Alexandre Leme Godoy-Santos

MMP‐1 promoter polymorphism is associated with primary tendinopathy of the posterior tibial tendon

Posterior tibial tendon (PTT) dysfunction is recognized as an etiology leading to acquired flatfoot in adults, causing significant functional loss. Many risk factors and systemic conditions have been proposed in literature. However, many patients present PTT dysfunction without any of these characteristics. This suggests that there could be a genetic influence associated with posterior tibial tendinopathy. The purpose of the present study is to investigate the association of the −1607 polymorphism in the promoter gene of MMP‐1 and posterior tibial tendinopathy. The test group included 50 women, who presented PTT dysfunction grade 2 or 3, and who were submitted to surgical treatment, with histopathological examination of the tendon and magnetic resonance image (MRI) confirming tendinopathy, while the control group was 100 asymptomatic women who presented intact PTT at MRI. The results were analyzed using the chi‐square test. The data showed a 75% incidence of the allele 1G and 62% of the genotype 1G/1G at the control group while, at the test group, they showed a 78% incidence of the allele 2G and 72% of the genotype 2G/2G (p < 0.001). The −1607 polymorphism of promoter gene of MMP‐1 is associated with the posterior tibial tendinopathy in the studied population.

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are collectively capable of cleaving virtually all extracellular matrix (ECM) substrates and play an important role in diverse physiological and pathological processes. The activity of MMPs is controlled at multiple levels, and the transcriptional regulation of MMPs appears to represent a necessary step in its regulation. MMP-3 is a key member of the MMP family with broad substrate specificity, and is crucial to the connective tissue remodeling process. It is also involved in the turnover of the numerous ECM components. A common functional promoter polymorphism of MMP-3, 5A/6A, affects its activity and has been associated with various diseases. This polymorphism may be used as a genetic marker for certain pathologies to identify individual susceptibility. This review discusses various topics related to MMP-3 in pathological processes, with a focus on the 5A/6A polymorphism.

Aseptic Loosening of Total Hip Arthroplasty: Preliminary Genetic Investigation

Femoral and acetabular loosening can be attributed different factors, but the causes and mechanism of early failure are still obscure. The objective of this study was to investigate the relationship between gene polymorphisms and early implant failure. Fifty-eight patients older than 50 years was recruited for analysis of MMP-1 promoter polymorphisms in early osseointegrated implant failure. The results showed in control group a frequency of 20.97% of 2G allele and 67.74% the genotype 1G/1G whereas, in the test group, a frequency of 83.33% of 2G allele and 66.66% the genotype 2G/2G. These results indicate that the polymorphism in the promoter of the MMP-1 gene could be a risk factor for early implant failure of total hip arthroplasty.

MMP-1 promoter genotype and haplotype association with posterior tibial tendinopathy

PURPOSE Posterior tibial tendon (PTT) is particularly vulnerable and its insufficiency is recognized as the main cause of adult acquired flatfoot. Some patients have a predisposition without clinically recognized cause, suggesting that individual characteristics play an important role in tendinopathy. The objective of the present study is to investigate the association of -519 (rs1144393) matrix metalloproteinase-1 (MMP-1) polymorphism and the -1607 (rs1799750) and -519 MMP-1 haplotypes and risk of PTT dysfunction. METHODS The test group included 50 females who presented PTT dysfunction Grade 2 or 3, and who were submitted to surgical treatment, with histopathological examination of the tendon and magnetic resonance image (MRI) confirming tendinopathy, while the control group was 100 asymptomatic women who present intact PTT at MRI. We analyzed functional polymorphisms MMP-1 and their haplotypes using polymerase chain reaction and restriction fragment length analysis. RESULTS There was a significant difference in the presence of the different alleles and genotypes between the control group and test group for the MMP-1 gene (p≤0.01). The G allele of the -519 MMP-1 polymorphism increased susceptibility to degeneration in the PTT tendon and seems to be a genetic risk factor. Global haplotype analysis indicated a significant difference between both groups (p<0.0001). Haplotypes G-2G and A-2G had statistically significant risk effect on PTT insufficiency. G-2G, p<0.001; OR=5.72 (CI, 2.84-11.52) and A-2G p=0.002, OR=3.95 (CI, 1.65-9.44). CONCLUSION According to our results, -519 MMP-1 isolated and -1607/-519 MMP-1 haplotypes are associated to tendinopathy in posterior tibial tendon.

Association of MMP-8 polymorphisms with tendinopathy of the primary posterior tibial tendon: a pilot study

