Increased levels of inflammatory markers in the subscapularis tendon and joint capsule in patients with subacromial impingement.

PURPOSE: To analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with subacromial impingement syndrome and compare them with samples from male patients with post-traumatic recurrent shoulder instability, to detect increased inflammatory activity that might be present inside the humeroscapular joint. METHODS: Twenty male patients scheduled for surgery for either subacromial decompression or Bankart reconstruction were included. Four biopsies from each patient were obtained during surgery from the capsule and the subscapularis tendon. Each specimen was analyzed for TNF-α, IL-6, CD-3 and CD-72. Multiplex fluorescence immunohistochemistry was performed on histological samples from the capsule and tendon to demonstrate the level of inflammatory markers. Fluorescence microscope images were acquired using an automated scanning system. On each slide, the number of pixels was registered and used in the analyses. RESULTS: The subacromial impingement syndrome group comprised eight patients, median age 53 (45-74) years, while the instability group 12, median age 27 (22-48) years (p < 0.00001). The amount of IL-6 and TNF-α was significantly higher in the subscapularis tendon of the patients with subacromial impingement syndrome compared with instability patients (p = 0.0015 and p = 0.0008 respectively). In the capsular samples, significantly higher amount of TNF-α and CD-72 was found in patients with subacromial impingement syndrome compared with instability patients (p < 0.0001 for both). On the other hand, the amount of CD-3 was significantly higher in the instability group (p = 0.0013). CONCLUSIONS: This study provides evidence that an extended inflammatory process is present, not only in the subacromial bursa but also in the glenohumeral joint in patients with subacromial impingement syndrome. LEVEL OF EVIDENCE: Level III. CLINICAL RELEVANCE: To develop a treatment targeted towards intra-articular inflammatory cytokines appears appealing.

ENDOCRINE REGULATION OF ERYTHROID LINEAGE OF HEMATOPOIESIS IN CHILDREN LIVING UNDER A LOW-DOSE RADIATION EXPOSURE AFTER THE CHORNOBYL NPP ACCIDENT. / ENDOKRYNNA REGULIaTsIIa ERYTROTsYTARNOÏ LANKY GEMOPOEZU V DITEI, IaKI ZhYVUT' NA RADIOAKTYVNO ZABRUDNENYKh TERYTORIIaKh PISLIa AVARIÏ NA ChAES.

OBJECTIVE: Elucidation of relationship between the levels of thyroid-stimulating hormone (TSH), free serum thyroxine, serum and urine cortisol and parameters of erythroid lineage of hematopoiesis to estimate the thyroid functionin children of prepubertal, pubertal, and postpubertal age permanently residing under a low-dose radiation exposureto determine the premorbid state of thyroid function. MATERIALS AND METHODS: Children aged 3 to 18 years old (n = 203) living in the most intensively radionuclide-contaminated regions of Kyiv, Zhytomyr and Chornihiv oblasts of Ukraine after the Chornobyl NPP accident wereenrolled. Complaints of ossalgia, arthralgia, fatigue, bone fractures in the history, bone dysembryogenetic stigmata,hypermobility syndrome degree, and types of somatic diseases were taken into account. Peripheral blood countparameters, biochemical indices of blood serum were studied, namely the levels of total protein, cholesterol, creatinine and alkaline phosphatase activity. Levels of the free thyroxine, pituitary TSH, serum and daily urine cortisol, anddoses of radiation exposure were determined. RESULTS: The radiation dose values in children ranged from (0.35 ± 0.09) mSv to (0.54 ± 0.12) mSv. There was nodifference between the parameters of erythroid lineage of hematopoiesis depending on radiation dose. At the levels of serum TSH up to 1.0 µIU/ml no correlation was found with cortisol levels; at TSH levels of 1.0-3.0 µIU/ml thecorrelation coefficient was r = 0.31; at TSH levels higher than 3.0 µIU/ml the correlation coefficient was r = 0.61probably indicating a compensatory role of adrenal cortex in children at risk of thyroid disease development. In children with joint hypermobility grade II there was a higher incidence of dentofacial anomalies (χ2 = 6.9), deformitiesof lower extremities (χ2 = 6.9), and dental caries (χ2 = 4.3) (p < 0.05). There was a direct correlation between theserum TSH level (over 3 µIU/ml) and micrognathia (brachygnathia) (r = 0.62) indicating the impact of thyroid disease on dentofacial development. The TSH at a level of upper limit of the reference range values may contribute toa decreased RBC count in peripheral blood, increased average volume and hemoglobin content in erythrocyte beingassociated with the initial manifestations of thyroid dysfunction. CONCLUSIONS: Abnormal endocrine regulation of hematopoiesis affects the connective tissue, stromal microenvironment of bone marrow, and accordingly the erythroid branch of hematopoiesis in children, which may be relevant inthe development and course of oncohematological diseases.

