Bone remodeling and calcium homeostasis in patients with spinal cord injury: a review.

Patients with spinal cord injury exhibit early and acute bone loss with the major functional consequence being a high incidence of pathological fractures. The bone status of these patients is generally investigated by dual-energy x-ray absorptiometry, but this technique does not reveal the pathophysiological mechanism underlying the bone loss. Bone cell activity can be indirectly evaluated by noninvasive techniques, including measurement of specific biochemical markers of bone formation (such as osteocalcin or bone-alkaline phosphatase) and resorption (such as procollagen type I N- or C-terminal propeptide). The bone loss in spinal cord injury is clearly due to an uncoupling of bone remodeling in favor of bone resorption, which starts just after the injury and peaks at about 1 to 4 months. Beyond 6 months, bone resorption activity decreases progressively but remains elevated for many years after injury. Conversely, bone formation is less affected. Antiresorptive treatment induces an early and acute reduction in bone resorption markers. Level of injury and health-related complications do not seem to be implicated in the intensity of bone resorption. During the acute phase, the hypercalcemic status is associated with the suppression of parathyroid hormone and vitamin D metabolites. The high sensitivity of these markers after treatment suggests that they can be used for monitoring treatment efficacy and patient compliance. The concomitant use of bone markers and dual-energy x-ray absorptiometry may improve the physician's ability to detect patients at risk of severe bone loss and subsequent fractures.

Arm-cranking exercise assisted by Functional Electrical Stimulation in C6 tetraplegia: a pilot study.

Tetraplegic volunteers undertook progressive exercise training, using novel systems for arm-cranking exercise assisted by Functional Electrical Stimulation (FES). The main aim was to determine potential training effects of FES-assisted arm-crank ergometry (FES-ACE) on upper limb strength and cardiopulmonary (fitness) in tetraplegia. Surface FES was applied to the biceps and triceps during exercise on an instrumented ergometer. Two tetraplegic volunteers with C6 Spinal Cord Injury (SCI) went through muscle strengthening, baseline exercise testing and three months of progressive FES-ACE training. Repeat exercise tests were carried out every four weeks during training, and post-training, to monitor upper-limb strength and cardiopulmonary fitness. At each test point, an incremental test was carried out to determine peak work rate, peak oxygen uptake, gas exchange threshold and oxygen uptake-work rate relationship during FES-ACE. Peak oxygen uptake for Subject A increased from 0.7 l/min to 1.1 l/min, and peak power output increased from 7 W to 38 W after FES-ACE training. For Subject B, peak oxygen uptake was unchanged, but peak power output increased from 3 W to 8 W. These case studies illustrate potential benefits of FES-ACE in tetraplegia, but also the differences in exercise responses between individuals.

Energy cost of the case Western reserve standing neuroprosthesis.

OBJECTIVE: To determine the oxygen consumption of a person with C7 American Spinal Injury Association (ASIA) grade B tetraplegia using the Case Western Reserve/Veterans Administration (CWRU/VA) standing neuroprosthesis. DESIGN: Measure the oxygen consumption and carbon dioxide production of a person with C7 ASIA grade B tetraplegia at rest, standing in the parallel bars with the CWRU/VA system on, ambulating in the parallel bars, and transferring from a wheelchair to a mat with the system on. SETTING: University medical center. PARTICIPANT: A 26-year-old man with C7 ASIA grade B tetraplegia. The subject was a recipient of the CWRU/VA standing neuroprosthesis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measurement of oxygen consumption and carbon dioxide production using a metabolic cart. RESULTS: Oxygen consumption of the subject was 1.22mL.kg(-1).min(-1) at rest. It was 4.7mL.kg(-1).min(-1) while standing in the parallel bars, 7.2mL.kg(-1).min(-1) while ambulating in the parallel bars, and 7.9mL.kg(-1).min(-1) when transferring from a wheelchair to a mat. CONCLUSIONS: Oxygen consumption of the subject when using the system is about 2 metabolic equivalent units, which is compatible with sustained use of the system for standing.

Improvement of metabolic and cardiorespiratory responses through treadmill gait training with neuromuscular electrical stimulation in quadriplegic subjects.

This work assessed the influence of treadmill gait training with neuromuscular electrical stimulation (NMES) on the metabolic and cardiorespiratory responses in quadriplegic subjects. The gait group (GG) (n=11) performed 6 months of treadmill training with 30-50% body weight support and with the help of physiotherapists, twice a week, allotting 20 min for each session. The control group (CG) (n=10), during the 6 months of training, did not perform any activity using NMES, performing instead conventional physiotherapy. Metabolic and cardiorespiratory responses (O(2) uptake [VO(2)], CO(2) production [VCO(2)], pulmonary ventilation (V(E)), heart rate [HR], and blood pressure [BP]) were measured on inclusion and after 6 months. For the GG, differences were found in all parameters after training (P<0.05), except for HR and diastolic BP. During gait, VO(2) (L/min) increased by 36%, VCO(2) (L/min) increased by 42.97%, V(E) (L/min) increased by 30.48%, and systolic BP (mm Hg) increased by 4.8%. For the CG, only VO(2) and VCO(2) (L/min) significantly increased at rest (30.82 and 16.39%, respectively) and during knee-extension exercise (26.29 and 17.37%, respectively). Treadmill gait with NMES was, therefore, more efficient toward increasing the aerobic capacity due to yielding higher metabolic and cardiovascular stresses.

Improved glucose tolerance and insulin sensitivity after electrical stimulation-assisted cycling in people with spinal cord injury.