Tendon disorders are common and are treated on a daily basis in orthopedic foot and ankle practices. Some tendons are particularly vulnerable to primary degenerative changes, such as the patellar, Achilles, rotator cuff, biceps, posterior tibial, and fibular tendons.1 Significant advances in histopathology and research imaging techniques have contributed to an improved understanding of the pathophysiology of tendon degeneration.2 However, both mechanical factors and vascular and neurological disorders have limitations in explaining the etiology of many cases.1,3,4 It is known that intense physical activity may predispose an individual to tendinopathy, but some individuals have a predisposition with no clinically recognized cause. The literature suggests that individual characteristics, including genetic inheritance, may influence the likelihood of developing tendinopathy. Thus, there is a group of individuals with a genetic background that causes increased susceptibility to diseases of the tendon. Matrix metalloproteinases (MMPs) are a pivotal family of zinc-dependent enzymes responsible for the degradation of extracellular matrix components, including basement membrane collagen, interstitial collagen, fibronectin and various proteoglycans, during normal remodeling, repair processes, development and inflammation. MMPs are expressed in response to specific stimuli by resident connective tissue cells and by the major inflammatory cell types that invade tissues during remodeling events, including tendinopathy. MMP-8, or collagenase-2, was initially discovered in neutrophils, in which it was thought to be exclusively produced, but this enzyme was subsequently shown to be expressed by a variety of other cell types, including endothelial cells, smooth muscle cells, macrophages, polymorphonuclear leukocytes, gingival fibroblasts, keratinocytes, chondrocytes, odontoblasts5-10 and oral11 cancer cells. It has been suggested that MMP-8 degrades type I collagen, thereby contributing to tissue degradation and remodeling.12 MMP-8 is an important mediator of tissue destruction in several inflammatory diseases and is related to cardiovascular disease,9 bronchiectasis,13 pulmonary insufficiency,14 periodontitis,15-17 melanoma,18 cancer of the head and neck,19 and diabetic wound healing.20 The MMP-8 gene, located on chromosome 11, contains functional polymorphisms in the promoter region, including the substitution of a cytosine by a thymine at position -799 (rs11225395).21 Alterations in this gene have been associated with chronic dilatation of the bronchi13 and breast cancer.22 The discovery of genetic markers of tendinopathy risk could allow for the identification of susceptible individuals and, thus, early therapeutic interventions. MMPs play key roles in tissue destruction and may have important roles in the pathogenesis of tendinopathy. Therefore, we hypothesized that the -799C/T polymorphism in MMP-8 was associated with tendinopathy of the primary posterior tibial tendon and could be a risk factor for this condition.

Estrogen receptor polymorphism and its relationship to pathological process.

Estrogens are present in both men and women; they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sex characteristics, such as breasts, and are also involved in the thickening of the endometrium and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the reproductive system that are important to the maturation of sperm and may be necessary for a healthy libido. Furthermore, there are several other structural changes induced by estrogen and it influences diverse other functions such as reduces muscle mass, increases bone formation and hepatic production of binding protein, alters coagulation, lipid metabolism, salt and water retention, and function gastrointestinal tract and lung. The physiological effects of estrogen are principally

Effectiveness of the Dorsal Thermoplastic Locking Orthosis to Prevent Floating Toes in Postoperative Follow-up of Weil Osteotomies Pilot Study

Background: The Weil oblique distal metatarsal osteotomy is regularly used in the treatment of primary metatarsalgia. The most frequent complication is the floating toe, which occurs in up to 36% of postoperative follow-up. The theory of reducing the plantar flexor mechanism tension associated with the retraction of the dorsal structures during the healing process of the surgical procedure may explain this negative evolution. Objective: This study aimed at assessing the effectiveness of the Tucade dorsal thermoplastic locking orthosis in the prevention of floating toe after Weil osteotomy. Methods: In all, 30 patients with metatarsalgia diagnosis submitted to Weil osteotomy were treated in the postoperative period with the Tucade dorsal thermoplastic locking orthosis. Results: The floating toe was not observed in this case series. There was 1 case of superficial wound irritation at the dorsal surgical incision and 1 case that evolved with transfer metatarsalgia. Statistical analyses were performed—American Orthopaedic Foot and Ankle Society Scale for lateral toes and extension of the lateral toes—using the t test, and P < .0001 was obtained for comparison of the preoperative and postoperative periods in the population studied. Conclusion: The Tucade dorsal thermoplastic locking orthosis during the postoperative period of Weil osteotomy proved to be effective in the prevention of floating toes. Level of Evidence: Therapeutic Level IV: Case Series

Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing

Background One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable. Objectives This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight-bearing status. Methods Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol. Results No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005). Conclusion The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option.

Foot and ankle fractures during childhood: review of the literature and scientific evidence for appropriate treatment.

Foot and ankle fractures represent 12% of all pediatric fractures. Malleolar fractures are the most frequent injuries of the lower limbs. Hindfoot and midfoot fractures are rare, but inadequate treatment for these fractures may results in compartment syndrome, three-dimensional deformities, avascular necrosis and early post-traumatic arthritis, which have a significant impact on overall foot and ankle function. Therefore, the challenges in treating these injuries in children are to achieve adequate diagnosis and precise treatment, while avoiding complications. The objective of the treatment is to restore normal anatomy and the correct articular relationship between the bones in this region. Moreover, the treatment needs to be planned according to articular involvement, lower-limb alignment, ligament stability and age. This article provides a review on this topic and presents the scientific evidence for appropriate treatment of these lesions.

Influence of investigator experience on reliability of adult acquired flatfoot deformity measurements using weightbearing computed tomography

BACKGROUND Our purpose was to assess the reliability of measurements of adult-acquired flatfoot deformity (AAFD) taken by investigators of different levels of clinical experience using weightbearing computed tomography (WBCT). METHODS Nineteen AAFD patients underwent WBCT. Three investigators with different levels of clinical experience made AAFD measurements in axial, coronal, and sagittal planes. Intra- and interobserver reliability were assessed. Mean values for each measurement were compared between investigators. RESULTS After a training protocol, substantial to perfect intra- and interobserver reliability was observed for most measures, regardless of the investigators experience level. Significant differences between investigators were observed in 2 of 21 measured parameters: medial cuneiform-first metatarsal angle (P=0.003) and navicular-medial cuneiform angle (P=0.001). CONCLUSIONS AAFD radiographic measurements can be performed reliably by investigators with different levels of clinical experience using WBCT. LEVEL OF EVIDENCE Level II, prospective comparative study.