In Vivo Syndesmotic Motion After Rigid and Flexible Fixation Using 4-Dimensional Computerized Tomography.

INTRODUCTION: Maintaining reduction after syndesmotic injury is crucial to patient function; however, malreduction remains common. Flexible suture button fixation may allow more physiologic motion of the syndesmosis compared with rigid screw fixation. Conventional syndesmotic imaging fails to account for physiologic syndesmotic motion with ankle range of motion (ROM), providing misleading results. Four-dimensional computerized tomography (4DCT) can image joints through a dynamic ROM. Our purpose was to compare syndesmotic motion after rigid and flexible fixation using 4DCT. METHODS: We analyzed 13 patients with syndesmotic injury who were randomized to receive rigid (n = 7) or flexible (n = 6) fixation. Patients underwent bilateral ankle 4DCT while moving between ankle dorsiflexion and plantar flexion. Measures of syndesmotic position and rotation were extracted from 4DCT to determine syndesmotic motion as a function of ankle ROM. RESULTS: Uninjured ankles demonstrated significant decreases in syndesmotic width of 1.0 mm with ankle plantar flexion (SD = 0.6 mm, P < 0.01). Initial rigid fixation demonstrated reduced motion compared with uninjured ankles in 4 of 5 measures (P < 0.01) despite all patients in the rigid fixation group having removed, loose, or broken screws by the time of imaging. Rigid fixation led to less motion than flexible fixation in 3 measures (P = 0.02-0.04). There were no observed differences in syndesmotic position or motion between flexible fixation and uninjured ankles. CONCLUSION: Despite the loss of fixation in all subjects in the rigid fixation group, initial rigid fixation led to significantly reduced syndesmotic motion. Flexible fixation recreated more physiologic motion compared with rigid fixation and may be used to reduce rates of syndesmotic malreduction. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Four-Dimensional CT Analysis of Normal Syndesmotic Motion.

BACKGROUND: The syndesmosis ligament complex stabilizes the distal tibiofibular joint while allowing for small amounts of physiologic motion. When injured, malreduction of the syndesmosis is the most important factor that contributes to inferior functional outcomes. Syndesmotic reduction is a dynamic measure, which is not adequately captured by conventional computed tomography (CT). Four-dimensional CT (4DCT) can image joints as they move through range of motion (ROM). The aim of this study was to employ 4DCT to determine in vivo syndesmotic motion with ankle ROM in uninjured ankles. METHODS: Uninjured ankles were analyzed in patients who had contralateral syndesmotic injuries, as well as a cohort of healthy volunteers with bilateral uninjured ankles. Bilateral ankle 4DCT scans were performed as participants moved their ankles between maximal dorsiflexion and plantarflexion. Multiple measures of syndesmotic width, as well as sagittal translation and fibular rotation, were automatically extracted from 4DCT using a custom program to determine the change in syndesmotic position with ankle ROM. RESULTS: Fifty-eight ankles were analyzed. Measures of syndesmotic width decreased by 0.7 to 1.1 mm as the ankle moved from dorsiflexion to plantarflexion (P < .001 for each measure). The fibula externally rotated by 1.2 degrees with ankle ROM (P < .001), but there was no significant motion in the sagittal plane (P = .43). No participants with bilateral uninjured ankles had a side-to-side difference in syndesmotic width of 2 mm or greater. CONCLUSION: 4DCT allows accurate, in vivo syndesmotic measurements, which change with ankle ROM, confirming prior work that was limited to biomechanical studies. Side-to-side syndesmotic measurements are consistent within subjects, validating the method of templating syndesmotic reduction off the contralateral ankle, in a consistent ankle position, to achieve anatomic reduction of syndesmotic injury. LEVEL OF EVIDENCE: Level II, prospective cohort study.

Oxidative Stress Mediates the Fetal Programming of Hypertension by Glucocorticoids.

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

Whole transcriptome analysis of adrenal glands from prenatal glucocorticoid programmed hypertensive rodents.

