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A summary of medical literature on standing exercise effects on bone loss

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    A summary of medical literature on standing exercise effects on bone loss

    Many people of the CareCure Community do passive standing exercises and take drugs to reverse bone loss. Over the past year, many people have repeatedly asked for information (see listed topics below) concerning the beneficial effects of standing and recommendations for duration of training. Unfortunately, this information is not available or well-summarized in the medical literature or on Internet. So, I thought that I would try to summarize it here and then polish this later for a full article.

    Spinal cord injury causes demineralization and greater fragility of bone below the injury site. Zehnder, et al. (2004) examined 100 paraplegic men and found that 15 had documented fractures of their lower limbs that increased with time after injury (1% during the first year and 4.6% in those >20 years after injury). Bone loss was greatest in the beginning and leveled off after 1-3 years after injury but there continued to be continuous and progressive loss of cortical bone. Frey-Rindova, et al. (2000) examined bone mineral density in 29 patients (27 males, 2 females) for 12 months after spinal cord injury. Tetraplegics had reduced trabecular mineral density in the wrists by 6 months (19% radius and 6% ulnar) and 12 months (28% radius and 15% ulnar); cortical bone density was decreased by 12 months (3% radius and 4% ulnar). Paraplegics showed no change in wrist bone density. Tibial bone density was reduced in both paraplegic and tetraplegics at 6 months (5%) and 12 months (15%). Physical activity and spasticity levels did not seem to influence the bone loss.

    Vanwanseele, et al., (2002, 2003, 2004) at the Swiss Federal Institute of Technology in Zurich found that cartilage also deteriorates in the absence of normal joint loading and movement after spinal cord injury. While the atrophy of bone and cartilage is generally attributed to cessation of regular weight-bearing activity (Giangregorio & Blimkie, 2002), Edgerton, et al. (2000) has proposed that reduced gravity and prolonged bedrest reduces growth hormone levels. Bauman & Spungen (2000) suggests that deficiency of anabolic hormones, vitamin D and calcium deficiency, and secondary hyperparathyroidism may contribute to bone loss. Aging often compounds the bone loss associated with spinal cord injury (Capoor & Stein, 2005).

    Although much speculated upon, the beneficial effects of passive standing on bone mineral density have not yet been demonstrated in people after spinal cord injury. Eng, et al. (2001) from the University of Vancouver BC surveyed 152 people with SCI (age 18-55) who stood an average of 40 minutes per session, 3-4 times a week. Perceived benefits of standing included better feelings of well-being, circulation, skin integrity, reflex activity, bowel and bladder function, digestion, sleep, pain, and fatigue. Although the study did not measure any of these benefits, the authors suggested that standing exercise may be beneficial. Ott (2001) suggested that weight-bearing or functional electrical stimulation may prevent some bone loss particularly in acutely injured patients but presented no data to support this suggestion, recommending that estrogen be considered for postmenopausal women, pointing out that bisphophonates "must not be used in recumbant patients", and that thiazides could be useful as adjunct therapy.

    Takata & Yasui (2001) pointed out that reversal of disuse osteoporosis is very slow and require many years, emphasizing that prevention of disuse osteoporosis is the best. de Bruin, et al., (1999) evaluated the efficacy of early mobilization to prevent bone mineral density loss after spinal cord injury. Of 10 subjects who were mobilized early showed no or insignificant loss of trabecular bone and 3 of the 10 showed greater bone strength. Those who were not mobilized showed greater bone loss and also less mechanical bone strength. Early mobilization meant getting the people out of bed.

    Standing may have different effects on tetra- and paraplegics. Faghri, et al. (2001) showed that heart rates increased significantly by 18.2% in paraplegics but only 6% in tetraplegics during passive standing. When the standing was associated with functional electrical stimulation of muscles, the heart rate difference between para- and tetraplegics was not significant. During passive standing, cardiac output, stroke volume and blood pressure decreased whereas as total peripheral resistance increased. In contrast, active (FES) standing maintained all these cardiac parameters.

    Walking with orthothesis is another option. Hawran & Biering-Sorenson (1996) surveyed 45 paraplegic patients who had been prescribed long leg calipers. At the time of the survey, more than 10 years after discharge from hospital, only 3 were still using their calipers. When asked why not, 38% said that it was too time-consuming to put the braces on, 19% said that they were impractical since their hands had to be occupied keeping balance and were not available for carrying things. The 3 patients who still used them only used them at most once a week. However, all the patients who were given access to the standing frame were still using them. They suggested that the standing frame is a good alternative to long leg calipers. Several groups have developed new and lighter orthoses with composite materials (Stallard, et al., 2003).

    Active stepping, such as with the Parastep system, results in increased activity of the heart and lungs, as well as measurable increase in strength, endurance, and bulk of leg muscles (Klose, et al. 1997). Some evidence suggests that functional electrical stimulation and cycling reduced bone loss. Bloomfield, et al., (1996) reported that training with functional electrical stimulation (FES) cycling significantly improved bone mineral density in the leg bones. However, Eser, et al. (2003) studied 38 subjects and showed that FES cycling slowed the rate of bone mineral density loss (i.e. 0.3% per month compared to 0.7% in the control group) but this was not statistically significant. They concluded that FES cycling applied shortly after injury did not significantly attenuate bone loss. Intensive exercise, however, preserves bone mass of upper limbs even though it does not retard demineraliation of the lower body (Jones, et al., 2002).

    Several studies have looked at the effects of physical exercise on bone mass in osteoporotic women. Kronhed & Moller (1998), for example, assessed women who trained for 60 minutes twice a week for a year and fond that they had a significant increase in bone mass density in the greater trochanter (knee). Prior, et al., (1996) and the Osteoporotic Society of Canada concluded that "moderate physical activity in people with osteoporosis can reduce the risk of falls and fractures,...", "may also stimulate bone gain and decrease bone loss", and "its positive effects are an adjunct to other interventions, such as hormonal therapy".

    Children with cerebral palsy often show significant bone mineral density loss. Caulton, et al. (2004) did a randomized controlled trial of a standing program in non-ambulant children with cerebral palsy. While they found significant improvement in vertebral bone mineral density, there was no difference in tibial bone mineral density. Most studies of osteoporosis after spinal cord injury have not looked at vertebral bone mineral density and have focused on tibial or other leg bones.

    Vibrating platforms have been used to stimulate bone remodelling in people with osteoporosis. Hannan, et al. (2004) used such a device for 6 months in a double-blind placebo-controlled trial, placing 24 women daily for 10 minutes of a vibrating platform. They found that high compliance and satisfaction level with the device and few adverse reactions. They recommended further testing to look for efficacy. Ward, et al. (2004) exposed 20 children with pre-pubertal disabilities to 10-minute vibrating platform treatments, 5 days/week for 6 months. Compared against placebo devices, children that stood on the active platforms showed a 6.4% increase in trabecular bone mineral density of the tibia. Likewise, Rubin, et al. (2004) showed that vibratory stimulation (20-90 Hz) for two 10-minute periods per day in women with post-menopausal women and found no significant effect on bone mineral density between the placebo and treated group but found a linear relationship between compliance and the bone mineral density in the treatment group. Rubin, et al. (2003) showed that even low level vibrations transmits readily in the legs and back of people. Rubin, et al. (2002a; 2002b) exposed hindlimbs of adult sheep to 20 min/day of low level 30 Hz mechanical vibration and showed a 32% increase in bone volume.

    Bone mineral density measurements by x-rays often do not reflect the strength of the bone. De Bruin, et al (2005) described a new method of measureing bone strength. Using a device called Bone Stiffness Measurement Device (BSMD) – Swing, they measured phase velocity measurements and showed a linear relationship between health status, tibia length, age, and phase velocity in elderly abled-bodied men and people with spinal cord injury. The device is applied ot the tibia.

