Accuracy of unguided and ultrasound guided Coracohumeral ligament infiltrations - a feasibility cadaveric case series.

BACKGROUND: Coracohumeral ligament (CHL) thickening, contracture, and fibroplasia have been identified in glenohumeral idiopathic adhesive capsulitis (GHIAC). The CHL is the main structure responsible for the range of motion limitations. Favorable outcomes have been reported with CHL surgical release. Intra-articular glenohumeral joint corticosteroid infiltrations are utilized to disrupt the inflammatory process and reduce pain in GHIAC. The aim of this study was to investigate whether the CHL could be accurately targeted with a periligamentous infiltration. METHODS: A convenience sample of 12 unembalmed cadaver shoulders (mean age: 74.5 years, range 66-87 years) without evidence of previous injury or surgery were utilized in this exploratory double factor feasibility cadaveric (unguided and ultrasound (US) guided) case series. Two clinicians trained in musculoskeletal infiltration techniques carried out the infiltrations on each shoulder with colored latex. One clinician infiltrated without guidance, the other with US-guidance. The injecting clinicians were blinded to the others infiltration procedure and the order was randomized. An anatomist blinded to the infiltration order performed a shoulder dissection and recorded the infiltrate location. Percentage calculation for accuracy of infiltration and a chi-square evaluation of the difference between unguided and US-guided infiltrations was applied. RESULTS: An accuracy of 75% was achieved for unguided infiltration and 80% for US-guided infiltration techniques. Chi-squared indicated there was no significant difference (p = 0.82) between the unguided and US-guided techniques. CONCLUSION: US-guided and unguided infiltrations achieved good accuracy targeting the CHL, suggesting infiltrations can specifically and accurately target the CHL. In vivo investigation using such infiltration techniques are warranted.

Anatomic Magnetic Resonance Imaging Measurements in First-Time Patellar Dislocators by Sex and Age.

CONTEXT: Anatomic differences of the knee in first-time patellar dislocators have not been clearly elucidated. OBJECTIVE: To compare structural differences of the knee in those who have sustained an acute first-time patellar dislocation resulting in a medial patellofemoral ligament (MPFL) tear by sex and age (≤17 years old, ≥18 years old). DESIGN: Case series. SETTING: Retrospective magnetic resonance imaging analysis. PATIENTS OR OTHER PARTICIPANTS: Thirty-five acute first-time patellar dislocators with an associated MPFL tear. MAIN OUTCOME MEASURE(S): Patellar height using 3 methods, patellar alignment using congruency angles, and trochlear morphology using the sulcus angle. We compared the means of these variables by sex and age. The intraclass correlation coefficient was then calculated to assess the agreement of the independent reviewers. RESULTS: A total of 21 left and 14 right knees were analyzed. The MPFL tear location did not differ by sex (P = .34) or age (P = .43). Patellar height did not differ as measured by the Caton-Deschamps ratio (P = .29 for sex, P = .49 for age), Insall-Salvati index (P = .15 for sex, P = .33 for age), or patellotrochlear index (P = .67 for sex, P = .49 for age). The congruence angle (P = .81 for sex, P = .06 for age) and trochlear morphology as measured by the sulcus angle (P = .64 for sex, P = .45 for age) were similar between groups. CONCLUSIONS: Patellar height and trochlear morphology did not differ by sex or age among patients whose first-time patellar dislocations resulted in an MPFL tear. In addition, the location of the tear did not appear to vary by sex or age.

Systematic review of treatment effectiveness and outcome measures for enthesitis in psoriatic arthritis.

Enthesitis is a characteristic feature of psoriatic arthritis (PsA) and is important in disease pathogenesis and classification. Use of clinical outcome measures for enthesitis is heterogeneous, and only 1 measure has been specifically developed and validated in PsA. Ultrasound and magnetic resonance imaging assessments of enthesitis may have advantages over clinical examination but are insufficiently studied. As part of an update of treatment recommendations by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), we performed a systematic literature review and identified randomized controlled trials with enthesitis outcomes in PsA. For each treatment agent we calculated treatment effect sizes (where applicable) and graded the level of evidence.

Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.

Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of ß2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits ß2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.

Contralateral cruciate survival in dogs with unilateral non-contact cranial cruciate ligament rupture.