FEATURES OF CLINICAL SYMPTOMS AND SIGNS, HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN CHILDREN WITH JOINT HYPERMOBILITY IN A LATE PERIOD UPON THE CHORNOBYL NPP ACCIDENT. / OSOBLYVOSTI KLINIChNOÏ SYMPTOMATYKY, GEMATOLOGIChNYKh TA BIOKhIMIChNYKh POKAZNYKIV U DITEY̆ Z GIPERMOBIL'NISTIu SUGLOBIV U VIDDALENYY̆ PERIOD PISLIa AVARIÏ NA ChORNOBYL'S'KIY̆ AES.

OBJECTIVE: establishing the types and frequency of disembriogenetic stigma in children with joint hypermobility given the clinical and laboratory features, genetic component and endocrine regulation of these disorders in a late period upon the accident. MATERIALS AND METHODS: Children (n = 109) inhabiting the radiologically contaminated territories and having the connective tissue dysplasia (CTD) signs were involved in the study. Diseases in family history, ossalgia complaints, fractures in a personal history, bone disembriogenetic stigma, joint hypermobility, type of somatic diseases, blood serum biochemical parameters (namely calcium, alkaline phosphatase, total protein, cholesterol, creatinine, iron, ferritin content), serum cortisol, free thyroxine, pituitary thyroid-stimulating hormone (TSH) levels, free amino acid composition in urine and radiation dose were considered. RESULTS: Radiation doses in children having the CTD ranged from (0.37 ± 0.11) mSv to (0.56 ± 0.10) mSv with no difference from that in those without CTD. Joint hypermobility (JHM) correlated with cancer in family history (rs = 0.53) and lower extremity varicose vein disease (rs = 0.40) (p < 0.05). Incidence of ossalgia, easy fatigability, and bone fractures was higher in children with CTD. Anomalies of the dentofacial system were first in line (38.5 %) in these children. Proportion of children with grade II JHM and platypodia was lower (rs = 0.42), but with lower extremity deformations was higher (rs = 0.68) (p < 0.05) vs. in the control group. Iron and ferritin deficiencies both with lymphocytosis were more common in children with CTD than in the comparison group (p < 0.05). The increased content of oxyproline, lysine, proline both with glycine deficiency were detected in children having the CTD, i.e. an imbalance of amino acids from the collagen content was observed featuring a predominance of catabolic processes over anabolic ones. There was a direct correlation between the TSH level and the JHM grade (rs = 0.49), although the values of hormone concentration in these children did not exceed the reference range (maximum values were 3.3 µIU/ml). CONCLUSIONS: The revealed abnormalities in amino acid content, ferrokinetics, and thyroid function indices can affect the collagen formation, organic matrix structure of bone tissue and significantly deregulate the hemato- poiesis. The later can underlie the pathways of haematologic malignancy development.

Measurement of Serum Tenascin-X in Joint Hypermobility Syndrome Patients.

