Accelerated Cortical Osteolysis of Metatarsals in Charcot Neuroarthropathy: A Cross-Sectional Observational Study.

Metatarsals are frequent sites of stress and fragility fractures in younger athletic populations and aging older adults. Metatarsal fractures are particularly common in Charcot neuroarthropathy (CN), a complication of diabetes mellitus (DM) and peripheral neuropathy (PN). Neuropathic metatarsal fractures may be caused by an accelerated cortical bone osteolysis and may be reflected as geometric-derived strength estimates from standard foot radiographs. The purpose of this cross-sectional study was to determine geometry and strength-derived estimates of the metatarsals in individuals with DM, PN, and CN compared with younger and older adult controls who were nondiabetic and nonneuropathic. We studied 62 participants: 20 young adult controls (YACs), 22 older adult controls (OACs), and 20 diagnosed with DMPN&CN. From weight-bearing radiographs, we measured the outer diaphysis diameter and inner marrow diameter at the distal, middle, and proximal diaphysis sites of the second and fifth metatarsal. From these diameters, we derived strength estimates of combined cortical width (CCt.Wi), percent cortical area (%Ct.rA), buckling ratio (BR), moment of inertia (MOI), and section modulus (SM) at each site in both metatarsals. DMPN&CN participants had an accelerated cortical thinning, decreased %Ct.Ar, increased BR, and lower MOI and SM compared with OACs and YACs. The OACs showed age-related decreases in CCt.Wi and % Ct.Ar, and increased BR. The BR demonstrated significant group × bone × site interaction with the distal fifth metatarsal in the DMPN&CN group having the lowest bone strength. The BR in the distal fifth metatarsal of DMPN&CN participants was 36% and 49% greater than in the OAC and YAC groups, respectively. DMPN&CN participants have lower metatarsal bone strength estimates compared with younger and older adult controls. Standard foot radiographs demonstrate an accelerated cortical osteolysis in DMPN&CN individuals, particularly in the distal fifth metatarsal diaphysis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Immobilization-induced osteolysis and recovery in neuropathic foot impairments.

BACKGROUND: Neuropathic foot impairments treated with immobilization and off-loading result in osteolysis. In order to prescribe and optimize rehabilitation programs after immobilization we need to understand the magnitude of pedal osteolysis after immobilization and the time course for recovery. OBJECTIVE: To determine differences in a) foot skin temperature; b) calcaneal bone mineral density (BMD) after immobilization; c) calcaneal BMD after 33-53weeks of recovery; and d) percent of feet classified as osteopenic or osteoporotic after recovery in participants with neuropathic plantar ulcers (NPU) compared to Charcot neuroarthropathy (CNA). METHODS: Fifty-five participants with peripheral neuropathy were studied. Twenty-eight participants had NPU and 27 participants had CNA. Bilateral foot skin temperature was assessed before immobilization and bilateral calcaneal BMD was assessed before immobilization, after immobilization and after recovery using quantitative ultrasonometry. RESULTS: Before immobilization, skin temperature differences in CNA between their index and contralateral foot were markedly higher than NPU feet (3.0 degree C versus 0.7 degree C, respectively, p<0.01); BMD in NPU immobilized feet averaged 486±136mg/cm2, and CNA immobilized feet averaged 456±138mg/cm2, p>0.05). After immobilization, index NPU feet lost 27mg/cm2; CNA feet lost 47mg/cm2 of BMD, p<0.05. After recovery, 61% of NPU index feet and 84% of CNA index feet were classified as osteopenic or osteoporotic. CONCLUSIONS: There was a greater osteolysis after immobilization with an attenuated recovery in CNA feet compared to NPU feet. The attenuated recovery of pedal BMD in CNA feet resulted in a greater percentage of feet classified as osteoporotic and osteopenic.

Persistent inflammation with pedal osteolysis 1year after Charcot neuropathic osteoarthropathy.