BACKGROUND: Non-contact cranial cruciate ligament rupture (CrCLR) is an important cause of lameness in client-owned dogs and typically occurs without obvious injury. There is a high incidence of bilateral rupture at presentation or subsequent contralateral rupture in affected dogs. Although stifle synovitis increases risk of contralateral CrCLR, relatively little is known about risk factors for subsequent contralateral rupture, or whether therapeutic intervention may modify this risk. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a longitudinal study examining survival of the contralateral CrCL in client-owned dogs with unilateral CrCLR in a large baseline control population (n = 380), and a group of dogs that received disease-modifying therapy with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline (n = 16), and were followed for one year. Follow-up in treated dogs included analysis of mobility, radiographic evaluation of stifle effusion and arthritis, and quantification of biomarkers of synovial inflammation. We found that median survival of the contralateral CrCL was 947 days. Increasing tibial plateau angle decreased contralateral ligament survival, whereas increasing age at diagnosis increased survival. Contralateral ligament survival was reduced in neutered dogs. Our disease-modifying therapy did not significantly influence contralateral ligament survival. Correlative analysis of clinical and biomarker variables with development of subsequent contralateral rupture revealed few significant results. However, increased expression of T lymphocyte-associated genes in the index unstable stifle at diagnosis was significantly related to development of subsequent non-contact contralateral CrCLR. CONCLUSION: Subsequent contralateral CrCLR is common in client-owned dogs, with a median ligament survival time of 947 days. In this naturally occurring model of non-contact cruciate ligament rupture, cranial tibial translation is preceded by development of synovial inflammation. However, treatment with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline does not significantly influence contralateral CrCL survival.

Sonoanatomy and injection technique of the iliolumbar ligament.

BACKGROUND: The iliolumbar ligament plays an important biomechanic role in anchoring the spine to the pelvic ring and stabilizing the sacroiliac joint. Iliolumbar syndrome is a back pain condition caused by pathology of the iliolumbar ligament. History and physical examination are important in the assessment of back pain, but they lack sufficient specificity. Injection of small volumes of local anesthetic into the structure considered to be the source of the pain (i.e. the iliolumbar ligament) increases the specificity of the diagnostic workup. OBJECTIVE: To describe an ultrasound - guided technique for injecting the iliolumbar ligament. STUDY DESIGN: Case report based on knowledge of topographic anatomy and sonoanatomy. SETTING: Outpatient clinic. METHODS: A patient with a clinical picture suggestive of iliolumbar syndrome was selected. An ultrasound-guided injection of the iliolumbar ligament with local anesthetic was performed. We recorded the patient's subjective assessment of pain and the change in range of movement and pain scores during provocative tests. RESULTS: Following the injection, the patient's pain score decreased, provocation tests became negative, and the range of movement increased. LIMITATIONS: Case report. Target specificity and dispersion of local anesthetic spread not confirmed with an independent technique (i.e. magnetic resonance imaging). CONCLUSIONS: Ultrasound guidance allows the selective deposition of small volumes of local anesthetic into structures believed to cause soft tissue back pain and thus to confirm or exclude the working diagnosis. Further studies are needed to confirm our conclusions and to prove the clinical feasibility of this technique.

Remodeling and repair of orthopedic tissue: role of mechanical loading and biologics: part II: cartilage and bone.

Orthopedic tissues respond to mechanical loads to maintain normal homeostasis and in response to injury. As the body of work on this continues to grow, it is important to synthesize the recent studies across tissues and specialties with one another and with past studies. Hence, this review highlights the knowledge gained since 2000, with only few exceptions, concerning the effects of mechanical load and biologics on remodeling and repair of orthopedic tissue.

Enthesitis in an inception cohort of enthesitis-related arthritis.

OBJECTIVE: To describe an enthesitis-related arthritis (ERA) inception cohort and determine which entheses and joints are most commonly affected. METHODS: We reviewed a retrospective inception cohort study of children with ERA who were diagnosed and treated at The Children's Hospital of Philadelphia between November 2007 and December 2009. RESULTS: During the study period, there were 32 newly diagnosed ERA patients. Fifty-nine percent were male, and the median age at the date of initial evaluation was 12.5 years (interquartile range [IQR] 10.2-14.3 years). The median number of tender entheses at presentation was 2 (IQR 0-5), and 21 subjects (66%) had at least 1 tender enthesis. The most prevalent tender entheses were the patellar ligament insertion at the inferior pole of the patella, the plantar fascial insertion at the calcaneus, the Achilles tendon insertion at the calcaneus, and the plantar fascial insertion at the metatarsal heads. Enthesitis was most often symmetric. The median number of active joints was 2 (IQR 0-4). The most commonly affected joints were the sacroiliacs, knees, and ankles. Sacroiliitis, which was defined clinically, was most often symmetric, while peripheral arthritis was most frequently asymmetric. The odds of having active enthesitis at 6 months increased significantly with each additional tender enthesis at the initial evaluation. CONCLUSION: Among pediatric patients with ERA, lower extremity enthesitis is prevalent at the time of diagnosis and is likely to persist 6 months later. Future studies should address standardization of the enthesitis examination, the pattern of enthesitis over time, enthesitis response to therapy, and the impact of enthesitis on quality of life.