Joint hypermobility syndrome (JHS) (also termed hypermobility type Ehlers-Danlos syndrome, hEDS) is a heritable connective tissue disorder that is characterized by generalized joint hypermobility, chronic pain, fatigue, and minor skin changes. Initially, it was reported that there is a small subset of patients with JHS/hEDS who have haploinsufficiency of tenascin-X (TNX). However, the relationship between TNXB and JHS/hEDS has not been reported at all afterwards. EDS was reclassified into thirteen types in 2017, and the causative gene of JHS/hEDS remained to be identified. Therefore, in this study in order to determine whether JHS/hEDS can be diagnosed by the concentrations of serum form of TNX (sTNX), we measured the concentrations of sTNX in 17 JHS/hEDS patients. The sTNX concentrations in half of the JHS/hEDS patients were significantly lower than those in healthy individuals. No mutations, insertions or deletions were detected in the TNX exon sequence of the JHS/hEDS patients except for one in patient. That patient has a heterozygous mutation. A correlation between sTNX concentration and mutation of the TNXB genomic sequence was not found in the JHS/hEDS patients. These results indicate that the decrease in sTNX concentration could be used as a risk factor for JHS/hEDS.

Adhesive capsulitis of the shoulder: protocol for the adhesive capsulitis biomarker (AdCaB) study.

BACKGROUND: Adhesive capsulitis (AC) is a disabling and poorly understood pathological condition of the shoulder joint. The current study aims to increase our understanding of the pathogenesis, diagnosis and clinical outcomes of people with AC by investigating: 1) transcriptome-wide alterations in gene expression of the glenohumeral joint capsule in people with AC compared to people with non-inflammatory shoulder instability (controls); 2) serum and urine biomarkers to better understand diagnosis and staging of AC; and 3) clinical outcomes in people with AC compared to controls 12-months following arthroscopic capsular release or labral repair respectively. METHODS: The study is a prospective multi-centre longitudinal study investigating people undergoing arthroscopic capsulotomy for AC compared to people undergoing arthroscopic stabilization for shoulder instability. Tissue samples collected from the anterior glenohumeral joint capsule during surgery will undergo RNA-seq to determine differences in gene expression between the study groups. Gene Set Enrichment Analysis will be used to further understand the pathogenesis of AC as well as guide serum and urine biomarker analysis. Clinical outcomes regarding pain, function and quality of life will be assessed using the Oxford Shoulder Score, Oxford Shoulder Instability Score, Quick DASH, American Shoulder and Elbow Society Score, EQ-5D-5 L and active shoulder range of movement. Clinical outcomes will be collected pre-operatively and 12-months post-operatively and study groups will be compared for statistically significant differences using linear regression, adjusting for baseline demographic variables. DISCUSSION: This study will provide much needed information regarding the pathogenesis, diagnosis and staging of AC. It will evaluate clinical outcomes for people undergoing arthroscopic release of AC by comparing this group to people undergoing arthroscopic surgery for shoulder instability. TRIAL REGISTRATION: ACTRN12618000431224 , retrospectively registered 26 March 2018.

Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients.

The tenascin-X (TNX) deficient type Ehlers-Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross-sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non-sense mRNA mediated decay. In short, patients with the TNX-deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.

Factors That Predict Risk of Cervical Instability in Rheumatoid Arthritis Patients.

