Effects of risedronate on femoral bone mineral density and bone strength in sciatic neurectomized young rats

Immobilization induces a rapid loss of bone density and bone strength in rats. The purpose of the present study was to examine the effects of risedronate (Ris) on the femoral bone density and bone strength of sciatic neurectomized young rats. Forty male Sprague–Dawley rats, 6 weeks of age, were randomized by the stratified weight method into the following four treatment groups of 10 rats each: sham-operation, bilateral sciatic neurectomy (NX), NX + low-dose Ris (0.25 mg/kg/day, orally), and NX + high-dose Ris (0.5 mg/kg/day, orally). After 8 weeks of feeding, the volumetric bone mineral density (vBMD) and stress strain index (SSI) of the femoral distal metaphysis and middiaphysis of the rats were measured by peripheral quantitative computed tomography. The mechanical properties of the femoral distal metaphysis and middiaphysis were measured by the compression and three-point bending tests, respectively. The femoral length was also measured. As compared with the findings in the sham-operated controls, NX resulted in a loss of femoral length, cancellous vBMD, SSI, maximum load, stiffness, and breaking energy of the femoral distal metaphysis; there was also loss of cortical thickness, SSI, maximum load, and stiffness of the femoral middiaphysis, with no significant effects on the cortical vBMD or breaking energy of the femoral middiaphysis. High-dose Ris increased the vBMD to values higher than those in the sham-operated controls, and prevented the loss of SSI, maximum load, and stiffness of the femoral distal metaphysis, while low-dose Ris prevented the loss of cancellous vBMD of the femoral distal metaphysis. Neither high- nor low-dose Ris affected any of the cortical bone parameters of the femoral middiaphysis, except for cortical thickness, or the femoral length. These findings suggest that Ris may prevent immobilization-induced loss of cancellous bone density and bone strength in a dose-dependent manner without interfering with bone growth, but has no apparent effects on the cortical bone in sciatic neurectomized young rats. The results of the present preclinical study should be taken into consideration prior to the commencement of Ris treatment for disabled children.     

脊髓损伤患者骨密度变化

目的 观察脊髓损伤患骨密度的变化。方法 用SPA法和US法对45例健康人,32例卧床2月病人和48例胸腰段脊髓损伤2月患行骨密度测量。结果 脊髓损伤患跟骨密度下降最为明显,卧床组次之。桡骨骨密度卧床组变化不明显,脊髓损伤组仍明显下降。结论 骨质疏松是脊髓损伤中层得的主要并发症之一,且机理复杂,应注意预防。     

Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats)

Summary

Spinal cord injury causes severe bone loss. We report osteoclast resorption with severe trabecular and cortical bone loss, decreased bone mineral apposition, and growth plate abnormalities in a rodent model of contusion spinal cord injury. These findings will help elucidate the mechanisms of osteoporosis following neurological trauma.

Introduction

Limited understanding of the mechanism(s) that underlie spinal cord injury (SCI)-induced bone loss has led to few treatment options. As SCI-induced osteoporosis carries significant morbidity and can worsen already profound disability, there is an urgency to advance knowledge regarding this pathophysiology.

Methods

A clinically relevant contusion model of experimental spinal cord injury was used to generate severe lower thoracic SCI by weight-drop (10 g?×?50 mm) in adolescent male Sprague-Dawley rats. Body weight and gender-matched naïve (no surgery) rats served as controls. Bone microarchitecture was determined by micro-computed tomographic imaging. Mature osteoclasts were identified by TRAP staining and bone apposition rate was determined by dynamic histomorphometry.

Results

At 10 days post-injury we detected a marked 48% decrease in trabecular bone and a 35% decrease in cortical bone at the distal femoral metaphysis by micro-CT. A 330% increase in the number of mature osteoclasts was detected at the growth plate in the injured animals that corresponded with cellular disorganization at the chondro-osseous junction. Appositional growth studies demonstrated decreased new bone formation with a mineralization defect indicative of osteoblast dysfunction.

Conclusions

Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation.     

