamento de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoUniversidade PaulistaUniversidade Estadual de Campinas Faculdade de Ciências MédicasUniversidade Estadual de Campinas Programa de Saúde da FamíliaUNIFESP, Depto. de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoSciEL

Regulation of hypoxia-inducible factor-1α (HIF-1α) expression by interleukin-1β (IL-1β), insulin-like growth factors I (IGF-I) and II (IGF-II) in human osteoarthritic chondrocytes

Objective: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α) can regulate cytokines (catabolic action) and/or growth factors (anabolic action) in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β) and insulin-like growth factors I (IGF-I) and II (IGF-II) and to determine the involvement of the phosphatidylinositol-3- kinase (PI-3K) pathway in this process. Methods: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. Results: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α, whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. Conclusion: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α. Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis. © 2012 CLINICS.6713540Martel-Pelletier, J., Pathophysiology of osteoarthritis (2004) Osteoarthritis Cartilage., 12 (SUPPL. A), pp. S31-S33. , doi: 10.1016/j.joca.2003.10.002Malemud, C.J., Cytokines as therapeutic targets for osteoarthritis (2004) BioDrugs., 18, pp. 23-35. , doi: 10.2165/00063030-200418010-00003van der Kraan, P.M., van den Berg, W.B., Anabolic and destructive mediators in osteoarthritis (2000) Curr Opin Clin Nutr Metab Care., 3, pp. 205-211. , doi: 10.1097/00075197-200005000-00007Semenza, G.L., Expression of hypoxia-inducible factor 1: Mechanisms and consequences (2000) Biochem Pharmacol., 59, pp. 47-53. , doi: 10.1016/S0006-2952(99)00292-0Semenza, G.L., Hypoxia-inducible factor 1: Control of oxygen homeostasis in health and disease (2001) Pediatr Res., 49, pp. 614-617. , doi: 10.1203/00006450-200105000-00002Bardos, J.I., Ashcroft, M., Negative and positive regulation of HIF-1: A complex network (2005) Biochim Biophys Acta., 1755, pp. 107-120Honorati, M.C., Cattini, L., Facchini, A., IL-17, IL-1beta and TNF-alpha stimulate VEGF production by dedifferentiated chondrocytes (2004) Osteoarthritis Cartilage., 12, pp. 683-691. , doi: 10.1016/j.joca.2004.05.009Coimbra, I.B., Jimenez, S.A., Hawkins, D.F., Piera-Velazquez, S., Stokes, D.G., Hypoxia inducible factor-1 alpha expression in human normal and osteoarthritic chondrocytes (2004) Osteoarthritis Cartilage., 2, pp. 336-345. , doi:10.1016/j.joca.2003.12.005Chevalier, X., Upregulation of enzymatic activity by interleukin-1 in osteoarthritis (1997) Biomed Pharmacother., 51, pp. 58-62. , doi: 10.1016/S0753-3322(97)87727-XTreins, C., Giorgetti-Peraldi, S., Murdaca, J., Semenza, G.L., van Obberghen, E., Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway (2002) J Biol Chem., 277, pp. 27975-27981. , doi: 10.1074/jbc.M204152200Feldser, D., Agani, F., Iyer, N.V., Pak, B., Ferreira, G., Semenza, G.L., Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2 (1999) Cancer Res., 59, pp. 3915-3918Blumenfeld, I., Livne, E., The role of transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-1, and interleukin (IL)-1 in osteoarthritis and aging of joints (1999) Exp Gerontol., 34, pp. 821-829. , doi:10.1016/S0531-5565(99)00062-5Loeser, R.F., Shanker, G., Autocrine stimulation by