Prenatal glucocorticoid exposure is associated with the development of hypertension in adults. We have previously demonstrated that antenatal dexamethosone (DEX) administration in Wistar-Kyoto dams results in offspring with increased blood pressure coupled with elevated plasma epinephrine levels. In order to elucidate the molecular mechanisms responsible for prenatal DEX-mediated programming of hypertension, a whole-transcriptome analysis was performed on DEX programmed WKY male adrenal glands using the Rat Gene 2.0 microarray. Differential gene expression (DEG) analysis of DEX-exposed offspring compared with saline-treated controls revealed 142 significant DEGs (109 upregulated and 33 downregulated genes). DEG pathway enrichment analysis demonstrated that genes involved in circadian rhythm signaling were most robustly dysregulated. RT-qPCR analysis confirmed the increased expression of circadian genes Bmal1 and Npas2, while Per2, Per3, Cry2 and Bhlhe41 were significantly downregulated. In contrast, gene expression profiling of Spontaneously Hypertensive (SHR) rats, a genetic model of hypertension, demonstrated decreased expression of Bmal1 and Npas2, while Per1, Per2, Per3, Cry1, Cry2, Bhlhe41 and Csnk1D were all upregulated compared to naïve WKY controls. Taken together, this study establishes that glucocorticoid programmed adrenals have impaired circadian signaling and that changes in adrenal circadian rhythm may be an underlying molecular mechanism responsible for the development of hypertension.

Increasing Rates of Arthroplasty for Psoriatic Arthritis in the United Kingdom Between 1995 and 2010.

OBJECTIVE: Arthroplasty requirements among patients with psoriatic arthritis (PsA) are not well known. This information is important to clinical and policy stakeholders for health-system planning and may serve as a surrogate for estimation of the efficacy of disease-modifying therapy. METHODS: We utilized The Health Improvement Network (THIN), a large general practice medical records database in the UK, to assess rates of primary total arthroplasty among patients with PsA and the general population between the years 1995 and 2010. Linear regression was used to estimate arthroplasty rates for the 2 cohorts during the study period, and Poisson regression was used to determine age- and sex-adjusted incidence rate ratios (IRRs) between the PsA and general population cohorts. RESULTS: We identified 5,619 patients with incident PsA and 5,090,814 eligible patients from the general population between 1995 and 2010. In total, 187 primary total arthroplasties were documented in patients with PsA, and 80,163 primary total arthroplasties were documented in the general population. A trend of increasing arthroplasty rates was observed for both the PsA (R2 = 0.809; P < 0.0001) and general population (R2 = 0.890; P < 0.0001) cohorts during the study period. After adjustment for age and sex, patients with PsA had a first arthroplasty incidence rate that was twice that of the general population (IRR 2.01 [95% confidence interval 1.73-2.34]; P < 0.0001), notably beyond the year 2003 when biologic therapies were introduced. CONCLUSION: Both the general population and patients with PsA have experienced increasing rates of first arthroplasty from 1995 to 2010, although the overall incidence rate was significantly higher for those with PsA.

Psoriasis and the risk of foot and ankle tendinopathy or enthesopathy in the absence of psoriatic arthritis: a population-based study.

OBJECTIVES: Imaging studies in patients with cutaneous psoriasis have demonstrated asymptomatic bone and tendon changes, commonly of the foot and ankle. We sought to determine if patients with cutaneous psoriasis have an increased risk of clinically significant foot and ankle tendinopathy or enthesopathy compared with the general population. METHODS: Patients with cutaneous psoriasis and a general population cohort were identified in The Health Improvement Network, a general practice medical records database from the UK. All patients with psoriatic arthritis were excluded. Cox proportional-hazards models (α=0.05) estimated the HR for development of foot and ankle tendinopathy or enthesopathy among patients with psoriasis, with adjustment for numerous covariates. RESULTS: In total, 78 630 patients with cutaneous psoriasis and 5 983 338 persons from the general population were identified. In an unadjusted model, patients with cutaneous psoriasis had a 25% increased risk of developing foot and ankle tendinopathy or enthesopathy compared with the general population (HR 1.25, 95% CI 1.20 to 1.30, p<0.0001). The HR remained unchanged and statistically significant after adjusting for covariates, and in sensitivity analyses. CONCLUSIONS: These data suggest that patients with psoriasis can have foot and ankle tendinopathy or enthesopathy without having psoriatic arthritis, presenting a diagnostic challenge to physicians. Further research is needed to elucidate mechanisms contributing to this increased risk.

