Novel FGF9 variant contributes to multiple synostoses syndrome 3.

Multiple synostoses syndromes (SYNS) are autosomal dominant syndromes characterized by multiple joint fusions commonly involving the carpal-tarsal, interphalangeal, humeroradial, and cervical spine joints. They display genetic heterogeneity with pathogenic variants reported in four separate genes (NOG, GDF5, FGF9, and GDF6) defining four different SYNS forms. FGF9 variants have been reported in SYNS3, a SYNS with multiple synostoses, normal cognition, normal hearing, and craniosynostosis. Here, we report a novel FGF9 c.569G > C p.(Arg190Thr) variant identified by whole-exome sequencing in a patient with multiple bony abnormalities. The patient initially presented with elbow instability and decreased range of motion. Imaging revealed bilateral radial head deformities, carpal-tarsal fusions, brachydactyly, and osteoarthritis of the sacroiliac joints. In silico protein modeling of the identified FGF9 variant predicts decreased stability of ligand-receptor binding supporting the pathogenicity of this finding. This finding expands the repertoire of FGF9 variants and phenotypic information reported for SYNS3 and suggest that genotype phenotype correlations due to localization seem less likely and more so due to the consequence of the pathogenic variant on the receptor. This is useful in the counseling in families as more de novo variants emerge.

Mouse fibroblast growth factor 9 N143T mutation leads to wide chondrogenic condensation of long bones.

Long bones of the appendicular skeleton are formed through endochondral ossification. Endochondral bone formation initiates with mesenchymal condensation, followed by the formation of a cartilage template which is replaced by bone. Fibroblast growth factor 9 (FGF9) regulates bone development. Fgf9-/- mice exhibit disproportionate shortening of proximal skeletal elements. Fgf9 missense mutations in mice and humans induce joint synostosis. Thus, FGF9 is critical for regulating bone length and joint formation. Conversely, mechanisms regulating bone width remain unclear. Here, we showed that the homozygous elbow knee synostosis (Eks) mutant mice harboring N143T mutation in Fgf9 have wide long bones at birth. We investigated the cellular and molecular mechanisms underlying the widened prospective humerus in Fgf9Eks/Eks embryos. Increased and expanded FGF signaling in concert with wider expression domain of Fgf receptor 3 (Fgfr3) during chondrogenic condensation of the humerus led to widened cartilage, which resulted in the formation of wider prospective humeri in neonatal Fgf9Eks/Eks mice. Increased and expanded FGF signaling during chondrogenic condensation led to increased density of chondrocytes of the humeri accompanied by increased proliferation of chondrocytes which express inappropriately higher levels of cyclin D1 in Fgf9Eks/Eks embryos. The results suggest that FGF9 regulates the width of prospective long bones by controlling the width of chondrogenic condensation.

Magnetic resonance imaging of posterolateral plica of the elbow joint: Asymptomatic vs. symptomatic subjects.

BACKGROUND: Magnetic resonance imaging (MRI) may be useful to diagnose a posterolateral plica syndrome of the elbow joint because this syndrome has less clear clinical features. The purposes of this study were to document mediolateral and sagittal dimensions of a posterolateral synovial fold and to determine the proportion of subjects with the posterolateral plica in asymptomatic elbows. We also aimed to determine whether the dimensions of the posterolateral synovial fold and the prevalence of the plica differ between symptomatic and asymptomatic subjects. MATERIALS AND METHODS: This retrospective review of prospectively collected data included 50 asymptomatic elbows (asymptomatic group) and 14 elbows with arthroscopically confirmed posterolateral plicae (plica group). The mediolateral and sagittal dimensions of the posterolateral synovial fold were measured. In addition, the criteria for the prevalence of posterolateral plica was determined with conventional MRI as synovial fold dimension ≥ 3 mm and coverage of radial head by synovial fold ≥ 30%. RESULTS: The plica group showed larger posterolateral synovial fold dimensions compared to the asymptomatic group. The median mediolateral and sagittal dimensions of the synovial fold in the asymptomatic group were 3.8 mm and 4.7 mm, respectively. Dimensions in the plica group were 7.0 mm and 7.4 mm, respectively. When the presence of posterolateral plica was determined using the dimension criteria, there was no difference in the prevalence of the plica between the asymptomatic and the plica group. However, using the coverage criteria, the prevalence of posterolateral elbow plica was significantly greater in the plica group than the asymptomatic group (64% vs. 18%; p < 0.001). CONCLUSIONS: The patients who underwent arthroscopic surgery for posterolateral plica syndrome had larger dimensions of the posterolateral synovial fold and higher prevalence of the posterolateral plica on conventional MRI compared to the asymptomatic subjects.