insulin-like growth factor 1 and insulin-like growth factor 2 mediates chondrocyte survival in vitro (2000) Arthritis Rheum., 43, pp. 1552-1559. , doi: 10.1002/1529-0131(200007)43:7,1552::AID-ANR20.3.0.CO;2-WKellgren, J.H., Lawrence, J.S., Radiological assessment of osteoarthrosis (1957) Ann Rheum Dis., 16 (4), pp. 494-502Reginato, A.M., Iozzo, R.V., Jimenez, S.A., Formation of nodular structures resembling mature articular cartilage in long-term primary cultures of human fetal epiphyseal chondrocytes on a hydrogel substrate (1994) Arthritis Rheum., 37, pp. 1338-1349. , doi: 10.1002/art.1780370912Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation (2001) Science., 292, pp. 468-472. , doi: 10.1126/science.1059796Dignam, J.D., Lebovitz, R.M., Roeder, R.G., Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei (1983) Nucleic Acids Res., 11, pp. 1475-1489. , doi: 10.1093/nar/11.5.1475Schipani, E., Ryan, H.E., Didrickson, S., Kobayashi, T., Knight, M., Johnson, R.S., Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival (2001) Genes Dev., 15, pp. 2865-2876Pfander, D., Kobayashi, T., Knight, M.C., Zelzer, E., Chan, D.A., Olsen, B.R., Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development (2004) Development., 131, pp. 2497-2508. , doi: 10.1242/dev.01138Hellwig-Burgel, T., Rutkowski, K., Metzen, E., Fandrey, J., Jelkmann, W., Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1 (1999) Blood., 94, pp. 1561-1567Qian, D., Lin, H.Y., Wang, H.M., Zhang, X., Liu, D.L., Li, Q.L., Normoxic induction of the hypoxic-inducible factor-1 alpha by interleukin-1 beta involves the extracellular signal-regulated kinase 1/2 pathway in normal human cytotrophoblast cells (2004) Biol Reprod., 70, pp. 1822-1827. , doi: 10.1095/ biolreprod.103.025031Jiang, B.H., Jiang, G., Zheng, J.Z., Lu, Z., Hunter, T., Vogt, P.K., Phosphatidylinositol 3-kinase signaling controls levels of hypoxiainducible factor 1 (2001) Cell Growth Differ., 12, pp. 363-369Haddad, J.J., Recombinant human interleukin (IL)-1 beta-mediated regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) stabilization, nuclear translocation and activation requires an antioxidant/ reactive oxygen species (ROS)-sensitive mechanism (2002) Eur Cytokine Netw., 13, pp. 250-260Yudoh, K., Nakamura, H., Masuko-Hongo, K., Kato, T., Nishioka, K., Catabolic stress induces expression of hypoxia-inducible factor (HIF)-1 alpha in articular chondrocytes: Involvement of HIF-1 alpha in the pathogenesis of osteoarthritis (2005) Arthritis Res Ther., 7, pp. R904-R914. , doi: 10.1186/ar1765Murata, M., Yudoh, K., Nakamura, H., Kato, T., Inoue, K., Chiba, J., Distinct signaling pathways are involved in hypoxia-and IL-1-induced VEGF expression in human articular chondrocytes (2006) J Orthop Res., 24, pp. 1544-1554. , doi: 10.1002/jor.20168Olney, R.C., Tsuchiya, K., Wilson, D.M., Mohtai, M., Maloney, W.J., Schurman, D.J., Chondrocytes from osteoarthritic cartilage have increased expression of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and-5, but not IGF-II or IGFBP-4 (1996) J Clin Endocrinol Metab., 81, pp. 1096-1103. , doi: 10.1210/jc.81.3.1096Fukuda, R., Hirota, K., Fan, F., Jung, Y.D., Ellis, L.M., Semenza, G.L., Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, 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Fatores associados ao histórico de quedas de idosos assistidos pelo Programa de Saúde da Família

