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Operative treatment is assumed to provide superior outcomes to nonoperative (conservative) treatment following Achilles tendon rupture, however, this remains controversial. This study explores the effect of surgical repair on Achilles tendon healing. Rat Achilles tendons (n = 101) were bluntly transected and were randomized into groups receiving repair or non-repair treatments. By 1 week after injury, repaired tendons had inferior mechanical properties, which continued to 3- and 6-week post-injury, evidenced by decreased dynamic modulus and failure stress. Transcriptomics analysis revealed7000 differentially expressed genes between repaired and non-repaired tendons after 1-week post-injury. While repaired tendons showed enriched inflammatory gene signatures, non-repaired tendons showed increased tenogenic, myogenic, and mechanosensitive gene signatures, with200-fold enrichment in Tnmd expression. Analysis of gastrocnemius muscle revealed elevated MMP activity in tendons receiving repair treatment, despite no differences in muscle fiber morphology. Transcriptional regulation analysis highlighted that the highest expressed transcription factors in repaired tendons were associated with inflammation (Nfκb, SpI1, RelA, and Stat1), whereas non-repaired tendons expressed markers associated with tissue development and mechano-activation (Smarca1, Bnc2, Znf521, Fbn1, and Gli3). Taken together, these data highlight distinct differences in healing mechanism occurring immediately following injury and provide insights for new therapies to further augment tendons receiving repaired and non-repaired treatments.

Although the safety of contact sports has improved over the years, participation in any sport always carries a risk of injury. When cervical or lumbar spine injuries do occur, prompt diagnosis is essential, and athletes must be held out of the sport if indicated to prevent further harm and allow for recovery. This article highlights some of the most common cervical spine pathologies (stinger/burners, strain, stenosis/cord neuropraxia, disc herniation, and fracture/instability) and lumbar spine pathologies (strain, disc degeneration, disc herniation, fracture, spondylolysis/spondylolisthesis, and scoliosis) encountered in sports and reviews the associated return to play guidelines and expectations for each condition.

Given its complex shape and relatively small size, the trapezium surface at the trapeziometacarpal (TMC) joint is a particularly attractive target for anatomic biologic joint resurfacing, especially given its propensity to develop osteoarthritis, and the limited and sub-optimal treatment options available. For this to advance to clinical translation, however, an appropriate large animal model is required. In this study, we explored the porcine accessory carpal bone (ACB) as a model for the human trapezium. We characterized ACB anatomy, geometry, joint and tissue-scale mechanics, and composition across multiple donors. We showed that the ACB is similar both in size, and in the saddle shape of the main articulating surface to the human trapezium, and that loads experienced across each joint are similar. Using this information, we then devised a fabrication method and workflow to produce patient-specific tissue-engineered replicas based on CT scans, and showed that when such replicas are implanted orthotopically in an ex vivo model, normal loading is restored. Data from this study establish the porcine ACB as a model system in which to evaluate function of engineered living joint resurfacing strategies. STATEMENT OF SIGNIFICANCE: Biologic joint resurfacing, or the replacement of a joint with living tissue as opposed to metal and plastic, is the holy grail of orthopaedic tissue engineering. However, despite marked advances in engineering native-like osteochondral tissues and in matching patient-specific anatomy, these technologies have not yet reached clinical translation. Given its propensity for developing osteoarthritis, as well as its small size and complex shape, the trapezial surface of the trapeziometacarpal joint at the base of the thumb presents a unique opportunity for pursuing a biologic joint resurfacing strategy. This work establishes the porcine accessory carpal bone as an animal model for the human trapezium and presents a viable test-bed for evaluating the function of engineered living joint resurfacing strategies.