Foot structure and knee joint kinetics during walking with and without wedged footwear insoles.

The relationship between static foot structure characteristics and knee joint biomechanics during walking, or the biomechanical response to wedged insoles are currently unknown. In this study, 3D foot scanning, dual X-ray absorptiometry and gait analysis methods were used to determine structural parameters of the foot and assess their relation to knee joint loading and biomechanical response to wedged insoles in 30 patients with knee osteoarthritis. In multiple linear regression models, foot fat content, height of the medial longitudinal arch and static hind foot angle were not associated with the magnitude of the knee adduction moment (R2 = 0.24, p = 0.060), knee adduction angular impulse (R2 = 0.21, p = 0.099) or 3D resultant knee moment (R2 = 0.23, p = 0.073) during gait. Furthermore, these foot structure parameters were not associated with the patients' biomechanical response to medial or lateral wedge footwear insoles (all p < 0.01). These findings suggest that static foot structure is not associated with gait mechanics at the knee, and that static foot structure alone cannot be utilized to predict an individual's biomechanical response to wedged footwear insoles in patients with knee osteoarthritis.

Syndesmotic Injury Assessment With Lateral Imaging During Stress Testing in a Cadaveric Model.

BACKGROUND: External rotation, lateral, and sagittal stress tests are commonly used to diagnose syndesmotic injuries, but their efficacy remains unclear. The purpose of this study was to characterize applied stresses with fibular motion throughout the syndesmotic injury spectrum. We hypothesized that sagittal fibular motion would have greater fidelity in detecting changes in syndesmotic status compared to mortise imaging. METHODS: Syndesmotic instability was characterized using motion analysis during external rotation, lateral, and sagittal stress tests on cadaveric specimens (n = 9). A progressive syndesmotic injury was created by sectioning the tibiofibular and deltoid ligaments. Applied loads and fibular motion were synchronously measured using a force transducer and motion capture, respectively, while mortise and lateral radiographs were acquired to quantify clinical measurements. Fibular motion in response to these 3 stress tests was compared between the intact, complete lateral syndesmotic injury and lateral injury plus a completely sectioned deltoid condition. RESULTS: Stress tests performed under lateral imaging detected syndesmotic injuries with greater sensitivity than the clinical-standard mortise view. Lateral imaging was twice as sensitive to applied loads as mortise view imaging. Specifically, half as much linear force generated 2 mm of detectable syndesmotic motion. In addition, fibular motion increased linearly in response to sagittal stresses (Pearson's r [ρ] = 0.91 ± 0.1) but not lateral stresses (ρ = 0.29 ± 0.66). CONCLUSION: Stress tests using lateral imaging detected syndesmotic injuries with greater sensitivity than a typical mortise view. In addition to greater diagnostic sensitivity, reduced loads were required to detect injuries. CLINICAL RELEVANCE: Syndesmotic injuries may be better diagnosed using stress tests that are assessed using lateral imaging than standard mortise view imaging.

Effect of Complete Syndesmotic Disruption and Deltoid Injuries and Different Reduction Methods on Ankle Joint Contact Mechanics.

BACKGROUND: Syndesmotic injuries can be associated with poor patient outcomes and posttraumatic ankle arthritis, particularly in the case of malreduction. However, ankle joint contact mechanics following a syndesmotic injury and reduction remains poorly understood. The purpose of this study was to characterize the effects of a syndesmotic injury and reduction techniques on ankle joint contact mechanics in a biomechanical model. METHODS: Ten cadaveric whole lower leg specimens with undisturbed proximal tibiofibular joints were prepared and tested in this study. Contact area, contact force, and peak contact pressure were measured in the ankle joint during simulated standing in the intact, injured, and 3 reduction conditions: screw fixation with a clamp, screw fixation without a clamp (thumb technique), and a suture-button construct. Differences in these ankle contact parameters were detected between conditions using repeated-measures analysis of variance. RESULTS: Syndesmotic disruption decreased tibial plafond contact area and force. Syndesmotic reduction did not restore ankle loading mechanics to values measured in the intact condition. Reduction with the thumb technique was able to restore significantly more joint contact area and force than the reduction clamp or suture-button construct. CONCLUSION: Syndesmotic disruption decreased joint contact area and force. Although the thumb technique performed significantly better than the reduction clamp and suture-button construct, syndesmotic reduction did not restore contact mechanics to intact levels. CLINICAL RELEVANCE: Decreased contact area and force with disruption imply that other structures are likely receiving more loads (eg, medial and lateral gutters), which may have clinical implications such as the development of posttraumatic arthritis.