不同类型坐骨神经损伤对相应脊髓节段基因表达的影响

目的：比较坐骨神经夹伤与坐骨神经结扎后神经元胞体基因表达的差异,探讨外周神经损伤后再生与否与基因表达差异的关系。方法：根据坐骨神经损伤基因表达谱分析的结果,选择部分表达变化的基因;通过RT-PCR的相对定量的方法检测其在坐骨神经夹伤与坐骨神经结扎后相应脊髓节段的表达水平。结果：比较两种模型差异表达的基因类别可以发现,可再生神经元胞体上调表达的基因与组织细胞的增殖(PCNA)、生长(FRAGl,NCAM)及抗凋亡(Bcl-2)有关;而不可再生的神经元胞体这些基因的表达下调。结论：外周神经元胞体对不同类型神经损伤的反应存在差异,这种差异可能与神经再生能力的不同有关。     

Evaluation of bone mineral loss in patients with chronic traumatic spinal cord injury in Iran

Objectives

We described the associations between demographic and injury-related factors on bone mineral density (BMD) of the spine and the hip among adult patients with chronic spinal cord injury (SCI).

Design

BMD in spinal and femoral bone sites were assessed. Multivariate analysis was performed to evaluate the relationship between anthropometric and injury-related factors with BMD. Serum level and amount of dietary intake of calcium, phosphor, and 25-hydroxy vitamin D were measured.

Setting

A referral tertiary rehabilitation center in Iran.

Participants

Patients with SCI who had no previous history of endocrine disorders and were not on specific medications entered the investigation. Those with non-traumatic SCI, pregnant, or with substance dependency were excluded as well.

Interventions

No interventions were applied.

Main study outcome measures

Dual X-ray absorptiometry was performed to estimate BMD. Body mass index was positively associated with higher femoral (P < 0.01, r = 0.56) and hip (P < 0.0001, r = 0.82) BMD only in female participants. The high prevalence of vitamin D deficiency (60%) was noticeable.

Results

Older male patients revealed lower BMD only in spinal vertebrae (P < 0.02, r = −0.21). A significant higher BMD loss in lumbar vertebras in male patients with complete spinal cord lesion (P < 0.009) was detected. Spinal reduction of BMD was more severe when the level of injury was above T6 (P < 0.02).

Conclusion

Along with the clarification of age, gender, post injury duration, and the other factors'' effect on the BMD in the SCI patients, here we have also shown the noticeable prevalence of the 25-hydoxy vitamin D deficiency in these patients which needs attention.     

Evaluation of bone mineral loss in patients with chronic traumatic spinal cord injury in Iran

Abstract

Objectives

We described the associations between demographic and injury-related factors on bone mineral density (BMD) of the spine and the hip among adult patients with chronic spinal cord injury (SCI).

Design

BMD in spinal and femoral bone sites were assessed. Multivariate analysis was performed to evaluate the relationship between anthropometric and injury-related factors with BMD. Serum level and amount of dietary intake of calcium, phosphor, and 25-hydroxy vitamin D were measured.

Setting

A referral tertiary rehabilitation center in Iran.

Participants

Patients with SCI who had no previous history of endocrine disorders and were not on specific medications entered the investigation. Those with non-traumatic SCI, pregnant, or with substance dependency were excluded as well.

Interventions

No interventions were applied.

Main study outcome measures

Dual X-ray absorptiometry was performed to estimate BMD. Body mass index was positively associated with higher femoral (P < 0.01, r = 0.56) and hip (P < 0.0001, r = 0.82) BMD only in female participants. The high prevalence of vitamin D deficiency (60%) was noticeable.

Results

Older male patients revealed lower BMD only in spinal vertebrae (P < 0.02, r = ?0.21). A significant higher BMD loss in lumbar vertebras in male patients with complete spinal cord lesion (P < 0.009) was detected. Spinal reduction of BMD was more severe when the level of injury was above T6 (P < 0.02).

Conclusion

Along with the clarification of age, gender, post injury duration, and the other factors' effect on the BMD in the SCI patients, here we have also shown the noticeable prevalence of the 25-hydoxy vitamin D deficiency in these patients which needs attention.     