Ultrasound-guided lateral femoral cutaneous nerve block: comparison of two techniques.

The aim of this study was to compare the feasibility and efficacy between two techniques of ultrasound-guided lateral femoral cutaneous nerve with or without locating the nerve. The study enrolled 106 patients undergoing knee surgery who received 5 ml of 1% mepivacaine immediately under the inguinal ligament 1 to 2 cm medial to the anterior superior iliac spine (subinguinal technique) or around the lateral femoral cutaneous nerve located (nerve-targeting technique). The time required to perform the block and the onset time of the block were similar for both techniques. However, a significantly higher percentage of patients obtained loss of pinprick sensation on the lateral thigh within 10 minutes with the subinguinal technique than with the nerve-targeting technique. The findings suggest that ultrasound-guided lateral femoral cutaneous nerve blocks can be easily performed and that injecting local anaesthetic immediately under the inguinal ligament rather than around the nerve itself blocks the nerve more reliably.

Desensitizing the posterior interosseous nerve alters wrist proprioceptive reflexes.

PURPOSE: The presence of wrist proprioceptive reflexes after stimulation of the dorsal scapholunate interosseous ligament has previously been described. Because this ligament is primarily innervated by the posterior interosseous nerve (PIN) we hypothesized altered ligamento-muscular reflex patterns following desensitization of the PIN. METHODS: Eight volunteers (3 women, 5 men; mean age, 26 y; range 21-28 y) participated in the study. In the first study on wrist proprioceptive reflexes (study 1), the scapholunate interosseous ligament was stimulated through a fine-wire electrode with 4 1-ms bipolar pulses at 200 Hz, 30 times consecutively, while EMG activity was recorded from the extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris, with the wrist in extension, flexion, radial deviation, and ulnar deviation. After completion of study 1, the PIN was anesthetized in the radial aspect of the fourth extensor compartment using 2-mL lidocaine (10 mg/mL) infiltration anesthesia. Ten minutes after desensitization, the experiment was repeated as in study 1. The average EMG results from the 30 consecutive stimulations were rectified and analyzed using Student's t-test. Statistically significant changes in EMG amplitude were plotted along time lines so that the results of study 1 and 2 could be compared. RESULTS: Dramatic alterations in reflex patterns were observed in wrist flexion, radial deviation, and ulnar deviation following desensitization of the PIN, with an average of 72% reduction in excitatory reactions. In ulnar deviation, the inhibitory reactions of the extensor carpi ulnaris were entirely eliminated. In wrist extension, no differences in the reflex patterns were observed. CONCLUSIONS: Wrist proprioception through the scapholunate ligament in flexion, radial deviation, and ulnar deviation depends on an intact PIN function. The unchanged reflex patterns in wrist extension suggest an alternate proprioceptive pathway for this position. Routine excision of the PIN during wrist surgical procedures should be avoided, as it alters the proprioceptive function of the wrist. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Case report: psoriatic erythroderma with bilateral osseous bridge across the acetabulum.

Abnormal reactions accompanied by bone formation in the osteoarticular region induced by long-term administration of etretinate have been reported. We treated a patient who received continuous treatment of psoriatic erythroderma with etretinate for 7 years, and who had an osseous bridge that extended across the acetabulum over the femur on both sides. The patient experienced a major gait disturbance and eventually was unable to walk. Functional gait was restored by resecting the ossified regions and radiotherapy. Histologic sections of the ossified lesions showed enchondral ossification in the ligament attachment site in the joint margin, with advancing ossification along the articular capsule; the pattern was similar to that in diffuse idiopathic skeletal hyperostosis. This is the first report of an osseous bridge associated with long-term administration of etretinate extending across the acetabulum over the femur on both sides.

Effects of Gardeniae Fructus extract and geniposide on promoting ligament cell proliferation and collagen synthesis.

