Prematriculation Predictors of Academic Difficulties During the First Year of a Doctor of Physical Therapy Program.

PURPOSE: To analyze the ability of pre-matriculation metrics to predict difficulties during the first year of a Doctor of Physical Therapy (DPT) program with a pass-fail grading system. METHODS: Undergraduate cumulative, science, and pre-requisite grade point averages (GPAs) and verbal and quantitative Graduate Record Examination (GRE) percentiles were collected during the admissions process of 190 students in an accredited DPT program at a southeastern US private university between 2019-2021. Students were dichotomized to groups with and without academic difficulties in coursework and a first-year comprehensive assessment (CA). Independent t-tests identified differences between groups, and logistic regression analyses identified predictors of academic difficulties. Receiver operating characteristic (ROC) curve analyses were performed to identify cut-off scores and risk ratios were calculated. RESULTS: Students with coursework difficulties had lower verbal (d=0.36, p=0.009) and quantitative (d=0.31, p=0.02) GRE scores. Verbal GRE scores were also lower in students who failed the CA (p=0.049). Students who scored less than the 47th percentile on the verbal GRE were 53% more likely to have academic difficulties and 4.2 times more likely to fail the CA than those who scored in the 70th percentile or higher. CONCLUSION: Verbal GRE percentile best predicted academic difficulty in the first year of a DPT program.

Offloading of Diabetic Neuropathic Plantar Ulcers: Secondary Analysis of Step Activity and Ulcer Healing.

OBJECTIVE: Although it is well-known that offloading devices facilitate healing in people with diabetes and neuropathic plantar ulcers, little is known about how step activity affects healing. The purposes of this study were to compare: (1) healing outcomes (time to healing, percentage of ulcers healed); (2) healing rates by ulcer location; and (3) step activity (daily step count, daily peak mean cadence) among patients using either total contact casts (TCCs) or removable cast walker boots (RCWs). METHODS: The study included 55 participants (TCC, 29; RCW, 26) with diabetes mellitus, peripheral neuropathy, and a Wagner grade 1 or 2 neuropathic plantar ulcer. Each participant wore an activity monitor for 14 consecutive days. Step activity and healing variables were assessed using independent t tests, Kruskal-Wallis, Kaplan-Meier, and Mantel-Cox log-rank tests. RESULTS: Mean participant age was 55 (SD, 11) years. The percentage of ulcers healed was lower in the RCW group versus the TCC group (65% vs 93%). If healed, average healing rate was 77 (SD, 48) days in the TCC group and 138 (SD, 143) days in the RCW group. Survival distribution by ulcer location was different for RCW forefoot than other locations (132 ± 13 days vs 91 ± 15, 75 ± 11, and 102 ± 36 days for TCC forefoot, TCC-midfoot/hindfoot, and RCW-midfoot/hindfoot, respectively; χ2 = 10.69, P = .014). Average step count was 2,597 in the RCW group versus 1,813 steps in the TCC group (P = .07). The daily peak mean cadence for 20-, 30-, or 60-minute periods was greater with RCW use. CONCLUSIONS: Step activity in participants with RCWs was increased compared with those with TCCs. Because of their potential to be easily removable, RCWs may impair ulcer healing by allowing greater step activity.

The effect of exercise, physical activity, stepping characteristics, and loading on diabetic foot ulcer healing: a systematic review.

The aim of this review was to investigate the effect of exercise, physical activity, stepping characteristics, and loading on DFU healing. A systematic review using proprietary software and a PRISMA 2020 checklist was performed by searching MEDLINE, ProQuest, Scopus, CINAHL, Ovid, and the Cochrane Library for eligible articles from 1960 to December 2020. The primary outcome was time to wound closure. Other outcomes included percentage of DFU healed and time to percentage reduction in DFU. Of the 9 articles included, 6 addressed step activity during the off-loading phase of healing and 3 investigated the addition of NWB exercise on wound healing. Reduced loading via lower daily step activity, less standing duration, and shorter walking bouts in combination with wearing an off-loading device facilitated more rapid wound healing. Exercise seemed to facilitate more rapid healing, as well. Reduced limb loading via daily activity and use of offloading devices improved DFU healing rates. Additional research is necessary to determine the optimal thresholds for exercise, activity, step characteristics, and loading to improve healing outcomes in persons with DFU.