脊髓损伤早期及制动后大鼠股骨远端骨量丢失的实验研究

目的:建立大鼠脊髓损伤及后肢废用模型,观察建模早期两种模型大鼠股骨远端骨密度及远端破骨细胞数量的改变。方法:24只SD大鼠随机分为3组(每组8只),对照组(A组),行T10椎板切除,不损伤硬膜及脊髓;脊髓损伤(SCI)组(B组):切除T10椎板后用Allen′s法(60g.cm势能)造成脊髓损伤;制动组(C组):采用大鼠双侧腿-尾缝合,造成双下肢制动。分别于造模后第1、7天采用BBB(Basso,Beattie and Bresnahan)评分评估脊髓损伤大鼠后肢运动功能,确定模型建立成功。建模第10天后处死,取一侧尺、桡骨及股骨远端,行骨密度检测。取另一侧股骨远端行TRAP染色,观察大鼠股骨远端破骨细胞数量的变化。结果:A、B、C 3组股骨远端骨密度值分别为0.114、0.096、0.108g/cm2,B组骨密度值最低,其次为C组,A组最高(P<0.05)。尺、桡骨骨密度3组比较无差异(P>0.05)。与A组比较,B组大鼠股骨干骺端破骨细胞数量增加显著,其次为C组,A组最少(P<0.01)。结论:脊髓损伤后,股骨远端破骨细胞数量大量增多,活性增强,骨吸收加强,引起脊髓损伤平面以下肢体骨量的迅速丢失,比废用性骨量丢失的程度更重。     

Bone biomarkers in patients with chronic traumatic spinal cord injury

Background contextBone loss after spinal cord injury (SCI) occurs because of pathologic changes in osteoblastic and osteoclastic activities due to mechanical unloading. Some biochemical changes in bone metabolism after SCI are described before that were related to bone mineral loss.PurposeOur purpose was to determine bone markers' changes and related effective factors in patients with chronic traumatic SCI.Study designThis investigation was designed as an observational cross-sectional study.Patient sampleAll patients with chronic SCI who were referred to Brain and Spinal Injury Research Center and did not meet our exclusion criteria entered the study.Outcome measuresSelf-reporting measures including patient's demographic features and date of accident were obtained using a questionnaire and physiologic measures including spinal magnetic resonance imaging to determine the level of injury accompanied with physical examination along with dual-energy X-ray absorptiometry were performed. Blood samples were analyzed in the laboratory.MethodsDual-energy X-ray was used to determine bone mineral density in femoral and spinal vertebrae bone sites. Serum level of C-telopeptide cross-linked Type 1 collagen (CTX), parathyroid hormone, calcitonin, osteocalcin, and bone alkaline phosphatase (BALP) were measured.ResultsWe detected a negative association between CTX level and bone mineral density in femoral and spinal bone sites that confirms that CTX is a bone resorption marker. C-telopeptide cross-linked Type 1 collagen and BALP levels did not show any significant correlation with postduration injury. Patients with spinal injury at lumbar level had the highest calcitonin level (p<.04). C-telopeptide cross-linked Type 1 collagen was positively related with osteocalcin and BALP (p<.0001, r=0.51), and osteocalcin was positively related with BALP (p<.0001, r=0.44). Osteocalcin was related negatively only to femoral intertrochanteric zone bone mineral density.ConclusionsSome bone biomarkers undergo noticeable changes after SCI. C-telopeptide cross-linked Type 1 collagen was positively correlated with BALP and osteocalcin that shows the coincidental occurrence of osteoblastic and osteoclastic activities. Our data also support this fact that although bone reduction after 2 years is slower than acute phase after SCI, bone resorption rate is higher than bone formation. These bone markers also revealed different site of action as osteocalcin level only affected femoral intertrochanteric bone mineral density. Generally, it seems that the coincidental consideration of these factors that influence bone mineral density can lead to a better understanding of bone changes after SCI.     

分娩前母血、脐血、新生儿血骨代谢相关激素水平及其意义

目的　测定新生儿血清骨代谢激素水平及探讨其临床意义。方法　采用放射免疫与免疫放射分析法测定８９ 例新生儿脐带血清,２２ 例出生３ 天婴儿血清骨钙素（ＢＧＰ）、降钙素（ｈ－ＣＴ）和甲状旁腺素（ｉＰＴＨ）水平。结果　新生儿脐带血ＢＧＰ、ｈ－ＣＴ 和 ｉＰＴＨ 水平分别为 １９．３±１６．８ μｇ／Ｌ、７８．９±５１．５ ｎｇ／Ｌ 和０．２２±０．１６ ｐｍ ｏｌ／Ｌ（ｘ±ｓ）,与分娩前母血比较,差异非常显著,Ｐ 值分别为Ｐ＜０．０１、Ｐ＜ ０．０１ 和Ｐ＜ ０．０１;出生３ 天婴儿血清ＢＧＰ、ｈ－ＣＴ 和ｉＰＴＨ 水平分别为７．４±２．３ μｇ／Ｌ、５７．８±１３．８ ｎｇ／Ｌ和５．６±１．６９ ｐｍ ｏｌ／Ｌ（ｘ±ｓ）,与新生儿脐带血比较差异非常显著,Ｐ 值分别为Ｐ＜ ０．０１、Ｐ＜ ０．０１ 和Ｐ＜ ０．０１。结论　本研究结果表明新生儿骨代谢激素的放射免疫测定是研究新生儿骨代谢变化的重要检测手段。     

