Quantitative ultrasound imaging monitoring progressive disuse osteopenia and mechanical stimulation mitigation in calcaneus region through a 90-day bed rest human study.

BACKGROUND: Osteoporosis parallels aging and functional mechanical unloading (e.g., space flight and bed rest), jeopardizing mineral density, microstructure, and integrity of bone and leading to an increased risk of fracture. A way to combat this deterioration is to harness the sensitivity of bone to mechanical signals. OBJECTIVE: This study evaluates the longitudinal effect of a dynamic mechanical loading through the heel on human bone in vivo during 90-day bed rest, monitored by quantitative ultrasound (QUS) imaging and dual-energy X-ray absorptiometry (DXA) in localized regions of interests, i.e., calcaneus. METHODS: A total of 29 bed rest individuals were evaluated (11 control and 18 treatment) with a brief (10-minute) daily low-intensity (0.3g), high-frequency (30Hz) dynamic mechanical stimulation countermeasure through vibrational inhibition bone erosion (VIBE). Both QUS and DXA detected longitudinal bone density and quality changes. RESULTS: Ultrasound velocity (UV) decreased in the control group and increased in the group treated with low-intensity loading. The UV increased by 1.9% and 1.6% at 60- and 90-day bed rest (p=0.01) in VIBE over control groups. A trend was found in broadband ultrasound attenuation (BUA), with a VIBE benefit of 1.8% at day 60 and 0.5% at day 90 in comparison with control (p=0.5). Bone mineral density (BMD) assessed by DXA decreased -4.50% for control individuals and -2.18% for VIBE individuals, showing a moderate effect of the mechanical intervention (p=0.19). Significant correlations between QUS and DXA were observed, with a combined BUA and UV vs. BMD: r2=0.70. CONCLUSION: These results indicated that low-intensity, high-frequency loading has the potential to mitigate regional bone loss induced by long-term bed rest and that QUS imaging may be able to assess the subtle changes in bone alteration. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Quantitative ultrasound has shown the efficacy of noninvasively assessing bone mass and structural properties in cadaver and isolated trabecular bone samples. While its ability in measuring in vivo bone quality and density is still unclear, a scanning confocal ultrasound imaging is developed and can perform an instant assessment for the subtle changes of such bone loss. This ultrasound imaging modality can potentially be used in the clinical assessment of bone mass. Moreover, physical stimulation has shown the ability to prevent bone loss induced by functional disuse and estrogen deficiency in animal models. However, its treatment capability is unclear. This study has shown that low-magnitude mechanical signals, introduced using low-intensity vibration (LIV), can mitigate regional bone loss caused by functional disuse. Thus localized mechanical treatment, and the quantitative ultrasound imaging have shown translational potential to noninvasively attenuate bone loss, and assess bone mass in the clinic, e.g., in an extreme condition such as long-term space mission, and long-term bedrest such as in case of spinal cord injury.

Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation.

In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague-Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.

Associations of Computed Tomography-Based Trunk Muscle Size and Density With Balance and Falls in Older Adults.

BACKGROUND: Deficits in balance and muscle function are important risk factors for falls in older adults. Aging is associated with significant declines in muscle size and density, but associations of trunk muscle size and density with balance and falls in older adults have not been previously examined. METHODS: Trunk muscle size (cross-sectional area) and attenuation (a measure of tissue density) were measured in computed tomography scans (at the L2 lumbar level) in a cohort of older adults (mean ± SD age of 81.9±6.4) residing in independent living communities. Outcome measures were postural sway measured during quiet standing and Short Physical Performance Battery (SPPB) at baseline, and falls reported by participants for up to 3 years after baseline measurements. RESULTS: Higher muscle density was associated with reduced postural sway, particularly sway velocities, in both men and women, and better Short Physical Performance Battery score in women, but was not associated with falls. Larger muscle size was associated with increased postural sway in men and women and with increased likelihood of falling in men. CONCLUSIONS: The results suggest that balance depends more on muscle quality than on the size of the muscle. The unexpected finding that larger muscle size was associated with increased postural sway and increased fall risk requires further investigation, but highlights the importance of factors besides muscle size in muscle function in older adults.

Spatial distribution and remodeling of elastic modulus of bone in micro-regime as prediction of early stage osteoporosis.

