Altered bioreactivity and limited osteoconductivity of calcium sulfate-based bone cements in the osteoporotic rat spine.

BACKGROUND CONTEXT: Previous studies documenting the osteoconductive nature of calcium sulfate (CaSO(4))-based biomaterials have been largely limited to animal models exhibiting nonosteoporotic bone biology. In addition to diminished bone mineral density (BMD) and altered bone microarchitecture, the osteoporosis phenotype is associated with a proinflammatory and pro-osteolytic state. Thus, osteoporosis may elicit an amplified bioreactivity to common orthopedic biomaterials, potentially limiting their full osteoconductive capabilities in vivo. PURPOSE: The purpose of this study is to test the hypothesis that CaSO(4)-based bone cements exhibit altered bioreactivity and limited osteoconductivity in response to osteoporotic conditions. STUDY DESIGN: 1) Microcomputed tomography (micro-CT) radiomorphometry study and 2) histological analysis. METHODS: Our laboratory has previously established a preclinical model of osteoporosis using the rodent osteoporotic spine (OS). Caudal vertebral defects were filled with either CaSO(4) or CaSO(4)/CaPO(4) (Hybrid) cement for each group (n=4). Over 8 weeks, cement resorption profiles, BMD, average cortical thickness, average trabecular thickness, average trabecular spacing, and diaphyseal bone volume fraction were assessed via micro-CT radiomorphometry. Histological analysis was performed on vertebrae obtained postsurgery and at Week 8. RESULTS: Both materials displayed an accelerated cement resorption profile after implantation into the OS vertebrae. Hybrid cement exhibited slower resorption compared with that of CaSO(4) under both normal female rats (NL) and OS conditions. The cement-mediated bone augmentation observed in the NL spine was altered under OS conditions. CONCLUSIONS: This study suggests that cement bioreactivity is heightened and osteoconductivity may be limited in a preclinical model of the OS. The disparity between the two resorption profiles suggests that this accelerated cement resorption is a material-dependent phenomenon. The proinflammatory and pro-osteolytic bone environment associated with the osteoporosis disease state may contribute to the accelerated resorption and altered osteoconductivity exhibited by both materials. Future study of potential biomaterials intended for use within the OS may necessitate further exploration of the relationship between biomaterial performance and osteoporosis bone biology.     

Microcracks: an alternative index for evaluating bone biomechanical quality

To investigate microcracks as a potential index of bone biomechanical quality in rats, 98 Sprague-Dawley (SD) rats, 10 months old, were used. Eight rats were killed at the beginning of the study, to serve as baseline controls. The remaining 90 rats were ovariectomized (OVX), and treated with 17 -estradiol (EST) at 10µg/kg per day, or sham-operated (sham). These 90 rats were killed at 3, 15, and 12 weeks post-surgery. Bone mineral density (BMD) of the total body, the lumbar spine L1–L4, and the tibiae was measured, using dual-energy X-ray absorptiometry (DXA). Bone histomorphometry of the right proximal tibial metaphysis was performed. Compressive testing was performed on the L5 vertebral body. Microcrack density (CrDn) and microcrack surface density (CrSDn) of L4 vertebral bodies that were fatigue-damaged in vitro were determined from bone sections. BMD at various sites, and CrDn and CrSDn were higher at weeks 15 and 21 than at week 3 post-operation. Trabecular separation (TbSp) increased, while trabecular number (TbN) decreased, and the maximum loading (ML) and elastic modulus (EM) of the vertebrae reached their peak values at week 15. At week 3 post-surgery, OVX rats displayed greater TbSp, CrDn, and CrSDn but less trabecular bone volume (BV) than both sham and EST rats. At week 15, BMD and ML were decreased in OVX rats compared with sham rats. At week 21, BMD, TbN, and TbAr were decreased in OVX compared with EST and sham rats. The OVX rats showed greater TbSp, bone formation rate, mineral apposition rate, percent labeled perimeter (%Pm), CrDn, and CrSDn, and lower ML and EM values than both EST and sham rats. Thus, microcrack parameters represent bone biomechanical quality changes associated with ovariectomy in rats, and they indicate the efficacy of estrogen replacement therapy.     

绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系

目的探讨绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系。方法选择骨质疏松性椎体骨折的绝经后妇女23例为骨折组,无椎体骨折的25例绝经后骨质疏松妇女为对照组。两组的年龄、绝经年限、身高、体重、体重指数差异无显著性,均行胸腰椎正侧位X线摄片。用双能X线吸收仪（DXA）测量的腰椎（L2-4）前后位骨密度（BMD）、骨矿含量（BMC）和T值。结果骨折组BMD、BMC和T值均低于对照组（P〈0.01）。结论腰椎BMD降低与绝经后妇女的骨质疏松性椎体骨折相关。绝经后骨质疏松妇女应重视BMD变化,预防椎体骨折的发生。     

硫酸钙骨水泥强化骨质疏松绵羊腰椎的生物力学研究

目的评价硫酸钙骨水泥(CSC)强化骨质疏松绵羊腰椎力学强度的效果。方法成年雌性绵羊4只,行去势手术后饲养1年,测量去势前后腰椎骨密度。取L2～5共16个椎体,分为CSC组和对照组,每组8个椎体。CSC组经椎弓根向椎体内注射CSC(2.0 ml),对照组不给于任何处理。CSC组于术后12周测量L2～5单个椎体的骨密度,然后处死绵羊。取出椎体行压缩实验,测量各组中椎体的最大压缩应力(σult)和能量吸收值(EAV)。结果去势1年后绵羊腰椎骨密度显著下降,与去势前比较差异有统计学意义(P<0.05),骨质疏松绵羊模型建立成功。注射CSC 12周后椎体骨密度(BMD)、σult、EAV均高于对照组(P<0.05),且椎体的σult和EAV均与BMD成正相关关系(P<0.05)。结论 CSC可以提高骨质疏松椎体的BMD,强化骨质疏松椎体的力学强度,有利于避免或减少骨质疏松椎体骨折的风险。     

Sequential and precise in vivo measurement of bone mineral density in rats using dual-energy x-ray absorptiometry.

In the design of new strategies for the treatment of osteoporosis, noninvasive, precise, and sensitive bone mass measurement capable of detecting changes over short periods of time in small animals is essential. Most of the models described thus far require the sacrifice of the animals and/or display low reproducibility. Using a dual-energy x-ray absorptiometer (DEXA; Hologic QDR-1000) in an ultrahigh-resolution mode, we measured bone mineral density (BMD) in rats at the levels of lumbar spine (L1-4), proximal tail (caudal vertebrae C2-4), and tibia. Accuracy was evaluated by measuring the mineral content of bone powder capsules (within the range of rat vertebrae BMD), under 0.5-3 cm water to mimic variations in soft tissue thickness. The bone powder capsule mineral content was highly correlated with chemically determined hydroxyapatite content (r = 0.999). In vivo reproducibility was evaluated by calculating the coefficient of variation (CV = 100 x SD/mean) of four to six BMD measurements, each time with repositioning, in seven rats (220-500 g body weight). CV was 1.36 +/- 0.32% (x +/- SD) for lumbar spine, 0.66 +/- 0.50% for proximal tail, and 1.12 +/- 0.45% for tibia. The ability to detect BMD changes was investigated by measuring BMD before and every 4 weeks after ovariectomy (OVX) in 270 g rats, pair fed during the whole experiment. Compared with sham-operated control animals, a highly significant difference in lumbar spine BMD was observed 4 weeks after OVX, which reached a maximum by 8 weeks and remained stable thereafter. At the level of the proximal tibia, the difference was maximal 4 weeks after OVX.(ABSTRACT TRUNCATED AT 250 WORDS)     

骨质疏松症患者腰椎平均BMD与腰椎椎体骨折相关性研究

目的 探讨骨质疏松症患者腰椎平均骨密度(BMD)与腰椎椎体骨折的关系.方法 选择2010年1月~2011年1月来我院治疗骨质疏松性椎体骨折96例患者为骨折组,42例无腰椎椎体骨折者作为对照组.采用双能X线骨密度仪对两组患者腰椎正位(L2-4)BMD进行测定.结果 骨质疏松患者腰椎椎体骨折组患者BMD相对对照组较低,差异具有统计学意义(P<0.05).结论 腰椎BMD降低与绝经后妇女的骨质疏松性椎体骨折相关.     