Cellular properties of extensor carpi radialis brevis and trapezius muscles in healthy males and females.

In this study, we sought to determine whether differences in cellular properties associated with energy homeostasis could explain the higher incidence of work-related myalgia in trapezius (TRAP) compared with extensor carpi radialis brevis (ECRB). Tissue samples were obtained from the ECRB (n = 19) and TRAP (n = 17) of healthy males and females (age 27.9 ± 2.2 and 28.1 ± 1.5 years, respectively; mean ± SE) and analyzed for properties involved in both ATP supply and utilization. The concentration of ATP and the maximal activities of creatine phosphokinase, phosphorylase, and phosphofructokinase were higher (P < 0.05) in ECRB than TRAP. Succinic dehydrogenase, citrate synthase, and cytochrome c oxidase were not different between muscles. The ECRB also displayed a higher concentration of Na(+)-K(+)-ATPase and greater sarcoplasmic reticulum Ca(2+) release and uptake. No differences existed between muscles for either monocarboxylate transporters or glucose transporters. It is concluded that the potentials for high-energy phosphate transfer, glycogenolysis, glycolysis, and excitation-contraction coupling are higher in ECRB than TRAP. Histochemical measurements indicated that the muscle differences are, in part, related to differing amounts of type II tissue. Depending on the task demands, the TRAP may experience a greater metabolic and excitation-contraction coupling strain than the ECRB given the differences observed.

Vascular remodeling underlies rebleeding in hemophilic arthropathy.

Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

Use of ultrasound-guided small joint biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy: recommendations for application to clinical trials.

OBJECTIVE: To examine in a cohort of rheumatoid arthritis (RA) patients undergoing serial ultrasound (US)-guided biopsies of small joints in the context of clinical trials whether sufficient synovial tissue could be obtained at both baseline and second biopsy to: 1) accurately evaluate the synovial immune phenotype, 2) permit adequate RNA extraction to determine molecular signatures, and 3) sensitively detect change in the number of synovial sublining macrophages (CD68+) following effective therapy. METHODS: Synovial samples from RA patients undergoing US-guided biopsy of small joints as part of 2 clinical trials (Barts Early Arthritis Cohort [n = 18] and the Clinical and Pathological Response to Certolizumab Pegol (CLIP-Cert) study [n = 17]) were examined, and the quality and quantity of histologic samples and RNA extracted per joint were determined and compared to synovial thickness and power Doppler scores determined by US before biopsy. Modulation of the number of CD68+ sublining macrophages was correlated with clinical response to treatment. RESULTS: Good quality synovial tissue that accurately reflected the synovial immune phenotype of the total joint was obtained in 80% of US-guided procedures when synovial thickness (higher than grade 2) was documented before biopsy. In 100% of the procedures, sufficient RNA was extracted to permit molecular analysis. There was a significant correlation between change in CD68+ sublining macrophage number and clinical response to treatment. CONCLUSION: This study provides minimum standards for sample retrieval for small joint biopsy. Furthermore, our findings confirm the clinical utility of the procedure in the largest reported cohort of US-guided small joint biopsies. The demonstration that small joint synovial tissue can be readily accessed by a technically simple, minimally invasive procedure is likely to facilitate critical advancements in the knowledge of RA pathobiology and personalized health care.

A myofibroblast-mast cell-neuropeptide axis of fibrosis in post-traumatic joint contractures: an in vitro analysis of mechanistic components.