    In a recent review, Maimoun, et al. (2005) pointed out that many people use medications, particularly anti-resorptive drugs such as calcitonin or calcium retaining drug such as diphosphonates, to prevent osteoporosis. Many of the drugs that are used come from treatments originally developed for post-menopausal women who develop osteoporosis (Checa, et al. 2005)

    Several drugs have been reported to be useful for the treatment of osteoporosis. Knopp, et al. (2005) reviewed clinical trials using calcitonin to reverse or prevent vertebral collapse due to osteoporosis. They found 5 clinical trials involving 246 patients, showing that calcitonin significantly reduced severity of pain associated with vertebral compression fractures, as early as 1 week into treatment and that this reduction continued for 4 weeks. The pain scores were also lower with activities such as sitting, standing and walking. Side-effects were generally minor and limited to gastrointestinal symptoms.

    Low sex hormonal levels, particularly low estrogen and testosterone levels can be associated with osteoporosis. Since oral preparations of testosterone are ineffective, Jockenhoval (2003) successfully used transdermal 50-100 mg gel testosterone patches on people. The testosterone can also be injected intramuscularly every 12-15 weeks. Shetty, et al. (1993) had earlier reported that quadriplegic men have low growth hormone levels that can be stimulated by exercise.

    In summary, standing exercise alone does not seem to prevent lower limb bone loss. However, standing combined with functional electrical stimulation, active walking, and cycling, as well as biphosphonates or other therapies may be effective in reducing bone loss and even restoring bone.