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

An annual infusion of zoledronic acid (ZOL) reduces fracture risk in osteoporotic patients. Previously, we showed that a single ZOL injection inhibited changes in bone microstructure and strength in rat tibiae after ovariectomy. Here, we determined the effects of a single ZOL injection as preventive and restorative treatment on the bone microstructure and strength in lumbar and caudal vertebrae of ovariectomized (OVX) rats. Twenty-nine female 35-week-old Wistar rats were divided into four groups: SHAM-OVX (n = 9), OVX (n = 5), OVX and early ZOL (n = 8), and OVX and late ZOL (n = 7). ZOL was given once (20 μg/kg body weight s.c.) at OVX in the early ZOL group and 8 weeks later in the late ZOL group; rats were killed 16 weeks after OVX. Trabecular and cortical bone microarchitecture were measured in lumbar (L3) and caudal (Cd6) vertebrae using micro-computed tomography, and compressive mechanical properties were determined in L3 vertebrae. Compared to SHAM-OVX, OVX rats had significantly lower BV/TV; SMI, Tb.N, Tb.Sp, and Conn.D tended to be deteriorated in lumbar vertebrae, while both ZOL groups did not differ from the SHAM-OVX group. Both ZOL groups had significantly higher BV/TV than OVX; the early ZOL group also had significantly lower SMI and higher Tb.Th. OVX tended to decrease mechanical properties, while early and late ZOL treatment inhibited OVX-induced degeneration. Neither OVX nor ZOL induced changes in the trabecular microarchitecture of caudal vertebrae. In summary, in adult rats a single ZOL injection inhibited OVX-induced changes in lumbar vertebral bone microarchitecture and strength.     

聚甲基丙烯酸甲酯强化对骨质疏松椎弓根螺钉固定的生物力学作用

目的探讨聚甲基丙烯酸甲酯 (polymethylmethacrylate,PMMA)骨水泥强化椎弓根螺钉的方法和评价 PMMA强化骨质疏松椎弓根螺钉后的生物力学性质。方法 6具新鲜老年女性胸腰段骨质疏松脊柱标本 (T10～ L5),使用双能 X线骨密度吸收仪测试每个椎体的骨密度,随机取 16个椎体 (32侧椎弓根 ),一侧椎弓根拧入 CCD螺钉,测量最大旋入力偶矩后拔出螺钉作为正常对照组,用 PMMA骨水泥强化椎弓根螺钉作为修复固定组,行螺钉拔出试验;另一侧经导孔直接强化椎弓根螺钉后拔出作为强化固定组,记录三组螺钉的最大轴向拔出力。结果椎体平均骨密度为 (0.445± 0.019)g/cm2;螺钉最大旋入力偶矩为（ 0.525± 0.104） Nm;正常对照组螺钉最大轴向拔出力为 (271.5± 57.3)N;修复固定组为 (765.9± 130.7)N;强化固定组为 (845.7± 105.0)N。 PMMA骨水泥强化或修复骨质疏松椎弓根螺钉后最大抗压力明显高于强化前,差异有非常显著性意义 (P< 0.01)。结论 PMMA骨水泥强化骨质疏松椎弓根螺钉能显著增加螺钉在椎体内的稳固性。     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

Hydroxyapatite-coating of pedicle screws improves resistance against pull-out force in the osteoporotic canine lumbar spine model: a pilot study.

BACKGROUND CONTEXT: In patients with spinal osteoporosis, the early achievement and maintenance of a biological bond between the pedicle screw and bone is important to avoid screw loosening complications. There are few reports of in vivo investigations involving biomechanical and histological evaluations in the osteoporotic spine. PURPOSE: To evaluate the effect of hydroxyapatite (HA)-coating on the pedicle screw in the osteoporotic lumbar spine and to investigate the relationship between resistance against the screw pull-out force and bone mineral density (BMD) of the vertebral body. STUDY DESIGN/SETTING: Mechanical and pathological investigations in the lumbar spine. METHODS: Two 24-month-old female beagle dogs were fed a calcium-free dog chow for 6 months after ovariectomy (OVX). BMD (in g/cm2) was measured by dual energy X-ray absorptiometry at pre-OVX and 6 months after OVX. Pedicle screws were placed from L1 to L6 at 6 months after OVX. Twenty-four pure titanium cortical screws (Synthes, #401-114) were used as pedicle screws (Ti-PS). Of these, 12 screws had HA-coating (HA-PS). The HA-PS screws were inserted into the right pedicles and the Ti-PS were inserted into the left pedicles. Ten days after this procedure, the lumbar spines were removed en bloc for screw pull-out testing and histological evaluation. RESULTS: The mean BMD value of the lumbar vertebrae 6 months after the OVX was 0.549+/-0.087 g/cm2, which was significantly less than the pre-OVX mean BMD of 0.603+/-0.092 g/cm2 (p < 0.001). The mean resistance against the pull-out force for the HA-PS was significantly greater at 165.6+/-26.5N than in the Ti-PS (103.1+/-30.2N, p < .001). The histological sections in the HA-PS clearly revealed new bone bonding with the apatite coating but only fibrous tissue bonding in the Ti-PS. CONCLUSIONS: The results of this study showed that the resistance to the pull-out force of HA-PS is 1.6 times that of Ti-PS. Furthermore, HA-PS has superior biological bonding to the surrounding bone, as early as 10 days after surgery in this osteoporotic spine model. Thus, in patients with osteoporosis, coating of the pedicle screw with HA may provide better stability and bonding between the pedicle screw and bone in the early postoperative period.     