Three-Dimensional Analysis of Fibular Motion After Fixation of Syndesmotic Injuries With a Screw or Suture-Button Construct.

BACKGROUND: Suture-button constructs are an alternative to screw fixation for syndesmotic injuries, and proponents advocate that suture-button constructs may allow physiological motion of the syndesmosis. Recent biomechanical data suggest that fibular instability with syndesmotic injuries is greatest in the sagittal plane, but the design of a suture-button construct, being a rope and 2 retention washers, is most effective along the axis of the rope (in the coronal plane). Some studies report that suture-button constructs are able to constrain fibular motion in the coronal plane, but the ability of a tightrope to constrain sagittal fibular motion is unknown. The purpose of this study was to assess fibular motion in response to an external rotation stress test in a syndesmotic injury model after fixation with a screw or suture-button constructs. METHODS: Eleven fresh-frozen cadaver whole legs with intact tibia-fibula articulations were secured to a custom fixture. Fibular motion (coronal, sagittal, and rotational planes) in response to a 6.5-Nm external rotation moment applied to the foot was recorded with fluoroscopy and a high-resolution motion capture system. Measures were taken for the following syndesmotic conditions: intact, complete lateral injury, complete lateral and deltoid injury, repair with a tetracortical 4.0-mm screw, and repair with a suture button construct (Tightrope; Arthrex, Naples, FL) aimed from the lateral fibula to the anterior medial malleolus. RESULTS: The suture-button construct allowed significantly more sagittal plane motion than the syndesmotic screw. Measurements acquired with mortise imaging did not detect differences between the intact, lateral injury, and 2 repair conditions. External rotation of the fibula was significantly increased in both injury conditions and was not restored to intact levels with the screw or the suture-button construct. CONCLUSION: A single suture-button placed from the lateral fibula to the anterior medial malleolus was unable to replicate the motion observed in the intact specimen when subjected to an external rotation stress test and allowed significantly more posterior motion of the fibula than when fixed with a screw in simulated highly unstable injuries. CLINICAL RELEVANCE: Fixation of a syndesmotic injury with a single suture-button construct did not restore physiological fibular motion, which may have implications for postoperative care and clinical outcomes.

Analysis of Total Ankle Arthroplasty Survival in the United States Using Multiple State Databases.

UNLABELLED: The aim of this study was to evaluate survivorship and risk factors for failure of total ankle arthroplasty (TAA) in the United States using large statewide, multipayer databases of inpatient discharges. TAA patients from 2005 to 2009 were identified from the Healthcare Cost and Utilization Project databases for 5 states (California, Florida, Nebraska, North Carolina, and Utah) and the New York Department of Health Statewide Planning and Research Cooperative System database. Patient demographics and clinical characteristics were extracted, and a multivariable logistic regression model was developed to assess risk factors for 90-day all-cause readmission and failure. Failure was defined as revision, arthrodesis, amputation, or implant removal. During the period of interest, 1545 patients received 1593 TAA. The coded etiology of arthritis was primary osteoarthritis (n = 854, 55.2%), posttraumatic arthritis (n = 466, 30.2%), rheumatoid arthritis (n = 129, 8.4%), and other (n = 96, 6.2%). The 5-year survival rate was 90.1%. Patients with a coded diagnosis of rheumatoid arthritis (odds ratio [OR] = 2.18; 95% confidence interval [CI] = 1.04-4.01) or who were readmitted within 90 days of TAA (OR = 3.41; 95% CI = 1.67-6.97) had significantly increased risk of failure. Risk factors for readmission were Charlson-Deyo Score ≥2 (OR = 3.05; 95% CI = 1.51-6.15) and increased length of stay during the arthroplasty (OR = 1.30; 95% CI = 1.16-1.47). LEVELS OF EVIDENCE: Therapeutic, Level IV: Observational study.

Image-Based Techniques for Percutaneous Iliosacral Screw Start-Site Localization.