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481.

Biomarkers of chronic kidney disease-mineral bone disorder (CKD-MBD) in the diabetic foot: A medical record review.

AIMS: Determine the prevalence and relative risk of having single and combinations of biomarkers of chronic kidney disease-mineral bone disorder (CKD-MBD) syndrome in the diabetic foot from an electronic medical record (EMR) review. METHODS: Review of 152 patients with one foot radiograph and diagnoses of both diabetes mellitus (DM) and chronic kidney disease (CKD) stages 1-5. Presence/absence of peripheral neuropathy (PN), targeted serum markers, and both pedal vessel calcification (PVC) and buckling ratio (BR) of 2nd and 5th metatarsals from radiographs were recorded. Prevalence of single and combinations of foot biomarkers are reported as count and percentage. Risk ratios (RR) with 95% confidence intervals (95% CI) were calculated to assess risk of foot biomarkers in each stage of CKD-MBD. RESULTS: Prevalence and RR of PVC, PN, and BR ≥ 3.5 biomarkers, both single and in combination, all increase with progression of CKD. The RR increases to 9.6 (95 % CI: 3, 26; p < 0.001) when all 3 biomarkers present in stage 5. CONCLUSIONS: PVC, PN, and BR ≥ 3.5 are prognostic biomarkers of CKD-MBD syndrome in the diabetic foot. Recognition of these foot biomarkers may allow earlier interventions to help reduce nontraumatic lower extremity amputation in individuals with diabetic CKD-MBD.

Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes.

Lifestyle therapy (energy restriction and exercise) is the cornerstone of therapy for people with type 2 diabetes (T2D) but is difficult to implement. We conducted an 8-month randomized controlled trial in persons with obesity and T2D (17 women and 1 man) to determine the therapeutic effects and potential mechanisms of intensive lifestyle therapy on cardiometabolic function. Intensive lifestyle therapy was conducted at the worksite to enhance compliance and resulted in marked (17%) weight loss and beneficial changes in body fat mass, intrahepatic triglyceride content, cardiorespiratory fitness, muscle strength, glycemic control, ß cell function, and multi-organ insulin sensitivity, which were associated with changes in muscle NAD+ biosynthesis, sirtuin signaling, and mitochondrial function and in adipose tissue remodeling. These findings demonstrate that intensive lifestyle therapy provided at the worksite has profound therapeutic clinical and physiological effects in people with T2D, which are likely mediated by specific alterations in skeletal muscle and adipose tissue biology.

Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults With Obesity While Dieting.

BACKGROUND: Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown. METHODS: In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait speed, and knee strength by dynamometry. RESULTS: IMAT and VAT decreased more in COMB than AEX and REX groups (IMAT; -41% vs -28% and -23% and VAT: -36% vs -19% and -21%; p = .003 to .01); IMAT and VAT decreased in all groups more than control (between-group p < .001). ISI increased more in COMB than AEX and REX groups (86% vs 50% and 39%; p = .005 to .03). PPT improved more in COMB than AEX and REX groups, while VO2peak improved more in COMB and AEX than REX group (all p < .05). Knee strength improved more in COMB and REX than AEX group (all p < .05). Changes in IMAT and VAT correlated with PPT (r = -0.28 and -0.39), VO2peak (r = -0.49 and -0.52), gait speed (r = -0.25 and -0.36), and ISI (r = -0.49 and -0.52; all p < .05). CONCLUSIONS: Weight loss plus combination aerobic and resistance exercise was most effective in improving ectopic fat deposition and physical and metabolic function in older adults with obesity.

Qualitative study of musculoskeletal tissues and their radiographic correlates in diabetic neuropathic foot deformity.