This study aims at identifying the sociodemographic, clinical-functional and psycho-cognitive factors associated with the history of falls of community-dwelling elderly individuals assisted by Programa Saúde da Família (PSF - Family Health Program). The sample comprised 96 elderly subjects equally divided into three groups according to the report of falls that occurred during the past year, as follows: without falls, one fall or recurrent falls. There were no significant differences between groups in relation to sociodemographic data. The non-faller group presented less complaints about pain (p=0.012) and dizziness (p=0.003), and less near-falls reports (p=0.003) when compared to the faller groups. Besides, it presented better mobility (pEste estudo tem como objetivo identificar os fatores sociodemográficos, clínico-funcionais e psicocognitivos associados ao histórico de quedas de idosos saudáveis. A amostra foi constituída por 96 idosos divididos igualmente em três grupos de acordo com o histórico de quedas ocorrido no último ano (sem queda, uma queda e quedas recorrentes). Não houve diferença entre os grupos quanto aos dados sociodemográficos. Os idosos do grupo sem quedas apresentaram menor queixa de dor (p = 0,012) e de tontura (p = 0,003), melhor mobilidade (p < 0,001), capacidade funcional (p < 0,001) e menor relato de quase quedas (p = 0,003) quando comparados aos idosos dos grupos com histórico de quedas. Na avaliação psicocognitiva os idosos com quedas recorrentes revelaram maior escore para humor deprimido (p = 0,009) e maior déficit cognitivo (p = 0,040) do que os sem quedas. As quedas interferem de forma negativa na vida do idoso, motivo da importância de identificação dos fatores protetores e potencializadores deste evento. Com o reconhecimento desses fatores é possível que os profissionais possam prevenir as quedas ou as consequências debilitantes causadas por sua ocorrência

Micromass cultures are effective for differentiation of human amniotic fluid stem cells into chondrocytes

OBJECTIVES: Articular cartilage is vulnerable to injuries and undergoes an irreversible degenerative process. The use of amniotic fluid mesenchymal stromal stem cells for the reconstruction of articular cartilage is a promising therapeutic alternative. The aim of this study was to investigate the chondrogenic potential of amniotic fluid mesenchymal stromal stem cells from human amniotic fluid from second trimester pregnant women in a micromass system (high-density cell culture) with TGF-β3 for 21 days. METHODS: Micromass was performed using amniotic fluid mesenchymal stromal stem cells previously cultured in a monolayer. Chondrocytes from adult human normal cartilage were used as controls. After 21 days, chondrogenic potential was determined by measuring the expression of genes, such as SOX-9, type II collagen and aggrecan, in newly differentiated cells by real-time PCR (qRT-PCR). The production of type II collagen protein was observed by western blotting. Immunohistochemistry analysis was also performed to detect collagen type II and aggrecan. This study was approved by the local ethics committee. RESULTS: SOX-9, aggrecan and type II collagen were expressed in newly differentiated chondrocytes. The expression of SOX-9 was significantly higher in newly differentiated chondrocytes than in adult cartilage. Collagen type II protein was also detected. CONCLUSION: We demonstrate that stem cells from human amniotic fluid are a suitable source for chondrogenesis when cultured in a micromass system. amniotic fluid mesenchymal stromal stem cells are an extremely viable source for clinical applications, and our results suggest the possibility of using human amniotic fluid as a source of mesenchymal stem cells

Periosteum as a source of mesenchymal stem cells: the effects of TGF-β3 on chondrogenesis

INTRODUCTION: Numerous experimental efforts have been undertaken to induce the healing of lesions within articular cartilage by re-establishing competent repair tissue. Adult mesenchymal stem cells have attracted attention as a source of cells for cartilage tissue engineering. The purpose of this study was to investigate chondrogenesis employing periosteal mesenchymal cells. METHODS: Periosteum was harvested from patients who underwent orthopedic surgeries. Mesenchymal stem cells were characterized through flow cytometry using specific antibodies. The stem cells were divided into four groups. Two groups were stimulated with transforming growth factor &#946;3 (TGF-&#946;3), of which one group was cultivated in a monolayer culture and the other was cultured in a micromass culture. The remaining two groups were cultivated in monolayer or micromass cultures in the absence of TGF-&#946;3. Cell differentiation was verified through quantitative reverse transcription-polymerase chain reaction (RT-PCR) and using western blot analysis. RESULT: In the groups cultured without TGF-&#946;3, only the cells maintained in the micromass culture expressed type II collagen. Both the monolayer and the micromass groups that were stimulated with TGF-&#946;3 expressed type II collagen, which was observed in both quantitative RT-PCR and western blot analysis. The expression of type II collagen was significantly greater in the micromass system than in the monolayer system. CONCLUSION: The results of this study demonstrate that the interactions between the cells in the micromass culture system can regulate the proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis and that this effect is enhanced by TGF-&#946;3

