Bone loss and impaired fracture healing in spinal cord injured mice

Summary

Spinal cord injury (SCI) results in impaired fracture healing in mice while leading to significant bone loss. Poor fracture healing following SCI is consistent with significant bone loss.

Introduction

SCI leads to significant bone loss in sublesional limbs, but there is few data concerning the relationship between fracture healing and bone loss following SCI. This study was undertaken to investigate the effect of SCI on fracture healing using a mouse femur fracture model.

Methods

One hundred twenty male C57BL/6J mice were randomly divided into SCI and control groups (n?=?60, respectively). A femoral shaft fracture was generated and fixed with intramedullary pins 3?weeks after SCI. Fracture healing was evaluated by micro-computed tomography (micro-CT) for callus formation and mineralization and neovascularization, and bone mineral density (BMD) was measured by DXA at 1, 2, and 4?weeks after fracture. Serum vascular endothelial growth factor (VEGF), osteocalcin, and alkaline phosphatase (ALP) were assessed using ELISA at each time point. Biomechanical testing was performed at 2 and 4?weeks.

Results

BMD in SCI mice was significantly lower compared to control mice at each time point, with callus volume and all vessel parameters reduced as measured by micro-CT. Ultimate stress of the femora was significantly lower in SCI mice than in control mice at 2 and 4?weeks after fracture, whereas Young's modulus between the SCI and control mice turned to be significantly different at 4?weeks. Serum VEGF was lower in SCI mice than in the control group at 2 and 4?weeks, whereas serum osteocalcin and ALP were lower in SCI mice than in control ones at each time point.

Conclusion

Significant bone loss and fracture healing impairment was noted in SCI mice. Decreased angiogenesis is consistent with the changes of microarchitecture and biomechanical properties during fracture healing.     

Bone loss following spinal cord injury in a rat model

The current study was undertaken to follow the time course of bone loss in the proximal tibia of rats over several weeks following thoracic contusion spinal cord injury (SCI) of varying severity. It was hypothesized that bone loss would be more pronounced in the more severely injured animals, and that hindlimb weight bearing would help prevent bone loss. Twenty-six female Sprague-Dawley rats (200-225 g, 6-7 weeks old) received standard thoracic (T9) injuries at energies of 6.25, 12.5, 25, or 50 g-cm. The rats were scored weekly for hindlimb function during locomotion. At 0, 2 or 3, and 8 weeks, high-resolution micro-CT images of each right tibia were obtained. Mechanical indentation testing was done to measure the compressive strength of the cancellous bone structure. The 6.25 g-cm group showed near normal locomotion, the 12.5 and 25 g-cm groups showed the ability to frequently or occasionally generate weight-supported plantar steps, respectively, and the 50 g-cm group showed only movement without weight-supported plantar stepping. The 6.25, 12.5 and 25 g-cm groups remained at the same level of bone volume fraction (cancBV/TV=0.24±0.07), while the 50 g-cm group experienced severe bone loss (67%), resulting in significantly lower (p<0.05) bone volume fraction (cancBV/TV=0.11±0.05) at 8 weeks. Proximal tibia cancellous bone strength was reduced by approximately 50% in these severely injured rats. Instead of a linear proportionality between injury severity and bone loss, there appears to be a distinct functional threshold, marked by occasional weight-supported stepping, above which bone loss does not occur.     

Skeletal muscle atrophy and increased intramuscular fat after incomplete spinal cord injury