Previous studies have implicated a myofibroblast-mast cell-neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule cells (JC) from human elbows with post-traumatic contractures and their interactions with mast cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the mast cell stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the mast cell stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast-mast cell-neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions.

Monitoring Hip and Elbow Dysplasia achieved modest genetic improvement of 74 dog breeds over 40 years in USA.

Hip (HD) and Elbow Dysplasia (ED) are two common complex developmental disorders of dogs. In order to decrease their prevalence and severity, the Orthopedic Foundation for Animals (OFA) has a voluntary registry of canine hip and elbow conformation certified by boarded radiologists. However, the voluntarily reports have been severely biased against exposing dogs with problems, especially at beginning period. Fluctuated by additional influential factors such as age, the published raw scores barely showed trends of improvement. In this study, we used multiple-trait mixed model to simultaneously adjust these factors and incorporate pedigree to derive Estimated Breeding Values (EBV). A total of 1,264,422 dogs from 74 breeds were evaluated for EBVs from 760,455 hip scores and 135,409 elbow scores. These EBVs have substantially recovered the reporting bias and the other influences. Clear and steady trends of genetic improvement were observed over the 40 years since 1970. The total genetic improvements were 16.4% and 1.1% of the phenotypic standard deviation for HD and ED, respectively. The incidences of dysplasia were 0.83% and 2.08%, and the heritabilities were estimated as 0.22 and 0.17 for hip and elbow scores, respectively. The genetic correlation between them was 0.12. We conclude that EBV is more effective than reporting raw phenotype. The weak genetic correlation suggested that selection based on hip scores would also slightly improve elbow scores but it is necessary to allocate effort toward improvement of elbow scores alone.

Hyperphosphatemic tumoral calcinosis.

Tumoral calcinosis (TC) is a rare locally aggressive lesion characterised by extra-articular soft tissue deposition of the calcium phosphate around large joints. The exact aetiology is not known. A 19-year-old boy presented with a painful progressive swelling around the bilateral elbow and left hip joints over a 6-month duration. Routine laboratory results showed a normal haemogram, and normal calcium and high phosphate levels. Imaging showed a soft tissue calcified mass around these joints. The cut surface of the excised mass showed myxoid material with areas of calcification. On microscopy, there were typical features of TC. Our case is being presented due to the rarity of the entity and the peculiar dual energy CT (DECT) finding which are being described for the first time in this pathology.

Oral consumption of electrokinetically modified water attenuates muscle damage and improves postexercise recovery.

The purpose of this study was to assess the effects of consuming electrokinetically modified water (EMW) on attenuating muscle damage and improving functional recovery following a single bout of isokinetic resistance exercise. Subjects were randomly assigned to an EMW (n = 20) or a placebo control (n = 20) group. Subjects consumed EMW or placebo water daily for 23 days. On day 19 subjects completed an exercise protocol for the biceps brachii to induce muscle damage. The protocol consisted of three sets of 20 repetitions using concentric and eccentric contractions of the elbow flexors. Blood draw and clinical measurements were performed preexercise as well as 24, 48, and 96 h postexercise. Clinical measures included maximal isometric strength, muscle soreness, pain with elbow extension, relaxed elbow angle (RANG), and self-report arm disability. Plasma samples were analyzed to determine concentrations of creatine kinase (CK) and high-sensitivity C-reactive protein (hsCRP). Pain with elbow extension and self-report arm disability were significantly higher in the placebo group compared with the EMW group at 48 h (P < 0.01) and 96 h (P < 0.01) after exercise, while RANG was significantly higher in the EMW group compared with placebo at 48 h (P < 0.01) and 96 h (P < 0.01) after exercise. Similarly, plasma concentrations for hsCRP and CK were significantly lower in the EMW group compared with placebo at 48 h (P < 0.05) and 96 h (P < 0.01) after exercise. Oral consumption of EMW significantly reduced exercise-induced muscle damage and inflammation and improved functional recovery.

Hydroxyapatite crystal deposition forming para-articular multiple large masses: a case report and literature review.