AIMS: To determine local and systemic markers of inflammation and bone mineral density (BMD) in the foot and central sites in participants with diabetes mellitus and peripheral neuropathy (DMPN) with and without acute Charcot neuropathic osteoarthropathy (CN). METHODS: Eighteen participants with DMPN and CN and 19 participants without CN had foot temperature assessments, serum markers of inflammation [C-reactive protein, (CRP) and erythrocyte sedimentation rate, (ESR)] and BMD of the foot, hip and lumbar spine at baseline and 1year follow-up. RESULTS: CN foot temperature difference was higher compared to DMPN controls at baseline (4.2±1.9°F vs. 1.2±0.9°F, P<0.01) and after 1year (2.9±3.2°F vs. 0.9±1.1°F, P<0.01). Serum inflammatory markers in the CN group were greater at baseline and remained elevated 1year later compared to DMPN controls (CRP, P=0.02, ESR, P=0.03). All pedal bones' BMD decreased an average of 3% in the CN foot with no changes in hip or lumbar spine. DMPN controls' foot, hip and lumbar spine BMD remained unchanged. CONCLUSIONS: Local and systemic inflammation persists 1 year after CN with an accompanying pedal osteolysis that may contribute to mid foot deformity which is the hallmark of the chronic Charcot foot.

Lower extremity mechanics during marching at three different cadences for 60 minutes.

During group marches, soldiers must walk in step with one another at the same imposed cadence. The literature suggests that shorter trainees may be more susceptible to injury due to overstriding that can occur when taller recruits dictate marching cadence. This study assessed the effects of fixed cadence simulated marching at cadences above and below preferred step rate (PSR) on lower extremity joint mechanics in individuals who were unaccustomed to marching. During three separate visits, 13 volunteers walked with a 20 kg load on a force-sensing treadmill at self-selected PSR, PSR+15% (shorter strides), and PSR-15% (longer strides) at 1.3 m/s for 60 min. Two-way RM ANOVAs (cadence by time) were performed during the stance phase. Ranges of motion and anteroposterior ground reaction force increased significantly as cadence decreased (P < .03). Knee extension moment increased slightly when step rate decreased from PSR+15% (shortest strides, 0.85 ± 0.2 N m/kg) to PSR (0.87 ± 0.3 N m/kg, 3% increase); however, this increase was substantially greater (20% increase) when cadence was decreased from PSR to PSR-15% (longest strides, 1.09 ± 0.3 N m/kg). Our results indicate that overstriding during fixed-cadence marching is a factor that can substantially increase mechanical stress on lower extremity joints.

Pedal bone density, strength, orientation, and plantar loads preceding incipient metatarsal fracture after charcot neuroarthropathy: 2 case reports.

STUDY DESIGN: Case report. BACKGROUND: Charcot neuroarthropathy is a progressive, noninfective, inflammatory destruction of bones and joints leading to foot deformities and plantar ulceration. Though individuals with Charcot neuroarthropathy typically have low areal bone mineral density, little is known regarding changes in volumetric bone mineral density (vBMD), bone geometry, joint malalignment, and biomechanical loads preceding fracture. CASE DESCRIPTION: Two women, aged 45 and 54 years at the onset of an acute, nonfracture Charcot neuroarthropathy event, received regular physical therapy with wound care and total-contact casting. Both enrolled in a larger research study that included plantar pressure assessment and quantitative computed tomography at enrollment and 3, 6, and 12 months later. The women sustained mid-diaphyseal fifth metatarsal fracture 10 to 11 months after enrollment. Quantitative computed tomography image-analysis techniques were used to measure vBMD; bone geometric indices reflecting strength in compression, bending, and cortical buckling; and 3-D bone-to-bone orientation angles reflecting foot deformity. OUTCOMES: Fifth metatarsal mid-diaphyseal vBMD decreased during offloading treatment from 0 to 3 months, then increased to above baseline levels by 6 months. All geometric strength indices improved from baseline through 6 months. Plantar loading in the lateral midfoot increased preceding fracture, concomitant with alterations in bone orientation angles, which suggest progressive development of metatarsus adductus and equinovarus foot deformity. DISCUSSION: Fractures may occur when bone strength decreases or when biomechanical loading increases. Incipient fracture was preceded by increased loading in the lateral midfoot but not by reductions in vBMD or geometric strength indices, suggesting that loading played a greater role in fracture. Moreover, the progression of foot deformities may be causally linked to the increased plantar loading. LEVEL OF EVIDENCE: Prognosis, level 4.

