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ObjectiveTo assess the safety and efficacy of a novel Wnt pathway modulator, lorecivivint (SM04690), for treating pain and inhibiting structural progression in moderately to severely symptomatic knee osteoarthritis (OA).MethodsSubjects in this 52-week, phase IIa, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial received a single 2-ml intraarticular injection of lorecivivint (dose of 0.03 mg, 0.07 mg, or 0.23 mg) or placebo. Efficacy was assessed based on change from baseline on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score subscales for pain and function (scale 0-100 for each) and change from baseline in the radiographic medial joint space width (JSW). Baseline-adjusted analysis of covariance with multiple imputation was performed separately to evaluate efficacy. This proof-of-concept study evaluated the intent-to-treat population as well as a prespecified group of subjects with unilateral symptoms of knee OA (designated UNI) and an additional post hoc subgroup of subjects with unilateral symptoms but without widespread pain (designated UNI WP-).ResultsIn this trial, 455 subjects were randomized to a treatment group. The primary end point, significant improvement in the WOMAC pain score compared with placebo at week 13, was not met by any lorecivivint dose group (mean ± SD change from baseline, -23.3 ± 2.2 in the 0.03 mg group, -23.5 ± 2.1 in the 0.07 mg group, -21.3 ± 2.2 in the 0.23 mg group, and -22.1 ± 2.1 in the placebo group; each P > 0.05 versus placebo). All groups (including placebo) demonstrated clinically meaningful (≥20-point) improvements from baseline in the WOMAC pain score. The durability of response was evaluated through week 52. In the prespecified UNI group and post hoc UNI WP- group at week 52, treatment with 0.07 mg lorecivivint significantly improved the WOMAC pain score (between-group difference versus placebo, -8.73, 95% confidence interval [95% CI] -17.44, -0.03 [P = 0.049] and -11.21, 95% CI -20.99, -1.43 [P = 0.025], respectively) and WOMAC function score (between-group difference versus placebo, -10.26, 95% CI -19.82, -0.69 [P = 0.036] and -13.38, 95% CI -24.33, -2.43 [P = 0.017], respectively). Relative to baseline, the mean change in the medial JSW at week 52 was -0.04 mm in the 0.03 mg cohort, -0.09 mm in the 0.07 mg cohort, -0.16 mm in the 0.23 mg cohort, and -0.14 mm in the placebo cohort; no treatment group achieved a significant change in medial JSW compared with placebo at week 52. In both unilateral symptom subgroups, the 0.07 mg lorecivivint dose significantly increased medial JSW compared with placebo at week 52 (medial JSW 0.39 mm, 95% CI 0.06, 0.72 in the UNI group [P = 0.021] and 0.42 mm, 95% CI 0.04, 0.80 in the UNI WP- group [P = 0.032]). Changes observed in the 0.03 mg and 0.23 mg dose groups were not significantly different from those in the placebo group for any of these measures. Lorecivivint appeared safe and well tolerated.ConclusionThis phase IIa, proof-of-concept trial in patients with symptomatic knee OA did not meet its primary end point. Nevertheless, the study identified a target population in whom to evaluate the potential efficacy of lorecivivint for the treatment of knee OA.

Background: The risk of tear of the intact anterior cruciate ligament in the contralateral knee after anterior cruciate ligament reconstruction of the opposite knee and the incidence of rupturing the [...]

Keywords: compartment syndrome; synostosis; fracture; leg pain; football injury ********** Tibiofibular synostosis has been shown to result in ankle or shin pain and functional disability. (4,6,10) This report describes the [...]

Musculoskeletal disease currently is one of the biggest public health issues in terms of associated morbidity and cost. Awareness about this problem is essential to the development of education programs that promote lifestyles conducive to good bone health. Children and teenagers are at particular risk for musculoskeletal problems. The current orthopedic literature and public health programs were reviewed to present an update on musculoskeletal injury and disease in this age group. More specifically, musculoskeletal trauma, osteoarthritis, and osteoporosis are discussed in terms of their impact on daily living and on the cost of health care. Recommendations are made on how to improve bone health in children and teenagers., Musculoskeletal conditions represent a common and costly burden to the American health care system. Roughly 1 of 7 Americans receives care for a musculoskeletal problem, (1) and more than $250 [...]

Focuses on surgical management for athletes with a posterior cruciate ligament deficient knee. Observation of a symptomatology warranting surgical intervention; Presence of symptoms affecting the performance of athletes in sports; Reconstruction of PCL based from a scientific perspective.

Acute brachial neuropathy is a pathologic condition of the nerve bundle or brachial plexus which provides the nerve supply to the upper extremity. This disease of unknown origin is characterized by excessive weakness, muscular wasting and pain in the shoulder. The condition can occur in anyone, but when it occurs in athletes it must be differentially diagnosed relative to other possible traumatic injuries. This study discusses the clinical presentation, evaluation and outcome of five athletes in whom a diagnosis of acute brachial neuropathy was made. These patients were seen in a sports medicine practice during an eight-year period. In preparation for this study they were contacted and agreed to return to the clinic to be re-evaluated. Physical examination, a review of their medical history and electrophysiologic tests were performed. The data from their original diagnosis was compared to the findings of the follow-up visit. The clinical case studies are presented in detail. Physicians must be alert to the possibility of acute brachial neuropathy in individuals who participate in both contact and noncontact sports. This diagnosis should be considered when there is a sudden onset of pain without apparent trauma, particularly when the symptoms continue despite rest. The neurologic examination may indicate a scattered or patch type of neurologic degeneration which can often be confirmed by the use of electrophysiologic testing, electromyography. Although the prognosis for the condition is generally good, residual deficits and recurrences do occur. Athletic activities may be resumed after recovery of adequate strength. Physician's judgement and a case by case determination is required for making this diagnosis.