DESIGN: Longitudinal training. OBJECTIVES: The purpose was to determine the effect of electrical stimulation (ES)-assisted cycling (30 min/day, 3 days/week for 8 weeks) on glucose tolerance and insulin sensitivity in people with spinal cord injury (SCI). SETTING: The Steadward Centre, Alberta, Canada. METHODS: Seven participants with motor complete SCI (five males and two females aged 30 to 53 years, injured 3-40 years, C5-T10) underwent 2-h oral glucose tolerance tests (OGTT, n=7) and hyperglycaemic clamp tests (n=3) before and after 8 weeks of training with ES-assisted cycling. RESULTS: Results indicated that subjects' glucose level were significantly lower at 2 h OGTT following 8 weeks of training (122.4+/-10 vs 139.9+/-16, P=0.014). Two-hour hyperglycaemic clamps tests showed improvement in all three people for glucose utilisation and in two of three people for insulin sensitivity. CONCLUSIONS: These results suggested that exercise with ES-assisted cycling is beneficial for the prevention and treatment of Type 2 diabetes mellitus in people with SCI. SPONSORSHIP: Supported by Alberta Paraplegic Foundation, Therapeutic Alliance.

Exercise-induced overexpression of key regulatory proteins involved in glucose uptake and metabolism in tetraplegic persons: molecular mechanism for improved glucose homeostasis.

Complete spinal cord lesion leads to profound metabolic abnormalities and striking changes in muscle morphology. Here we assess the effects of electrically stimulated leg cycling (ESLC) on whole body insulin sensitivity, skeletal muscle glucose metabolism, and muscle fiber morphology in five tetraplegic subjects with complete C5-C7 lesions. Physical training (seven ESLC sessions/wk for 8 wk) increased whole body insulin-stimulated glucose uptake by 33+/-13%, concomitant with a 2.1-fold increase in insulin-stimulated (100 microU/ml) 3-O-methylglucose transport in isolated vastus lateralis muscle. Physical training led to a marked increase in protein expression of GLUT4 (378+/-85%), glycogen synthase (526+/-146%), and hexokinase II (204+/-47%) in vastus lateralis muscle, whereas phosphofructokinase expression (282+/-97%) was not significantly changed. Hexokinase II activity was significantly increased, whereas activity of phosphofructokinase, glycogen synthase, and citrate synthase was not changed after training. Muscle fiber type distribution and fiber area were markedly altered compared to able-bodied subjects before ESLC training, with no change noted in either parameter after ECSL training. In conclusion, muscle contraction improves insulin action on whole body and cellular glucose uptake in cervical cord-injured persons through a major increase in protein expression of key genes involved in the regulation of glucose metabolism. Furthermore, improvements in insulin action on glucose metabolism are independent of changes in muscle fiber type distribution.

Immediate endocrine and metabolic consequences of traumatic quadriplegia in a young woman.

Onset of paralysis by cervical spinal cord injury led immediately to temporary adrenocortical activation and, within 2 days, to sustained skin and bone breakdown. Urine cAMP was increased, blood parathyroid hormone, renin activity, and electrolytes were normal, and fluid and electrolytes balance became negative during the initial 6 days of paralysis.

Metabolic effects of sodium restriction and thiazides in tetraplegic patients.

The metabolic effects of sodium restriction, alone or with thiazide, were studied in 12 healthy subjects, in 24 tetraplegics during the intial 8 months of paralysis (early) and in 16 others during the subsequent period (late). The diuresis caused by both treatments led to more haemoconcentration in early than in late patients. In contrast with the healthy subjects on low sodium, the tetraplegics had a delayed urinary sodium retention and no fall in calciuria. During thiazide, urinary sodium depletion occurred early and the urine calcium fell after 3 days in all tetraplegics. During both treatments, aldosterone and renin increased more in early patients than in the other groups. The clinical implications of inducing dehydration and a sustained stimulation of the renin-angiotensin-aldosterone axis in recently injured tetraplegics with severe orthostatic hypotension are discussed.

Bone metabolism in quadriplegia: dissociation between calciuria and hydroxyprolinuria.

Relationships between duration of paralysis, recumbency, muscular activity, and urinary loss of calcium (Cau), phosphorus (Pu), and hydroxyproline (OHPu) were studied daily in 32 traumatic quadriplegic patients during comprehensive rehabilitation and randomly in those readmitted for treatment. Within days after onset, quadriplegic patients had increases in Pu, then OHPu, and finally, Cau. Patients actively engaged in rehabilitation exercises showed a steady fall in OHPu, whereas CAU remained high for up to 18 months. Patients paralyzed for over 18 months (late) had low Cau, Pu and OHPu; but if the patients were kept in bed, OHPu increased rapidly. Patients with early quadriplegia have an increased bone remodeling, suggesting that the excess OHPu and Cau are derived from resorbed bone. Patients with late quadriplegia have little bone remodeling, therefore the excess OHPu occurring during recumbency may be derived from the resorption of new collagen produced during the removal of weight bearing without further change in muscular activity. Resorbed new collagen is excreted in part as large, OHP-containing polypeptides; these were found in the urine of quadriplegic patients, and therefore were present in blood and may play a role in initiating ectopic bone and renal calculi. The presence of OHP in 11 bladder calculi from quadriplegic patients tends to support this hypothesis. These studies indicate that muscular activity and weight bearing influence the bone metabolism of quadriplegic patients and suggest that the presence in body fluids of increased catabolic products from bone may have a role in bone-related complications.