STUDY DESIGN: Retrospective data analysis. OBJECTIVE: To identify factors affecting the atlantodental interval, the Ranawat value, and subaxial translation after rheumatoid arthritis (RA) diagnosis. In addition, factors predictive for cervical spine instability (CSI) development after RA diagnosis were examined. SUMMARY OF BACKGROUND DATA: Development of CSI affects the prognosis and mortality of RA patients. Previous studies described that obesity is associated with reduced radiographic joint damage in RA patients. We hypothesized that body mass index (BMI) is also associated with radiographic cervical damage in RA patients. METHODS: Cervical radiographs were taken at full flexion, neutral position, and full extension to measure the geometric length of the anterior atlantodental interval, the Ranawat value, and subaxial translation. These values were entered into multivariable linear regression analysis based on potential associated factors. Hazard ratios were calculated to identify independent factors predictive of CSI. RESULTS: Of the patients diagnosed with RA between January 2005 and August 2015, 1611 who underwent at least one cervical radiograph were included. After adjusting for sex, age, BMI category, CSI, rheumatoid factor, and RA medication, multivariate analysis revealed that the risk of atlantoaxial subluxation in the underweight and normal BMI groups was about 1.6-fold (hazard ratio, 1.63; 95% CI, 1.10-2.43; P = 0.015) and 1.7-fold higher, respectively, than that in the obese group, and that the risk of vertical subluxation was about 2.5-fold (hazard ratio, 2.52; 95% CI, 1.32-4.83; P = 0.005) higher in the underweight group than in the obese group. We also found that the rheumatoid factor positivity was a predictive risk factor for CSI development. CONCLUSION: We identified risk factors predictive for CSI occurrence after RA diagnosis through cervical radiograph assessment. We found that BMI was an independent predictor for development of CSI. Further large-scale prospective studies are required to confirm these findings. LEVEL OF EVIDENCE: 3.

Serum Cartilage Biomarkers and Shoulder Instability.

Differences in cartilage biomarkers have been noted in patients with anterior cruciate ligament tears, but little is known about any similar relationship with shoulder instability. This study evaluated the relationship between serum cartilage biomarkers and shoulder instability. The authors present a prospective cohort study of young athletes followed from 2006 to 2010. A nested case-control analysis was conducted within this cohort to evaluate the association between preinjury collagen type II cleavage (a marker for type II collagen cleavage) and procollagen II carboxy propeptide (a marker of cartilage synthesis) and the subsequent likelihood of shoulder instability during the 4-year follow-up period. Preinjury collagen type II cleavage and procollagen II carboxy propeptide levels in 51 subjects who had shoulder instability were compared with levels in 210 subjects without documented anterior cruciate ligament or shoulder instability (control group) with commercially available enzyme-linked immunosorbent assay kits. Mean preinjury collagen type II cleavage levels in patients who subsequently had shoulder instability were significantly lower than those in the control group (73.91 vs 79.24 pg/mL, P=.03). No significant difference was found in preinjury procollagen II carboxy propeptide levels compared with the control group (359.94 vs 396.37, P=.24). This study is the first to examine the relationship between baseline collagen biomarkers and subsequent shoulder instability. The finding of lower baseline collagen type II cleavage levels in patients with subsequent shoulder instability may represent a genetic predisposition or a compensatory mechanism by which cartilage degradation is decreased in those who are more likely to have instability. [Orthopedics. 2017; 40(1):34-36.].

Association Between Serum Relaxin and Subsequent Shoulder Instability.

Ligamentous laxity correlates with shoulder instability. Relaxin is a hormone that has been linked to laxity in the knee and has been shown to be a risk factor for anterior cruciate ligament (ACL) injury. This study prospectively evaluated the association between relaxin and acute shoulder instability. A prospective cohort study of 1050 young athletes was performed between 2006 and 2010. The authors conducted a nested case-control analysis within this cohort to evaluate the association between preinjury serum relaxin concentration and the likelihood of subsequent shoulder instability. The study compared 53 patients who had shoulder instability and 53 control subjects who were matched for sex, age, height, and weight. The serum relaxin concentration in preinjury baseline samples was tested with enzyme-linked immunosorbent assay analysis in duplicate. Independent t tests were performed to identify differences in mean serum relaxin concentration between patients with shoulder instability and uninjured control subjects. Logistic regression was used to evaluate whether preinjury baseline serum relaxin concentration was associated with the subsequent likelihood of shoulder instability. Of the 53 patients with instability, 13 (25%) had a detectable serum relaxin concentration compared with 9 (17%) of uninjured control subjects (P=.34). Mean serum relaxin concentration in the injury group was 3.69±1.78 pg/mL and 2.20±0.97 pg/mL in uninjured control subjects (P=.02). Increased serum relaxin concentration was associated with the subsequent likelihood of acute shoulder instability. Subjects were 2.18 times (odds ratio, 2.18; 95% confidence interval, 1.01-4.76) more likely to have acute shoulder instability during the follow-up period for every 1-pg/mL increase in serum relaxin concentration at baseline. The findings suggest that serum relaxin concentration is associated with a risk of subsequent shoulder instability in young athletes. Further research on the role of relaxin in shoulder instability is warranted. [Orthopedics. 2016; 39(4):e724-e728.].