Reliability of clinically relevant 3D foot bone angles from quantitative computed tomography.

BACKGROUND: Surgical treatment and clinical management of foot pathology requires accurate, reliable assessment of foot deformities. Foot and ankle deformities are multi-planar and therefore difficult to quantify by standard radiographs. Three-dimensional (3D) imaging modalities have been used to define bone orientations using inertial axes based on bone shape, but these inertial axes can fail to mimic established bone angles used in orthopaedics and clinical biomechanics. To provide improved clinical relevance of 3D bone angles, we developed techniques to define bone axes using landmarks on quantitative computed tomography (QCT) bone surface meshes. We aimed to assess measurement precision of landmark-based, 3D bone-to-bone orientations of hind foot and lesser tarsal bones for expert raters and a template-based automated method. METHODS: Two raters completed two repetitions each for twenty feet (10 right, 10 left), placing anatomic landmarks on the surfaces of calcaneus, talus, cuboid, and navicular. Landmarks were also recorded using the automated, template-based method. For each method, 3D bone axes were computed from landmark positions, and Cardan sequences produced sagittal, frontal, and transverse plane angles of bone-to-bone orientations. Angular reliability was assessed using intraclass correlation coefficients (ICCs) and the root mean square standard deviation (RMS-SD) for intra-rater and inter-rater precision, and rater versus automated agreement. RESULTS: Intra- and inter-rater ICCs were generally high (≥ 0.80), and the ICCs for each rater compared to the automated method were similarly high. RMS-SD intra-rater precision ranged from 1.4 to 3.6° and 2.4 to 6.1°, respectively, for the two raters, which compares favorably to uni-planar radiographic precision. Greatest variability was in Navicular: Talus sagittal plane angle and Cuboid: Calcaneus frontal plane angle. Precision of the automated, atlas-based template method versus the raters was comparable to each rater's internal precision. CONCLUSIONS: Intra- and inter-rater precision suggest that the landmark-based methods have adequate test-retest reliability for 3D assessment of foot deformities. Agreement of the automated, atlas-based method with the expert raters suggests that the automated method is a valid, time-saving technique for foot deformity assessment. These methods have the potential to improve diagnosis of foot and ankle pathologies by allowing multi-planar quantification of deformities.

Dual-energy X-ray absorptiometry of human metatarsals: precision, least significant change and association to ex vivo fracture force.

BACKGROUND: Fractures are common in foot bones, but clinicians lack adequate indices of bone strength. OBJECTIVES: We used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD) and content (BMC) of excised human metatarsals, determined intra- and inter-rater measurement precision, and assessed associations between BMD/BMC and ex vivo bone fracture strength. METHODS: Two raters each made two measurements of whole-bone and sub-regional BMD and BMC in both second and third metatarsals from 10 cadavers. Variance components analysis was used to assess variability attributable to repeat measurements, raters, sub-regions, bones, sides, and cadavers. Root-mean-square standard deviation (RMS-SD) and least-significant change (LSC) were used to assess rater precision and ultimate forces during 3-point bending were tested for correlations with BMD and BMC. RESULTS: Variation due to repeat measurements and rater was low (<1% combined) for BMD and BMC. RMS-SD for whole metatarsal BMD of both metatarsals ranged from 0.004 to 0.010 g/cm(2) and 0.062 to 0.086 g for BMC. Whole metatarsal and sub-region BMD and BMC were strongly correlated to ex vivo fracture force (r(2)=0.67-0.93). CONCLUSIONS: DXA measurements of BMD and BMC have high intra- and inter-rater precision and are strongly correlated to ex vivo bone strength.

Neuropathic midfoot deformity: associations with ankle and subtalar joint motion.