Articular cartilage injury can lead to joint-wide erosion and the early onset of osteoarthritis. To address this, we recently developed a rapid fabrication method to produce patient-specific engineered cartilage tissues to replace an entire articular surface. Here, we extended that work by coupling a mesenchymal stromal cell-laden hydrogel (methacrylated hyaluronic acid) with the porous polycaprolactone (PCL) bone integrating phase and assessed the composition and mechanical performance of these constructs over time. To improve initial construct stability, PCL/hydrogel interface parameters were first optimized by varying PCL pretreatment (with sodium hydroxide before ethanol) before hydrogel infusion. Next, cylindrical osteochondral constructs were formed and cultured in media containing transforming growth factor β3 for up to 8 weeks, with constructs evaluated for viability, histological features, and biochemical content. Mechanical properties were also assessed in axial compression and via an interface shear strength assay. Results showed that the fabrication process was compatible with cell viability, and that construct biochemical content and mechanical properties increased with time. Interestingly, compressive properties peaked at 5 weeks, while interfacial shear properties continued to improve beyond this time point. Finally, these fabrication methods were combined with a custom mold developed from limb-specific computed tomography imaging data to create an anatomic implantable cell-seeded biologic joint surface, which showedmaturation similar to the osteochondral cylinders. Future work will apply these advances in large animal models of critically sized osteochondral defects to study repair and whole joint resurfacing.

Background: Hyperpronation of the first metatarsal in hallux valgus (HV) is poorly understood by conventional weightbearing radiography. We aimed to evaluate this parameter using weightbearing computed tomography (WBCT) and to understand its association with other standard measurements. Methods: Retrospective evaluation of WBCT and weightbearing radiographs (WBXRs) was performed for 20 patients with HV feet and 20 controls with no such deformity. Axial computed tomography images of both groups were compared for the first metatarsal pronation angle (alpha angle) and tibial sesamoid subluxation (TSS) grades. The HV angle (HVA), first-second intermetatarsal angle (IMA), first metatarsal-medial cuneiform angle (MMCA), Meary’s angle, and calcaneal pitch (CP) angle of the study and control groups were compared on both WBXR and the corresponding 2-dimensional images of WBCT. All measurements were independently performed by 1 musculoskeletal radiology fellow and 1 foot and ankle surgical fellow. Measurements were averaged and interobserver reliability was calculated. Results: The HV group demonstrated significantly higher values for TSS grade ( P < .001) but not for alpha angle ( P = .121) compared with controls. Likewise, significantly elevated HVA and IMA were noted in the HV group on both imaging modalities, while no such differences were observed for the CP angle. Higher MMCA and Meary’s angle in the HV group were evident only on WBXR (MMCA, P = .039; Meary’s, P = .009) but not on WBCT (MMCA, P = .183; Meary’s, P = .171). Among all, the receiver operating characteristic (ROC) curves demonstrated the greatest area under the curve (AUC) for HVA, followed by IMA. The alpha angle performed only just outside the range of chance (AUC, 0.65; 95% CI, 0.52-0.69). The Pearson’s correlations of the alpha angle, in the HV group, revealed a significant linear relationship with TSS grade and with HVA on WBXR, and only trended toward a weak linear relationship with IMA and with HVA on WBCT. Conclusion: The alpha angle, a measure of abnormal hyperpronation of the first metatarsal, was an independent factor that may coexist with other parameters in HV, but in isolation had limited diagnostic utility. “Abnormal” alpha angles were even observed in individuals without HV. Increases in IMA and MMCA were not necessarily associated with similar increases in alpha angle, despite moderate correlations with TSS grade and HVA on WBXR. Nevertheless, the WBCT was a useful method for assessing hyperpronation and guiding surgical management in individual cases. Level of Evidence: Level III, retrospective comparative study.