    Relevant Topics

    Cite References
    • Bauman WA and Spungen AM (2000). Metabolic changes in persons after spinal cord injury. Phys Med Rehabil Clin N Am 11: 109-40. Persons with chronic SCI have several metabolic disturbances. As a consequence of inactivity and the body compositional changes of decreased skeletal muscle with a relative increase in adiposity, a state of insulin resistance and hyperinsulinemia has been demonstrated to exist, associated with abnormalities in oral carbohydrate handling. Elevated plasma insulin levels in persons with SCI probably contribute to the cause of frequent dyslipidemia and hypertension. This constellation of metabolic changes represents an atherogenic pattern of CHD risk factors with many of the distinctive features of a cardiovascular dysmetabolic syndrome that is called syndrome X. Reduction in modifiable risk factors for CHD should decrease the occurrence of catastrophic cardiovascular events. There is evidence to suggest that endogenous anabolic hormone levels are depressed in a proportion of individuals with SCI. Depression of serum testosterone and growth hormone/IGF-I levels may exacerbate the adverse lipid and body compositional changes, reduce exercise tolerance, and have deleterious effects on quality of life. Because of immobilization, individuals with paraplegia have osteoporosis of the pelvis and lower extremities, and those with tetraplegia also have osteoporosis of the upper extremities. In addition, there is evidence to suggest that bone loss progresses with time in persons with chronic SCI. This may be caused by chronic immobilization per se or may be a consequence of adverse hormonal changes, including deficiency of anabolic hormones or deficiency of vitamin D and calcium with secondary hyperparathyroidism. Serum thyroid function abnormalities resembling the euthyroid sick "low T3 syndrome" have been reported in those with acute and chronic spinal cord injury. Depressed serum T3 and elevated rT3 in chronic SCI may be caused by associated illness. Current practice has been hesitant to treat abnormal serum thyroid chemistries associated with nonthyroidal illness. Recognition of metabolic abnormalities in individuals with SCI is vital as a first step in improving clinical care. The application of appropriate interventions to correct or ameliorate these abnormalities promises to improve longevity and quality of life in persons with SCI. Department of Medicine, Mount Sinai Medical Center, New York, USA. Bauman.W@Bronx.VA.GOV
    • Bloomfield SA, Mysiw WJ and Jackson RD (1996). Bone mass and endocrine adaptations to training in spinal cord injured individuals. Bone. 19: 61-8. Department of Health & Kinesiology, Texas A&M University, College Station 77843-4243, USA. To investigate whether exercise training can produce increases in bone mass in spinal cord-injured (SCI) individuals with established disuse osteopenia, nine subjects (age 28.2 years, time since injury 6.0 years, level of injury C5-T7) were recruited for a 9-month training program using functional electrical stimulation cycle ergometry (FES-CE), which produces active muscle contractions in the paralyzed limb. After training, bone mineral density (BMD, by X-ray absorptiometry) increased by 0.047 +/- 0.010 g/cm2 at the lumbar spine; changes in BMD at the femoral neck, distal femur, and proximal tibia were not significant for the group as a whole. In a subset of subjects training at > or = 18 W for at least 3 months (n = 4), BMD increased by 0.095 +/- 0.026 g/cm2 (+18%) at the distal femur. By 6 months of training, a 78% increase in serum osteocalcin was observed, indicating an increase in bone turnover. Urinary calcium and hydroxyproline, indicators of resorptive activity, did not change over the same period. Serum PTH increased 75% over baseline values (from 2.98 +/- 0.15 to 5.22 +/- 0.62 pmol/L) after 6 months' training, with several individual values in hyperparathyroid range; PTH declined toward baseline values by 9 months. These data establish the feasibility of stimulating site-specific increases in bone mass in severely osteopenic bone with muscle contractions independent of weight-bearing for those subjects able to achieve a threshold power output of 18 W with FES-CE. Calcium supplementation from the outset of training in osteopenic individuals may be advisable to prevent training-induced increases in PTH.
    • Capoor J and Stein AB (2005). Aging with spinal cord injury. Phys Med Rehabil Clin N Am 16: 129-61. The years after SCI may be associated with acceleration of the aging process because of diminished physiologic reserves and increased demands on functioning body systems. Clinicians with expertise in the treatment and prevention of SCI-specific secondary complications need to collaborate with gerontologists and primary care specialists and need to invest in the training of future physicians to ensure a continuum of accessible, cost-effective, and high-quality care that meets the changing needs of the SCI population. Managed care payers often do not adequately cover long-term disability needs to prevent secondary SCI-specific complications. In this era of increasing accountability, evidence-based clinical practice guidelines are needed to document scientific evidence and professional consensus to effectively diagnose, treat, and manage clinical conditions; to reduce unnecessary testing and procedures; and to improve patient outcomes. Longitudinal research is needed to minimize cohort effects that contribute to misinterpretation of cross-sectional findings as representative of long-term changes in health and functioning. However, longitudinal studies confound chronologic age, time since injury, and environmental change. Thus, time-sequential research, which controls for such confounding effects, is essential, as is research on the effects of gender,culture, and ethnicity. If we consider how much progress has been made over the past 50 years with respect to SCI mortality related to infectious disease, we can expect to achieve even greater progress against the effects of aging in the next 50 years. Recent developments in molecular biology regarding growth and neuro-trophic factors are bringing us closer to the goal of repairing the damaged spinal cord. The challenge remains for rehabilitation professionals to provide the most comprehensive and holistic approach to long-term follow-up, with an emphasis on health promotion and disease prevention, to postpone functional decline and enhance QOL. Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
    • Caulton JM, Ward KA, Alsop CW, Dunn G, Adams JE and Mughal MZ (2004). A randomised controlled trial of standing programme on bone mineral density in non-ambulant children with cerebral palsy. Arch Dis Child 89: 131-5. BACKGROUND: Severely disabled children with cerebral palsy (CP) are prone to low trauma fractures, which are associated with reduced bone mineral density. AIMS: To determine whether participation in 50% longer periods of standing (in either upright or semi-prone standing frames) would lead to an increase in the vertebral and proximal tibial volumetric trabecular bone mineral density (vTBMD) of non-ambulant children with CP. METHODS: A heterogeneous group of 26 pre-pubertal children with CP (14 boys, 12 girls; age 4.3-10.8 years) participated in this randomised controlled trial. Subjects were matched into pairs using baseline vertebral vTBMD standard deviation scores. Children within the pairs were randomly allocated to either intervention (50% increase in the regular standing duration) or control (no increase in the regular standing duration) groups. Pre- and post-trial vertebral and proximal tibial vTBMD was measured by quantitative computed tomography (QCT). RESULTS: The median standing duration was 80.5% (9.5-102%) and 140.6% (108.7-152.2%) of the baseline standing duration in the control group and intervention group respectively. The mean vertebral vTBMD in the intervention group showed an increase of 8.16 mg/cm3 representing a 6% mean increase in vertebral vTBMD. No change was observed in the mean proximal tibial vTBMD. CONCLUSION: A longer period of standing in non-ambulant children with CP improves vertebral but not proximal tibial vTBMD. Such an intervention might reduce the risk of vertebral fractures but is unlikely to reduce the risk of lower limb fractures in children with CP. The Manchester School of Physiotherapy, Manchester Royal Infirmary, Manchester, UK.
    • de Bruin ED, Eser P, Ring M and Stussi E (2005). A validity study of phase velocity measurements in spinal cord injury. J Rehabil Res Dev 42: 55-63. We measured a cross-section of able-bodied (AB) men (n = 175) and men with chronic spinal cord injury (SCI) (n = 33) residing in the community, 14 to 65 years old, to identify associations between dietary factors, physical activity, health status, and mechanical properties of long bones assessed by phase velocity measurement of flexural waves in the tibia during the second to seventh decades. This study (1) evaluated the influence of different types of osteoporosis risk factors on measured phase velocity of tibia bone as measured by Bone Stiffness Measurement Device (BSMD)-Swing in AB men and in men with long-standing SCI and (2) estimated the construct validity of phase velocity measurements by assessing the discriminatory capability of the BSMD-Swing. Linear regression analysis suggests a direct relationship between health status, tibia length, age, and phase velocity (R(2) = 23%). An analysis of variance results in significant differences in phase velocity values between AB controls and individuals with SCI with and without pathologic fracture history. Phase velocity measurements in the tibia shaft provide useful information about bone status in populations at risk for low-trauma fractures and seems well suited for assessing tibia bone status in SCI. Laboratory for Biomechanics, Department of Material Sciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