Augmentation of mechanical properties in osteoporotic vertebral bones – a biomechanical investigation of vertebroplasty efficacy with different bone cements

Recent clinical trials have reported favorable early results for transpedicular vertebral cement reinforcement of osteoporotic vertebral insufficiencies. There is, however, a lack of basic data on the application, safety and biomechanical efficacy of materials such as polymethyl-methacrylate (PMMA) and calciumphospate (CaP) cements. The present study analyzed 33 vertebral pairs from five human cadaver spines. Thirty-nine vertebrae were osteoporotic (bone mineral density < 0.75 g/cm2), 27 showed nearly normal values. The cranial vertebra of each pair was augmented with either PMMA (Palacos E-Flow) or experimental brushite cement (EBC), with the caudal vertebra as a control. PMMA and EBC were easy to inject, and vertebral fillings of 20-50% were achieved. The maximal possible filling was inversely correlated to the bone mineral density (BMD) values. Cement extrusion into the spinal canal was observed in 12% of cases. All specimens were subjected to axial compression tests in a displacement-controlled mode. From load-displacement curves, the stiffness, S, and the maximal force before failure, Fmax, were determined. Compared with the native control vertebrae, a statistically significant increase in vertebral stiffness and Fmax was observed by the augmentation. With PMMA the stiffness increased by 174% (P = 0.018) and Fmax by 195% (P = 0.001); the corresponding augmentation with EBC was 120% (P = 0.03) and 113% (P = 0.002). The lower the initial BMD, the more pronounced was the augmentation effect. Both PMMA and EBC augmentation reliably and significantly raised the stiffness and maximal tolerable force until failure in osteoporotic vertebral bodies. In non-porotic specimens, no significant increase was achieved.     

Adjacent vertebral failure after vertebroplasty: a biomechanical study of low-modulus PMMA cement

PMMA is the most common bone substitute used for vertebroplasty. An increased fracture rate of the adjacent vertebrae has been observed after vertebroplasty. Decreased failure strength has been noted in a laboratory study of augmented functional spine units (FSUs), where the adjacent, non-augmented vertebral body always failed. This may provide evidence that rigid cement augmentation may facilitate the subsequent collapse of the adjacent vertebrae. The purpose of this study was to evaluate whether the decrease in failure strength of augmented FSUs can be avoided using low-modulus PMMA bone cement. In cadaveric FSUs, overall stiffness, failure strength and stiffness of the two vertebral bodies were determined under compression for both the treated and untreated specimens. Augmentation was performed on the caudal vertebrae with either regular or low-modulus PMMA. Endplate and wedge-shaped fractures occurred in the cranial and caudal vertebrae in the ratios endplate:wedge (cranial:caudal): 3:8 (5:6), 4:7 (7:4) and 10:1 (10:1) for control, low-modulus and regular cement group, respectively. The mean failure strength was 3.3 ± 1 MPa with low-modulus cement, 2.9 ± 1.2 MPa with regular cement and 3.6 ± 1.3 MPa for the control group. Differences between the groups were not significant (p = 0.754 and p = 0.375, respectively, for low-modulus cement vs. control and regular cement vs. control). Overall FSU stiffness was not significantly affected by augmentation. Significant differences were observed for the stiffness differences of the cranial to the caudal vertebral body for the regular PMMA group to the other groups (p < 0.003). The individual vertebral stiffness values clearly showed the stiffening effect of the regular cement and the lesser alteration of the stiffness of the augmented vertebrae using the low-modulus PMMA compared to the control group (p = 0.999). In vitro biomechanical study and biomechanical evaluation of the hypothesis state that the failure strength of augmented functional spine units could be better preserved using low-modulus PMMA in comparison to regular PMMA cement.     