Proteomic analysis for the identification of serum diagnostic markers for joint hypermobility syndrome.

Joint hypermobility syndrome (JHS) (also termed Ehlers-Danlos syndrome, hypermobility type) is a heritable connective tissue disorder which is characterized by generalized joint hypermobility, chronic pain, dizziness, fatigue, and minor skin changes. However, it has yet to be determined in patients with JHS whether specific genetic factors are involved in the risk of developing the disorder. Therefore, interventions have been limited to symptomatic treatments, and biomarkers for diagnosis and therapy have not yet been identified. In the present study, to identify potential serum biomarkers for JHS, we examined proteins with differential levels in sera from patients with JHS and in sera from control individuals using isobaric tags for relative and absolute quantitation (iTRAQ) labeling in combination with nano LC-MALDI-TOF/TOF-MS/MS followed by ProteinPilot analysis. In the sera of patients with JHS, a total of 106 proteins with differential levels were identified, and they were further narrowed down to 6 proteins (p<0.05, patient vs. control). Of the 6 proteins, proteins involved in the complement system including complement C1r subcomponent (C1R), vitronectin (VTN), complement component C9 (C9), and C4b-binding protein alpha chain (C4BPA) were identified as increased proteins in sera from patients with JHS compared with those in sera from controls. We confirmed increased levels of C1R and VTN in sera from patients with JHS by western blot analyses. The results indicate the possibility of a locally occurring inflammatory process in patients with JHS.

17ß-Estradiol Induced Effects on Anterior Cruciate Ligament Laxness and Neuromuscular Activation Patterns in Female Runners.

BACKGROUND: We investigate the effects of 17ß-Estradiol across phases of menstrual cycle on the laxness of the anterior cruciate ligament (ACL) and the neuromuscular control patterns around the knee joint in female runners. METHODS: Twelve healthy female runners who reported normal menstrual cycles for the previous 6 months were tested twice across one complete menstrual cycle for serum levels of 17ß-estradiol, and knee joint laxity (KJL). Electromyographic (EMG) activity of the quadriceps and hamstrings muscles was also recorded during running on a treadmill. The changes in the EMG activity, KJL, and hormonal concentrations were recorded for each subject during the follicular and the ovulatory phases across the menstrual cycle. RESULTS: An observed increase in KJL in response to peak estradiol during the ovulatory phase was associated with increased preactivity of the hamstring muscle before foot impact (p<0.001). A consistent pattern was also observed in the firing of the quadriceps muscle recruitment pattern throughout the follicular phase associated with decreased hamstring recruitment pattern during weight acceptance phase of running (p=0.02). Additionally, a low ratio of medial to lateral quadriceps recruitment was associated with a significant reduction of the quadriceps to hamstring co-contraction ratio during the follicular phase. CONCLUSIONS: Changes in KJL during the menstrual cycle in response to 17ß-estradiol fluctuations changes the neuromuscular control around the knee during running. Female runners utilize different neuromuscular control strategies during different phases of the menstrual cycle, which may contribute to increased ACL injury risk.

Serum relaxin levels in benign hypermobility syndrome.