    • de Bruin ED, Frey-Rindova P, Herzog RE, Dietz V, Dambacher MA and Stussi E (1999). Changes of tibia bone properties after spinal cord injury: effects of early intervention. Arch Phys Med Rehabil. 80: 214-20. Department of Material Sciences, Laboratory for Biomechanics ETH, Zurich, Switzerland. OBJECTIVE: To evaluate the effectiveness of an early intervention program for attenuating bone mineral density loss after acute spinal cord injury (SCI) and to estimate the usefulness of a multimodality approach in diagnosing osteoporosis in SCI. DESIGN: A single-case, experimental, multiple-baseline design. SETTING: An SCI center in a university hospital. METHODS: Early loading intervention with weight-bearing by standing and treadmill walking. PATIENTS: Nineteen patients with acute SCI. OUTCOME MEASURES: (1) Bone density by peripheral computed tomography and (2) flexural wave propagation velocity with a biomechanical testing method. RESULTS: Analysis of the bone density data revealed a marked decrease of trabecular bone in the nonintervention subjects, whereas early mobilized subjects showed no or insignificant loss of trabecular bone. A significant change was observed in 3 of 10 subjects for maximal and minimal area moment of inertia. Measurements in 19 subjects 5 weeks postinjury revealed a significant correlation between the calculated bending stiffness of the tibia and the maximal and minimal area moment of inertia, respectively. CONCLUSION: A controlled, single-case, experimental design can contribute to an efficient tracing of the natural history of bone mineral density and can provide relevant information concerning the efficacy of early loading intervention in SCI. The combination of bone density and structural analysis could, in the long term, provide improved fracture risk prediction in patients with SCI and a refined understanding of the bone remodeling processes during initial immobilization after injury.
    • Edgerton VR, Roy RR, Recktenwald MR, Hodgson JA, Grindeland RE and Kozlovskaya I (2000). Neural and neuroendocrine adaptations to microgravity and ground-based models of microgravity. J Gravit Physiol. 7: 45-52. Brain Research Institute and Department of Physiological Science, University of California, Los Angeles, CA, USA. The functional properties of the motor system of humans and non-human primates are readily responsive to microgravity. There is a growing body of evidence that significant adaptations occur in the spinal cord and muscle in response to prolonged exposure to microgravity. Further, there is evidence that the processing of sensory information from the periphery, particularly that input associated with the function of muscle tendons and joints, is significantly altered as a result of prolonged microgravity. We present evidence that the fundamental neural mechanisms that control the relative activity of the motor pools of a slow and fast extensor muscle is changed such that a slow, postural muscle is less readily activated during locomotion following spaceflight. Another type of change observed in mammals exposed to spaceflight relates to the release of a growth factor, called bioassayable growth hormone, which is thought to be released from the pituitary. When an individual generates a series of isometric plantarflexor contractions, the plasma levels of bioassayable growth hormone increases significantly. This response is suppressed after several days of continuous bedrest or spaceflight. These results suggest a unique neuroendocrine control system and demonstrate its sensitivity to chronic patterns of proprioceptive input associated with load-bearing locomotion.
    • Eng JJ, Levins SM, Townson AF, Mah-Jones D, Bremner J and Huston G (2001). Use of prolonged standing for individuals with spinal cord injuries. Phys Ther. 81 (8): 1392-9. Summary: BACKGROUND AND PURPOSE: Prolonged standing in people with spinal cord injuries (SCIs) has the potential to affect a number of health-related areas such as reflex activity, joint range of motion, or well-being. The purpose of this study was to document the patterns of use of prolonged standing and their perceived effects in subjects with SCIs. SUBJECTS: The subjects were 152 adults with SCIs (103 male, 49 female; mean age=34 years, SD=8, range=18-55) who returned mailed survey questionnaires. METHODS: A 17-item self-report survey questionnaire was sent to the 463 members of a provincial spinal cord support organization. RESULTS: Survey responses for 26 of the 152 respondents were eliminated from the analysis because they had minimal effects from their injuries and did not need prolonged standing as an extra activity. Of the 126 remaining respondents, 38 respondents (30%) reported that they engaged in prolonged standing for an average of 40 minutes per session, 3 to 4 times a week, as a method to improve or maintain their health. The perceived benefits included improvements in several health-related areas such as well-being, circulation, skin integrity, reflex activity, bowel and bladder function, digestion, sleep, pain, and fatigue. The most common reason that prevented the respondents from standing was the cost of equipment to enable standing. DISCUSSION AND CONCLUSION: Considering the many reported benefits of standing, this activity may be useful for people with SCI. This study identified a number of body systems and functions that may need to be investigated if clinical trials of prolonged standing in people with SCI are undertaken. <> School of Rehabilitation Sciences, University of British Columbia, T325- 2211 Wesbrook Mall, Vancouver, British Columbia, Canada V6T
    • Faghri PD, Yount JP, Pesce WJ, Seetharama S and Votto JJ (2001). Circulatory hypokinesis and functional electric stimulation during standing in persons with spinal cord injury. Arch Phys Med Rehabil. 82: 1587-95. School of Allied Health, University of Connecticut, Storrs, CT 06269-2101, USA. OBJECTIVE: To evaluate the effects of functional electric stimulation (FES) of lower limb muscles during 30 minutes of upright standing on the central and peripheral hemodynamic response in persons with spinal cord injury (SCI). DESIGN: A repeated-measure design. Subjects were used as their own control and underwent 2 testing protocols of FES-augmented standing (active standing) and non-FES standing (passive standing). SETTING: Rehabilitation hospital. PARTICIPANTS: Fourteen individuals with SCI (7 with tetraplegia, 7 with paraplegia). INTERVENTIONS: During active standing, FES was administered to 4 muscle groups of each leg in an overlapping fashion to produce a pumping mechanism during standing. During passive standing, subjects stood for 30 minutes using a standing frame with no FES intervention. MAIN OUTCOME MEASURES: Central hemodynamic responses of stroke volume, cardiac output, heart rate, arterial blood pressure, total peripheral resistance (TPR), and rate pressure product (RPP) were evaluated by impedance cardiography. All measurements were performed during supine and sitting positions before and after standing, and during 30 minutes of upright standing. RESULTS: Comparisons between the groups with paraplegia and tetraplegia showed a significant increase in heart rate in the paraplegics after 30 minutes of active standing. During active standing, paraplegics' heart rate increased by 18.2% (p = .015); during passive standing, it increased by 6% (p = .041). TPR in the tetraplegics significantly (p = .003) increased by 54% when compared with the paraplegics during passive standing. Overall, the tetraplegic group had a significantly lower systolic blood pressure (p = .013) and mean arterial pressure (p = .048) than the paraplegics during passive standing. These differences were not detected during active standing. When data were pooled from both groups and the overall groups response to active and passive standing were compared, the results showed that cardiac output, stroke volume, and blood pressure significantly decreased (p < .05) during 30 minutes of passive standing, whereas TPR significantly increased [p < .05). All of the hemodynamic variables were maintained during 30 minutes of active standing, and there were increases in RPP and heart rate after 30 minutes of active standing. CONCLUSION: FES of the lower extremity could be used by persons with SCI as an adjunct during standing to prevent orthostatic hypotension and circulatory hypokinesis. This effect may be more beneficial to those with tetraplegia who have a compromised autonomic nervous system and may not be able to adjust their hemodynamics to the change in position.
    • Giangregorio L and Blimkie CJ (2002). Skeletal adaptations to alterations in weight-bearing activity: a comparison of models of disuse osteoporosis. Sports Med. 32: 459-76. Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada. The removal of regular weight-bearing activity generates a skeletal adaptive response in both humans and animals, resulting in a loss of bone mineral. Human models of disuse osteoporosis, namely bed rest, spinal cord injury and exposure to micro-gravity demonstrate the negative calcium balance, alterations in biochemical markers of bone turnover and resultant loss of bone mineral in the lower limbs that occurs with reduced weight-bearing loading. The site-specific nature of the bone response is consistent in all models of disuse; however, the magnitude of the skeletal adaptive response may differ across models. It is important to understand the various manifestations of disuse osteoporosis, particularly when extrapolating knowledge gained from research using one model and applying it to another. In rats, hindlimb unloading and exposure to micro-gravity also result in a significant bone response. Bone mineral is lost, and changes in calcium metabolism and biochemical markers of bone turnover similar to humans are noted. Restoration of bone mineral that has been lost because of a period of reduced weight bearing may be restored upon return to normal activity; however, the recovery may not be complete and/or may take longer than the time course of the original bone loss. Fluid shear stress and altered cytokine activity may be mechanistic features of disuse osteoporosis. Current literature for the most common human and animal models of disuse osteoporosis has been reviewed, and the bone responses across models compared.