BACKGROUND: Diabetes mellitus (DM) with peripheral neuropathy (PN) results in foot deformity increasing ulceration, joint dislocation, and amputation risk. This study describes the frequency and severity of foot and ankle musculoskeletal abnormalities and their relationship to radiographic alignment in people with DMPN with (DMPN + MCD) and without (DMPN - MCD) medial column deformity (MCD) compared to age- and body mass index-matched controls without DMPN or MDC. METHODS: DMPN + MCD (n = 11), DMPN - MCD (n = 12), and controls (n = 12) were studied. A radiologist scored foot and ankle magnetic resonance images (MRI) for abnormalities in tendons/fascia, ligaments, muscles, joints, and bones. Higher scores represent greater abnormalities. Foot alignment was measured from lateral weightbearing radiographs. Frequency of abnormalities between groups and relationships between abnormalities and foot alignment in the combined group (n = 35) were examined. RESULTS: DMPN + MCD had higher total muscle, joint, and bone scores compared to controls and higher total joint scores than DMPN - MCD. DMPN - MCD had higher total muscle scores than controls. DMPN + MCD higher bone and joint scores were driven by increased frequency of osteophytes, cartilage damage, focal bone marrow edema, new bone formation, and subchondral cysts. Significant correlations included cuboid height and total bone and joint scores (ρ = -0.37 and ρ = -0.40, respectively) and talar declination angle and total joint score (ρ = 0.38). CONCLUSION: High contrast resolution MRI allowed identification of structural lesions of the foot affecting the cartilage surfaces, bone marrow, and soft tissue supports in patients with DMPN + MCD. As expected, the presence of bone and joint lesions on MRI were strongly associated with DMPN + MCD; surprisingly, although the sample is small, lesions of the soft tissue supports were not associated with MCD. While MRI is not done routinely to investigate MCD, opportunistic use of the information from MRI done for the common clinical indications may allow early identification of the structural lesions associated with MCD and facilitate early, aggressive therapy. LEVEL OF EVIDENCE: III.

A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.

BACKGROUND: Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. METHODS: The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. RESULTS: Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. CONCLUSIONS: Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients.

Deficits in the Skeletal Muscle Transcriptome and Mitochondrial Coupling in Progressive Diabetes-Induced CKD Relate to Functional Decline.

Two-thirds of people with type 2 diabetes mellitus (T2DM) have or will develop chronic kidney disease (CKD), which is characterized by rapid renal decline that, together with superimposed T2DM-related metabolic sequelae, synergistically promotes early frailty and mobility deficits that increase the risk of mortality. Distinguishing the mechanisms linking renal decline to mobility deficits in CKD progression and/or increasing severity in T2DM is instrumental both in identifying those at high risk for functional decline and in formulating effective treatment strategies to prevent renal failure. While evidence suggests that skeletal muscle energetics may relate to the development of these comorbidities in advanced CKD, this has never been assessed across the spectrum of CKD progression, especially in T2DM-induced CKD. Here, using next-generation sequencing, we first report significant downregulation in transcriptional networks governing oxidative phosphorylation, coupled electron transport, electron transport chain (ETC) complex assembly, and mitochondrial organization in both middle- and late-stage CKD in T2DM. Furthermore, muscle mitochondrial coupling is impaired as early as stage 3 CKD, with additional deficits in ETC respiration, enzymatic activity, and increased redox leak. Moreover, mitochondrial ETC function and coupling strongly relate to muscle performance and physical function. Our results indicate that T2DM-induced CKD progression impairs physical function, with implications for altered metabolic transcriptional networks and mitochondrial functional deficits as primary mechanistic factors early in CKD progression in T2DM.

Skeletal Muscle Regeneration in Advanced Diabetic Peripheral Neuropathy.

BACKGROUND: Decreased lean muscle mass in the lower extremity in diabetic peripheral neuropathy (DPN) is thought to contribute to altered joint loading, immobility, and disability. However, the mechanism behind this loss is unknown and could derive from a reduction in size of myofibers (atrophy), destruction of myofibers (degeneration), or both. Degenerative changes require participation of muscle stem (satellite) cells to regenerate lost myofibers and restore lean mass. Determining the degenerative state and residual regenerative capacity of DPN muscle will inform the utility of regeneration-targeted therapeutic strategies. METHODS: Biopsies were acquired from 2 muscles in 12 individuals with and without diabetic neuropathy undergoing below-knee amputation surgery. Biopsies were subdivided for histological analysis, transcriptional profiling, and satellite cell isolation and culture. RESULTS: Histological analysis revealed evidence of ongoing degeneration and regeneration in DPN muscles. Transcriptional profiling supports these findings, indicating significant upregulation of regeneration-related pathways. However, regeneration appeared to be limited in samples exhibiting the most severe structural pathology as only extremely small, immature regenerated myofibers were found. Immunostaining for satellite cells revealed a significant decrease in their relative frequency only in the subset with severe pathology. Similarly, a reduction in fusion in cultured satellite cells in this group suggests impairment in regenerative capacity in severe DPN pathology. CONCLUSION: DPN muscle exhibited features of degeneration with attempted regeneration. In the most severely pathological muscle samples, regeneration appeared to be stymied and our data suggest that this may be partly due to intrinsic dysfunction of the satellite cell pool in addition to extrinsic structural pathology (eg, nerve damage). CLINICAL RELEVANCE: Restoration of DPN muscle function for improved mobility and physical activity is a goal of surgical and rehabilitation clinicians. Identifying myofiber degeneration and compromised regeneration as contributors to dysfunction suggests that adjuvant cell-based therapies may improve clinical outcomes.