Changes in Bone Mass,Bone Structure,Bone Biomechanical Properties,and Bone Metabolism after Spinal Cord Injury: A 6-Month Longitudinal Study in Growing Rats

Spinal cord injury (SCI) results in a great decline in bone mineral density (BMD) and deterioration of bone microarchitecture. The objective of this study was to investigate the time course of the changes in BMD, microarchitecture, biomechanical properties, and bone turnover in male growing rats following SCI. Sixty male growing Sprague-Dawley rats, 6 weeks of age, were randomly divided into SCI (lower thoracic cord transection) and sham-operated groups, and bone tissues and blood samples were examined at 3 weeks, 6 weeks, and 6 months after surgery. SCI rats had low bone weight (wet, dry, and ash weight) and BMD of the femora, tibiae, and third lumbar vertebrae at all time points compared to sham rats, while in forelimbs, there was a decrease of dry and ash weight compared to sham rats only at 3 weeks but not BMD. Bone microarchitecture and trabecular connectivity were deteriorated in SCI rats and remained so after. Bone formation rate and serum osteocalcin level in SCI rats were significantly increased 3 weeks after SCI surgery. However, eroded surface/bone surface and serum N-terminal telopeptide of type I collagen level remained elevated from 3 weeks to 6 months. In addition, SCI rats showed poor biomechanical properties in the proximal tibiae and femora but not in the humeri. In conclusion, SCI causes profound BMD loss, disturbances in bone microarchitecture, decreased mechanical strength in the lower extremity and lumbar spine, and high bone turnover. These findings will allow better understanding of osteoporosis following SCI.     

Differences of bone mass and bone structure in osteopenic rat models caused by spinal cord injury and ovariectomy

Summary Both spinal cord injury and ovariectomy can result in ostepenia in rats. SCI induces more deterioration of cortical geometric structure and trabecular microstructure in the proximal tibial metaphysis than OVX. The proximal tibial metaphysis microstructure significantly correlates with its biomechanical properties. Introduction The purpose of the present study was to compare the effects of spinal cord injury (SCI) and ovariectomy (OVX) on bone gain in young female rats. Methods Thirty young female Sprague-Dawley rats were randomized into three groups: age-matched intact control (CON), OVX and SCI. The tibiae were assessed for DXA and micro-CT analysis, biomechanical testing, the upper tibial epiphyseal plate height, and blood samples for biochemical analysis. Results SCI rats showed lower aBMD in the proximal tibiae as compared with OVX rats. Cortical geometric structural parameters of the tibial midshaft in SCI rats were significantly lower than OVX rats. SCI or OVX induced significant changes in all trabecular microstructural parameters in the proximal tibial metaphysis. The trabecular separation (Tb.Sp) and structure mode index (SMI) in SCI rats were significantly higher than in OVX rats. BV/TV explained 84% of the variation of ultimate load of the proximal tibial metaphysis. There was no difference of the upper tibial epiphyseal plate height between SCI and OVX rats. Serum NTX level in SCI rats was significantly higher than in OVX rats. Conclusions SCI induces more deterioration of cortical bone geometric structure and trabecular microstructure in the proximal tibial metaphysis than OVX.     

大鼠脊髓损伤后坐骨神经GDNFmRNA表达变化及意义

目的探讨大鼠脊髓损伤后坐骨神经表达GDNFmRNA的变化及其意义.方法 Allen's方法致伤大鼠T13段脊髓,造成不完全性脊髓损伤,截取坐骨神经,以β-Actin(β-肌动蛋白)为内参照物,应用半定量RT-PCR方法,观察大鼠坐骨神经在脊髓损伤前、后不同时间GDNFmRNA表达变化.结果脊髓损伤前GDNFmRNA在大鼠坐骨神经仅有微量表达,脊髓损伤后24小时表达增加4倍,72小时增加15倍,7天增加3倍,10天仍高于正常水平.结论脊髓损伤后坐骨神经高表达GDNF,是神经元通过"胞体-轴突-靶器官"途径自我保护的一种反应形式,GDNF治疗脊髓损伤时应早期用药.     