Body composition as a frailty marker for the elderly community

Body composition (BC) in the elderly has been associated with diseases and mortality; however, there is a shortage of data on frailty in the elderly. To investigate the association between BC and frailty, and identify BC profiles in nonfrail, prefrail, and frail elderly people. A cross-sectional study comprising 235 elderly (142 females and 93 males) aged > 65 years, from the city of Amparo, State of Sao Paulo, Brazil, was undertaken. Sociodemographic and cognitive features, comorbidities, medication, frailty, body mass index (BMI), muscle mass, fat mass, bone mass, and fat percent (%) data were evaluated. Aiming to examine the relationship between BC and frailty, the Mann-Whitney and Kruskal-Wallis nonparametric tests were applied. The statistical significance level was P<0.05. The nonfrail elderly showed greater muscle mass and greater bone mass compared with the prefrail and frail ones. The frail elderly had greater fat % than the nonfrail elderly. There was a positive association between grip strength and muscle mass with bone mass (P<0.001), and a negative association between grip strength and fat % (P<0.001). Gait speed was positively associated with fat mass (P=0.038) and fat % (P=0.002). The physical activity level was negatively associated with fat % (P=0.022). The weight loss criterion was positively related to muscle mass (P<0.001), bone mass (P=0.009), fat mass (P=0.018), and BMI (P=0.003). There was a negative association between fatigue and bone mass (P=0.008). Frailty in the elderly was characterized by a BC profile/phenotype with lower muscle mass and lower bone mass and with a higher fat %. The BMI was not effective in evaluating the relationship between BC and frailty. The importance of evaluating the fat % was verified when considering the tissue distribution in the elderly BC1016611667COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPE

Body Composition As A Frailty Marker For The Elderly Community.

Body composition (BC) in the elderly has been associated with diseases and mortality; however, there is a shortage of data on frailty in the elderly. To investigate the association between BC and frailty, and identify BC profiles in nonfrail, prefrail, and frail elderly people. A cross-sectional study comprising 235 elderly (142 females and 93 males) aged ≥65 years, from the city of Amparo, State of São Paulo, Brazil, was undertaken. Sociodemographic and cognitive features, comorbidities, medication, frailty, body mass index (BMI), muscle mass, fat mass, bone mass, and fat percent (%) data were evaluated. Aiming to examine the relationship between BC and frailty, the Mann-Whitney and Kruskal-Wallis nonparametric tests were applied. The statistical significance level was P<0.05. The nonfrail elderly showed greater muscle mass and greater bone mass compared with the prefrail and frail ones. The frail elderly had greater fat % than the nonfrail elderly. There was a positive association between grip strength and muscle mass with bone mass (P<0.001), and a negative association between grip strength and fat % (P<0.001). Gait speed was positively associated with fat mass (P=0.038) and fat % (P=0.002). The physical activity level was negatively associated with fat % (P=0.022). The weight loss criterion was positively related to muscle mass (P<0.001), bone mass (P=0.009), fat mass (P=0.018), and BMI (P=0.003). There was a negative association between fatigue and bone mass (P=0.008). Frailty in the elderly was characterized by a BC profile/phenotype with lower muscle mass and lower bone mass and with a higher fat %. The BMI was not effective in evaluating the relationship between BC and frailty. The importance of evaluating the fat % was verified when considering the tissue distribution in the elderly BC.101661-166