STUDY DESIGN: Cross-sectional and longitudinal design. OBJECTIVES: (1) To quantify skeletal muscle cross-sectional area (CSA) after correcting for intramuscular fat (IMF) in thigh muscle groups 6 weeks after incomplete spinal cord injury (SCI), (2) to monitor the changes in muscle CSA and IMF after 3 months from the initial measurement. SETTING: Academic institution Athens, GA, USA. METHODS: Six incomplete SCI patients (28+/-4 years, 178+/-5 cm and 78+/-6 kg, mean+/-SE, C7 to L3, American Spinal Injury Association B or C) were tested at 5+/-1 weeks and 3 months after the initial measurement. T1-weighted magnetic resonance images were taken of both thighs. Six able-bodied (AB) controls were matched in age, sex, height and weight (29+/-4 years, four male and two female subjects, 179+/-5 cm and 77+/-6 kg). RESULTS: At 6 weeks post-injury, muscle CSA was 82+/-4 cm(2) in incomplete SCI and 123+/-21 cm(2) in AB controls (P=0.04). IMF CSA was 5.2+/-1.3 and 2.3+/-0.6 cm(2) in incomplete SCI and AB controls, respectively (P=0.03). Relative IMF was three-fold higher (P=0.03) in the SCI group versus AB controls (5.8+/-1.4 versus 2.0+/-0.6%). After 3 months, IMF increased 26% in the SCI group compared to the initial measurement (P=0.02). CONCLUSIONS: Skeletal muscle atrophy is associated with greater IMF accumulation in SCI group 6 weeks post-injury compared to AB controls. Moreover, IMF continues to increase over time in incomplete SCI.     

Bone mineral loss at the proximal femur in acute spinal cord injury

Summary

This study used quantitative computed tomography to assess changes in bone mineral at the proximal femur after acute spinal cord injury (SCI). Individuals with acute SCI experienced a marked loss of bone mineral from a combination of trabecular and endocortical resorption. Targeted therapeutic interventions are thus warranted in this population.

Introduction

SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. Some 10 to 20 % of these fractures occur at the proximal femur. The purpose of this study was to quantify changes to bone mineral, geometry, and measures of strength at the proximal femur in acute SCI.

Methods

Quantitative computed tomography analysis was performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range, 2.6–4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at the femoral neck, trochanteric, and total proximal femur regions. Changes in bone volumes, cross-sectional areas, and surrogate measures of compressive and bending strength were also determined.

Results

During the acute period of SCI, subjects experienced a 2.7–3.3 %/month reduction in integral BMC (p?<?0.001) and a 2.5–3.1 %/month reduction in integral vBMD (p?<?0.001). Trabecular BMC decreased by 3.1–4.7 %/month (p?<?0.001) and trabecular vBMD by 2.8–4.4 %/month (p?<?0.001). A 3.9–4.0 %/month reduction was observed for cortical BMC (p?<?0.001), while the reduction in cortical vBMD was noticeably lower (0.8–1.0 %/month; p?≤?0.01). Changes in bone volume and cross-sectional area suggested that cortical bone loss occurred primarily through endosteal resorption. Declines in bone mineral were associated with a 4.9–5.9 %/month reduction in surrogate measures of strength.

Conclusions

These data highlight the need for therapeutic interventions in this population that target both trabecular and endocortical bone mineral preservation.     

New rehabilitation interventions in spinal cord injury

Progress in the care of people with spinal cord injury (SCI) spans every aspect, from research in neuroregeneration to pharmacologic interventions. This article focuses on advances in rehabilitation interventions, which have employed bioengineering, computerization, and advanced therapeutic techniques. These interventions are being applied to functional deficits of the bladder, bowel, upper extremities, and respiratory system, as well as to improvements in ambulation and mobility. Functional electrical stimulation (FES) is being used to augment the function of the lower extremities, the upper extremities (Freehand System), and the bowel and bladder (Vocare System). Tendon transfer is a reconstructive technique used to improve upper extremity function; it is sometimes combined with FES. Body weight-supported treadmill training is being used to improve ambulation in people with incomplete SCI, and advances in wheelchair technology are expanding options for mobility. Cushion design and pressure mapping are modalities being used to reduce the high risk for pressure ulcers in the SCI population. Research on shoulder stressors is being applied to transfer techniques, exercise regimens, adaptive equipment and wheelchair mechanics to minimize shoulder pain, another common complication. The effectiveness of rehabilitation interventions needs to be documented by evidence-based research. Researchers are focusing on the identification of outcomes measures that will form the basis for established standards of care for individuals with SCI. Perhaps the combination of conventional and newer therapies may enhance neurological recovery. Well-designed studies are needed before we can make this determination.     