Histomorphometric Evaluation of the Effects of Ovariectomy on Bone Turnover in Rat Caudal Vertebrae

The purpose of this study was to learn whether caudal vertebrae can be used to evaluate the effects of ovariectomy (OVX) in rats. Seven-month-old female Wistar rats were divided into two groups: the OVX group and the untreated control group. All rats were killed at 8 weeks and their 4th lumbar (L4), 1st caudal (C1), 3rd caudal (C3), and 5th caudal (C5) vertebrae were processed undecalcified and sectioned with Villanueva bone stain for quantitative bone histomorphometry. Both length of vertebral bodies and the cancellous tissue area in C1 were similar in size to L4 but significantly bigger than C3 and C5. Within the groups, cancellous bone volume (BV/TV) and trabecular thickness in both groups gradually increased in caudal vertebrae in relation to the distal direction. Between the groups, OVX rats exhibited a significantly lower BV/TV relative to control rats at L4 and C1, however, no significant difference were seen at C3 and C5. Bone formation-related parameters such as osteoid and mineralizing surface, and eroded surface were higher in the OVX group than in the control group in caudal as well as in lumbar vertebrae. By quantitative analysis of bone marrow composition, yellow marrow volume in C3 and C5 was significantly higher than that in L4 and C1, in both groups. Our results suggest that C1 is similar to L4 in size, bone turnover, and bone marrow composition. However, further experiments are needed to evaluate the possibility that C1 vertebra could be used as an alternative site for histomorphometric evaluation of bone changes in OVX rats. Received: 12 August 1997 / Accepted: 11 May 1998     

磷酸钙骨水泥强化骨质疏松绵羊腰椎力学强度的动态观察

目的观察磷酸钙骨水泥（calcium phosphate cement,CPC）强化骨质疏松绵羊腰椎生物力学强度的体内动态变化。方法成年雌性绵羊12只行去势手术后饲养1年,测量去势前后腰椎骨密度。取L2~L5为实验对象,空白组不给予任何处理,CPC组中,经椎弓根向椎体内注射CPC 2.0 mL。于术后1 d、6周、12周和24周四个时间点各随机处死3只绵羊,对椎体行压缩实验,分别测量各组中椎体的最大压缩应力（ultimate compressive stress,σult）和能量吸收值（energy absorption value,EAV）,对比分析同一时间点不同方法之间和同一方法的不同时间点之间的力学指标。结果去势1年后绵羊腰椎骨密度显著下降,差异具有统计学意义（P〈0.05）,骨质疏松绵羊模型建立成功。空白组中各时间点之间的σult和EAV均无显著性差异（P〉0.05）,而CPC组中各时间点之间的σult和EAV也均无显著性差异（P〉0.05）;在同一时间点,CPC组螺钉的σult和EAV均显著高于对照组（P〈0.05）。结论 CPC对骨质疏松椎体的即时强度和远期强度均有显著的强化效果,它对椎体的强化效果在体内是动态稳定的,为脊柱达到坚强骨性融合提供了良好的力学环境。CPC作为一种生物相容性好、可降解吸收、可促骨生成和机械强度好的材料具有广阔临床应用前景。     

Adjacent vertebral failure after vertebroplasty. A biomechanical investigation

Vertebroplasty, which is the percutaneous injection of bone cement into vertebral bodies has recently been used to treat painful osteoporotic compression fractures. Early clinical results have been encouraging, but very little is known about the consequences of augmentation with cement for the adjacent, non-augmented level. We therefore measured the overall failure, strength and structural stiffness of paired osteoporotic two-vertebra functional spine units (FSUs). One FSU of each pair was augmented with polymethylmethacrylate bone cement in the caudal vertebra, while the other served as an untreated control. Compared with the controls, the ultimate failure load for FSUs treated by injection of cement was lower. The geometric mean treated/untreated ratio of failure load was 0.81, with 95% confidence limits from 0.70 to 0.92, (p < 0.01). There was no significant difference in overall FSU stiffness. For treated FSUs, there was a trend towards lower failure loads with increased filling with cement (r2 = 0.262, p = 0.13). The current practice of maximum filling with cement to restore the stiffness and strength of a vertebral body may provoke fractures in adjacent, non-augmented vertebrae. Further investigation is required to determine an optimal protocol for augmentation.     