Suicide and depression among orthopaedic surgeons have recently emerged as rising concerns. Prior research has suggested that orthopaedic surgeons have the highest prevalence of suicide among surgical specialties. We sought to determine the factors associated with depression and suicidal ideation (SI) in orthopaedics, including subspecialty.A survey including demographic questions, the Beck Depression Inventory, and the Columbia-Suicide Severity Rating Scale was administered electronically via a listserv to the orthopaedic subspecialties of trauma, adult reconstruction, hand and upper extremity, shoulder and elbow, foot and ankle, spine, pediatrics, sports medicine, and oncology. The responses were quantified according to previously published criteria. The associations of demographic factors, training, and current practice environment with depression and suicidality were assessed using Fisher exact tests. Reverse stepwise multivariable logistic regression models were developed to identify factors associated with depression and SI.The responses were obtained from 661 board-certified, practicing orthopaedic surgeons. In this study, 156 surgeons (23.6%) endorsed some level of active SI in their lifetime, 200 surgeons (30.3%) reported either active or passive SI in their lifetime, and 33 surgeons (5%) reported that, on at least 1 occasion in their lifetime, they had experienced active SI with a specific plan and intention to harm themselves. Gender, relationship status, having children, and residency and/or current practice region were significantly associated with depression and/or SI. Younger age, divorce, adult reconstruction and foot and ankle subspecialties, and attending residency in the Western U.S. were found on multivariable testing to be associated with symptoms of depression and SI (odds ratios, 1.03 [per 1-year decrease in age] to 8.28).Symptoms of depression and suicidality are not uncommon among orthopaedic surgeons, and variation by gender, relationship status, and geographic location are supported by prior research. Based on our results, depression and/or SI likely affect someone close to you or someone with whom you work. The normalization of discussions surrounding emotional well-being, depression, and SI is imperative.

In this issue, a Centers for Disease Control and Prevention–funded Vaccine Safety Datalink study of 2 943 493 vaccinated persons reported an additional 7.78 cases of subdeltoid bursitis per 1 milli...

Purpose To evaluate intraoperative and early postoperative clinical outcomes using the Nice knot as an auxiliary reduction technique in displaced comminuted patellar fractures. Methods Thirty-nine patients with unilateral closed displaced comminuted patellar fractures received open reduction and internal fixation (ORIF), utilizing either Nice knot (the NK group, 24 patients) or traditional reduction (the TR group, 23 patients) techniques, were retrospectively reviewed in this study. Intra-operative surgical time and peri-operative hemoglobin were recorded. Post-operative clinical outcomes were measured using visual analgesic score, range of motion of the knee joint and the Bostman scales, and radiographic outcomes were used to evaluate fracture healing. Complications including infection, bone non-union, implant loosening, fragment displacement and painful hardware were also assessed. Results In-hospital records indicated significantly shorter surgical duration (32.6 min) in the NK group than in the TR group (63.9 min). Intraoperative blood loss was also significantly decreased in the NK group (64.7 ml) compared to the TR group (189.1 ml). Patients in the NK and TR groups were followed for mean of 12.9 months and 12.5 months respectively. The union rate was 100% (24/24) in the NK group and 91.3% (21/23) in the TR group. In the TR group, there were two non-unions, including one infected non-union. There was no difference in the visual analgesic score, the range of motion of the knee joint or the Bostman scale at last follow-up between the two groups. Conclusion The sliding, self-stabilizing Nice knot was associated with reduced surgical time, decreased intraoperative blood loss, and satisfactory postoperative outcomes in the treatment of displaced patellar fractures. Future studies are needed to ensure the generalizability of these findings to additional patient populations at other institutions.

The number of total hip arthroplasty (THA) procedures performed annually continues to rise. Specific challenges, including acetabular bone loss, are commonly encountered at the time of revision surgery, and orthopaedic surgeons must be prepared to address them. This review focuses on topics related to acetabular reconstruction, including pre-operative patient evaluation (clinical and radiographic), pre-operative planning, common causes of acetabular failure, classification of acetabular bone loss, methods of acetabular reconstruction, and clinical results based on reconstruction method. Pre-operative patient evaluation for revision THA begins with a thorough history and physical examination as well as laboratory workup to rule out infection. Detailed radiographic evaluation and pre-operative planning are also essential and will facilitate communication amongst all members of the operative team. Although there are several ways to describe acetabular bone loss, the Paprosky classification system – defined by anterosuperior and posteroinferior acetabular column integrity – is the system most commonly used today and will guide treatment strategy. Several treatment strategies have been developed and may be termed either “cemented” (e.g. impaction grafting, ring and cage construction, structural allograft) or “uncemented” (e.g. hemispheric shell ± porous metal augment, cup-cage, custom triflange acetabular component). Although each strategy has its advantages and disadvantages, the general principles remain the same. Successful treatment depends upon detailed pre-operative assessment, planning, and team-based plan execution. Uncemented techniques that allow for biologic fixation are preferred. In the special case of pelvic discontinuity, acetabular distraction is the authors’ preferred technique. Longer term studies are still needed to evaluate the longevity of each of the various reconstruction methods presented.