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.

Early-Onset Physical Frailty in Adults With Diabesity and Peripheral Neuropathy.

OBJECTIVES: Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. METHODS: We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m2); 13 with diabesity only (53 years of age, BMI 34 kg/m2) and 10 obese controls (67 years of age, BMI 32 kg/m2). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. RESULTS: Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. CONCLUSIONS: Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline.

A Candidate Imaging Marker for Early Detection of Charcot Neuroarthropathy.

Inflammation-mediated foot osteopenia may play a pivotal role in the etiogenesis, pathogenesis, and therapeutic outcomes in individuals with diabetes mellitus (DM), peripheral neuropathy (PN), and Charcot neuroarthropathy (CN). Our objective was to establish a volumetric quantitative computed tomography-derived foot bone measurement as a candidate prognostic imaging marker to identify individuals with DMPN who were at risk of developing CN. We studied 3 groups: 16 young controls (27 ± 5 years), 20 with DMPN (57 ± 11 years), and 20 with DMPN and CN (55 ± 9 years). Computed tomography image analysis was used to measure metatarsal and tarsal bone mineral density in both feet. The mean of 12 right (7 tarsals and 5 metatarsals) and 12 left foot bone mineral densities, maximum percent difference in bone mineral density between paired bones of the right and the left feet, and the mean difference of the 12 right and the 12 left bone mineral density measurements were used as input variables in different classification analysis methods to determine the best classifier. Classification tree analysis produced no misclassification of the young controls and individuals with DMPN and CN. The tree classifier found 7 of 20 (35%) individuals with DMPN to be classified as CN (1 participant developed CN during follow-up) and 13 (65%) to be classified as healthy. These results indicate that a decision tree employing 3 measurements derived from volumetric quantitative computed tomography foot bone mineral density defines a candidate prognostic imaging marker to identify individuals with diabetes and PN who are at risk of developing CN.

Reliability of analysis of the bone mineral density of the second and fifth metatarsals using dual-energy x-ray absorptiometry (DXA).

BACKGROUND: Metatarsal fractures, especially of the fifth metatarsal, are common injuries of the foot in a young athletic population, but the risk factors for this injury are not well understood. Dual-energy x-ray absorptiometry (DXA) provides reliable measures of regional bone mineral density to predict fracture risk in the hip and lumbar spine. Recently, sub-regional metatarsal reliability was established in fresh cadaveric specimens and associated with ultimate fracture force. The purpose of this study was to assess the reliability of DXA bone mineral density measurements of sub-regions of the second and fifth metatarsals in a young, active population. METHODS: Thirty two recreationally active individuals participated in the study, and the bone density of the second (2MT) and fifth (5MT) metatarsals of each subject was measured using a Hologic QDR x-ray bone densitometer. Scans were analyzed separately by two raters, and regional bone mineral density, bone mineral content, and area measurements were calculated for the proximal, shaft, and distal regions of the bone. Intra-rater, inter-rater, and scan-rescan reliability were then determined for each region. RESULTS: Proximal and shaft bone mineral density measurements of the second and fifth metatarsal were reliable. ICC's were variable across regions and metatarsals, with the distal region being the poorest. CONCLUSIONS: Bone mineral density measurements of the metatarsals may be a better indicator of fracture risk of the metatarsals than whole body measurements. A reliable method for measuring the regional bone mineral densities of the metatarsals was found. However, inter-rater reliability and scan-rescan reliability for the distal regions were poor. Future research should examine the relationship between DXA bone mineral density measurements and fracture risk at the metatarsals.