The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures.

STUDY DESIGN: A biomechanical study comparing two materials for augmentation of osteoporotic vertebral bodies and vertebral bodies after compression fracture. OBJECTIVES: To compare an injected, biodegradable calcium phosphate bone substitute with injected polymethylmethacrylate bone cement for strengthening osteoporotic vertebral bodies and improving the integrity of vertebral compression fractures. SUMMARY OF BACKGROUND DATA: Injection of polymethylmethacrylate bone cement into fractured vertebral bodies has been used clinically. However, there is concern about thermal damage to the neural elements during polymerization of the polymethylmethacrylate bone cement as well as its negative effects on bone remodeling. Biodegradable calcium phosphate bone substitutes have been studied for enhancement of fixation in fractured vertebrae. METHODS: Forty fresh osteoporotic thoracolumbar vertebrae were used for two separate parts of this study: 1) injection into osteoporotic vertebrae: intact control (n = 8), calcium phosphate (n = 8), and polymethylmethacrylate bone cement (n = 8) groups. Each specimen then was loaded in anterior compression until failure; 2) injection into postfractured vertebrae: calcium phosphate (n = 8) and polymethylmethacrylate bone cement (n = 8) groups. Before and after injection, the specimens were radiographed in the lateral projection to determine changes in vertebral body height and then loaded to failure in anterior bending. RESULTS: For intact osteoporotic vertebrae, the average fracture strength was 527 +/- 43 N (stiffness, 84 +/- 11 N/mm), 1063 +/- 127 N (stiffness, 157 +/- 21 N/mm) for the group injected with calcium phosphate, and 1036 +/- 100 N (stiffness, 156 +/- 8 N/mm) for the group injected with polymethylmethacrylate bone cement. The fracture strength and stiffness in the calcium phosphate bone substitute group and those in the polymethylmethacrylate bone cement group were similar and significantly stronger than those in intact control group (P < 0.05). For the compression fracture study, anterior vertebral height was increased 58.5 +/- 4.6% in the group injected with calcium phosphate and 58.0 +/- 6.5% in the group injected with polymethylmethacrylate bone cement as compared with preinjection fracture heights. No significant difference between the two groups was found in anterior vertebral height, fracture strength, or stiffness. CONCLUSION: This study demonstrated that the injection of a biodegradable calcium phosphate bone substitute to strengthen osteoporotic vertebral bodies or improve vertebral compression fractures might provide an alternative to the use of polymethylmethacrylate bone cement.     

Bone three-dimensional microstructural features of the common osteoporotic fracture sites

Osteoporosis is a common metabolic skeletal disorder characterized by decreased bone mass and deteriorated bone structure, leading to increased susceptibility to fractures. With aging population, osteoporotic fractures are of global health and socioeconomic importance. The three-dimensional microstructural information of the common osteoporosis-related fracture sites, including vertebra, femoral neck and distal radius, is a key for fully understanding osteoporosis pathogenesis and predicting the fracture risk. Low vertebral bone mineral density (BMD) is correlated with increased fracture of the spine. Vertebral BMD decreases from cervical to lumbar spine, with the lowest BMD at the third lumbar vertebra. Trabecular bone mass of the vertebrae is much lower than that of the peripheral bone. Cancellous bone of the vertebral body has a complex heterogeneous three-dimensional microstructure, with lower bone volume in the central and anterior superior regions. Trabecular bone quality is a key element to maintain the vertebral strength. The increased fragility of osteoporotic femoral neck is attributed to low cancellous bone volume and high compact porosity. Compared with age-matched controls, increased cortical porosity is observed at the femoral neck in osteoporotic fracture patients. Distal radius demonstrates spatial inhomogeneous characteristic in cortical microstructure. The medial region of the distal radius displays the highest cortical porosity compared with the lateral, anterior and posterior regions. Bone strength of the distal radius is mainly determined by cortical porosity, which deteriorates with advancing age.     