Effects of spinal cord injury and hindlimb immobilization on sublesional and supralesional bones in young growing rats

Both spinal cord injury (SCI) and hindlimb cast immobilization (HCI) cause reduction in maturation-related bone gain in young rats, but the effects of the two interventions on bone pathophysiology may be different. The objective of this study was to compare the effects of SCI and HCI on the sublesional/supralesional bones and bone turnover indicators in young rats. Forty male Sprague-Dawley rats (six-week-old) were randomized into four groups, with ten rats in each group. The groups were classified as follows: base-line control, age-matched intact control, HCI, and SCI groups. Bone tissues, blood, and urine samples were studied at 4 weeks after treatments. The tibial dry weights and ash weights in SCI were remarkably reduced by 7.5% (dry weights) and 8.2% (ash weights) compared with HCI. SCI rats showed lower areal bone mineral density in the proximal tibiae compared with HCI rats (- 14%). Cortical thickness and cortical area of the tibial midshaft in SCI were lower than HCI (- 23%, - 33% respectively). The bone surface/bone volume, trabecular separation, trabecular number, connectivity of the trabecular network, and structure model index of the proximal tibiae were remarkably different between SCI and HCI groups. In SCI tibiae, the mineralizing surface, mineral apposition rate, and surface-based bone formation rate were significantly higher than HCI groups (12%, 47%, and 29% respectively). In the compression test, the ultimate load, the energy of ultimate load, and Young's modulus of the proximal tibiae in SCI rats were significantly lower than HCI rats. The serum levels of osteocalcin and the urinary levels of deoxypyridinoline in SCI were higher than those in HCI. There were no significant changes in supralesional bones between SCI and HCI rats. SCI results in a rapid bone loss with more deterioration of trabecular microstructure and cortical bone geometric structure in sublesional bones. High bone turnover rate and low biomechanics strength were found in tibiae in SCI rats. This might be the result of the imbalance of bone resorption and bone formation induced by the impaired neuronal function.     

Assessment of anthropometric,systemic, and lifestyle factors influencing bone status in the legs of spinal cord injured individuals

The aim of the present study was to assess the influence of muscle spasms, systemic or lifestyle factors on bone mass and geometry of the femur and the tibia in people with long-standing spinal cord injury (SCI). Fifty-four motor complete SCI people with paralysis duration of between 5 and 50 years were included in the study. Spasticity was measured by means of the Ashworth scale. Distal epiphyses and mid shafts of the femur, tibia, and radius were measured by peripheral quantitative computed tomography. From the epiphyseal scans, trabecular and total bone mineral density (BMDtrab and BMDtot) were calculated, and from the shaft scans, cortical BMD (BMDcort), total and cortical cross-sectional area (CSAtot and CSAcort), and muscle cross-sectional areas (CSAmus) were determined. Personal characteristics, anthropometric, as well as life-style factors, were assessed by means of a questionnaire. A Spearman correlation matrix was produced with measured data. Correlation coefficients exceeding 0.3 were tested for significance by performing linear regression for parametric data and ANOVA for non-parametric data. Subjects with higher spasticity scores had significantly larger CSAmus in the upper and lower leg. Both spasticity and CSAmus were found to be significantly related to BMDtrab and BMDtot of the distal epiphysis of the femur and to CSAcort of the femoral shaft. In the lower leg, bone parameters of the tibia were found to be strongly related to corresponding bone parameters of the radius, which suggests a systemic origin. No significant relationships were found between bone parameters and any of the life-style factors. The extent of bone loss caused by disuse of the lower extremities in people with long-standing SCI is influenced by systemic factors. Additionally, spasticity has a positive effect on bone parameters of the femur.     