OBJECTIVE: In this study, we investigated the activity of serum relaxin in female patients with benign joint hypermobility syndrome (BJHS), locomotor system findings accompanying BJHS, and its relation to relaxin. METHODS: Into the study, female patients with BJHS and healthy women as the control group were included. The patients were diagnosed by using the Brighton 1998 criteria. Examination of the locomotor system for study groups were performed. Serum relaxin levels of both patient and control group were measured. RESULTS: There were 48 female patients with BJHS and 40 healthy women in the study. With respect to the control group, the level of serum relaxin was higher in the patients (47.1 ± 20.3, 34.4 ± 22.1; p> 0.05). Again compared with the control group, arthralgia (p= 0.00), myalgia (p= 0.01), shoulder impingement syndrome (p= 0.05), pes planus (p= 0.01), and hyperkyphosis (p= 0.000) were higher in the patients. The level of relaxin median was significantly higher in the patients with pesplanus and hyperkyphosis than those who did not have them (p= 0.05, p= 0.01, respectively). CONCLUSIONS: Although serum relaxin level is not considered a causative factor for BJHS, the significant increases found in those patients with hyperkyphosis and pes planus suggest the hypothesis that relaxin has a limited and indefinite role in patients with BJHS.

Serum prolidase activity in benign joint hypermobility syndrome.

BACKGROUND: Moderate joint laxity is widespread in many joints of the body, and this condition is considered to be caused by an abnormality in the collagen structure. This study was carried out to determine the serum prolidase activity in female patients with benign joint hypermobility syndrome (BJHS), and to evaluate its correlation with their clinical features. METHODS: A total of 45 patients with BJHS and 40 healthy controls were included in the study. All of the patients with BJHS met the Beighton diagnostic criteria. All the patients and the control group underwent a comprehensive examination of the locomotor system and took the New York Posture Rating Test. The examination and test results were recorded. Serum prolidase activity was measured in both the groups. RESULTS: Prolidase activity was significantly lower in patients with BJHS (479.52 ± 126.50) compared to the healthy controls (555.97 ± 128.77) (p = 0.007). We found no correlation between serum prolidase activity and Beighton scores or New York rating test scores. On the other hand, mean prolidase activity was significantly lower in patients with pes planus or hyperlordosis compared to those without (p = 0.05, p = 0.03, respectively). We did not find such a correlation with the other clinical features. CONCLUSIONS: Significantly lower prolidase activity in patients with BJHS suggests that prolidase may affect the collagen metabolism and cause hyperlaxity.

Relationship of relaxin hormone and thumb carpometacarpal joint arthritis.

BACKGROUND: The female predominance in thumb carpometacarpal (CMC) joint arthritis has led to speculation that reproductive hormones or hypermobility are responsible. Evidence shows that patients with pathologic laxity have a higher rate of thumb CMC arthritis. Relaxin hormone increases laxity in the pelvic ligaments through upregulation of matrix metalloproteases (MMPs). It is thus a hormone of interest in the development of thumb CMC arthritis. QUESTIONS/PURPOSES: Our goals were to identify demographic and hormonal factors associated with joint laxity in patients with CMC arthritis and to evaluate the relationship among serum relaxin, relaxin receptors, and MMPs in the anterior oblique ligament (AOL) of the thumb. We hypothesized that serum relaxin was correlated with joint laxity as well as with relaxin receptors and MMPs in the AOL. METHODS: Forty-nine patients undergoing thumb CMC arthroplasty underwent laxity examination, blood draw, and AOL sampling. Ligaments were analyzed for relaxin receptor and MMPs 1 and 3 using quantitative reverse-transcriptase polymerase chain reaction. RESULTS: Women demonstrated more joint laxity than men (p < 0.001). RNA analysis confirmed relaxin receptors in the AOL as well as MMPs 1 and 3. There was a significant correlation between serum relaxin and MMP-1 (p = 0.04). Detectable serum relaxin was negatively correlated with relaxin receptors in the AOL (p = 0.02). CONCLUSIONS: Further studies are needed to evaluate the role of laxity and sex hormones in thumb CMC arthritis. CLINICAL RELEVANCE: Relaxin hormone may play a role in the development of arthritis at the thumb CMC joint. LEVEL OF EVIDENCE: Level I, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Relationship of serum relaxin to generalized and trapezial-metacarpal joint laxity.