Rotator cuff tendon tears and tendinopathies are common injuries affecting a large portion of the population and can result in pain and joint dysfunction. Incidence of rotator cuff tears significantly increases with advancing age, and up to 90% of these tears involve the supraspinatus. Previous literature has shown that aging can lead to inferior mechanics, altered composition, and changes in structural properties of the supraspinatus. However, there is little known about changes in supraspinatus mechanical properties in context of other rotator cuff tendons. Alterations in tendon mechanical properties may indicate damage and an increased risk of rupture, and thus, the purpose of this study was to use a rat model to define age-related alterations in rotator cuff tendon mechanics to determine why the supraspinatus is more susceptible to tears due to aging than the infraspinatus, subscapularis, and teres minor. Fatigue, viscoelastic, and quasi-static properties were evaluated in juvenile, adult, aged, and geriatric rats. Aging ubiquitously and adversely affected all rotator cuff tendons tested, particularly leading to increased stiffness, decreased stress relaxation, and decreased fatigue secant and tangent moduli in geriatric animals, suggesting a common intrinsic mechanism due to aging in all rotator cuff tendons. This study demonstrates that aging has a significant effect on rotator cuff tendon mechanical properties, though the supraspinatus was not preferentially affected. Thus, we are unable to attribute the aging-associated increase in supraspinatus tears to its mechanical response alone.

Conservative (non-operative) treatment of Achilles tendon ruptures is a common alternative to operative treatment. Following rupture, ankle immobilization in plantarflexion is thought to aid healing by restoring tendon end-to-end apposition. However, early activity may improve limb function, challenging the role of immobilization position on tendon healing, as it may affect loading across the injury site. This study investigated the effects of ankle immobilization angle in a rat model of Achilles tendon rupture. We hypothesized that manipulating the ankle from full plantarflexion into a more dorsiflexed position during the immobilization period would result in superior hindlimb function and tendon properties, but that prolonged casting in dorsiflexion would result in inferior outcomes. After Achilles tendon transection, animals were randomized into eight immobilization groups ranging from full plantarflexion (160°) to mid-point (90°) to full dorsiflexion (20°), with or without angle manipulation. Tendon properties and ankle function were influenced by ankle immobilization position and time. Tendon lengthening occurred after 1 week at 20° compared to more plantarflexed angles, and was associated with loss of propulsion force. Dorsiflexing the ankle during immobilization from 160° to 90° produced a stiffer, more aligned tendon, but did not lead to functional changes compared to immobilization at 160°. Although more dorsiflexed immobilization can enhance tissue properties and function of healing Achilles tendon following rupture, full dorsiflexion creates significant tendon elongation regardless of application time. This study suggests that the use of moderate plantarflexion and earlier return to activity can provide improved clinical outcomes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Conservative treatment (non-operative) of Achilles tendon ruptures is suggested to produce equivalent capacity for return to function; however, long term results and the role of return to activity (RTA) for this treatment paradigm remain unclear. Therefore, the objective of this study was to evaluate the long term response of conservatively treated Achilles tendons in rodents with varied RTA. Sprague Dawley rats (n=32) received unilateral blunt transection of the Achilles tendon followed by randomization into groups that returned to activity after 1-week (RTA1) or 3-weeks (RTA3) of limb casting in plantarflexion, before being euthanized at 16-weeks post-injury. Uninjured age-matched control animals were used as a control group (n=10). Limb function, passive joint mechanics, tendon properties (mechanical, histological), and muscle properties (histological, immunohistochemical) were evaluated. Results showed that although hindlimb ground reaction forces and range of motion returned to baseline levels by 16-weeks post-injury regardless of RTA, ankle joint stiffness remained altered. RTA1 and RTA3 groups both exhibited no differences in fatigue properties; however, the secant modulus, hysteresis, and laxity were inferior compared to uninjured age-matched control tendons. Despite these changes, tendons 16-weeks post-injury achieved secant stiffness levels of uninjured tendons. RTA1 and RTA3 groups had no differences in histological properties, but had higher cell numbers compared to control tendons. No changes in gastrocnemius fiber size or type in the superficial or deep regions were detected, except for type 2x fiber fraction. Together, this work highlights RTA-dependent deficits in limb function and tissue-level properties in long-term Achilles tendon and muscle healing.