We assessed the local distribution of bone mechanical properties on a micro-nano-scale and its correlation to strain distribution. Left tibia samples were obtained from 5-month old female Sprague Dawley rats, including baseline control (n=9) and hindlimb suspended (n=9) groups. Elastic modulus was measured by nanoindentation at the dedicated locations. Three additional tibias from control rats were loaded axially to measure bone strain, with 6-10N at 1Hz on a Bose machine for strain measurements. In the control group, the difference of the elastic modulus between periosteum and endosteum was much higher at the anterior and posterior regions (2.6GPa), where higher strain differences were observed (45µÉ›). Minimal elastic modulus difference between periosteum and endosteum was observed at the medial region (0.2GPa), where neutral axis of the strain distribution was oriented with lower strain difference (5µÉ›). In the disuse group, however, the elastic modulus differences in the anterior posterior regions reduced to 1.2GPa from 2.6GPa in the control group, and increased in the medial region to 2.7GPa from 0.2GPa. It is suggested that the remodeling rate in a region of bone is possibly influenced by the strain gradient from periosteum to endosteum. Such pattern of moduli gradients was compromised in disuse osteopenia, suggesting that the remodeling in distribution of micro-nano-elastic moduli among different regions may serve as a predictor for early stage of osteoporosis.

Dynamic parameters of balance which correlate to elderly persons with a history of falls.

Poor balance in older persons contributes to a rise in fall risk and serious injury, yet no consensus has developed on which measures of postural sway can identify those at greatest risk of falling. Postural sway was measured in 161 elderly individuals (81.8y±7.4), 24 of which had at least one self-reported fall in the prior six months, and compared to sway measured in 37 young adults (34.9y±7.1). Center of pressure (COP) was measured during 4 minutes of quiet stance with eyes opened. In the elderly with fall history, all measures but one were worse than those taken from young adults (e.g., maximal COP velocity was 2.7× greater in fallers than young adults; p<0.05), while three measures of balance were significantly worse in fallers as compared to older persons with no recent fall history (COP Displacement, Short Term Diffusion Coefficient, and Critical Displacement). Variance of elderly subjects' COP measures from the young adult cohort were weighted to establish a balance score ("B-score") algorithm designed to distinguish subjects with a fall history from those more sure on their feet. Relative to a young adult B-score of zero, elderly "non-fallers" had a B-score of 0.334, compared to 0.645 for those with a fall history (p<0.001). A weighted amalgam of postural sway elements may identify individuals at greatest risk of falling, allowing interventions to target those with greatest need of attention.

Safety and severity of accelerations delivered from whole body vibration exercise devices to standing adults.

OBJECTIVES: Whole body vibration devices are used as a means to augment training, and their potential to treat a range of musculoskeletal diseases and injuries is now being considered. The goal of this work is to determine the degree to which acceleration delivered by whole body vibration devices at the plantar surfaces of a standing human is transmitted through the axial and appendicular skeleton, and how this mechanical challenge corresponds to the safety threshold limit values established by the International Standards Organization ISO-2631. DESIGN: Non-blinded laboratory assessment of a range of whole body vibration devices as it pertains to acceleration transmission to healthy volunteers. METHODS: Using skin and bite-bar mounted accelerometers, transmissibility to the tibia and cranium was determined in six healthy adults standing on a programmable whole body vibration device as a function of frequency and intensity. Measures of transmissibility were then made from three distinct types of whole body vibration platforms, which delivered a 50-fold range of peak-to-peak acceleration intensities (0.3-15.1 gp-p; where 1g is Earth's gravitational field). RESULTS: For a given frequency, transmissibility was independent of intensity when below 1g. Transmissibility declined non-linearly with increasing frequency. Depending on the whole body vibration device, vibration ranged from levels considered safe by ISO-2631 for up to 8h each day (0.3 gp-p @ 30 Hz), to levels that were seven times higher than what is considered a safe threshold for even 1 min of exposure each day (15.1 gp-p @ 30 Hz). Transmissibility to the cranium was markedly attenuated by the degree of flexion in the knees. CONCLUSIONS: Vibration can have adverse effects on a number of physiologic systems. This work indicates that readily accessible whole body vibration devices markedly exceed ISO guidelines for safety, and extreme caution must be practiced when considering their use.

Transmission of low-intensity vibration through the axial skeleton of persons with spinal cord injury as a potential intervention for preservation of bone quantity and quality.