脊髓损伤后骨代谢

脊髓损伤(spinal cord injury)使机体的骨代谢发生改变并产生严重的并发症，其中骨质疏松(osteoporosis)与异位骨化(heterotopic ossification或ectopic ossification)是脊髓损伤患者常见的并发症。骨质疏松使肢体骨折风险性加大，异位骨化通常发生于大关节的周围，使关节功能受限，严重影响其生活质量。笔者就脊髓损伤后骨代谢改变研究进展作一综述。     

Urological rehabilitation of spinal cord injury patients

The urological rehabilitation of spinal cord injury patients depends on an optimal urological treatment plan and good cooperation between the patient, general practitioner, urologist, and a centre that specialises in treating spinal cord injuries. Because of medical advancements in neuro-urology, one can assume that in cases of lifelong urological care, the individual's life expectancy will be almost normal. The recognition that nonphysiological bladder storage pressure results in restricted kidney function has led to various therapeutic strategies with complementary goals, such as protection of the upper urinary tract, urinary continence, individualized bladder management.     

A systematic review of the efficacy of gait rehabilitation strategies for spinal cord injury

OBJECTIVE: To systematically review the evidence for the efficacy of different rehabilitation strategies on functional ambulation following spinal cord injury (SCI). METHODS: A keyword literature search of original articles was used to identify published literature evaluating the effectiveness of any treatment or therapy on functional ambulation in people with SCI. The rigor and quality of each study were scored on standardized scales by two independent reviewers. RESULTS: The search yielded 160 articles, of which 119 were excluded for not meeting our inclusion criteria. The remaining 41 articles covered various strategies for improving gait: bodyweight supported treadmill training (BWSTT) (n=12), functional electrical stimulation (FES) (n=7), braces/orthoses (n=10), or a combination of these (n=12). There is strong evidence from randomized controlled trials that functional ambulation outcomes following body-weight supported treadmill training (BWSTT) are comparable to an equivalent intensity of overground gait training in sub-acute SCI. In chronic SCI, evidence from pre-test/post-test studies shows that BWSTT may be effective in improving functional ambulation. Pre-test/post-test or post-test only studies provide evidence that FES may augment functional ambulation in sub-acute/chronic SCI while braces may afford particular benefits to people with complete SCI to stand up and ambulate with assistive devices. CONCLUSIONS: Rehabilitation strategies that facilitate repeated practice of gait offer the greatest benefits to functional ambulation in sub-acute or chronic SCI. Supportive devices may augment functional ambulation particularly in people with incomplete SCI.     

跳跃性脊柱骨折并脊髓损伤的治疗

目的：探讨跳跃性脊柱骨折的诊断和治疗方法。方法 22例手术治疗12例,保守治疗10例,结果 漏诊率达22．7％,按Frankel功能分级,手术治疗和保守治疗脊髓功能均有恢复但差异不明显。结论 对该类损伤要明确受伤机制,仔细检查,以防漏诊。适当放宽手术指征,警惕其他脏器合并伤。     

Inpatient rehabilitation outcomes in neoplastic spinal cord compression vs. traumatic spinal cord injury