Background: Although nicotine and tobacco use are well established to have adverse health effects, the effects on tendons are less well understood. The purpose of this study was to investigate the effect of chronic nicotine exposure on Achilles tendon (AT) and supraspinatus tendon (SS) physiologic and mechanical properties in a rodent model. Methods: Sprague-Dawley rats (n = 20) were exposed to either 0.9% saline or 36 mg/mL nicotine through an implantable osmotic pump for 12 weeks. At 12 weeks, the AT was imaged in vivo with contrast-enhanced ultrasound (CE-US) to assess vascularity. Bilateral AT and SS were then harvested for ex vivo biomechanical analysis. Statistical analysis was performed using Student t test and Mann Whitney U test. Results: AT CE-US demonstrated a significantly increased wash-in rate in the nicotine group compared to the saline group, indicating an increase in tissue perfusion rate in the nicotine group. AT percent stress relaxation, a measure of tendon viscoelasticity, was significantly increased in the nicotine group compared to the saline group. Similarly, there was a trend toward increased SS percent stress relaxation in the nicotine group compared to the saline group. No differences in other mechanical properties were observed. Conclusion: AT perfusion rate increased and both AT and SS viscoelasticity were altered with chronic nicotine exposure at a clinically relevant dose that models the average smoker in the United States (14 cigarettes per day). Further studies are necessary to link these properties with tendon degeneration and injury. Clinical Relevance: Chronic nicotine exposure affects tendon health. Patients should be counseled as such.

The Achilles tendon is the most commonly ruptured tendon in the human body. Numerous studies have reported incidence of these injuries to be upwards of five times as common in men than women. Therefore, the objective of this study was to investigate the sex- and hormone-specific differences between Achilles tendon and muscle between female, ovariectomized female (ovarian hormone deficient), and male rats. Uninjured tissues were collected from all groups for mechanical, structural, and histological analysis. Our results showed that while cross-sectional area and failure load were increased in male tendons, female tendons exhibited superior tendon material properties and decreased muscle fiber size. Specifically, linear and dynamic moduli were increased while viscoelastic properties (e.g., hysteresis, percent relaxation) were decreased in female tendons, suggesting greater resistance to deformation under load and more efficient energy transfer, respectively. No differences were identified in tendon organization, cell shape, cellularity, or proteoglycan content. Additionally, no differences in muscle fiber type distribution were observed between groups. In conclusion, inferior tendon mechanical properties and increased muscle fiber size may explain the increased susceptibility for Achilles tendon injury observed clinically in men compared to women.

Background The saline load test has previously been shown to be an effective tool to diagnose traumatic arthrotomies, but no studies have assessed the test's efficacy in the wrist. The purpose of this study was to investigate the amount of fluid required during a saline load test to detect intra-articular wrist involvement of traumatic wounds with high sensitivity. Methods A cadaveric study was conducted using 7 thawed, fresh-frozen forequarter amputations from 7 different donors (3 male, 4 female). Specimen age (mean: 67.7 y, range: 52 to 80 y), laterality (1 right, 6 left), body weight (mean: 164.3 lbs, range: 100 to 223 lbs), and wrist range of motion (ROM) was assessed before testing. The wrist capsule was punctured with an 11-blade scalpel through the 6R radiocarpal portal site under fluoroscopic guidance to ensure the injury was intra-articular. A 19-G needle was then placed through the 3,4 radiocarpal portal site and confirmed with fluoroscopy to ensure intra-articular placement. Normal saline was then injected at a steady rate into the 3,4 radiocarpal portal site until extravasation of the saline was observed from the 6R radiocarpal arthrotomy site. The volume of saline required for extravasation from the 6R radiocarpal arthrotomy was recorded as the volume required to detect the arthrotomy. A plot of saline volumes (by percentile) was created, and a logarithmic distribution was calculated. A Wilcoxon rank-sum test was used to compare injection volumes between male and female specimens, and Pearson Coefficients were used to determine any correlations between injection volume and ROM. Results The average amount of saline that resulted in extravasation was 4 mL (range: 2 to 7 mL). In order to identify 75%, 90%, 95%, and 99% of the simulated wrist arthrotomies, 5 (95% confidence interval: 3-7), 6 (4-9), 7 (4-10), and 9 (5-14) mL were required, respectively. Pretest ROM did not correlate with saline volume. Conclusions This study demonstrates the efficacy of the saline load test in detecting traumatic arthrotomies of the wrist joint with 95% sensitivity after loading 7 mL of saline. Prompt and accurate diagnosis of traumatic arthrotomies is paramount to guide management and optimize postinjury outcomes.