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.

Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.

BACKGROUND: Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. METHODS: In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs - aerobic training, resistance training, or combined aerobic and resistance training - or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions. RESULTS: A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (P<0.001 for between-group comparisons). Peak oxygen consumption (milliliters per kilogram of body weight per minute) increased more in the combination and aerobic groups (17.2 to 20.3 [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons). Strength increased more in the combination and resistance groups (272 to 320 kg [18% increase] and 288 to 337 kg [19% increase], respectively) than in the aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body weight decreased by 9% in all exercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events included musculoskeletal injuries. CONCLUSIONS: Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults. (Funded by the National Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).

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.

Explanators of Sarcopenia in Individuals With Diabesity: A Cross-Sectional Analysis.

BACKGROUND AND PURPOSE: Excess lower extremity intermuscular adipose tissue (IMAT), reduced strength, and functional limitations are common in obese individuals with and without diabetes (the former termed diabesity). Individuals with diabesity are particularly susceptible to accelerated sarcopenia, which may be underdiagnosed. The purpose of this study was to determine critical values for leg IMAT volume, plantar flexor (PF) muscle strength, and physical performance that help identify individuals with diabesity who have sarcopenia. METHODS: Forty-three age- and sex-matched obese adults were studied: 12 with type 2 diabetes, 21 with diabetes and peripheral neuropathy, and 10 nondiabetic controls. Dual-energy x-ray absorptiometry-derived skeletal muscle index determined classification of sarcopenia. Leg fat (% IMAT), ankle (PF) peak torque, and power while ascending 10 steps, were used as explanators of sarcopenia. Receiver operating curves identified critical values for each explanator individually. Logistic regression models using all 3 explanators, and only PF torque and stair power, were also created. Receiver operating curve analyses identified the predicted probability that maximized each model's sensitivity and specificity. A leave-one-out cross validation was used to simulate the models' performance in an independent sample. RESULTS AND DISCUSSION: Thirty-two participants were sarcopenic, and 11 were not. Critical values for individual explanators were 21% IMAT, 68 Nm PF torque, and 441 watts of stair power. Predicted probabilities of .76 and .67 were chosen as the optimal cutoff probabilities for the model combining all 3 explanators, and the model combining PF torque and stair power, respectively. The cross-validation analysis produced an accuracy of 82.4%, using the cutoff probability of .5, and an accuracy of 76.5% using the cutoff of 0.76. The area under the curve for the cross validation receiver operating curve analysis was 0.82. Critical values of leg % IMAT, PF torque, and stair power can classify individuals with diabesity as sarcopenic. The results of the cross validation give us confidence that the sample used in this study was representative of the target population, and suggests models created from this sample may perform well in externally derived data sets. CONCLUSION: Clinicians may be able to use these critical values to select interventions that specifically target sarcopenia. Measures of % IMAT, PF torque, and stair power may offer a customized alternative to traditional sarcopenic classification systems, which may not be optimally suited to the common impairments among individuals with diabesity.

Physical Training and Activity in People With Diabetic Peripheral Neuropathy: Paradigm Shift.

Diabetic peripheral neuropathy (DPN) occurs in more than 50% of people with diabetes and is an important risk factor for skin breakdown, amputation, and reduced physical mobility (ie, walking and stair climbing). Although many beneficial effects of exercise for people with diabetes have been well established, few studies have examined whether exercise provides comparable benefits to people with DPN. Until recently, DPN was considered to be a contraindication for walking or any weight-bearing exercise because of concerns about injuring a person's insensitive feet. These guidelines were recently adjusted, however, after research demonstrated that weight-bearing activities do not increase the risk of foot ulcers in people who have DPN but do not have severe foot deformity. Emerging research has revealed positive adaptations in response to overload stress in these people, including evidence for peripheral neuroplasticity in animal models and early clinical trials. This perspective article reviews the evidence for peripheral neuroplasticity in animal models and early clinical trials, as well as adaptations of the integumentary system and the musculoskeletal system in response to overload stress. These positive adaptations are proposed to promote improved function in people with DPN and to foster the paradigm shift to including weight-bearing exercise for people with DPN. This perspective article also provides specific assessment and treatment recommendations for this important, high-risk group.