Gardeniae Fructus is a traditional medicine used for the treatment of contusion such as ankle sprain. Geniposide is one of the main components of Gardeniae Fructus with diverse biological activities. In order to gain further insight into the therapeutic action of Gardeniae Fructus extract (GFE) and geniposide on ligament injuries, a new in vitro model was developed in the present study. Rat hind ankle ligament fibroblasts (RHALFs) derived from Sprague-Dawley rats were cultured, and the cell proliferation and collagen content were examined by MTT and a Sirius Red-based colorimetric assay after stimulating with each drug. The cell growth of RHALFs was promoted by culturing with 37.5-150 microg/mL of GFE and 25-200 microM of geniposide. The content of collagen in the RHALFs was significantly increased up to 131.4% and 124.2% of the control value by culturing with the GFE and geniposide, respectively. By contrast, both cell growth and collagen content were impaired by adding 25-200 microM of diclofenac, one of the common medications for ligament injuries. The findings suggest that GFE and geniposide may ameliorate the treatment of ligament injuries by proliferating ligament fibroblasts and promoting the synthesis of collagen. However, the use of diclofenac to treat acute ligament injuries should be reassessed although it possesses a potential effect on relieving symptoms.

The use of prolotherapy in the sacroiliac joint.

OBJECTIVE: In this study the effectiveness of prolotherapy in the treatment of deficient load transfer of the sacroiliac joint (SIJ) was determined. DESIGN: A prospective descriptive study. SETTING: Authors' private practice. PARTICIPANTS: 25 patients who consented to treatment and attended for at least one follow-up visit and assessment. STUDY PERIOD: From April 2004 to July 2007. INTERVENTION: Three injections of hypertonic dextrose solution into the dorsal interosseous ligament of the affected SIJ, under CT control, 6 weeks apart. MAIN OUTCOME MEASURES: Quebec Back Pain Disability Scale, Roland-Morris 24, Roland-Morris 24 Multiform questionnaires and clinical examination by two authors independently. RESULTS: All patients included in this study attended at least one follow-up visit at 3, 12 or 24 months.. The number of patients at follow-up decreased at 12 and 24 months. Functional questionnaires demonstrated significant improvements for those followed-up at 3, 12 and 24 months (p<0.05). Clinical scores showed significant improvement from commencement to 3, 12 and 24 months (p<0.001). CONCLUSIONS: This descriptive study of prolotherapy in private practice has shown positive clinical outcomes for the 76% of patients who attended the 3-month follow-up visit (76% at 12 months and 32% at 24 months). Similar results were found in the questionnaires (Quebec Back Pain Disability Scale, Roland-Morris 24 and Roland-Morris 24 Multiform questionnaires) at 3, 12 and 24 months.

Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in swine.

Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1x), medium (5x), or high (10x) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.

Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. WHAT THIS STUDY ADDS: The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) is not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. AIMS: The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. METHODS: This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18-60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day(-1). RESULTS: One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day(-1) of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. CONCLUSIONS: The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction.

Case series on chronic whiplash related neck pain treated with intraarticular zygapophysial joint regeneration injection therapy.

BACKGROUND: Although in clinical use, there is only 1 published case report on the efficacy of intraarticular regeneration injection therapy (RIT) (a.k.a. prolotheraphy). This report supports a rationale for future clinical trials of this technique. OBJECTIVE: To assess the efficacy of intraarticular zygapophysial joint RIT in patients with chronic whiplash related neck pain that failed other conservative and interventional procedures. Patients were treated with intraarticular RIT and reassessed over 1 year. DESIGN: Retrospective case review of prospective data. MATERIALS AND METHODS: Eighteen consecutive patients were treated with intraarticular prolotherapy by placing 0.5 - 1mL of 20% dextrose solution into each zygapophysial joint, after confirmation of intraarticular location with radiographic contrast, using 25-gauge spinal needles and fluoroscopic guidance. Solution was prepared by diluting D50W with 1% lidocaine. RESULTS: Fifteen patients completed treatment. Three patients had bilateral treatment, leaving 18 sides for analysis. Mean Neck Disability Index (NDI) pre-treatment was 24.71 and decreased post-treatment to 14.21 (2 months), 13.45 (6 months), 10.94 (12 months). Average change NDI=13.77 (p<0.0001) baseline versus 12 months. Symptoms for 14 patients were from motor vehicle accident, of which 13 were in litigation. Patients attending physiotherapy over the course of treatment had better outcomes than those without physiotherapy. Women needed more injections (5.4) than men (3.2) p=0.0003. CONCLUSION: Intraarticular RIT improved pain and function in this case series. The procedure appears safe, more effective than periarticular RIT, and lasted as long, or longer, than those patients with previous radiofrequency neurotomy. Concurrent physiotherapy helped reduce post-procedure neck stiffness. Future trials should consider gender when deciding how many treatments to administer. Litigation was not a barrier to recovery.