PURPOSE: The reproductive hormone relaxin acts to loosen pelvic ligaments in preparation for childbirth and is thought to be a mediator of joint laxity. The purpose of this study was to evaluate the correlation of serum relaxin with radiographic laxity at the trapezial-metacarpal joint and with generalized joint laxity. METHODS: We enrolled 289 healthy subjects prospectively. Participants completed a demographic questionnaire and were examined for generalized joint hypermobility using the Beighton-Horan scale. Stress radiographs of the trapezial-metacarpal joint were obtained in 163 subjects (56%). Blood samples were collected, and serum relaxin was measured for 287 subjects using enzyme-linked immunosorbent assay for human relaxin-2. RESULTS: The mean serum relaxin level among all subjects was 1.84 pg/mL (range, 0-45.25 pg/mL). Relaxin was not detectable in 166 of 287 samples, whereas the mean serum relaxin level among the 121 subjects with a detectable relaxin level (of 287 total relaxin samples) was 4.37 pg/mL (range, 0.46-45.25 pg/mL). Mean trapezial-metacarpal subluxation ratio scores were higher among those with a detectable relaxin level compared to those without a detectable relaxin level (0.34 vs 0.30 pg/mL). The average Beighton-Horan laxity score was 1.8 (range, 0-9). There was no correlation between generalized joint laxity measures and serum relaxin levels. CONCLUSIONS: In a large volunteer population, we demonstrated a relationship between circulating relaxin and trapezial-metacarpal joint laxity. However, we were unable to show a direct link between serum relaxin and generalized joint laxity. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Serum relaxin levels in young athletic men are comparable with those in women.

Relaxin was originally described as a reproductive hormone that mediated joint laxity in pregnant women and has been minimally studied in men. The purpose of this descriptive laboratory and clinical study was to evaluate serum relaxin in a young, primarily male population and compare levels between the sexes. In addition, the authors evaluated the relationship between relaxin and generalized laxity.

In vivo serum titanium ion levels following modular neck total hip arthroplasty--10 year results in 67 patients.

The objective of the present cross-sectional study was to determine in vivo titanium ion levels following cementless total hip arthroplasty (THA) using a modular stem system with different shapes for femoral canal fit and multiple neck options. A consecutive series of 173 patients (190 hips) who underwent cementless modular neck THA and a ceramic on polyethylene bearing with a median follow-up of 9 (7-13) years was evaluated retrospectively. According to a standardized protocol, titanium ion measurements were performed on 67 patients using high-resolution inductively coupled plasma-mass spectrometry. Ion levels were compared to a control group comprising patients with non-modular titanium implants (n=11) and to individuals without implants (n=23). Modular neck THA did not result in elevated titanium ion levels compared to non-modular THA. Compared to individuals without implants, both modular THA and non-modular THA showed elevated titanium ion levels. Absolute titanium ion levels, however, were comparatively low for both implants. The data suggest that the present modular stem system does not result in elevated systemic titanium ion levels in the medium term when compared to non-modular stems. Further longitudinal studies are needed to evaluate the use of systemic titanium ion levels as an objective diagnostic tool to identify THA failure and to monitor patients following revision surgery.

Changes in serum collagen markers, IGF-I, and knee joint laxity across the menstrual cycle.