    • Hannan MT, Cheng DM, Green E, Swift C, Rubin CT and Kiel DP (2004). Establishing the compliance in elderly women for use of a low level mechanical stress device in a clinical osteoporosis study. Osteoporos Int 15: 918-26. Non-pharmacologic approaches to prevent bone loss are well suited for elderly patients to avoid polypharmacy and medication side effects. One potential treatment is a vibrating platform that delivers low-level mechanical loading stimulating bone remodeling. However, compliance is a major concern with any daily treatment, and is unknown for an elderly group using this device. Thus we assessed compliance with standing 10 min/day on a vibrating platform device in elderly women, the target population for osteoporosis therapy. We also assessed satisfaction with daily use of the device. We conducted a randomized, placebo-controlled, double-blinded 6-month study for daily use of a 10-min vibrating platform treatment in elderly women who were residents of a Continuing Care Retirement community. Compliance for each subject was calculated as the number of days attended divided by the 182 days in the 6-month trial. The 24 elderly women (mean age 86, range 79-92 years) had 83% compliance (95% CI: 70.5, 94.5) for daily treatment over 6 months. Excluding three study drop-outs, the 21 women had 93% compliance (95% CI: 89.8, 95.6), with no difference in compliance between active and placebo treatment. Main reasons for missing treatment days over the 6 months were vacation (54% of missed days) and illness (29%). Three adverse events occurred; one (syncope) was possibly related to device use, whereas the other two were not related to device use. Among participants, 95% reported overall satisfaction with daily use of the vibrating platform, and 57% preferred the platform versus daily oral medications for prevention of bone loss. Elderly women showed high compliance, high satisfaction and few adverse experiences with a daily non-pharmacological treatment designed to inhibit bone loss. Larger randomized controlled trials should evaluate the long-term efficacy of vibrating platform devices for treatment of low bone mass and osteoporosis in elderly individuals. Research & Training Institute, Hebrew Rehabilitation Center for Aged and Harvard Medical School Division on Aging, Boston, Mass., USA.
    • Knopp JA, Diner BM, Blitz M, Lyritis GP and Rowe BH (2005). Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomized, controlled trials. Osteoporos Int 16: 1281-90. Vertebral collapse is one of the most common fractures associated with osteoporosis. The subsequent back pain is severe and often requires medications, bed rest and hospitalization to control pain and improve mobilization. The purpose of this systematic review was to assess the effects of calcitonin versus placebo for the treatment of acute pain in patients sustaining stable, recent, osteoporotic vertebral compression fractures. MEDLINE (1966-2003), EMBASE (1980-2003), Cochrane Controlled Trial Registry (2003, volume 3), other databases, and conference proceedings were searched for relevant research. Primary study authors and the pharmaceutical manufacturer were contacted, and bibliographies of relevant papers were hand-searched. Randomized, double-blind, placebo-controlled trials comparing calcitonin versus placebo for the acute pain of recent osteoporotic vertebral compression fractures were included. Two reviewers extracted data, performed numeric calculations and extrapolated graphical data independently. The combined results from five randomized controlled trials, involving 246 patients, determined that calcitonin significantly reduced the severity of pain using a visual analogue scale following diagnosis. Pain at rest was reduced as early as 1 week into treatment (weighted mean difference [WMD] =3.08; 95% confidence interval [CI]: 2.64, 3.52) and this effect continued weekly to 4 weeks (WMD =4.03; 95% CI: 3.70, 4.35). A similar pattern was seen for pain scores associated with sitting, standing, and walking. Side effects were gastrointestinal, minor and often self-limited. Calcitonin appears to be effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilization. Family Medicine SF1, 22 WMC, University of Alberta Hospital, Edmonton, Alberta T6G 2B7, Canada.
    • Jockenhovel F (2003). Testosterone supplementation: what and how to give. Aging Male 6: 200-6. Several epidemiological studies have demonstrated a gradual decrease of serum testosterone with aging in men. A considerable number of men will experience hypogonadal androgen levels, defined by the normal range for young men. Thus, in addition to the long-standing use of androgen replacement therapy in the classical forms of primary and secondary hypogonadism, age-associated testosterone deficiency has led to considerable developments in application modes for testosterone. Since oral preparations of testosterone are ineffective, due to the first-pass effect of the liver, or, in case of 17 alpha-alkylation, cause hepatotoxicity, intramuscular injection of long-acting esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. However, the large fluctuations of serum testosterone levels cause unsatisfactory shifts of mood and sexual function in some men; combined with the frequent injections, this delivery mode is thus far from being ideal. In contrast, the transdermal testosterone patches are characterized by favorable pharmacokinetic behavior and have proven to be an effective mode of delivery. Safety data over 10 years indicate no negative effect on the prostate. Nevertheless, the scrotal testosterone patch system is hampered by the application site, which is not easily accepted by many subjects; the non-scrotal patch has a high rate of skin irritations. In view of the drawbacks of the currently available preparations, the most recent developments in testosterone supplementation appear to be highly promising agents. Androgen, which has been available in the United States since mid-2000, will be introduced this year in most European markets as Testogel, a hydroalcoholic gel containing 1% testosterone. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and to correct the signs and symptoms of hypogonadism. The gel has shown to be very effective and successful in American patients, who have benefited from its availability for almost 3 years. Furthermore, in phase II and III clinical studies, the intramuscular injection of 1000 mg testosterone undecanoate every 12-15 weeks has led to extremely stable serum testosterone levels for a prolonged period of time and has resulted in excellent efficacy. It is very likely in the future that these products will be the mainstay of testosterone supplementation. Whereas the indication for testosterone substitution for men with classical forms of hypogonadism is unequivocal, the use of testosterone in men with age-associated hypogonadism is less uniformly accepted. Yet, the few studies addressing this question indicate that men with testosterone serum levels below the lower normal limit for young adult men and with lack of energy, libido, depressed mood and osteoporosis may benefit from testosterone supplementation. However, it should be kept in mind that the experience documented in studies is limited. Nevertheless, serious side-effects, especially in regard to the prostate, did not occur, with the longest study extending over 3 years. Medical Department, Evangelisches Krankenhaus Herne, Wiescherstrasse 24, 44623 Herne, Germany.
    • Hawran S and Biering-Sorensen F (1996). The use of long leg calipers for paraplegic patients: a follow-up study of patients discharged 1973-82. Spinal Cord. 34: 666-8. Centre for Spinal Cord Injured, Rigshospitalet, The National University Hospital, Denmark. We reviewed the medical records of 45 paraplegic patients discharged with long leg calipers, during the 10 year period 1973-82, from the Rehabilitation Hospital in Hornbaek, Denmark. A follow-up interview was carried out during 1993-94 for all 40 patients who were still alive. Thirty had complete paraplegia (seven women) and 10 had incomplete paraplegia (two women). At the follow-up interview only three were still using their calipers. The main reasons for giving up the use of calipers was, in 38%, that it was too time consuming to put them on and take them off. For 22% the main reason was a fear of falling, while 19% reported that the calipers were impractical, as their hands had to be occupied in keeping balance and therefore could not be used for other purposes, including carrying items. The three paraplegic patients who did not totally give up the use of long leg calipers used them very little, at a maximum once a week. In contrast all 10 paraplegic patients who had been provided with a standing frame made use of this at least once a month. The majority of the remaining subjects were interested in having a standing frame. We therefore believe that a standing frame could be a good alternative to long leg calipers to facilitate standing for spinal cord injured patients.
    • Jones LM, Legge M and Goulding A (2002). Intensive exercise may preserve bone mass of the upper limbs in spinal cord injured males but does not retard demineralisation of the lower body. Spinal Cord. 40: 230-5. The School of Physical Education, University of Otago, Dunedin, New Zealand. STUDY DESIGN: Cross-sectional study comparing a group of active spinal cord injured (SCI) males carefully matched for age, height, and weight with active able-bodied male controls. OBJECTIVES: To compare bone mass of the total body, upper and lower limbs, hip, and spine regions in active SCI and able-bodied individuals. SETTING: Outpatient study undertaken in two centres in New Zealand. METHODS: Dual energy X-ray absorptiometry (DEXA) scanning was used to determine bone mass. Questionnaires were used to ascertain total time spent in weekly physical activity for each individual. The criterion for entry into the study was regular participation in physical activity of more than 60 min per week, over and above that required for rehabilitation. RESULTS: Seventeen SCI and their able-bodied controls met our required activity criterion. Bone mineral density (BMD) values of the total body and hip regions were significantly lower in the SCI group than in their controls (P=0.0001). Leg BMD and bone mineral content (BMC) were also significantly lower in the SCI group (P=0.0001). By contrast, lumbar spine BMD and arm BMD and BMC did not differ between the SCI and control groups. Arm BMD and BMC were greater (not significant) than the reference norms (LUNAR database) for both groups. CONCLUSION: Intensive exercise regimens may contribute to preservation of arm bone mass in SCI males, but does not prevent demineralisation in the lower body.