Multiple para-articular large masses are a rare form of hydroxyapatite (HA) crystal deposition, thereby limiting the clinical and imaging recognition and the ability to optimize diagnostic tools. The imaging features of para-articular large mass caused by HA crystal deposition are not well described in the sonographic literature. In this report, we present the case of a uremia patient with long period of maintenance hemodialysis, who was complicated with HA crystals depositing on the para-articular of elbow, knee, and shoulder and forming multiple large masses. We reviewed the literature to explore the ideal methods to establish a diagnosis. In addition, we performed a characterization of the sonographic features of HA crystals. We have established methods which serve to distinguish HA crystal deposition from other crystal deposit conditions.

Plasma matrix metalloproteinase-9 response to eccentric exercise of the elbow flexors.

Recent efforts to establish a role for plasma matrix metalloproteinase-9 (MMP-9) as a marker of exercise-induced muscle damage have been inconsistent. Methodological and experimental design issues have contributed to confusion in this area. The purpose of this study was to use a damaging eccentric arm task to evaluate the relationship between activity-induced muscle damage and plasma MMP-9 levels in humans while controlling for physical activity history and quantifying day-to-day variability of the dependent variables. Fourteen physically inactive males performed 6 sets of 10 eccentric contractions of the elbow flexors at 120% of their voluntary concentric maximum. Soreness ratings, maximum voluntary isometric strength, range of motion (ROM), limb circumference, and plasma creatine kinase (CK) and MMP-9 levels were measured at 2 time points before, immediately after, and 1, 2, 4, and 7 days post-exercise. Changes in traditional markers of muscle damage mirrored patterns previously reported in the literature, but plasma MMP-9 concentration and activity measured by ELISA and gelatin zymography were unchanged at all time points examined. Plasma levels of the MMP-9 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), were also unchanged post-exercise. Finally, although mean MMP-9 levels were not significantly different between the two pre-exercise timepoints, the high total error of measurement and low day-to-day correlation suggest substantial within and between subject variability. Plasma MMP-9 levels are not a robust or reliable marker for eccentric exercise-induced damage of the elbow flexor musculature, though this may not preclude a role for MMPs in skeletal muscle remodeling in response to injury.

A novel dominant-negative mutation in Gdf5 generated by ENU mutagenesis impairs joint formation and causes osteoarthritis in mice.

Growth and differentiation factor 5 (GDF5) has been implicated in chondrogenesis and joint formation, and an association of GDF5 and osteoarthritis (OA) has been reported recently. However, the in vivo function of GDF5 remains mostly unclarified. Although various human GDF5 mutations and their phenotypic consequences have been described, only loss-of-function mutations that cause brachypodism (shortening and joint ankylosis of the digits) have been reported in mice. Here, we report a new Gdf5 allele derived from a large-scale N-ethyl-N-nitrosourea mutagenesis screen. This allele carries an amino acid substitution (W408R) in a highly conserved region of the active signaling domain of the GDF5 protein. The mutation is semi-dominant, showing brachypodism and ankylosis in heterozygotes and much more severe brachypodism, ankylosis of the knee joint and malformation with early-onset OA of the elbow joint in homozygotes. The mutant GDF5 protein is secreted and dimerizes normally, but inhibits the function of the wild-type GDF5 protein in a dominant-negative fashion. This study further highlights a critical role of GDF5 in joint formation and the development of OA, and this mouse should serve as a good model for OA.

Structural and biochemical evaluation of the elbow capsule after trauma.

This study evaluates the structural and biochemical alterations of the elbow capsule after trauma through microscopy and immunohistochemistry. We compared capsules from 37 patients undergoing surgery for elbow contracture with normal capsules from 7 donors. Contracture capsules were significantly thicker than control capsules (P < .05) and exhibited extensive disorganization of collagen fiber bundle arrangement. Levels of specific cytokines involved in connective tissue turnover were measured. The results showed that the levels of cytokines matrix metalloproteinase (MMP) 1, MMP-2, and MMP-3 were greater as compared with control capsules (P < .05). This was associated with collagen disorganization, fibroblast infiltration, and in some specimens, lymphocytic infiltration in the capsular tissue. In contracture specimens, there was a localization of tissue inhibitor of matrix metalloproteinase 2 staining only in the vicinity of the synovial membrane and in blood vessels. Immunohistochemistry for type III collagen showed a greater presence in the control capsules compared with contracture capsules. This study demonstrates pathologic thickening, disorganization of the collagen fiber arrangement, and involvement of cytokines in the pathology of post-traumatic contracture of the elbow.