Variations in serum markers of collagen production (CICP) and degradation (ICTP), insulin-like growth factor I (IGF-I) and anterior knee laxity (AKL) were measured in 20 women [10 with spontaneous cycles (eumenorrheic), 10 using oral contraceptives] over 5 consecutive days at menses (M1-M5, 1st pill week), the initial estrogen rise near ovulation (O1-O5, 2nd pill week), the initial progesterone rise of the early luteal phase (EL1-EL5, 3rd pill week) and post-progesterone peak of the late luteal phase (LL1-LL5, 4th pill week). ICTP was higher in oral contraceptive women (5.3 ± 1.7 vs. 3.7 ± 1.3 µg/L; p = 0.030), primarily during days near ovulation and the early luteal phase when concentrations decreased in eumenorrheic women (p = 0.04). IGF-I concentrations increased during menses then decreased and remained lower during the early and late luteal phase in oral contraceptive women, resulting in lower concentrations compared to eumenorrheic women at EL2 and LL1 (p = 0.03). CICP decreased in early and late luteal days (p <0.01), and there was a trend toward lower concentrations in eumenorrheic versus oral contraceptive women (85.7 ± 35.7 ng/ml vs. 123.2 ± 49.8 ng/ml; p = 0.07). Lower CICP and greater IGF-I concentrations predicted greater AKL across the 20 cycle days in both groups (R(2) = 0.310 and 0.400). Sex hormone concentration changes across the menstrual cycle are of sufficient magnitude to influence collagen metabolism, and may indirectly influence knee structure and function.

Alterations in knee joint laxity during the menstrual cycle in healthy women leads to increases in joint loads during selected athletic movements.

BACKGROUND: It has been speculated that the hormonal cycle may be correlated with higher incidence of ACL injury in female athletes, but results have been very contradictory. HYPOTHESIS: Knee joint loads are influenced by knee joint laxity (KJL) during the menstrual cycle. STUDY DESIGN: Controlled laboratory study. METHODS: Serum samples and KJL were assessed at the follicular, ovulation, and luteal phases in 26 women. Knee joint mechanics (angle, moment, and impulse) were measured and compared at the same intervals. Each of the 26 subjects had a value for knee laxity at each of the 3 phases of their cycle, and these were ordered and designated low, medium, and high for that subject. Knee joint mechanics were then compared between low, medium, and high laxity. RESULTS: No significant differences in knee joint mechanics were found across the menstrual cycle (no phase effect). However, an increase in KJL was associated with higher knee joint loads during movement (laxity effect). A 1.3-mm increase in KJL resulted in an increase of approximately 30% in adduction impulse in a cutting maneuver, an increase of approximately 20% in knee adduction moment, and a 20% to 45% increase in external rotation loads during a jumping and stopping task (P < .05). CONCLUSION: Changes in KJL during the menstrual cycle do change knee joint loading during movements. Clinical Relevance Our findings will be beneficial for researchers in the development of more effective ACL injury prevention programs.

Changing hormone levels during the menstrual cycle affect knee laxity and stiffness in healthy female subjects.

BACKGROUND: Whether knee laxity varies throughout the menstrual cycle remains controversial. As increased laxity may be a risk factor for anterior cruciate ligament (ACL) injury, further research is warranted. HYPOTHESIS: Variation in estradiol and progesterone levels during the menstrual cycle influences knee laxity and stiffness. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: The serum estradiol and progesterone levels of 26 healthy female subjects were recorded in the follicular phase, ovulation, and the luteal phase. Knee joint laxity was assessed using a standard knee arthrometer at the same intervals. Stiffness changes in the load-displacement curve were determined. Hormone levels across the cycle were compared between responders and nonresponders, defined by whether changes in knee laxity at 89 N occurred. RESULTS: Greater laxity at 89 N during ovulation was observed (ovulation: 5.13 +/- 1.70 mm vs luteal: 4.55 +/- 1.54 mm, P = .012). In knee laxity testing at manual maximum load, greater laxity was noticed during ovulation (14.43 +/- 2.60 mm, P = .018), as compared with the follicular phase (13.35 +/- 2.53 mm). A reduction in knee stiffness of approximately 17% (ovulation: 12.48 +/- 5.46 N/mm vs luteal: 15.02 +/- 7.71 N/mm, P = .042) during ovulation was observed. However, there were no differences in hormone levels between responders and nonresponders at 89 N. CONCLUSION: Female hormone levels are related to increased knee joint laxity and decreased stiffness at ovulation. To understand subject variations in knee joint laxity during the menstrual cycle in female athletes, further investigation is warranted.