    • Klose KJ, Jacobs PL, Broton JG, Guest RS, Needham-Shropshire BM, Lebwohl N, Nash MS and Green BA (1997). Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 1. Ambulation performance and anthropometric measures. Arch Phys Med Rehabil. 78: 789-93. The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, FL 33136, USA. OBJECTIVE: To describe performance parameters and effects on anthropometric measures in spinal cord injured subjects training with the Parastep 1 system. DESIGN: Before-after trial. SETTING: Human spinal cord injury applied research laboratory. PARTICIPANTS: Thirteen men and 3 women with thoracic (T4-T11) motor-complete spinal cord injury: mean age, 28.8yrs; mean duration postinjury, 3.8yrs. INTERVENTION: Thirty-two functional neuromuscular stimulation ambulation training sessions using a commercially available system (Parastep-1). The hybrid system consists of a microprocessor-controlled stimulator and a modified walking frame with finger-operated switches that permit the user to control the stimulation parameters and activate the stepping. OUTCOME MEASURES: Distance walked, time spent standing and walking, pace, circumferential (shoulders, chest, abdomen, waist, hips, upper arm, thigh, and calf) and skinfold (chest, triceps, axilla, subscapular, supraillium, abdomen, and thigh) measurements, body weight, thigh cross-sectional area, and calculated lean tissue. RESULTS: Statistically significant changes in distance, time standing and walking, and pace were found. Increases in thigh and calf girth, thigh cross-sectional area, and calculated lean tissue, as well as a decrease in thigh skinfold measure, were all statistically significant. CONCLUSIONS: The Parastep 1 system enables persons with thoracic-level spinal cord injuries to stand and ambulate short distances but with a high degree of performance variability across individuals. The factors that influence this variability have not been completely identified.
    • Kronhed AC and Moller M (1998). Effects of physical exercise on bone mass, balance skill and aerobic capacity in women and men with low bone mineral density, after one year of training--a prospective study. Scand J Med Sci Sports. 8: 290-8. Primary Health Care Centre, Vadstena, Sweden. Vadstena is a small community in the county of Ostergotland, Sweden, where a project began in 1989 to prevent osteoporosis and to lower the expected incidence of osteoporotic fractures. Persons aged 40-70 years who had a low bone mineral density (BMD) value at screening of the distal radius by single-photon absorptiometry (SPA) were invited to participate in a training study during one year. The definition of low BMD was a densitometry value below -1 SD (standard deviation) from a sex- and age-specific reference value (z-score). Fifteen persons wanted to exercise in a group and 15 persons wanted to become a control group. All participants answered a questionnaire about lifestyle, occupation, diseases, medication and heredity. Clinical tests were made regarding mobility of the joints and muscles, balance and physical fitness. BMD for the hip and the lumbar spine were assessed by dual-energy X-ray absorptiometry (DXA) before and after the investigation period. The training programme was carried out for 60 min twice a week during one year and had the intention to improve bone mass, muscle strength and flexibility, balance skill and aerobic capacity. After the training period there was a significant increase in BMD at the greater trochanter (P < 0.01), in balance skill [standing on one leg with closed eyes and "ski step"-test) [P < 0.05) and in oxygen uptake capacity [P < 0.05) in the exercise group. In the control group, there was a significant increase in BMD at the lumbar spine [P < 0.05). However, these results should be judged with caution because several participants were over the age of 60, and at that age degenerative changes in the lumbar spine may increase to a greater or lesser extent. Regular weight-bearing exercises during one year seem to influence BMD at the greater trochanter in a training group comprising both women and men. However, our study was small in number and further training studies are needed to assess the effect of weight-bearing training on bone mass in different sex- and age-specific groups.
    • Maimoun L, Fattal C, Micallef JP, Peruchon E and Rabischong P (2005). Bone loss in spinal cord-injured patients: from physiopathology to therapy. Spinal Cord Study design:Review article on bone metabolism and therapeutic approach on bone loss in patients with spinal cord injury (SCI).Objective:The first part aims to describe the process of bone demineralization and its effects on bone mass in patients with SCI. The second part describes and discusses the therapeutic approaches to limiting the alteration in bone metabolism related to neurological lesions.Setting:Propara Rehabilitation Center, Montpellier, France.Resultsuring the first 24 months postinjury, demineralization occurs exclusively in the sublesional areas and predominantly in weight-bearing skeletal sites such as the distal femur and proximal tibia, both of which are trabecular-rich sites. Reduced bone mass, in association with a modified bone matrix property and composition, is very likely at the origin of pathological fractures after minor trauma to which these patients are frequently exposed. Since these fractures may be asymptomatic yet may lead to complications, preventing and managing 'neurological osteoporosis' remains a considerable challenge. Two main approaches are considered: the first consists in applying a mechanical stimulus to the bone tissue by standing, orthotically aided walking or functional electrical stimulation (FES). The second uses medications, particularly antiresorptive drugs such as calcitonin or diphosphonates.Conclusion:To develop well-adapted treatments, a more precise understanding of bone loss etiology is needed. The current rehabilitation programs are based on the idea that the bone physiological changes observed in patients with SCI are due to immobility, but results indicate that alterations inherent to neurological damage may play an even greater role in inducing osteoporosis.Spinal Cord advance online publication, 13 September 2005; doi:10.1038/ [1] 1Centre Mutualiste Neurologique Propara, Montpellier, France [2] 2Groupe de Recherche Interdisciplinaire Sur le Metabolisme Osseux (GRISMO), Montpellier, France.
    • Ott SM (2001). Osteoporosis in women with spinal cord injuries. Phys Med Rehabil Clin N Am. 12: 111-31. Department of Medicine, University of Washington, Seattle 98195-6426, USA. Decreased bone density and increased fracture risk are seen in patients with SCI. The bone resorption rate is markedly increased. Hypercalciuria, low PTH, and low 1,25 (OH)2 vitamin D are commonly seen. Bed-rest studies show similar findings, but of lesser magnitude. Therapies to treat or prevent osteoporosis include optimal nutrition (with care to avoid exacerbating hypercalciuria). Weight-bearing or functional electrical stimulation cycle ergometry may prevent some of the bone loss, especially in acutely injured patients. Estrogen should be considered in postmenopausal or amenorrheic women, but not if they are at high risk of thromboembolism. More research on effects of estrogen is needed in this population. Bisphosphonates may also help prevent the acute bone loss; oral routes must not be used in recumbent patients. Thiazides could be useful as adjunct therapy.
    • Prior JC, Barr SI, Chow R and Faulkner RA (1996). Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 5. Physical activity as therapy for osteoporosis. Cmaj. 155: 940-4. Department of Medicine, University of British Columbia, Vancouver. OBJECTIVE: To examine exercise as a therapy for people with osteoporosis. OPTIONS: Immobilization, standing low-load and high-load physical activities. OUTCOMES: Risk of injury, quality of life, risk of falls and fractures, strength and posture and pain management. EVIDENCE: Relevant epidemiologic studies, clinical trials and reviews were examined, including the large-scale FICSIT trial in the United States, a prospective 4-year study of women enrolled in an exercise program in Toronto and the large-scale Study of Osteoporotic Fractures. VALUES: Minimizing risk of injury and increasing quality of life were given a high value. BENEFITS, HARMS, AND COSTS: Moderate physical activity in people with osteoporosis can reduce the risk of falls and fractures, decrease pain and improve fitness and overall quality of life. It may also stimulate bone gain and decrease bone loss. Its positive effects are an adjunct to other interventions, such as hormonal therapy. It may give patients the confidence to resume regular activity and can provide social interaction and support. During exercise programs, proper nutrition is necessary to prevent excessive weight loss and impaired immune function resulting from inadequate protein, vitamin and mineral intake. RECOMMENDATIONS: Immobilization should be avoided if possible in anyone with osteoporosis or at increased risk for osteoporosis. Regular, moderate physical activity is recommended for those with osteoporosis. Elderly people should be assessed for risk of falling to identify those in greatest need of an exercise program. Community group exercise programs are beneficial. Younger people with osteoporosis also need exercise that will preserve or improve bone mass, muscular strength, endurance and cardiovascular fitness. Weight loss as a result of physical activity should be avoided and adequate intake of protein, vitamins and minerals assured. Because the benefits of physical activity are independent of the effect of other therapies, physical activity is an essential adjunct to appropriate nutrition and other therapies. Validation: These recommendations were developed by the Scientific Advisory Board of the Osteoporosis Society of Canada at its 1995 Consensus Conference. They are in agreement with the position taken on osteoporosis and exercise by the United States Center for Disease Control and Prevention and the American College of Sports Medicine. SPONSORS: Sponsors of the 1995 conference included the Dairy Farmers of Canada, Eli Lilly Canada, Inc., Hoffmann-La Roche Canada Ltd., Merck Frosst Canada Inc. and Procter & Gamble Pharmaceuticals Canada Inc.