BACKGROUND/OBJECTIVE: Persons with spinal cord injury (SCI) develop marked bone loss from paralysis and immobilization. Low-intensity vibration (LIV) has shown to be associated with improvement in bone mineral density in post-menopausal women and children with cerebral palsy. We investigated the transmissibility of LIV through the axial skeleton of persons with SCI as an initial approach to determine whether LIV may be used as a clinical modality to preserve skeletal integrity. METHODS: Transmission of a plantar-based LIV signal (0.27 +/- 0.11 g; 34 Hz) from the feet through the axial skeleton was evaluated as a function of tilt-table angle (15, 30, and 45 degrees) in seven non-ambulatory subjects with SCI and ten able-bodied controls. Three SCI and five control subjects were also tested at 0.44 +/- 0.18 g and 34 Hz. Transmission was measured using accelerometers affixed to a bite-bar to determine the percentage of LIV signal transmitted through the body. RESULTS: The SCI group transmitted 25, 34, and 43% of the LIV signal, and the control group transmitted 28, 45, and 57% to the cranium at tilt angles of 15, 30, and 45 degrees, respectively. No significant differences were noted between groups at any of the three angles of tilt. CONCLUSION: SCI and control groups demonstrated equivalent transmission of LIV, with greater signal transmission observed at steeper angles of tilt. This work supports the possibility of the utility of LIV as a means to deliver mechanical signals in a form of therapeutic intervention to prevent/reverse skeletal fragility in the SCI population.

Postural instability caused by extended bed rest is alleviated by brief daily exposure to low magnitude mechanical signals.

Loss of postural stability, as exacerbated by chronic bed rest, aging, neuromuscular injury or disease, results in a marked increase in the risk of falls, potentiating severe injury and even death. To investigate the capacity of low magnitude mechanical signals (LMMS) to retain postural stability under conditions conducive to its decline, 29 healthy adult subjects underwent 90 days of 6-degree head down tilt bed-rest. Treated subjects underwent a daily 10 min regimen of 30 Hz LMMS at either a 0.3g-force (n=12) or a 0.5g-force (n=5), introduced by Low Intensity Vibration (LIV). Control subjects (n=13) received no LMMS treatment. Postural stability, quantified by dispersions of the plantar-based center of pressure, deteriorated significantly from baseline in control subjects, with displacement and velocity at 60 days increasing 98.7% and 193%, respectively, while the LMMS group increased only 26.7% and 6.4%, reflecting a 73% and 97% relative retention in stability as compared to control. Increasing LMMS magnitude from 0.3 to 0.5 g had no significant influence on outcomes. LMMS failed to spare loss of muscle extension strength, but helped to retain flexion strength (e.g., 46.2% improved retention of baseline concentric flexion strength vs. untreated controls; p=0.01). These data suggest the potential of extremely small mechanical signals as a non-invasive means of preserving postural control under the challenge of chronic bed rest, and may ultimately represent non-pharmacologic means of reducing the risk of debilitating falls in elderly and infirm.

Short applications of very low-magnitude vibrations attenuate expansion of the intervertebral disc during extended bed rest.

BACKGROUND CONTEXT: Loss of functional weightbearing during spaceflight or extended bed rest (BR) causes swelling of the lumbar intervertebral discs (IVDs), elongates the spine, and increases the incidence of low back pain (LBP). Effective interventions for the negative effects of unloading are critical but not yet available. PURPOSE: To test the hypothesis that high-frequency, low-magnitude mechanical signals (LMMS) can attenuate the detrimental morphologic changes in the lumbar IVDs. STUDY DESIGN/SETTING: Volunteers were subjected to 90d of BR and 7d of reambulation. While retaining this supine position, 18 random subjects received LMMS (30Hz) for 10min/d, at peak-to-peak acceleration magnitudes of either 0.3g (n=12) or 0.5g (n=6). The remaining subjects served as controls (CTRs). PATIENT SAMPLE: Eighteen males and 11 female (33+/-7y) healthy subjects of astronaut age (35+/-7y, 18 males, 11 females) and without a history of back pain participated in this study. OUTCOME MEASURES: A combination of magnetic resonance imaging and computed tomography scans of the lumbar spine of all subjects were taken at baseline, 60d, 90d, and 7d post-BR. Back pain was self-reported. METHODS: IVD morphology, spine length, and back pain were compared between CTR and LMMS subjects. RESULTS: Compared with untreated CTRs, LMMS attenuated mean IVD swelling by 41% (p<.05) at 60d and 30% (p<.05) at 90d. After 7 days of reambulation, disc volume of the CTR group was still 8% (p<.01) greater than at baseline, whereas that for the LMMS group returned the disc volume to baseline levels. In contrast to BR alone, LMMS also retained disc convexity at all time points and reduced the incidence of LBP by 46% (p<.05). CONCLUSIONS: These data indicate that short daily bouts of LMMS can mitigate the detrimental changes in disc morphology, which arise during nonweightbearing, and provides preliminary support for a novel means of addressing spinal deterioration both on earth and in space.

Lateral trans-biceps popliteal block for elective foot and ankle surgery performed after induction of general anesthesia.

