Nigel Zheng

SCLEROSTIN INHIBITION PREVENTS SPINAL CORD INJURY INDUCED CANCELLOUS BONE LOSS

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte‐derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl‐Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl‐Ab to that of testosterone‐enanthate (TE), an agent that we have previously shown prevents SCI‐induced bone loss. Fifty‐five (nu2009=u200911–19/group) skeletally mature male Sprague‐Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate‐severe (250 kilodyne) SCI, (C) 250 kilodyne SCIu2009+u2009TE (7.0u2009mg/wk, im), or (D) 250 kilodyne SCIu2009+u2009Scl‐Ab (25u2009mg/kg, twice weekly, sc) for 3 weeks. Twenty‐one days post‐injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via μCT and histomorphometry) and distal femur (via μCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and platelike trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl‐Ab and TE both prevented SCI‐induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl‐Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCIu2009+u2009Scl‐Ab and SCIu2009+u2009TE animals, whereas only Scl‐Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI‐induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl‐Ab prevents osteoporosis in the SCI population.

Influence of Aromatase Inhibition on the Bone‐Protective Effects of Testosterone

The influence of the aromatase enzyme in androgen‐induced bone maintenance after skeletal maturity remains somewhat unclear. Our purpose was to determine whether aromatase activity is essential to androgen‐induced bone maintenance. Ten‐month‐old male Fisher 344 rats (nu2009=u200973) were randomly assigned to receive Sham surgery, orchiectomy (ORX), ORXu2009+u2009anastrozole (AN; aromatase inhibitor), ORXu2009+u2009testosterone‐enanthate (TE, 7.0u2009mg/wk), ORXu2009+u2009TEu2009+u2009AN, ORXu2009+u2009trenbolone‐enanthate (TREN; nonaromatizable, nonestrogenic testosterone analogue; 1.0u2009mg/wk), or ORXu2009+u2009TRENu2009+u2009AN. ORX animals exhibited histomorphometric indices of high‐turnover osteopenia and reduced cancellous bone volume compared with Shams. Both TE and TREN administration suppressed cancellous bone turnover similarly and fully prevented ORX‐induced cancellous bone loss. TE‐ and TREN‐treated animals also exhibited greater femoral neck shear strength than ORX animals. AN co‐administration slightly inhibited the suppression of bone resorption in TE‐treated animals but did not alter TE‐induced suppression of bone formation or the osteogenic effects of this androgen. In TREN‐treated animals, AN co‐administration produced no discernible effects on cancellous bone turnover or bone volume. ORX animals also exhibited reduced levator ani/bulbocavernosus (LABC) muscle mass and elevated visceral adiposity. In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co‐administration did not alter androgen‐induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon–bone interface

Treatment of tendon–bone junction injuries is a challenge because tendon–bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet‐rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft–bone tunnel model. The experimental rats received KGN‐PRP or PRP injections in the tendon graft–bone tunnel interface. The control group received saline. After 4, 8 and 12u2005weeks, Safranin O staining of the tendon graft–bone tunnels revealed abundant proteoglycans in the KGN‐PRP group indicating the formation of cartilage‐like transition zone. Immunohistochemical and immuno‐fluorescence staining revealed collagen types I (Col‐I) and II (Col‐II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage‐like tissues and minimal Col‐I and Col‐II staining. Some gaps were also present in the saline control group. Finally, pull‐out strength in the KGN‐PRP‐treated group at 8u2005weeks was 1.4‐fold higher than the PRP‐treated group and 1.6‐fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN‐PRP may be used as a convenient cell‐free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon–bone interface and hence the clinical outcome of these procedures. Copyright

Reliability of the sub-components of the instrumented timed up and go test in ambulatory children with traumatic brain injury and typically developed controls