Objective: To compare neurological and functional outcomes, and complications of patients with neoplastic vs traumatic spinal cord injury (SCI) after in-patient rehabilitation.Design: This study is a retrospective analysis.Setting: In-patient rehabilitation unit of a tertiary research hospital.Participants: A total of 252 patients with a SCI were included; 43 with neoplastic SCI (mean age: 60.9 ± 15.7 years, 60.5% were males) and 209 with traumatic SCI (mean age: 43.1 ± 16.8 years, 71.3% were males).Outcome measures: Comparisons were made of demographic characteristics, etiology, American Spinal Injury Association (ASIA) impairment scale, functional independence measurement (FIM) and Functional Ambulation Categories (FAC) scores, length of stay (LOS), bladder independence, medical comorbidities and complications in both groups.Results: Patients with neoplastic SCI were significantly older than those with traumatic SCI (P < 0.01). No difference was present between the groups in terms of sex and lesion level (P > 0.05). Incomplete SCI was significantly higher in the neoplastic group when compared with the traumatic group (P < 0.01). The LOS was significantly shorter in the neoplastic group than traumatic group (34.8 ± 41.03 vs. 60.02 ± 53.1, P < 0.01). There were no differences in the admission FIM scores (69.3 ± 24.7 vs. 58.7 ± 18.9, P > 0.05), discharge FIM scores (82.1 ± 25.1 vs. 74.02 ± 23.3, P > 0.05) and FIM efficiencies (0.43 ± 0.72 vs. 0.36 ± 0.51, P > 0.05) for the neoplastic and traumatic groups, respectively. However, neoplastic SCI patients demonstrated lower FIM gains compared to traumatic patients (12.9 ± 11.9 vs. 15.4 ± 15.2, P < 0.05). During rehabilitation, urinary tract infection (48.4% vs. 69.4%) and decubitus ulcer (11.6% vs. 35.9%) were significantly more common in the traumatic group than the neoplastic group (P < 0.05).Conclusion: Neoplastic SCI patients who commonly present at rehabilitation units exhibit different characteristics from traumatic SCI patients but the rehabilitation results are similar. Similar functional development can be achieved in a shorter period of time with inpatient rehabilitation in the neoplastic SCI group.     

MRSA colonisation in spinal cord injury: implications on patients rehabilitation

MRSA has become a major cause of nosocomial and community acquired infections in the past few years. Our hypothesis is that MRSA colonisation affects the length of stay in hospital, thereby adding a strain on resources. Data from the last 20 patients admitted to the Spinal Injury Care Unit (SICU) who were MRSA positive (study group) have been analysed and then matched with data from 20 patients who were MRSA negative (control group) to compare their total hospital stay and the factors which affect the length of hospital stay. The mean age of the study group patients was 38.8 years. The average time between injury and admission in SICU was 76.5 days in the study group compared to 28.7 days in the control. The mean stay duration was 412.15 days in the study group as opposed to 187.2 days in the control group. Nearly 45% had developed pressure sores in the study group as compared to 25% in the control group. Our study indicates that MRSA colonisation in spinal injured patients leads to longer hospital stay, delay in admission to spinal care units, and development of pressure sores and further infection. These factors have adverse effects on patients' rehabilitation.     

Bone mineral and stiffness loss at the distal femur and proximal tibia in acute spinal cord injury

Summary

Computed tomography and finite element modeling were used to assess bone mineral and stiffness loss at the knee following acute spinal cord injury (SCI). Marked bone mineral loss was observed from a combination of trabecular and endocortical resorption. Reductions in stiffness were 2-fold greater than reductions in integral bone mineral.

Introduction

SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. The large majority of these fractures occur around regions of the knee. Our purpose was to quantify changes to bone mineral, geometry, strength indices, and stiffness at the distal femur and proximal tibia in acute SCI.

Methods

Quantitative computed tomography (QCT) and patient-specific finite element analysis were performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range 2.6–4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. Changes in bone volumes, cross-sectional areas, strength indices and stiffness were also determined.

Results

Bone mineral loss was similar in magnitude at the distal femur and proximal tibia. Reductions were most pronounced at epiphyseal regions, ranging from 3.0 % to 3.6 % per month for integral BMC (p?<?0.001) and from 2.8 % to 3.4 % per month (p?<?0.001) for integral vBMC. Trabecular BMC decreased by 3.1–4.4 %/month (p?<?0.001) and trabecular vBMD by 2.7–4.7 %/month (p?<?0.001). A 3.8–5.4 %/month reduction was observed for cortical BMC (p?<?0.001); the reduction in cortical vBMD was noticeably lower (0.6–0.8 %/month; p?≤?0.01). The cortical bone loss occurred primarily through endosteal resorption, and reductions in strength indices and stiffness were some 2-fold greater than reductions in integral bone mineral.

Conclusions

These findings highlight the need for therapeutic interventions targeting both trabecular and endocortical bone mineral preservation in acute SCI.