BACKGROUND: The purpose of this study was to determine safety and efficacy of lateral transtendinous popliteal blocks performed after induction of general anesthesia for intraoperative and postoperative pain control in elective foot and ankle surgery. METHODS: The charts of 475 consecutive patients were retrospectively reviewed. The technique was a lateral transtendinous popliteal block under nerve stimulator direction (described in the text). Patient records were retrospectively evaluated from the postanesthesia care unit, as well as at followup on postoperative day 1 and weeks 2, 6, and 12. RESULTS: The block was complete in 398 patients (83.7%). An incomplete block was found in 77 patients (16.2 %). In the incomplete category, 21 patients (4.4%) had no pain but some motor function, 32 patients (6.5%) reported mild to moderate pain, and 24 patients (5.3%) had severe pain. The average block duration was 16.5 hours. There were no adverse effects documented in any patient at followup. CONCLUSIONS: Lateral popliteal nerve block after induction of general anesthesia appears to be safe and effective for intraoperative and postoperative pain control in elective foot and ankle surgery.

Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome.

UNLABELLED: Complex Regional Pain Syndrome (CRPS) is a disorder that can be accompanied by severe pain that is often both chronic and resistant to conventional therapy. Harbut and Correll previously reported the successful treatment of a 9-year case of intractable Type I CRPS with an intravenous inpatient infusion of ketamine in an adult female patient. OBJECTIVE: The purpose of this study was to ascertain if indeed the use of subanesthetic inpatient infusions of ketamine provide meaningful improvements in pain scores, and thus, quality of life, in patients suffering from CRPS. To achieve this objective we focused our analysis on the relief of pain obtained by patients undergoing this novel treatment option developed at Mackay Base Hospital, Queensland, Australia. METHODS: Case notes of 33 patients whose CRPS pain was treated by the inpatient administration of a continuous subanesthetic intravenous infusion of ketamine were reviewed. The dose and duration of ketamine therapy and the degree and duration of relief obtained were recorded. Notable side effects were also recorded. The degree of relief obtained (immediately after the infusion) was assessed using pre- and posttreatment numeric pain scores. The duration of relief obtained (throughout the follow-up period) was analyzed using a Kaplan-Meier cumulative survival curve analysis. RESULTS: A total of 33 patients with diagnoses of CRPS who had undergone ketamine treatment at least once were identified. Due to relapse, 12 of 33 patients received a second course of therapy, and two of 33 patients received a third. The degree of relief obtained following the initial course of therapy was impressive (N=33); there was complete pain relief in 25 (76%), partial relief in six (18%), and no relief in two (6%) patients. The degree of relief obtained following repeat therapy (N=12) appeared even better, as all 12 patients who received second courses of treatment experienced complete relief of their CRPS pain. The duration of relief was also impressive, as was the difference between the duration of relief obtained after the first and after the second courses of therapy. In this respect, following the first course of therapy, 54% of 33 individuals remained pain free for >/=3 months and 31% remained pain free for >/=6 months. After the second infusion, 58% of 12 patients experienced relief for >/=1 year, while almost 33% remained pain free for >3 years. The most frequent side effect observed in patients receiving this treatment was a feeling of inebriation. Hallucinations occurred in six patients. Less frequent side effects also included complaints of lightheadedness, dizziness, and nausea. In four patients, an alteration in hepatic enzyme profile was noted; the infusion was terminated and the abnormality resolved thereafter. CONCLUSION: This retrospective review suggests that limited subanesthetic inpatient infusions of ketamine may offer a promising therapeutic option in the treatment of appropriately selected patients with intractable CRPS. More study is needed to further establish the safety and efficacy of this novel approach.

Epidural hematoma associated with dextran infusion.

The authors describe a case of epidural hematoma in association with dextran infusion in a patient who had undergone a peripheral vascular operation with epidural analgesia. Possible mechanisms for the anticoagulant effect of dextran and guidelines for the use of anticoagulant therapy in patients undergoing epidural anesthesia are discussed.

Sustained-release niacin for prevention of migraine headache.

Considerable advances in the diagnosis and treatment of migraine headache have occurred during the past decade, but treatment options for acute migraine attacks have expanded at a faster rate than those for prophylaxis. We describe a patient whose migraine headaches responded dramatically to sustained-release niacin as preventive treatment. Niacin is not generally considered to be effective for migraine prevention. However, low plasma levels of serotonin have been implicated in migraine pathogenesis, and niacin may act as a negative feedback regulator on the kynurenine pathway to shunt tryptophan into the serotonin pathway, thus increasing plasma serotonin levels. Sustained-release niacin merits further study as a potentially useful preventive therapy for migraine headache.