The ilioinguinal approach for psoas recession over the pelvic brim allows for direct visualization and protection of the femoral nerve while preserving hip flexion strength. Hip flexion contracture is a common problem in patients with spastic paresis such as cerebral palsy and may also affect patients who have sustained trauma about the hip. These contractures may impair gait and the ability to carry out activities of daily living. The iliopsoas muscle is the main deforming force; however, contraction of the hip capsule and surrounding soft tissue may also contribute1. Iliopsoas tenotomy at the level of the lesser trochanter treats the contracture at the cost of hip flexor strength, making it difficult for ambulatory patients to climb stairs or even walk on a level surface2,3. Intramuscular psoas recession over the pelvic brim is an alternative that preserves hip flexor strength while correcting the flexion contracture4-8. In this procedure, the psoas tendon is lengthened as it traverses the pelvic brim while the iliacus is preserved (Video 1). Thus, the iliopsoas unit is fractionally lengthened, preserving its ability to flex the hip. Previous studies have shown that hip flexion strength against gravity and manual resistance is maintained while improving dynamic pelvic tilt and step length during gait after this procedure4,8. Video 1 Introduction to psoas recession over the pelvic brim. An image in the video is copyrighted by, and reproduced with permission of, the AO Foundation, Switzerland.

Purpose In the setting of acute deep upper extremity infections, evidence is lacking to guide the decision whether to send atypical cultures (fungal and acid-fast-bacillus [AFB]) during surgical debridement, especially in the presence of purulent fluid that is commonly observed with typical bacterial infections. Our purpose was to determine the frequency of positive atypical cultures and the frequency with which they alter treatment, and identify factors associated with positive atypical cultures. Methods We retrospectively identified 100 adult patients undergoing surgical debridement of acute deep infections of the upper extremity in which fungal and/or AFB cultures were sent. Necrotizing and superficial infections were excluded. Descriptive statistics were used to describe patient characteristics, infection diagnoses, number of cultures sent with corresponding rates of positivity, and treatments. Cohorts with positive and negative atypical cultures were compared with bivariate analysis for all collected variables. Results One or more immunocompromising comorbidities were present in 46% of patients. Diagnoses included soft tissue abscess (46%), suppurative flexor tenosynovitis (22%), septic arthritis (21%), osteomyelitis (9%), and septic bursitis (2%). Aerobic bacterial, anaerobic bacterial, fungal, and AFB cultures were sent in 100%, 99%, 94%, and 82% of patients, respectively. Corresponding rates of positivity were 74%, 34.3%, 5.3%, and 2.4%, respectively. Atypical cultures were positive for 7% of patients and 2.9% of all atypical tests sent. Antibiotic treatment was influenced by atypical culture data for 4% of patients. For patients with positive atypical cultures, purulence was observed during surgery in 86% of cases. Bivariate analysis demonstrated symptom duration greater than 7 days as potentially associated with atypical culture positivity. Conclusions Intraoperative purulence at the time of surgical intervention should not deter the surgeon from obtaining atypical cultures. As expected, atypical cultures are infrequently positive given the rarity of associated diseases. Symptoms greater than 7 days may predict a higher incidence of atypical culture positivity for patients being treated surgically within 30 days of initial symptom onset. Type of study/level of evidence Diagnostic IV.