Despite the routine use of iliosacral screws for the treatment of a variety of pelvic fractures, the technique is demanding, and complications are well described. This article describes a novel image-based technique for accurately identifying and reproducing the appropriate placement of iliosacral screws. Using the stab-incision technique presented here allows for more accurate landmark identification and safer placement of implants.

Intraoperative skull-femoral traction in posterior spinal arthrodesis for adolescent idiopathic scoliosis: the impact on perioperative outcomes and health resource utilization.

STUDY DESIGN: Retrospective, single-center cohort study. OBJECTIVE: To study how the systematic use of intraoperative skull-femoral traction (IOSFT) in posterior arthrodesis for adolescent idiopathic scoliosis impacts perioperative outcomes and health resource utilization. SUMMARY OF BACKGROUND DATA: Large scoliosis curves have been associated with increased morbidity and utilization of health resources. When used with reliable neurophysiological monitoring, IOSFT has shown to be safe and to reduce curve magnitude intraoperatively. Thus, we hypothesized that the systematic use of IOSFT may contribute to reducing health resource utilization by reducing curve magnitudes intraoperatively. METHODS: Seventy-three consecutive patients with adolescent idiopathic scoliosis who underwent single-stage posterior spinal arthrodesis from 2008 to 2012 at a tertiary children's hospital were identified. Forty-five patients were operated with IOSFT (traction group) and 28 patients were operated without IOSFT (nontraction group). Outcome measures included operative time, calculated blood loss, blood transfusion requirement, traction-related complications, and cost comparisons. RESULTS: Operative time was 375.6 minutes for the traction group (P=0.0001) and 447.6 minutes for the nontraction group. Calculated blood loss was significantly less in the traction group (P=0.027). Thirty-three percent of patients in the traction group required blood transfusion compared with 64% of patients in the nontraction group (P=0.01, absolute risk reduction of 31%). There was no significant difference in curve magnitude correction (P=0.49). There were no significant complications with the use of traction. There was a significant reduction in cost per surgical procedure in the traction group (P=0.0003). CONCLUSION: The systematic use of IOSFT in posterior spinal arthrodesis for adolescent idiopathic scoliosis contributed to significant reductions in health resource utilization, with no added morbidity. Further research is warranted to investigate the generalizability of these findings. LEVEL OF EVIDENCE: 4.

Reconstruction of the medial talonavicular joint in simulated flatfoot deformity.

BACKGROUND: Reconstructing the ligamentous constraints of the medial arch associated with adult acquired flatfoot deformity remains a challenge. The purpose of this study was to test the efficacy of several reconstruction techniques of the medial arch. We hypothesized that an anatomic reconstruction of the spring ligament complex would correct the deformity better than other techniques tested. METHODS: Three reconstructions of the medial support structures were performed on each specimen to recreate the different lines of action and insertions of the medial ligamentous complex in 12 specimens with a simulated flatfoot deformity. Talonavicular and tibiocalcaneal (hindfoot) orientations were measured in the axial, sagittal, and coronal planes in the intact, flatfoot, and reconstructed conditions. RESULTS: While each reconstruction technique corrected the deformity (P < .05), proximal fixation of the graft corrected the greatest amount of talonavicular deformity while also correcting hindfoot valgus (P < .05). CONCLUSION: The fixation points and lines of action of a medial arch reconstruction have important implications on deformity correction in a flatfoot model. Despite its fidelity to the native structure, the anatomic spring ligament reconstruction provided the least amount of correction. These findings suggest that other ligamentous structures of the medial arch are critical in supporting the midfoot. CLINICAL RELEVANCE: Reconstruction of the ligamentous supports of the medial arch might be able to correct substantial amounts of deformity without osseous procedures like calcaneal osteotomies or midfoot fusions.

Diagnosis of occult scaphoid fractures: a randomized, controlled trial comparing bone scans to radiographs for diagnosis.

