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Background: High-dose testosterone replacement therapy (TRT), paired with finasteride (type II 5α-reductase inhibitor), improves body composition, muscle strength, and bone mineral density (BMD) in older men, without inducing prostate enlargement—a side effect associated with TRT. Men with spinal cord injury (SCI) exhibit neuromuscular impairment, muscle atrophy, bone loss, and increased central adiposity, along with low testosterone. However, sparse evidence supports TRT efficacy after SCI. Methods: This parallel-group, double-blind, placebo-controlled, and randomized clinical trial (RCT) is a pilot study that enrolled men (N = 12) with low to low–normal testosterone and gait impairments after chronic motor-incomplete SCI. Participants received high-dose intramuscular TRT (testosterone-enanthate, 125 mg/week) with finasteride (5 mg/day) vs. vehicle+placebo for 12 months. Change relative to baseline was determined for body composition, musculoskeletal outcomes, and prostate size, with effect sizes calculated between groups using Hedges' g. Adverse events and feasibility were assessed. Results: TRT + finasteride consistently increased testosterone (g = 1.16–3.08) and estradiol (g = 0.43–3.48), while concomitantly reducing dihydrotestosterone (g = 0.31–2.27). Very large effect sizes at both 6 and 12 months suggest TRT + finasteride increased whole-body fat-free (lean) mass (+3–4% vs. baseline, g = 2.12–2.14) and knee extensor (KE) whole-muscle cross-sectional area (+8–11% vs. baseline, g = 2.06–2.53) more than vehicle+placebo. Moderate-to-large effect sizes suggest TRT + finasteride increased KE maximal voluntary isometric torque (+15–40% vs. baseline, g = 0.47–1.01) and femoral neck and distal femur BMD from 6 months onward (g = 0.51–1.13), compared with vehicle+placebo, and reduced fat mass 9–14% within the whole-body, trunk, and android (visceral) regions at 12 months (g = 0.77–1.27). TRT + finasteride also produced small effect sizes favoring lesser prostate growth than vehicle+placebo (g = 0.31–0.43). The participant retention, drug compliance, and incidence and severity of adverse events were similar among the groups. Conclusion: These data provide proof-of-concept and rationale for larger RCTs aimed at discerning the impact of TRT + finasteride on body composition, musculoskeletal health, and physical function in men with SCI, along with effect sizes and variance of responses to assist in planning subsequent trials. Clinical trial registration: ClinicalTrials.gov, identifier NCT02248701. [ABSTRACT FROM AUTHOR]

It is unknown whether activity-based physical therapy (ABPT) modalities that mobilize the paralyzed limbs improve bone integrity at the highly fracture-prone epiphyseal regions of the distal femur and proximal tibia following severe spinal cord injury (SCI). In this study, 4-mo-old skeletally mature littermate-matched male Sprague-Dawley rats received either SHAM surgery or severe contusion SCI. At 1 wk postsurgery, SCI rats were stratified to undergo no-ABPT, two 20-min bouts/day of quadrupedal bodyweight-supported treadmill training (qBWSTT), or hindlimb passive isokinetic bicycle (cycle) training, 5 days/wk for another 3 wk. We assessed locomotor recovery and plantar flexor muscle mass, tracked cancellous and cortical bone microstructure at the distal femoral and proximal tibial epiphyses using in vivo microcomputed tomography (microCT), and evaluated bone turnover at the tibial epiphysis with histomorphometry. All SCI animals displayed persistent hindlimb paralysis and pervasive muscle atrophy. Over the initial 2 wk, which included 1 wk of no exercise and 1 wk of ABPT acclimation, a similar magnitude of bone loss developed in all SCI groups. Thereafter, cancellous bone loss and cortical bone decrements increased in the SCI no-ABPT group. qBWSTT attenuated this trabecular bone loss but did not prevent the ongoing cortical bone deficits. In comparison, twice-daily cycle training increased the number and activity of osteoblasts versus other SCI groups and restored all bone microstructural parameters to SHAM levels at both epiphyseal sites. These data indicate that a novel passive isokinetic cycle training regimen reversed cancellous and cortical bone deterioration at key epiphyseal sites after experimental SCI via osteoblast-mediated bone anabolic mechanisms, independent of locomotor recovery or increased muscle mass. NEW & NOTEWORTHY: This study was the first to assess how quadrupedal bodyweight-supported treadmill training or passive isokinetic bicycle (cycle) training impacts bone recovery at the distal femoral and proximal tibial epiphyses in a rat model of severe contusion spinal cord injury. Our results demonstrate that passive isokinetic cycle training completely restored cancellous and cortical bone microstructural parameters at these sites via osteoblast-mediated bone anabolic actions, independent of locomotor recovery or increased plantar flexor muscle mass. [ABSTRACT FROM AUTHOR]