BACKGROUNDnStudies have evaluated the test-re-test reliability of subcomponents of the timed up and-go test in adults by using body-worn inertial sensors. However, studies in children have not been reported in the literature.nnnRESEARCH QUESTIONnTo evaluate the within-session reliability of subcomponents of a newly developed electronically augmented timed upand-go test (EATUG) in ambulatory children with traumatic brain injury (TBI) and children with typical development (TD).nnnMETHODnThe timed up and go test was administered to twelve consecutive ambulatory children with moderate to severe TBI (6 males and 6 females, age 10.5u202f±u202f1.5 years, range 8-13 years, during inpatient rehabilitation at 27.0u202f±u202f11.8 days following injury) and 10 TD age and sex-matched children (5 males and 5 females, 10.4u202f±u202f1.3 years, range 8-11u202fyears). Participants wore a single chest-mounted inertial measurement sensor package with custom software that measured angular and acceleration velocity and torso flexion and extension angles, while they performed 6 trials of the EATUG test. Measures were derived from the overall time to complete the TUG test, angular velocity and angular displacement data for torso flexion and extension during sit-to-stand and stand-to-sit segments and both mean and peak angular velocities for two turning segments (i.e. turning around a cone and turning-before-sitting).nnnRESULTSnWithin-session reliability of the subcomponents of the TUG test for children with TBI assessed by the intra-class correlation coefficient was ICC (1,1)u202f=u202f0.84, (range 0.82-0.96), and for TD children ICC (1,1)u202f=u202f0.73, (range 0.53-0.89). Scores on Total Time, maximum torso flexion/extension angle and peak flexion angular velocity during sit-tostand, and peak turn angular velocity for both turns around the cone and turns before sitting were lower for children with TBI than for TD children (pu202f≤u202f0.05).nnnSIGNIFICANCEnThe EATUG test is a reliable measure of physical function in children with TBI who are being discharged from inpatient rehabilitation.

Biceps Tenodesis: Biomechanical Assessment of 3 Arthroscopic Suprapectoral Techniques.

Biceps tenodesis maintains the cosmetic appearance and length-tension relationship of the biceps with an associated predictable clinical outcome compared with tenotomy. Arthroscopic suprapectoral techniques are being developed to avoid the disadvantages of the open subpectoral approach. This study biomechanically compared 3 arthroscopic suprapectoral biceps tenodesis techniques performed with a suture anchor with lasso loop technique, an interference screw, and a compressive rivet. For a total of 15 randomized paired tests, 15 pairs of human cadaveric shoulders were used to test 1 technique vs another 5 times with 3 customized setups. Biomechanical testing was performed with an electromechanical testing system. The tendon was preloaded with 10 N and cyclically loaded at 0 to 40 N for 50 cycles. Load to failure testing was performed at 1 mm/s until failure occurred. The compressive rivet, interference screw, and suture anchor with lasso loop had mean load to failure of 97.1 N, 146.4 N, and 157.6 N, respectively. The difference in ultimate strength between the suture anchor with lasso loop and the compressive rivet was statistically significant (P=.04). No significant differences were found between the suture anchor with lasso loop and the interference screw (P=.93) or between the interference screw and the rivet (P=.10). When adjusted for sex, the load to failure overall among the 3 constructs was not significantly different. All 3 techniques had a different predominant mechanism of failure. The suture anchor with lasso loop showed superior load to failure compared with the compressive rivet. The minimum load to failure required to achieve clinically reliable biceps tenodesis is unknown. [Orthopedics. 2017; 40(6):e1009-e1016.].

Kartogenin: A Novel Cell Free Treatment Modality for Tendon-Bone Junction Injuries

Introduction/Purpose: Tendon-bone junction (TBJ) injuries are very common and optimal treatment modalities are lacking. TBJ injuries often heal without formation of the fibrocartilage transition zone increasing the risk of rerupture. Current treatments only attach tendons to bones but do not promote healing or regeneration of the fibrocartilage zone. Therefore, we developed a novel approach to heal wounded TBJ using a small molecule called kartogenin (KGN). KGN was previously shown to induce chondrogenesis of tendon stem/progenitor cells (TSCs) in vitro and enhance wound healing in injured rat TBJs in vivo after shortterm treatment (2 weeks). It is not known whether these effects can be maintained longterm. Therefore, we studied the long term (3 months) effects of KGN on achilles-tendon-bone junction healing.