脊髓损伤对大鼠骨转换及骨密度的影响

目的：探讨脊髓损伤（spinal cord injury,SCI）对大鼠骨转换及骨密度的影响。方法：60只3月龄SD大鼠均分为SCI组与对照组。SCI组于T10处完全横断脊髓;对照组仅行椎板切除术。术后1、3、6周时处死动物测血清钙（Ca）、磷（P）、碱性磷酸酶（ALP）、尿钙、磷、肌酊（Cr）以及股骨、股骨骨密度（bone mineral density,BMD）。:桂花 血钙、尿钙、尿钙／肌酝在伤后不同时间段均升高;血ALP在伤后1周时显著下降,3、6周时恢复正常。胫骨近端,股骨远、近端的BMD在6周时较对照组下降且差异显著。结论：SCI大鼠可见明显的骨转换增高以及破骨活性增强,其生化、骨密度的改变与人体有较好的相关性。SD大鼠可用于评价SCI后骨代谢改变,具可以作为SCI后骨质疏松的模型。     

藤黄健骨胶囊对去卵巢骨质疏松大鼠骨密度和骨代谢的影响

目的研究藤黄健骨胶囊对骨质疏松大鼠骨密度和骨代谢的影响。方法采用去卵巢法制备大鼠骨质疏松症模型,灌胃藤黄健骨胶囊干预,灌胃1个月后取材。称重法检测各组大鼠的体重,酶联免疫吸附(ELISA)试剂盒检测血清骨钙素(osteocalcin,BGP)和抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,trACP)含量;双能X线吸收测量仪测量获得骨密度(bone mineral density,BMD);AG-IX生物力学万能实验机检测最大载荷和断裂载荷;HE染色法观察股骨的病理形态学变化。结果与假手术组比较,模型组大鼠体重明显升高,血清抗酒石酸酸性磷酸酶明显升高(P0.05);而模型组大鼠血清骨钙素明显降低,骨密度明显减少,最大载荷和断裂载荷明显减少(P0.05);模型组骨小梁结构不完整、丢失、断裂严重。与模型组相比,藤黄健骨胶囊组大鼠血清骨钙素的含量和抗酒石酸酸性磷酸酶的活性得到纠正(P0.05),股骨的骨微观参数骨密度均得到了良好地修复,骨生物力学参数中最大载荷、断裂载荷得到了明显修复(P0.05),骨小梁排列规则,数目增多、增宽。结论藤黄健骨胶囊能够修复去卵巢骨质疏松症大鼠股骨微观结构破坏和股骨生物力学性能的下降,提示藤黄健骨胶囊具有良好的抗骨质疏松作用。     

Reduced loading due to spinal-cord injury at birth results in “slender” bones: a case study

Introduction The present case study compared bone density, bone geometry and muscle cross-sectional area (CSA) in a male who sustained spinal-cord injury (SCI) at birth (from here called SCI-B) with two matched controls without SCI, and also with four individuals with SCI of similar level and injury completeness but sustained at age 15 or greater. Methods All subjects with SCI were at least 3 years post-injury and had experienced motor incomplete lesions at the cervical level. Computed tomography was used to measure volumetric bone density, indices of bone strength [CSA and maximum, minimum and polar area moments of inertia (I _max, I _min, I _pol)] and muscle CSA at the tibia (66% of tibia length, measured proximally from the distal end). Results Lower leg muscle CSA of SCI-B was 63±6% of values in non-SCI controls, and 72±12% of values in other males with SCI. In SCI-B, bone CSA was roughly half (52±4%) that of non-SCI controls and 73±16% of bone CSA values in other males with SCI. The magnitudes of the area moment of inertia variables (I _max, I _min, and I _pol) in SCI-B were ~25% of control values. Further, the moment of inertia variables in SCI-B were 27–54% of values obtained in other males with SCI, indicating that experiencing SCI in the early stages of life has a remarkable impact on bone shape. Interestingly, tibia bone density did not appear to be affected; the average difference in bone density between SCI-B and non-SCI controls was −1.2±0.7%. The bone densities of other males with SCI were 4–19% lower than in SCI-B. Conclusions Muscle atrophy and bone loss are commonly reported consequences of SCI. This case reveals that important changes in bone geometry occur after SCI, and that mechanical loading during growth plays a vital role in the development of bone size and shape.     

Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report

BACKGROUND Severe spasticity may negatively impact functionality and quality of life after spinal cord injury(SCI). Intrathecal baclofen treatment(IBT) is effectively used to manage severe spasticity and reduce comorbidities. However, long-term IBT may have a negative effect on bone mineral content(BMC), bone mineral density(BMD) and body composition(such as percentage fat mass and lean body mass). We demonstrated the negative effects of long-term IBT use in a single case compared with two non-IBT users.CASE SUMMARY A 46-year old Caucasian male Veteran(case) with a 21 year history of complete tetraplegia(complete C6 SCI) was implanted with IBT for 20 years. The case was matched to two participants with different time since injuries [2(match 1) and 13(match 2) years] without IBT. Knee BMC and BMD at the epiphysis and metaphysis of the distal femur and proximal tibia were evaluated using dual knee and the dual femur modules of GE Lunar i DXA software. Total and leg body composition assessments were also conducted for the three participants. Potential effect of long-term IBT was demonstrated by changes in BMD, consistent with bone demineralization, at the distal femur and proximal tibia and changes in percentage fat mass and lean mass of legs. The case showed 113% lower BMD at the distal femur, and 78.1% lower at the proximal tibia compared to match 1, moreover the case showed 45% lower BMD at the distal femur, and no observed changes at the proximal tibia compared to match 2. The case had 27.1% and 16.5% greater leg %fat mass compared to match 1 and match 2, respectively. Furthermore, the case had 17.4% and 11.8% lower % leg lean mass compared to match 1 and match 2, respectively.CONCLUSION Long-term IBT may impact bone health and body composition parameters in persons with complete SCI. It may be prudent to encourage regular screening of individuals on long-term IBT considering the prevalence of osteoporosis related fractures, cardiovascular diseases, and metabolic disorders in this population.     

阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的临床研究

目的观察阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的影响。方法初次诊断为未绝经的甲状腺功能减退女性患者64例,按随机数字表法将其分为治疗组32例,对照组32例。对照组给予左旋甲状腺素替代治疗,治疗组在对照组治疗的基础上给予阿仑膦酸钠70 mg/周,为期12个月。测定治疗不同时间段患者,腰椎1-4(L_(1-4))、左侧股骨颈BMD及血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3、碱性磷酸酶(ALP)、血清Ⅰ型胶原羧基端吡啶并啉交联肽(ICTP)以及血清骨钙蛋白(bone gla-protein,BGP)水平的变化情况。结果治疗前两组患者的骨密度及骨生化、代谢指标比较不具有统计学意义(P0.05);治疗12个月后,治疗组患者的腰椎1-4(L_(1-4))及股骨颈BMD均显著高于治疗前及同时期对照组(P0.05);治疗后12个月后,两组患者的血ALP、ICTP及BGP均有不同程度升高,治疗组的BGP升高程度明显大于对照组;而对照组的ALP及ICTP升高程度明显大于治疗组,比较有统计学意义(P0.05)。治疗前后两组患者血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3比较无明显差异(P0.05)。结论阿仑膦酸钠可以明显提升甲状腺功能减患者骨密度,改善骨生化和代谢状态。     

Effects of spinal cord injury on osteoblastogenesis,osteoclastogenesis and gene expression profiling in osteoblasts in young rats

Introduction Spinal cord injury (SCI) causes a significant amount of bone loss in the sublesional area in animals and humans, and this type of bone loss is different from other forms of osteoporosis such as disuse osteoporosis and postmenopausal osteoporosis. However, no data is available on the cellular and molecular changes of osteoblastogenesis and osteoclastogenesis during SCI-induced bone loss. Methods SCI and SHAM rats were used in this study to investigate osteoblastogenesis and osteoclastogenesis in bone-marrow culture. We also measured bone mass and bone histomorphometry, as well as the expression of alkaline phosphatase (ALP), core binding factor α1 (Cbfa-1), osterix, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in osteoblast-like cells in bone-marrow culture obtained from SCI and SHAM rats. Results Bone mineral density (BMD) measurement showed serious bone loss in the tibial ephiphyses and metaphyses of SCI rats compared with SHAM rats. In addition, bone histomorphometry analysis of the tibial metaphyses of SCI rats demonstrated that bone microarchitecture in SCI rats deteriorated further than in SHAM rats, and increased eroded surfaces and bone formation rates were observed in SCI rats. The number of osteoclasts that developed from bone marrow of SCI rats at equal density was significantly increased compared with SHAM rats, and the area of the resorption pits formed in the bone marrow culture from SCI rats was significantly greater than SHAM rats, whereas the number of CFU-F and CFU-OB was similar in both groups. RANKL mRNA and protein levels in osteoblast-like cells in culture obtained from SCI rats were significantly higher than those from the SHAM rats, whereas OPG levels decreased slightly. The ratios of RANKL to OPG expression in SCI rats were significantly higher than those in SHAM rats. However, osteogenic gene profiling of Cbfa-1, ALP and osterix in SCI rats remained similar with SHAM rats. Conclusion These changes favor increased osteoclast activity over osteoblast activity, and may explain, in part, the imbalance in bone formation and resorption following SCI.