Myofibroblast upregulators are elevated in joint capsules in posttraumatic contractures.

We hypothesized specific growth factors are increased in the elbow capsules of patients with post traumatic elbow contractures. A model of surgically induced joint contracture in rabbit knees was developed to study the growth factor expression in joint contractures. This study demonstrates this model mimics the human condition and analyzes how the growth factor levels decrease with time in rabbit knees with contractures. Reverse transcription polymerase chain reaction was used to measure mRNA levels of transforming growth factor-beta1, connective tissue growth factor, ED-A of fibronectin, and alpha-smooth muscle actin normalized to a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. In the joint capsules of patients with elbow contractures, mRNA levels were increased for transforming growth factor- beta1, connective tissue growth factor, and alpha-smooth muscle actin. In the joint capsules of rabbit knees with contractures, mRNA levels were increased for transforming growth factor- beta1, connective tissue growth factor, ED-A of fibronectin, and alpha-smooth muscle actin. The mRNA levels for transforming growth factor-beta1, connective tissue growth factor, and alpha-smooth muscle actin decreased with time in rabbit knees. The elevated levels of these myofibroblast up-regulators and fibrogenic growth factors could explain the previously reported increase in myofibroblasts and collagen mRNA levels. The rabbit knee model correlated well with the human post traumatic elbow contractures.

Regional variation is present in elbow capsules after injury.

Myofibroblast numbers and alpha-smooth muscle actin expression are increased in anterior joint capsules of patients with posttraumatic elbow contractures. The purpose of our study was to determine whether these changes occur regionally or throughout the entire joint capsule. We hypothesized that the alpha-smooth muscle actin mRNA expression and the myofibroblast numbers in posterior joint capsules would be elevated in elbows obtained from patients with posttraumatic joint contractures compared with joint capsules obtained from organ donor elbows without contractures. Semiquantitative reverse transcription-polymerase chain reaction was used to evaluate relative mRNA levels of alpha-smooth muscle actin. Glyceraldehyde-3-phosphate dehydrogenase was used to normalize the levels. Immunohistochemical analysis was used to determine the myofibroblast cell numbers. Higher alpha-smooth muscle actin mRNA levels were observed in elbows of patients with contractures compared with organ donor elbows without contractures. Immunohistochemical studies determined that myofibroblast numbers and the percentage of total cells that were myofibroblasts were elevated (2-2.5-fold) in the joint capsules from patients with posttraumatic joint contractures compared with similar tissue obtained from organ donor elbows without contractures. These results suggest elevated myofibroblast numbers occur throughout the whole joint capsule in posttraumatic elbow contractures, although there is some regional variation.

Mechanism of accumulation of 99mTc-sulesomab in inflammation.