BACKGROUND: Neuropathic deformities impair foot and ankle joint mobility, often leading to abnormal stresses and impact forces. The purpose of our study was to determine differences in radiographic measures of hind foot alignment and ankle joint and subtalar joint motion in participants with and without neuropathic midfoot deformities and to determine the relationships between radiographic measures of hind foot alignment to ankle and subtalar joint motion in participants with and without neuropathic midfoot deformities. METHODS: Sixty participants were studied in three groups. Forty participants had diabetes mellitus (DM) and peripheral neuropathy (PN) with 20 participants having neuropathic midfoot deformity due to Charcot neuroarthropathy (CN), while 20 participants did not have deformity. Participants with diabetes and neuropathy with and without deformity were compared to 20 young control participants without DM, PN or deformity. Talar declination and calcaneal inclination angles were assessed on lateral view weight bearing radiograph. Ankle dorsiflexion, plantar flexion and subtalar inversion and eversion were assessed by goniometry. RESULTS: Talar declination angle averaged 34±9, 26±4 and 23±3 degrees in participants with deformity, without deformity and young control participants, respectively (p< 0.010). Calcaneal inclination angle averaged 11±10, 18±9 and 21±4 degrees, respectively (p< 0.010). Ankle plantar flexion motion averaged 23±11, 38±10 and 47±7 degrees (p<0.010). The association between talar declination and calcaneal inclination angles with ankle plantar flexion range of motion is strongest in participants with neuropathic midfoot deformity. Participants with talonavicular and calcaneocuboid dislocations result in the most severe restrictions in ankle joint plantar flexion and subtalar joint inversion motions. CONCLUSIONS: An increasing talar declination angle and decreasing calcaneal inclination angle is associated with decreases in ankle joint plantar flexion motion in individuals with neuropathic midfoot deformity due to CN that may contribute to excessive stresses and ultimately plantar ulceration of the midfoot.

Impact of Charcot neuroarthropathy on metatarsal bone mineral density and geometric strength indices.

Charcot neuroarthropathy (CN), an inflammatory condition characterized by rapid and progressive destruction of pedal bones and joints, often leads to deformity and ulceration in individuals with diabetes mellitus (DM) and peripheral neuropathy (PN). Repetitive, unperceived joint trauma may trigger initial CN damage, causing a proinflammatory cascade that can result in osteolysis and contribute to subsequent neuropathic fracture. We aimed to characterize osteolytic changes related to development and progression of CN by measuring bone mineral density (BMD) and geometric strength indices using volumetric quantitative computed tomography. Twenty individuals with DM+PN were compared to twenty age-, sex-, and race-matched individuals with DM+PN and acute CN. We hypothesized that individuals with acute CN would have decreased BMD and decreased total area, cortical area, minimum section modulus, and cortical thickness in the diaphysis of the second and fifth metatarsals. Results showed BMD was lower in both involved and uninvolved feet of CN participants compared to DM+PN participants, with greater reductions in involved CN feet compared to uninvolved CN feet. There was a non-significant increase in total area and cortical area in the CN metatarsals, which helps explain the finding of similar minimum section modulus in DM+PN and CN subjects despite the CN group's significantly lower BMD. Larger cortical area and section modulus are typically considered signs of greater bone strength due to higher resistance to compressive and bending loads, respectively. In CN metatarsals, however, these findings may reflect periosteal woven bone apposition, i.e., a hypertrophic response to injury rather than increased fracture resistance. Future research using these techniques will aid further understanding of the inflammation-mediated bony changes associated with development and progression of CN and other diseases.

Predicting ex vivo failure loads in human metatarsals using bone strength indices derived from volumetric quantitative computed tomography.

We investigated the capacity of bone quantity and bone geometric strength indices to predict ultimate force in the human second metatarsal (Met2) and third metatarsal (Met3). Intact lower extremity cadaver samples were measured using clinical, volumetric quantitative computed tomography (vQCT) with positioning and parameters applicable to in vivo scanning. During processing, raw voxel data (0.4mm isotropic voxels) were converted from Hounsfield units to apparent bone mineral density (BMD) using hydroxyapatite calibration phantoms to allow direct volumetric assessment of whole-bone and subregional metatarsal BMD. Voxel data were realigned to produce cross-sectional slices perpendicular to the longitudinal axes of the metatarsals. Average mid-diaphyseal BMD, bone thickness, and buckling ratio were measured using an optimized threshold to distinguish bone from non-bone material. Minimum and maximum moments of inertia and section moduli were measured in the mid-diaphysis region using both a binary threshold for areal, unit-density measures and a novel technique for density-weighted measures. BMD and geometric strength indices were strongly correlated to ultimate force measured by ex vivo 3-point bending. Geometric indices were more highly correlated to ultimate force than was BMD; bone thickness and density-weighted minimum section modulus had the highest individual correlations to ultimate force. Density-weighted geometric indices explained more variance than their binary analogs. Multiple regression analyses defined models that predicted 85-89% of variance in ultimate force in Met2 and Met3 using bone thickness and minimum section modulus in the mid-diaphysis. These results have implications for future in vivo imaging to non-invasively assess bone strength and metatarsal fracture risk.