    • Rubin C, Recker R, Cullen D, Ryaby J, McCabe J and McLeod K (2004). Prevention of postmenopausal bone loss by a low-magnitude, high-frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety. J Bone Miner Res 19: 343-51. A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass. INTRODUCTION: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20-90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3-8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human. MATERIALS AND METHODS: Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment. RESULTS AND CONCLUSIONS: The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention. Department of Biomedical Engineering, State University of New York, Stony Brook, New York, USA.
    • Rubin C, Turner AS, Muller R, Mittra E, McLeod K, Lin W and Qin YX (2002). Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res 17: 349-57. The skeleton's sensitivity to mechanical stimuli represents a critical determinant of bone mass and morphology. We have proposed that the extremely low level (< 10 microstrain), high frequency (20-50 Hz) mechanical strains, continually present during even subtle activities such as standing are as important to defining the skeleton as the larger strains typically associated with vigorous activity (>2000 microstrain). If these low-level strains are indeed anabolic, then this sensitivity could serve as the basis for a biomechanically based intervention for osteoporosis. To evaluate this hypothesis, the hindlimbs of adult female sheep were stimulated for 20 minutes/day using a noninvasive 0.3g vertical oscillation sufficient to induce approximately 5 microstrain on the cortex of the tibia. After 1 year of stimulation, the physical properties of 10-mm cubes of trabecular bone from the distal femoral condyle of experimental animals (n = 8) were compared with controls (n = 9), as evaluated using microcomputed tomography (microCT) scanning and materials testing. Bone mineral content (BMC) was 10.6% greater (p < 0.05), and the trabecular number (Tb.N) was 8.3% higher in the experimental animals (p < 0.01), and trabecular spacing decreased by 11.3% (p < 0.01), indicating that bone quantity was increased both by the creation of new trabeculae and the thickening of existing trabeculae. The trabecular bone pattern factor (TBPf) decreased 24.2% (p < 0.03), indicating trabecular morphology adapting from rod shape to plate shape. Significant increases in stiffness and strength were observed in the longitudinal direction (12.1% and 26.7%, respectively; both, p < 0.05), indicating that the adaptation occurred primarily in the plane of weightbearing. These results show that extremely low level mechanical stimuli improve both the quantity and the quality of trabecular bone. That these deformations are several orders of magnitude below those peak strains which arise during vigorous activity indicates that this biomechanically based signal may serve as an effective intervention for osteoporosis. Musculo-Skeletal Research Laboratory, Department of Biomedical Engineering, State University of New York, Stony Brook 11794-2580, USA.
    • Shetty KR, Sutton CH, Mattson DE and Rudman D (1993). Hyposomatomedinemia in quadriplegic men. Am J Med Sci 305: 95-100. Many studies have shown that vigorous exercise acutely stimulates growth hormone (GH) release but the relative contribution of daily physical activity to maintaining the GH/somatomedin C (SmC) axis is not known. It has been reported that basal and post-exercise plasma SmC values are higher in physically conditioned young men than in sedentary men of similar age. To assess the effect of severe inactivity on the plasma SmC level, basal concentrations of this hormone were measured in patients with quadriplegia (QP) resulting from spinal cord injury (SCI). Venous blood samples were obtained after overnight fast in 41 QP men, ages 24-66, and compared with 119 healthy men of similar ages. Nonparametric analysis of variance showed SmC to be significantly lower in QP than in healthy men (p < .007). Plasma SmC below 0.35 U/ml in adults usually indicates little or no GH secretion by the pituitary gland. In QP, 46% of plasma SmC values were < 0.35 U/ml compared to 24% in the healthy group (p < .02). In both groups, an inverse relationship of SmC and increasing age was observed (p < .01). The data suggest that severe inactivity or SCI tend to cause hyposomatomedinemia. The latter endocrine alteration may contribute to the decrease in lean body mass and muscle atrophy of QP patients, and add further functional impairment to the original neurologic deficit. In addition, hyposomatomedinemia could increase the tendency for pressure sore formation and osteoporosis in SCI patients. Department of Medicine, Medical College of Wisconsin, Milwaukee.
    • Stallard J, McLeod N, Woollam PJ and Miller K (2003). Reciprocal walking orthosis with composite material body brace: initial development. Proc Inst Mech Eng [H]. 217: 385-92. Orthotic Research and Locomotor Assessment Unit, Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust, Oswestry, Shropshire, UK. Reciprocal walking orthoses are routinely used by thoracic lesion patients for ambulation using crutches. A primary reason for their prescription is to provide therapeutic benefit and improved independence. To achieve this, maximum efficiency of walking and acceptance of the device is necessary to promote long-term compliance. Lateral rigidity in the orthosis influences walking efficiency, but the structural properties of conventional techniques for producing a sufficiently rigid body brace makes them unattractive. Currently patients and clinicians are forced to choose between greater efficiency or cosmesis of the orthosis. Composite materials have the potential to permit the required rigidity in a structure that is less obtrusive. However, their material properties could lead to unsafe forms of failure unless suitable manufacturing methods are devised. It is therefore inappropriate to supply prototypes to patients for field evaluation until laboratory investigation of innovative production methods has ensured that the orthosis is safe. A production technique has been devised that is ostensibly suitable. Prototype body braces have been tested and have been shown to have improved structural properties and safe failure modes. A test programme implemented on a complete concept orthosis has confirmed that improved lateral rigidity can be achieved with a less obtrusive body brace, and that it will behave safely for long enough to permit field evaluation.
    • Takata S and Yasui N (2001). Disuse osteoporosis. J Med Invest. 48: 147-56. Department of Orthopedic Surgery, University of Tokushima School of Medicine, Kuramoto-cho, Tokushima 770-8503, Japan. Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation and accelerates osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization due to motor paralysis from injury of the central nervous system or peripheral nerves, application of cast to treat fractures, a common causes of disuse osteoporosis. Imaging diagnosis shows coarse trabecular pattern and thinning of cortical bones. Bone metabolism markers have been used to evaluate bone metabolism. From the viewpoint of bone metabolism, antiresorptive agents should be administered to inhibit bone resorption. Rehabilitation, including bed positioning, therapeutic exercise and electrical stimulation, should be prescribed to subject the atrophied bone to an appropriate level of mechanical stress. In spite of these aggressive and continuous treatments, most cases of disuse osteoporosis require a long time for bone to recover its bone mineral density and strength. Hence, we have to keep in mind that there are no treatments better than prophylaxis of disuse osteoporosis.
    • Vanwanseele B, Eckstein F, Knecht H, Stussi E and Spaepen A (2002). Knee cartilage of spinal cord-injured patients displays progressive thinning in the absence of normal joint loading and movement. Arthritis Rheum 46: 2073-8. OBJECTIVE: Alterations in the morphologic, biochemical, and mechanical properties of cartilage occur after unloading and immobilization in animals. However, the findings have been inconsistent and it is unclear whether such changes also take place in humans. This study tested the hypothesis that progressive thinning of knee joint cartilage is observed after spinal cord injury. METHODS: In this in vivo study, knee cartilage was assessed in patients with complete, traumatic spinal cord injury at 6 (n = 9), 12 (n = 11), and 24 months (n = 6) after injury. Morphologic parameters of the knee cartilage (mean and maximum thickness as well as surface area) were computed from magnetic resonance imaging (MRI) data, and results were compared with those in young, healthy volunteers (n = 9). RESULTS: After 6 months of injury, the mean articular-cartilage thickness was significantly less in the patella and medial tibia (decrease of 10% and 16%, respectively; P < 0.05), but not in the lateral tibia (decrease of 10%), compared with the MRI findings in healthy volunteers. After 12 and 24 months of injury, the differences amounted to a reduction of 21% and 23%, respectively, in the patella, 24% and 25%, respectively, in the medial tibia, and 16% and 19%, respectively, in the lateral tibia. The changes were significant in all 3 surfaces of the spinal cord-injured joint cartilage (P < 0.05-0.01). CONCLUSION: Our data show, for the first time, that progressive thinning (atrophy) of human cartilage occurs in the absence of normal joint loading and movement. This may have important implications for patient management, in particular for spinal cord-injured patients and patients who are immobilized after surgery. Swiss Federal Institute of Technology, Zurich, Switzerland, Catholic University Leuven, Leuven, Belgium.