Ulnar Collateral Ligament and Elbow Joint Loading During Throwing

Ulnar collateral ligament (UCL) rupture is one of the most common throwing arm injuries for throwing athletes. Reconstructive surgery known as Tommy John surgery is often performed to restore joint stability [1]. According to the 2002 Major League Baseball Disability Analysis, almost 70% of players on the disabled list are pitchers and throwing arm related injuries account for 53% of all disabled list placements. To reach a high ball speed, pitchers cock, or excessively externally rotate their pitching arm to or near an extreme ROM of 180° [2]. The shoulder is then immediately internally rotated at over 7000°/s after the leading foot contact. The excessive external rotation ROM and astonishing internal rotation velocity are thought to contribute to throwing arm injury [3]. Repeated exposure to the large valgus torque may cause excessive laxity and catastrophic rupture of UCL [2]. A recent study showed that uninjured pitchers with higher elbow valgus torque exhibited UCL thickening whereas uninjured pitchers with lower elbow valgus torque did not have such adaptation in UCL appearance [4]. It is believed that microtear and catastrophic rupture of UCL are related to higher elbow valgus torque [2]. However, it is not clear how the conditions of the UCL are related to the elbow valgus torque during throwing. Therefore, it is our interest to investigate risk factors to throwing arm injuries. In this study, we investigated the elbow joint loading during throwing among subjects without UCL injury at the time of testing and after testing, with UCL reconstruction (UCL-R) at the time of testing, and UCL reconstruction after testing (PUCL-R). It was hypothesized that there was no significant differences in elbow joint loading between subjects with UCL-R, PUCL-R and uninjured groups. Findings from this may improve our understanding of UCL injury and assist us to identify risk factors for UCL injury.Copyright

Knee Joint Rotation and Loading During Turning After Anterior Cruciate Ligament Reconstruction

Abnormal knee movement during dynamic activities after ACL rupture has been reported[1–3]. A reconstructive surgery is recommended by orthopedic surgeons to restore joint stability. After ACL reconstructive surgery and rehabilitation that follows the normal knee movement has not been fully restored, especially for the nonsagittal plane rotations, during walking and high demanding activities (stairs, pivoting, cutting, jump and landing, etc.) [2, 4–10].© 2012 ASME

Shoulder Rotational Laxity is Related to Joint Loading During Throwing

Throwing arm injuries are common and often related to shoulder rotational laxity. Both shoulder external and internal rotational laxity are often checked in a physical assessment. The shoulder external rotation of the throwing arm during physical assessment is reported to be about 10 degree greater than the non-throwing arm [1]. Throwing arm injuries often occur during throwing activities. High forces and torques were generated during throwing activity. Extremely high shoulder external rotation (about 180°) and high internal rotation velocity (over 7000°/s) during baseball pitching are reported [2].Copyright

Shoulder Rotation Laxity is Related to Pitching Mechanics

According to the 2002 Major League Baseball Disability Analysis, almost 70% of players on the disabled list are pitchers and throwing arm related injuries account for 53% of all disabled list placements. To reach a high ball speed, pitchers cock, or excessively externally rotate their pitching arm to or near an extreme ROM of 180° [1]. The shoulder is then immediately internally rotated to an astonishing 7000°/s after the leading foot contact. The excessive external rotation ROM and astonishing internal rotation velocity are thought to contribute to injury [2]. Repeated exposure to the excessive ROM and large shoulder loads may cause excessive laxity to the anterior shoulder and/or damage the soft tissue [2]. This can lead to shoulder instability and excessive humeral head translation that may cause impingement [3]. Therefore, the mobility and stability of the thrower’s shoulder are extremely relevant to performance and injury prevention.Copyright