Hypercholesterolemia is a serious health problem that is associated not only with heart disease, but also tendon pathology. In high cholesterol environments (e.g. familial hyperlipidemia), lipids accumulate within the tendon extracellular matrix and form deposits called xanthomas. Lipid-related changes are known to affect several tendon mechanical properties, including stiffness and modulus, in uninjured and injured tendons, alike. Mechanisms to explain these cholesterol-related changes are multiple, including alterations in tenocyte gene and protein expression, matrix turnover, tissue vascularity, and cytokine production. Clinically, rotator cuff tear and Achilles tendon rupture are clearly associated with metabolic derangements, and elevated total cholesterol is often among the specific metabolic parameters implicated. Treatment of hypercholesterolemia using statin medications has also been shown to affect tendon properties, resulting in normalization of tendon thickness and improved tendon healing. Despite current work, the pathophysiology of lipid-related tendon pathology remains incompletely understood, and additional hypothesis-generating studies, including those incorporating whole-genome and whole-transcriptome technologies, will help to point the field in new directions.

Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior postinjury tendon properties compared with females. Male, female, and OVX Sprague-Dawley rats ( n = 32/group) underwent acclimation and treadmill training before blunt transection of the Achilles tendon midsubstance. Injured hindlimbs were immobilized for 1 wk, followed by gradual return to activity and assessment of active and passive hindlimb function. Animals were euthanized at 3 or 6 wk postinjury to assess tendon structure, mechanics, and composition. Passive ankle stiffness and range of motion were superior in females at 3 wk; however, by 6 wk, passive and active function were similar in males and females but remained inferior in OVX. At 6 wk, female tendons had greater normalized secant modulus, viscoelastic behavior, and laxity compared with males. Normalized secant modulus, cross-sectional area and tendon glycosaminoglycan composition were inferior in OVX compared with females at 6 wk. Total fatigue cycles until tendon failure were similar among groups. Postinjury muscle fiber size was better preserved in females compared with males, and females had greater collagen III at the tendon injury site compared with males at 6 wk. Despite male and female Achilles tendons withstanding similar durations of fatigue loading, early passive hindlimb function and tendon mechanical properties, including secant modulus, suggest superior healing in females. Ovarian hormone loss was associated with inferior Achilles tendon healing.

The Achilles tendon is the most commonly ruptured tendon in the human body. Numerous studies have reported incidence of these injuries to be upwards of five times as common in men than women. Therefore, the objective of this study was to investigate the sex- and hormone-specific differences between Achilles tendon and muscle between female, ovariectomized female (ovarian hormone deficient), and male rats. Uninjured tissues were collected from all groups for mechanical, structural, and histological analysis. Our results showed that while cross-sectional area and failure load were increased in male tendons, female tendons exhibited superior tendon material properties and decreased muscle fiber size. Specifically, linear and dynamic moduli were increased while viscoelastic properties (e.g., hysteresis, percent relaxation) were decreased in female tendons, suggesting greater resistance to deformation under load and more efficient energy transfer, respectively. No differences were identified in tendon organization, cell shape, cellularity, or proteoglycan content. Additionally, no differences in muscle fiber type distribution were observed between groups. In conclusion, inferior tendon mechanical properties and increased muscle fiber size may explain the increased susceptibility for Achilles tendon injury observed clinically in men compared to women.

Hypercholesterolemia is a serious health problem that is associated not only with heart disease, but also tendon pathology. In high cholesterol environments (e.g. familial hyperlipidemia), lipids accumulate within the tendon extracellular matrix and form deposits called xanthomas. Lipid-related changes are known to affect several tendon mechanical properties, including stiffness and modulus, in uninjured and injured tendons, alike. Mechanisms to explain these cholesterol-related changes are multiple, including alterations in tenocyte gene and protein expression, matrix turnover, tissue vascularity, and cytokine production. Clinically, rotator cuff tear and Achilles tendon rupture are clearly associated with metabolic derangements, and elevated total cholesterol is often among the specific metabolic parameters implicated. Treatment of hypercholesterolemia using statin medications has also been shown to affect tendon properties, resulting in normalization of tendon thickness and improved tendon healing. Despite current work, the pathophysiology of lipid-related tendon pathology remains incompletely understood, and additional hypothesis-generating studies, including those incorporating whole-genome and whole-transcriptome technologies, will help to point the field in new directions.