UNLABELLED: 99mTc-Sulesomab, the Fab fragment of anti-NCA-90, is used as an in vivo granulocyte labeling agent for imaging inflammation. It is not clear to what extent it targets cells that have already migrated into the interstitial space of an inflammatory lesion as opposed to circulating cells. The contribution to signal of radioprotein diffusion in the setting of increased vascular permeability is also poorly documented. METHODS: We compared the local kinetics of (99m)Tc-sulesomab and (99m)Tc-labeled human serum albumin (HSA), which have similar molecular sizes, in 7 patients with orthopedic infection proven by clearly positive (111)In-leukocyte scintigraphy. (99m)Tc-Sulesomab and (99m)Tc-HSA were administered in sequence separated by an interval of 2-6 d. Images were obtained 1, 3, 4, and 6 h after injection, and multiple venous blood samples were obtained for blood clearance measurement. Patlak-Rutland (P-R) analysis was performed to measure lesion and control tissue protein clearance. Target-to-background tissue (T/Bkg) ratios were calculated for each radioprotein and compared with the T/Bkg ratio for (111)In-leukocytes. (99m)Tc-Sulesomab binding to granulocytes was measured in vitro and ex vivo and to primed and activated granulocytes in vitro. RESULTS: After intravenous injection, <5% of the circulating radioactivity was cell bound with both radioproteins so that the P-R curves could therefore be assumed to represent extravascular uptake of free protein. The blood clearance (mean +/- SD) of sulesomab was 23.4 +/- 11.7 mL/min, approximately 5 times greater than that of HSA, for which it was 4.8 +/- 3.1 mL/min. Likewise, clearance into the lesion of sulesomab was consistently higher than that of HSA, on average about 3 times as high. Nevertheless, the T/Bkg ratios for sulesomab and HSA were similar, except at 6 h when that of HSA (2.14 +/- 0.6) was higher than that of sulesomab (1.93 +/- 0.5; P approximately 0.01). Both values were considerably less than the T/Bkg ratio on the (111)In-leukocyte images, which, at 22 h, was 12.3 +/- 5.3. Moderate clearance of sulesomab, but not HSA, was seen in the control tissue. Granulocytes bound significantly more (99m)Tc-sulesomab in vitro when primed or activated. CONCLUSION: (a) Sulesomab does not localize in inflammation as a result of binding to circulating granulocytes; (b) sulesomab is cleared into inflammation nonspecifically via increased vascular permeability; nevertheless, it may be cleared after local binding to primed granulocytes or bind to activated, migrated extravascular granulocytes; and (c) HSA produces a similar or higher T/Bkg ratio than sulesomab because sulesomab is cleared into normal tissues and because image positivity in inflammation is significantly dependent on local blood-pool expansion.

Ausência de variação da flexibilidade durante o ciclo menstrual em universitárias / Lack of flexibility variation during menstrual cycle in university students

FUNDAMENTAÇÃO: Algumas variáveis da aptidão física são marcadamente influenciadas pelas fases do ciclo menstrual (CM); contudo, há pouca informação sobre eventuais modificações na flexibilidade. OBJETIVO: Analisar o comportamento da flexibilidade corporal - global, por articulação e por movimento - em mulheres adultas jovens nas diferentes fases do CM. MÉTODOS: Estudou-se uma amostra de 15 mulheres. O grupo experimental (GE) foi constituído de alunas eumenorréicas, enquanto o grupo controle (GC) incluía alunas em uso regular havia pelo menos um mês de anticoncepcional oral (AO). Dados referentes ao período menstrual e ao uso de AO foram obtidos através da aplicação de um questionário. A flexibilidade foi avaliada pelo Flexiteste, permitindo uma análise da flexibilidade global (Flexíndice), por articulação, por movimento e em sua variabilidade. Os Flexíndices foram ainda comparados com os correspondentes percentis para gênero e idade. Para a análise estatística das três medidas do GE - fases folicular, ovulatória e lútea - e das duas do GC entre dias cinco e 26 do ciclo, utilizou-se ANOVA ou teste t conforme apropriado. RESULTADOS: Não houve diferenças na flexibilidade, movimento a movimento ou Flexíndice nas diferentes fases do CM no GE e nas duas medidas do GC (p > 0,05). O percentil do Flexíndice para o GC variou de 14 a 35 e no GE, de 14 a 80. Analisando as articulações e os índices de variabilidade, não foram encontradas diferenças significativas com as fases do CM (p > 0,05), com a exceção do índice de variabilidade distal-proximal entre as fases ovulatória e folicular no GE. CONCLUSÃO: Os dados obtidos não corroboram a impressão empírica de que a flexibilidade varia durante as fases do CM. Não se pode, contudo, afastar a hipótese de que a ausência de variações tenha ocorrido devido a alguma característica da amostra ou por limitações do Flexiteste em identificar mínimas variações, sendo necessária a realização de outros estudos.