Removable cast walker boots yield greater forefoot off-loading than total contact casts.

BACKGROUND: Elevated plantar loading has been implicated in the etiology of plantar ulceration in individuals with diabetes mellitus and peripheral neuropathy. Total contact casts and cast walker boots are common off-loading strategies to facilitate ulcer healing and prevent re-ulceration. The purpose of this study was to compare off-loading capabilities of these strategies with respect to plantar loading during barefoot walking. METHODS: Twenty-three individuals with diabetes, peripheral neuropathy, and plantar ulceration were randomly assigned to total contact cast (n=11) or removable cast walker boot (n=12). Each subject underwent plantar loading assessment walking barefoot and wearing the off-loading device. Analysis of covariance was used to compare loading patterns in the off-loading devices for the whole foot, hindfoot, midfoot, and forefoot while accounting for walking speed and barefoot loading. FINDINGS: For the foot as a whole, there were no differences in off-loading between the two techniques. Subjects wearing cast walker boots had greater reductions in forefoot peak pressure, pressure-time integral, maximum force, and force-time integral with respect to barefoot walking. Healing times were similar between groups, but a greater proportion of ulcers healed in total contact casting compared to cast walker boots. INTERPRETATION: In subjects with diabetes, peripheral neuropathy, and plantar ulceration, cast walker boots provided greater load reduction in the forefoot, the most frequent site of diabetic ulceration, though a greater proportion of subjects wearing total contact casts experienced ulcer healing. Taken together, the less effective ulcer healing in cast walker boots despite superior forefoot off-loading suggests an important role for patient compliance in ulcer healing.

Effects of a lower-body exoskeleton device on metabolic cost and gait biomechanics during load carriage.

This study investigated the effects on metabolic cost and gait biomechanics of using a prototype lower-body exoskeleton (EXO) to carry loads. Nine US Army participants walked at 1.34 m/s on a 0% grade for 8 min carrying military loads of 20 kg, 40 kg and 55 kg with and without the EXO. Mean oxygen consumption (VO(2)) scaled to body mass and scaled to total mass were significantly higher, by 60% and 41% respectively, when the EXO was worn, compared with the control condition. Mean VO(2) and mean VO(2) scaled to body mass significantly increased with load. The kinematic and kinetic data revealed significant differences between EXO and control conditions, such as walking with a more flexed posture and braking with higher ground reaction force at heel strike when wearing the EXO. Study findings demonstrate that the EXO increased users' metabolic cost while carrying various loads and altered their gait biomechanics compared with conventional load carriage. STATEMENT OF RELEVANCE: An EXO designed to assist in load bearing was found to raise energy expenditure substantially when tested by soldiers carrying military loads. EXO weight, weight distribution and design elements that altered users' walking biomechanics contributed to the high energy cost. To realise the potential of EXOs, focus on the user must accompany engineering advances.

Effects of two different eight-week training programs on military physical performance.