BACKGROUND: Many patients with suspected scaphoid fractures but negative radiographs are immobilized for ≥ 2 weeks and are eventually found to have no fracture. Bone scans are reportedly 99% sensitive for these injuries if done ≥ 72 hours postinjury. OBJECTIVE: The purpose of this study was to determine if early bone scans would allow for shorter cast immobilization periods in patients with suspected scaphoid fractures. METHODS: Twenty-seven patients with clinically suspected scaphoid fractures and negative radiographs were randomized to early diagnosis (bone scan within 3-5 days; n  =  12) or traditional diagnosis (radiographs 10-14 days postinjury; n  =  15). The primary outcome was number of days immobilized in a cast. RESULTS: The mean number of days immobilized was 26 in the traditional group and 29 in the bone scan group. Overall, 6 patients had scaphoid fractures (2 in the traditional diagnosis group and 4 in the bone scan group; p > 0.05), and 8 had other types of fractures. These other types of fractures included four distal radius fractures, two triquetral fractures, one trapezoid fracture, and one hamate fracture. There was no significant difference in the number of other types of fractures between groups. The Kaplan-Meier survival analysis using the log-rank test revealed that there was no statistically significant difference between days immobilized between the radiograph and bone scan groups (p  =  0.38). CONCLUSIONS: The current study suggests that the use of bone scans to help diagnose occult scaphoid fractures does not reduce the number of days immobilized and that the differential diagnosis of occult scaphoid fractures should remain broad because other injuries are common.

Combined acetabulum and pelvic ring injuries.

Combined fractures of the acetabulum and pelvic ring are more common than previously believed, with an incidence as high as 15.7%. Recent series that include combined injuries indicate that the incidence of lateral compression and anteroposterior compression pelvic ring injuries is similar and that transverse and both-column acetabular fractures are the most common acetabular fracture patterns. Combined injuries most often are the result of high-energy mechanisms, and, compared with patients who present with isolated pelvic or acetabular injury, patients with combined injury typically have higher injury severity scores, higher transfusion requirements, and lower systolic blood pressure, with reported mortality rates of 1.5% to 13%. Treatment requires a multidisciplinary approach. The first priority is resuscitation following the Advanced Trauma Life Support protocols. Once the patient is stable, acetabular fractures and pelvic ring injuries should be assessed individually, and the most appropriate treatment for each should be outlined. These treatments should then be integrated to develop the most appropriate overall treatment strategy. Although outcomes data are available for isolated acetabulum and pelvic ring disruptions, no such data currently exist for combined injuries.

Leptin Deficiency and Its Effects on Tibial and Vertebral Bone Mechanical Properties in Mature Genetically Lean and Obese JCR:LA-Corpulent Rats.

Leptin signaling deficient rodents have emerged as models of obesity/insulin resistance syndrome. Altered leptin signaling, however, can affect axial and appendicular bone geometrical properties differently, and, thus, we hypothesized that leptin-deficiency would differentially influence mechanical properties of vertebrae and tibiae compared to lean rats. Mature (9 mo) leptin receptor deficient obese (cp/cp; n = 8) and lean (+/?; n = 7) male JCR:LA-corpulent rats were used to test that hypothesis. Tibiae and the sixth lumbar vertebrae (L(6)) were scanned with micro-CT and were broken in three point-bending (tibiae) or axial loading (L(6)). Supporting the hypothesis, vertebrae and tibiae were differentially affected by leptin signaling deficiency. Tibiae, but not vertebrae, were significantly shorter in obese rats and achieved a significantly greater load (>18%), displacement (>15%), and stress (>18%) at the proportional limit, relative to the lean rats. Conversely, L(6) in obese rats had significantly reduced displacement (>25%) and strain (>32%) at proportional limit, relative to the lean rats. Those combined results suggest that the etiology and duration of obesity may be important determinants of bone mechanical properties, and axial and appendicular bones may be affected differently.

Strain rate influences periosteal adaptation in mature bone.