    • Vanwanseele B, Eckstein F, Knecht H, Spaepen A and Stussi E (2003). Longitudinal analysis of cartilage atrophy in the knees of patients with spinal cord injury. Arthritis Rheum. 48: 3377-81. Swiss Federal Institute of Technology, Zurich, Switzerland. OBJECTIVE: A previous cross-sectional study indicated that the morphology of patellar and tibial cartilage is subject to change after spinal cord injury (SCI). The aim of this study was to perform a longitudinal analysis of cartilage atrophy in all knee compartments, including the femoral condyles, in SCI patients over 12 months. METHODS: The right knees of 9 patients with complete, traumatic SCI were examined shortly after the injury (mean +/- SD 9 +/- 4 weeks) and at 6 and 12 months postinjury. Three-dimensional morphology of the patellar, tibial, and femoral cartilage (mean and maximum thickness, volume, and surface area) was determined from coronal and transversal magnetic resonance images (fat-suppressed gradient-echo sequences) using validated postprocessing techniques. RESULTS: The mean thickness of knee joint cartilage decreased significantly during the first 6 months after injury (range 5-7%; P < 0.05). The mean change at 12 months was 9% in the patella, 11% in the medial tibia, 11% in the medial femoral condyle, 13% in the lateral tibia, and 10% in the lateral femoral condyle [P < 0.05 for all compartments). CONCLUSION: This is the first report of a longitudinal analysis of cartilage atrophy in patients with SCI. These data show that human cartilage atrophies in the absence of normal joint loading and movement after SCI, with a rate of change that is higher than that observed in osteoarthritis [OA). A potential clinical implication is that cartilage thinning after SCI may affect the stress distribution in the joint and render it vulnerable to OA. Future studies should focus on whether specific exercise protocols and rehabilitation programs can prevent cartilage thinning.
    • Vanwanseele B, Eckstein F, Hadwighorst H, Knecht H, Spaepen A and Stussi E (2004). In vivo precision of quantitative shoulder cartilage measurements, and changes after spinal cord injury. Magn Reson Med 51: 1026-30. Recent advances in MRI have enabled the quantitative assessment of articular cartilage morphology in human joints. In this study, we tested the hypothesis that the precision of quantitative shoulder cartilage measurements is sufficient to detect changes between and within patients, and that shoulder cartilage thickness in paraplegic patients increases due to increased loading. We imaged the shoulders of seven healthy volunteers four times using a coronal 3D, fat-suppressed, gradient-echo sequence. The humeral head cartilage in seven paraplegic patients was evaluated soon after injury and 1 year post injury. A precision of 4.5% (root mean square (RMS) average coefficient of variation (CV) %) was found for shoulder cartilage thickness measurements in the humeral head. Whereas a significant decrease of cartilage thickness (-11%, P < 0.05) was observed in the knee, there was no significant change in articular cartilage thickness in the shoulder (-1.1%). Our data show, for the first time, that articular cartilage of the humeral head can be quantified with acceptable precision in vivo. It was demonstrated that, in contrast to the knee, the articular cartilage morphology of the humeral head changes very little (i.e., there is no significant increase or decrease in thickness) after spinal cord injury (SCI). Laboratory for Biomechanics, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
    • Ward K, Alsop C, Caulton J, Rubin C, Adams J and Mughal Z (2004). Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res 19: 360-9. The osteogenic potential of short durations of low-level mechanical stimuli was examined in children with disabling conditions. The mean change in tibia vTBMD was +6.3% in the intervention group compared with -11.9% in the control group. This pilot randomized controlled trial provides preliminary evidence that low-level mechanical stimuli represent a noninvasive, non-pharmacological treatment of low BMD in children with disabling conditions. INTRODUCTION: Recent animal studies have demonstrated the anabolic potential of low-magnitude, high-frequency mechanical stimuli to the trabecular bone of weight-bearing regions of the skeleton. The main aim of this prospective, double-blind, randomized placebo-controlled pilot trial (RCT) was to examine whether these signals could effectively increase tibial and spinal volumetric trabecular BMD (vTBMD; mg/ml) in children with disabling conditions. MATERIALS AND METHODS: Twenty pre-or postpubertal disabled, ambulant, children (14 males, 6 females; mean age, 9.1 +/- 4.3 years; range, 4-19 years) were randomized to standing on active (n = 10; 0.3g, 90 Hz) or placebo (n = 10) devices for 10 minutes/day, 5 days/week for 6 months. The primary outcomes of the trial were proximal tibial and spinal (L2) vTBMD (mg/ml), measured using 3-D QCT. Posthoc analyses were performed to determine whether the treatment had an effect on diaphyseal cortical bone and muscle parameters. RESULTS AND CONCLUSIONS: Compliance was 44% (4.4 minutes per day), as determined by mean time on treatment (567.9 minutes) compared with expected time on treatment over the 6 months (1300 minutes). After 6 months, the mean change in proximal tibial vTBMD in children who stood on active devices was 6.27 mg/ml (+6.3%); in children who stood on placebo devices, vTBMD decreased by -9.45 mg/ml (-11.9%). Thus, the net benefit of treatment was +15.72 mg/ml (17.7%; p = 0.0033). In the spine, the net benefit of treatment, compared with placebo, was +6.72 mg/ml, (p = 0.14). Diaphyseal bone and muscle parameters did not show a response to treatment. The results of this pilot RCT have shown for the first time that low-magnitude, high-frequency mechanical stimuli are anabolic to trabecular bone in children, possibly by providing a surrogate for suppressed muscular activity in the disabled. Over the course of a longer treatment period, harnessing bone's sensitivity to these stimuli may provide a non-pharmacological treatment for bone fragility in children. Clinical Radiology, Imaging Science & Biomedical Engineering, University of Manchester, Manchester, United Kingdom.
    • Zehnder Y, Luthi M, Michel D, Knecht H, Perrelet R, Neto I, Kraenzlin M, Zach G and Lippuner K (2004). Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men. Osteoporos Int. Swiss Paraplegic Center, CH-6207, Nottwil, Switzerland. To study the time course of demineralization and fracture incidence after spinal cord injury (SCI), 100 paraplegic men with complete motor loss were investigated in a cross-sectional study 3 months to 30 years after their traumatic SCI. Fracture history was assessed and verified using patients' files and X-rays. BMD of the lumbar spine (LS), femoral neck (FN), distal forearm (ultradistal part = UDR, 1/3 distal part = 1/3R), distal tibial diaphysis (TDIA), and distal tibial epiphysis (TEPI) was measured using DXA. Stiffness of the calcaneus (QUI.CALC), speed of sound of the tibia (SOS.TIB), and amplitude-dependent SOS across the proximal phalanges (adSOS.PHAL) were measured using QUS. Z-Scores of BMD and quantitative ultrasound (QUS) were plotted against time-since-injury and compared among four groups of paraplegics stratified according to time-since-injury (<1 year, stratum I; 1-9 years, stratum II; 10-19 years, stratum III; 20-29 years, stratum IV). Biochemical markers of bone turnover [deoxypyridinoline/creatinine [D-pyr/Cr), osteocalcin, alkaline phosphatase) and the main parameters of calcium phosphate metabolism were measured. Fifteen out of 98 paraplegics had sustained a total of 39 fragility fractures within 1,010 years of observation. All recorded fractures were fractures of the lower limbs, mean time to first fracture being 8.9 +/- 1.4 years. Fracture incidence increased with time-after-SCI, from 1% in the first 12 months to 4.6%/year in paraplegics since >20 years ( p<.01). The overall fracture incidence was 2.2%/year. Compared with nonfractured paraplegics, those with a fracture history had been injured for a longer time [ p<.01). Furthermore, they had lower Z-scores at FN, TEPI, and TDIA [ p<.01 to <.0001), the largest difference being observed at TDIA, compared with the nonfractured. At the lower limbs, BMD decreased with time at all sites [ r=.49 to.78, all p<.0001). At FN and TEPI, bone loss followed a log curve which leveled off between 1 to 3 years after injury. In contrast, Z-scores of TDIA continuously decreased even beyond 10 years after injury. LS BMD Z-score increased with time-since-SCI [ p<.05). Similarly to DXA, QUS allowed differentiation of early and rapid trabecular bone loss [QUI.CALC) vs slow and continuous cortical bone loss [SOS.TIB). Biochemical markers reflected a disproportion between highly elevated bone resorption and almost normal bone formation early after injury. Turnover declined following a log curve with time-after-SCI, however, D-pyr/Cr remained elevated in 30% of paraplegics injured >10 years. In paraplegic men early (trabecular) and persistent (cortical) bone loss occurs at the lower limbs and leads to an increasing fracture incidence with time-after-SCI.
    Last edited by Wise Young; 31 Dec 2005, 12:25 AM.

    Thank you Dr. Young. We look forward to having this available as an article on the homepage!


      Dr. Young, New question about this study

      I read this and still have the question: Does walking with long leg braces help any with osteoporosis? Is it similar to passive standing in a standing frame or active walking, when it comes to effect on oseoporosis? In my standing frame I have started to weight shift from side to side and lift my feet off the footplate a little when I lean. Does that do anything like "loading and unloading" which I've read does help with osteoporosis.? I can use some of my quads, adductors and abductors, but am flaccid below my knees and do not respond to FES. What is the best thing I can do for osteoporosis?
      my website & blog


        I updated the summary with some more references. wise.