Various physical demands are placed on soldiers, whose effectiveness and survivability depend on their combat-specific physical fitness. Because sport training programs involving weight-based training have proven effective, this study examined the value of such a program for short-term military training using combat-relevant tests. A male weight-based training (WBT) group (n = 15; mean +/- SD: 27.0 +/- 4.7 years, 173.8 +/- 5.8 cm, 80.9 +/- 12.7 kg) performed full-body weight-based training workouts, 3.2-km runs, interval training, agility training, and progressively loaded 8-km backpack hikes. A male Army Standardized Physical Training (SPT) group (n = 17; mean +/- SD: 29.0 +/- 4.6 years, 179.7 +/- 8.2 cm, 84.5 +/- 10.4 kg) followed the new Army Standardized Physical Training program of stretching, varied calisthenics, movement drills, sprint intervals, shuttle running, and distance runs. Both groups exercised for 1.5 hours a day, 5 days a week for 8 weeks. The following training-induced changes were statistically significant (P < 0.05) for both training groups: 3.2-km run or walk with 32-kg load (minutes), 24.5 +/- 3.2 to 21.0 +/- 2.8 (SPT) and 24.9 +/- 2.8 to 21.1 +/- 2.2 (WBT); 400-m run with 18-kg load (seconds), 94.5 +/- 14.2 to 84.4 +/- 11.9 (SPT) and 100.1 +/- 16.1 to 84.0 +/- 8.4 (WBT); obstacle course with 18-kg load (seconds), 73.3 +/- 10.1 to 61.6 +/- 7.7 (SPT) and 66.8 +/- 10.0 to 60.1 +/- 8.7 (WBT); 5 30-m sprints to prone (seconds), 63.5 +/- 4.8 to 59.8 +/- 4.1 (SPT) and 60.4 +/- 4.2 to 58.9 +/- 2.7 (WBT); and 80-kg casualty rescue from 50 m (seconds), 65.8 +/- 40.0 to 42.1 +/- 9.9 (SPT) and 57.6 +/- 22.0 to 44.2 +/- 8.8 (WBT). Of these tests, only the obstacle course showed significant difference in improvement between the two training groups. Thus, for short-term (i.e., 8-week) training of relatively untrained men, the Army's new Standardized Physical Training program and a weight-based training experimental program can produce similar, significant, and meaningful improvements in military physical performance. Further research would be needed to determine whether weight-based training provides an advantage over a longer training period.

Prediction of simulated battlefield physical performance from field-expedient tests.

Predictive models of battlefield physical performance can benefit the military. To develop models, 32 physically trained men (mean +/- SD: 28.0 +/- 4.7 years, 82.1 +/- 11.3 kg, 176.3 +/- 7.5 cm) underwent (1) anthropometric measures: height and body mass; (2) fitness tests: push-ups, sit-ups, 3.2-km run, vertical jump, horizontal jump; (3) simulated battlefield physical performance in fighting load: five 30-m sprints prone to prone, 400-m run, obstacle course, and casualty recovery. Although greater body mass was positively associated with better casualty recovery performance, it showed trends toward poorer performance on all the other fitness and military performance tests. Regression equations well predicted the simulated battlefield performance from the anthropometric measures and physical fitness tests (r = 0.77-0.82). The vertical jump entered all four prediction equations and the horizontal jump entered one of them. The equations, using input from easy to administer tests, effectively predict simulated battlefield physical performance.

Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis.

OBJECTIVE: To determine the relationship between change in body mass and knee-joint moments and forces during walking in overweight and obese older adults with knee osteoarthritis (OA) following an 18-month clinical trial of diet and exercise. METHODS: Data were obtained from 142 sedentary, overweight, and obese older adults with self-reported disability and radiographic evidence of knee OA who underwent 3-dimensional gait analysis. Gait kinetic outcome variables included peak knee-joint forces and peak internal knee-joint moments. Mixed regression models were created to predict followup kinetic values, using followup body mass as the primary explanatory variable. Baseline body mass was used as a covariate, and thus followup body mass was a surrogate measure for change in body mass (i.e., weight loss). RESULTS: There was a significant direct association between followup body mass and peak followup values of compressive force (P = 0.001), resultant force (P = 0.002), abduction moment (P = 0.03), and medial rotation moment (P = 0.02). A weight reduction of 9.8 N (1 kg) was associated with reductions of 40.6 N and 38.7 N in compressive and resultant forces, respectively. Thus, each weight-loss unit was associated with an approximately 4-unit reduction in knee-joint forces. In addition, a reduction in body weight of 9.8 N (1 kg) was associated with a 1.4% reduction (0.496 Nm) in knee abduction moment. CONCLUSION: Our results indicate that each pound of weight lost will result in a 4-fold reduction in the load exerted on the knee per step during daily activities. Accumulated over thousands of steps per day, a reduction of this magnitude would appear to be clinically meaningful.