Effect of GDF-5 on ligament healing.

The effects of growth and differentiation factor-5 (GDF-5) on ligament healing were studied using a gap injury model of the medial collateral ligament in rat knee joints. The administration of GDF-5 once at the time of surgery significantly improved the mechanical properties of the femur-ligament-tibia complex. At 3 weeks after surgery, 30 microg of GDF-5 improved the ultimate tensile strength of the complex by 41%, and the stiffness by 60%, compared with the vehicle control (p < 0.05 for both; Fisher's PLSD test). The observation with a transmission electron microscopy revealed that GDF-5 increased the diameter of collagen fibrils in the repair tissue, which was considered to be a possible mechanism for the positive result in the biomechanical testing. Quantitative PCR and in situ hybridization revealed enhanced type I procollagen expression by GDF-5, and the PCR analysis also revealed that the GDF-5 treatment reduced the expression of type III procollagen relative to type I procollagen. The PCR analysis further showed that the expression of decorin and fibromodulin was relatively reduced against type I procollagen by the growth factor, which was considered to be responsible for the increase of collagen fibril diameter in the repair tissue. No adverse effects were observed, and the use of GDF-5 was considered a promising approach to facilitate ligament healing.

Knee ligament mechanical properties are not influenced by estrogen or its receptors.

Women are at greater risk of tearing their knee anterior cruciate ligament (ACL) than men participating in similar athletic activities. There is currently no conclusive explanation for this disparity; however, as ACL injuries in women have been linked with estrogen fluctuations during the menstrual cycle, one hypothesis is that estrogen has a direct detrimental effect on knee ligament mechanical properties. This study investigated the influence of estrogen and its receptors (ER alpha and ER beta) on knee ligament mechanical properties. This was achieved by testing the viscoelastic and tensile mechanical properties of knee medial collateral ligaments (MCL) and ACLs from: 1) male Sprague-Dawley rats treated with either estrogen (17alpha-ethynylestradiol; 0.03 mg/kg) or an ER alpha-specific agonist (propyl pyrazole triol; 2 mg/kg), and 2) female mice with a null mutation of the gene encoding for ER beta. Estrogen treatment had no significant effects on the viscoelastic or tensile mechanical properties of the rat MCL or ACL. Similarly, pharmacological stimulation of ER alpha using a selective agonist in rats and genetic modulation of ER beta by null mutation of its gene in mice did not influence MCL or ACL properties. These data indicate that estrogen does not have a major direct effect on ligament mechanical properties. Energies for the prevention of the disproportionately high rate of knee ligament injuries in women may be better spent focusing on more established and modifiable risk factors, such as abnormalities in neuromuscular control about the knee.

Influence of a single systemic corticosteroid injection on mRNA levels for a subset of genes in connective tissues of the rabbit knee: a comparison of steroid types and effect of skeletal maturity.

OBJECTIVE: . To determine the effect of glucocorticoid treatment on mRNA levels for matrix molecules and enzymes in knee connective tissues from skeletally mature and skeletally immature rabbits. METHODS: Intraarticular and extraarticular connective tissues of the knee were collected from skeletally mature or immature rabbits at 72 and/or 24 h postinjection of a single intramuscular inoculation of 10 mg/kg methylprednisolone or dexamethasone (skeletally mature rabbits) or 1 mg/kg (skeletally immature rabbits). Total RNA was isolated and mRNA levels for matrix molecules, matrix metalloproteinases (MMP) and their inhibitors, cyclooxygenase-2, transforming growth factor-ss, glucocorticoid receptor, and heat shock protein 90 alpha and beta were assessed by RT-PCR. RESULTS: Glucocorticoid treatment resulted in significant alterations in mRNA levels for a specific subset of genes in a tissue-specific and time-dependent manner in both maturity groups. Most notably, glucocorticoid treatment resulted in significant suppression of mRNA levels for collagens I and III, and MMP-3 and MMP-13. CONCLUSION: mRNA levels for both anabolic genes (collagens) and catabolic genes (MMP) in connective tissues are rapidly affected by systemic glucocorticoid treatment irrespective of skeletal maturity. This glucocorticoid sensitivity of normal tissues may lead to unwanted bystander effects when corticosteroids are used therapeutically, effects that could contribute to a negative influence on the functioning of such tissues.