Mechanical forces influence bone form and function. Although the adaptive capabilities of bone are well known, the nuances of the mechanical stimuli regulating adaptation remain elusive. Recently, it was suggested that strain rate influences bone adaptation, and impact exercises with high strain rates during growth may be more osteogenic than low impact aerobic exercises. Building on those findings, we hypothesized that higher rates of mechanical loading would evoke greater adaptive responses than lower rates of loading in mature bone. To test that hypothesis, skeletally mature (16 weeks) female C57BL/6 mice underwent non-invasive exogenous cantilever bending of the right tibia with a 1 Hz trapezoidal waveform for 60 s, 5 days per week, for 4 weeks. Loading was calibrated (strain gauge) to induce peak magnitudes of 1000 microepsilon on the lateral tibial middiaphysis. Mice were randomly assigned to three groups based on strain rate of the applied load: low (0.004 s(-1); n = 14), medium (0.020 s(-1); n = 15), and high (0.100 s(-1); n = 14). Calcein injections (i.p., 10 mg kg(-1)) permitted histomorphometric analyses of bone formation. Loading significantly enhanced periosteal mineral apposition rate (MAR), mineralizing surface (MS), and bone formation rate (BFR BS(-1)) in all three strain rate groups, relative to control tibiae. Furthermore, a graded dose-response relation was observed between the applied strain rate and periosteal BFR BS(-1). These increases in MAR, MS, and BFR BS(-1) were not seen on the endosteal surface. Endosteal adaptation was not statistically different between loaded and control tibiae in most endosteal indices of bone adaptation. Moreover, endosteal adaptation did not increase with strain rate. Understanding the nature of the stimuli to which bone cells respond to may underpin the development of non-pharmacological treatments devised to enhance bone mass.

Dietary restriction does not adversely affect bone geometry and mechanics in rapidly growing male wistar rats.

The present study assessed the effects of dietary restriction on tibial and vertebral mechanical and geometrical properties in 2-mo-old male Wistar rats. Two-month-old male Wistar rats were randomized to the ad libitum (n=8) or the 35% diet-restricted (DR) feeding group (n=9) for 5 mo. Tibiae and L6 vertebrae were dissected out for microcomputed tomography (microCT) scanning and subsequently fractured in biomechanical testing to determine geometrical and mechanical properties. The DR group had significantly lower mean tibial length, mass, area, and cross-sectional moment of inertia, as well as vertebral energy to maximal load. After adjustment for body mass, however, DR tibial mean maximal load and stiffness, and DR vertebral area, height, volume, and maximal load were significantly greater, relative to ad libitum means. No significant differences were found between the DR and ad libitum mineral ash fractions. Because the material properties of the tibiae between the two groups were not significantly different, presumably the material integrity of the bones was not adversely affected as a consequence of DR. The similar material characteristics were consistent with mineral ash fractions that were not different between the two groups. Vertebral maximal load and stiffness were not significant between the DR and ad libitum animals. Importantly, we show that a level of dietary restriction (35%) that is less severe than many studies (40%), and without micronutrient compensation does not adversely affect tibial and vertebral mechanical properties in young growing male rats when normalized for body mass.

Rest insertion combined with high-frequency loading enhances osteogenesis.

Mechanical loading can significantly affect skeletal adaptation. High-frequency loading can be a potent osteogenic stimulus. Additionally, insertion of rest periods between consecutive loading bouts can be a potent osteogenic stimulus. Thus we investigated whether the insertion of rest-periods between short-term high-frequency loading bouts would augment adaptation in the mature murine skeleton. Right tibiae of skeletally mature (16 wk) female C57BL/6 mice were loaded in cantilever bending at peak of 800 microepsilon, 30 Hz, 5 days/wk for 3 wk. Left tibiae were the contralateral control condition. Mice were randomly assigned into one of two groups: continuous high-frequency (CT) stimulation for 100 s (n = 9), or 1-s pulses of high-frequency stimuli followed by 10 s of rest (RI) for 100 s (n = 9). Calcein labels were administered on days 1 and 21; label incorporation was used to histomorphometrically assess periosteal and endosteal indexes of adaptation. Periosteal surface referent bone formation rate (pBFR/BS) was significantly enhanced in CT (>88%) and RI (>126%) loaded tibiae, relative to control tibiae. Furthermore, RI tibiae had significantly greater pBFR/BS, relative to CT tibiae (>72%). The endosteal surface was not as sensitive to mechanical loading as the periosteal surface. Thus short-term high-frequency loading significantly elevated pBFR/BS, relative to control tibiae. Furthermore, despite the 10-fold reduction in cycle number, the insertion of rest periods between bouts of high-frequency stimuli significantly augmented pBFR/BS, relative to tibiae loaded continually. Optimization of osteogenesis in response to mechanical loading may underpin the development of nonpharmacological regiments designed to increase bone strength in individuals with compromised bone structures.