Context: Following a lateral ankle sprain, ~40% of individuals develop chronic ankle instability (CAI), characterized by recurrent injury and sensations of giving way. Deafferentation due to mechanoreceptor damage postinjury is suggested to contribute to arthrogenic muscle inhibition (AMI). Whole-body vibration (WBV) has the potential to address the neurophysiologic deficits accompanied by CAI and, therefore, possibly prevent reinjury. Objective: To determine if an acute bout of WBV can improve AMI and proprioception in individuals with CAI. Design and Participants: The authors examined if an acute bout of WBV can improve AMI and proprioception in individuals with CAI with a repeated-measures design. A total of 10 young adults with CAI and 10 age-matched healthy controls underwent a control, sham, and WBV condition in randomized order. Setting: Biomechanics laboratory. Intervention: WBV. Main Outcome Measures: Motoneuron pool recruitment was assessed via Hoffmann reflex (H-reflex) in the soleus. Proprioception was evaluated using ankle joint position sense at 15° and 20° of inversion. Both were assessed prior to, immediately following, and 30 minutes after the intervention (pretest, posttest, and 30mPost, respectively). Results: Soleus maximum H-reflex:M-response (H:M) ratios were 25% lower in the CAI group compared with the control group (P = .03). Joint position sense mean constant error did not differ between groups (P = .45). Error at 15° in the CAI (pretest 0.8 [1.6], posttest 2.0 [2.8], 30mPost 2.0 [1.9]) and control group (pretest 0.8 [2.0], posttest 0.6 [2.9], 30mPost 0.5 [2.1]) did not improve post-WBV. Error at 20° did not change posl-WBV in the CAI (pretest 1.3 [1.7], posttest 1.0 [2.4], 30mPost 1.5 [2.2]) or control group (pretest -0.3 [3.0], posttest 0.8 [2.1 ], 30mPost 0.6 [1.8]). Conclusion: AMI is present in the involved limb of individuals with CAI. The acute response following a single bout of WBV did not ameliorate the presence of AMI nor improve proprioception in those with CAI. [ABSTRACT FROM AUTHOR]

Background: Action-intentional programs control "when" we initiate, inhibit, continue, and stop motor actions. The purpose of this study was to learn if there are changes in the action-intentional system with healthy aging, and if these changes are asymmetrical (right versus left upper limb) or related to impaired interhemispheric communication.Methods: We administered tests of action-intention to 41 middle-aged and older adults (61.9 ± 12.3 years).Results: Regression analyses revealed that older age predicted a decrement in performance for tests of crossed motor response inhibition as well as slower motor initiation with the left hand.Conclusion: Changes in action-intention with aging appear to be related to alterations of interhemispheric communication and/or age-related right hemisphere dysfunction; however, further research is needed to identify the mechanisms for age-related changes in the brain networks that mediate action-intention. [ABSTRACT FROM AUTHOR]

Neuromuscular impairment and reduced musculoskeletal integrity are hallmarks of spinal cord injury (SCI) that hinder locomotor recovery. These impairments are precipitated by the neurological insult and resulting disuse, which has stimulated interest in activity-based physical rehabilitation therapies (ABTs) that promote neuromuscular plasticity after SCI. However, ABT efficacy declines as SCI severity increases. Additionally, many men with SCI exhibit low testosterone, which may exacerbate neuromusculoskeletal impairment. Incorporating testosterone adjuvant to ABTs may improve musculoskeletal recovery and neuroplasticity because androgens attenuate muscle loss and the slow-to-fast muscle fiber-type transition after SCI, in a manner independent from mechanical strain, and promote motoneuron survival. These neuromusculoskeletal benefits are promising, although testosterone alone produces only limited functional improvement in rodent SCI models. In this review, we discuss the (1) molecular deficits underlying muscle loss after SCI; (2) independent influences of testosterone and locomotor training on neuromuscular function and musculoskeletal integrity post-SCI; (3) hormonal and molecular mechanisms underlying the therapeutic efficacy of these strategies; and (4) evidence supporting a multimodal strategy involving ABT with adjuvant testosterone, as a potential means to promote more comprehensive neuromusculoskeletal recovery than either strategy alone. [ABSTRACT FROM AUTHOR]