不同充填材料应用于山羊经皮椎体成形术的组织学研究

目的:研究聚甲基丙烯酸甲酯(PMMA)、磷酸钙人工骨(CPC)和复合重组人骨形态发生蛋白-2的磷酸钙人工骨(rhBMP-2/CPC)在山羊骨质疏松症模型上行经皮椎体成形术(PVP)后的组织学表现。方法:6～8岁雌性山羊8只,均行双侧卵巢切除术,术后4个月建立骨质疏松症模型。在C形臂X线机监视下,随机选取8只山羊的L2-L6的两节椎体行PVP,分别充填PMMA、CPC和rhBMP-2/CPC,保证每只山羊的两节穿刺椎体的充填材料各不相同,术后4个月处死所有动物,取出椎体,组织学观察。结果:8只山羊16个椎体的PVP均成功,共出现4个椎体的渗漏。肉眼观察:PMMA与松质骨界限清晰,一个椎体取材时交界面出现破碎和脱落现象;而CPC和rhBMP-2/CPC与椎体内松质骨界限不清,互相融合生长。HE染色光镜观察:PMMA与骨小梁松散结合,界限明显,未见PMMA吸收和新生骨形成;CPC均匀分布于骨小梁和骨髓组织内,有CPC吸收现象,同时可见有新生软骨样团块形成,并有新生骨组织形成向其中心长入;rhBMP-2/CPC除了CPC的表现外,可见成骨活动活跃。结论:在组织学上,rhBMP-2/CPC和CPC均具有降解活性和骨传导活性,优于PMMA。rhBMP-2/CPC还具有诱导成骨活性,可能成为PVP中强化骨质疏松性椎体的首选充填材料。     

The Less Potent Estrogenic Effect of Tamoxifen on Bone in Ovariectomized Rats With Established Osteopenia

The longitudinal effects of tamoxifen (TAM) treatment on bone metabolism, spinal bone mineral density (BMD), and bone mineral content (BMC) were compared with those of estrogen in ovariectomized (OVX) rats with established osteopenia. The 6-month-old rats were divided into Sham (n = 8) and OVX (n = 24) groups. First, the OVX rats were allowed to lose bone for 6 weeks. Six weeks after ovariectomy they were divided into three groups: (1) OVX rats treated with solvent vehicle (OVX+Vehicle), (2) OVX rats injected with TAM subcutaneously six times a week at a dosage of 1.0 mg/kg body weight (OVX+TAM), (3) OVX rats injected with 17-β estradiol subcutaneously six times a week at a dosage of 0.1 mg/kg body weight (OVX+ET). The longitudinal effects of TAM and estrogen on bone were studied by dual energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr). Ovariectomy resulted in a significant increase in urinary Pyr, Dpyr, and a significant decrease in spine BMD and BMC. TAM treatment completely inhibited the further bone loss in OVX rats with established osteopenia, however, estrogen increased spine BMD and BMC significantly compared with OVX+Vehicle, OVX+TAM, and baseline of treatment. Both TAM and estrogen treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Our findings indicate that TAM acts as an estrogen agonist with respect to effects on spine BMD, BMC, and bone resorption in OVX rats with established osteopenia, but fails to restore spine BMD and BMC to the extent observed with estrogen in this study.     

Long-term minodronic acid (ONO-5920/YM529) treatment suppresses increased bone turnover, plus prevents reduction in bone mass and bone strength in ovariectomized rats with established osteopenia

The present study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone histomorphometry and bone strength in ovariectomized (OVX) rats. Female F344/DuCrj rats, aged 14 weeks, were OVX or sham operated. After 3 months, the OVX rats showed an increase in bone turnover, and a decrease in bone mass and bone strength. Minodronic acid was administered orally once a day for 12 months at doses of 0, 0.006, 0.03 and 0.15 mg/kg from 3 months after OVX. Minodronic acid dose-dependently inhibited the decrease in BMD of lumbar vertebrae and femur. In the femur, treatment with 0.15 mg/kg minodronic acid increased the BMD of distal and mid sites to sham levels. Minodronic acid dose-dependently suppressed OVX-induced increase in urinary deoxypyridinoline, a bone resorption marker, after a month of treatment and these effects were maintained for 12 months of treatment. Minodronic acid also decreased serum osteocalcin, a bone formation marker. In bone histomorphometric analysis after 12 months of treatment, OVX rats showed an increase in bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (MS/BS and BFR/BV) at lumbar vertebral bodies. Minodronic acid suppressed the OVX-induced increase in bone turnover at tissue level. Trabecular bone volume, trabecular thickness and trabecular number of lumbar vertebral bodies were decreased after OVX. Minodronic acid increased these structural indices, indicating that it prevented the deterioration in trabecular architecture. In a mechanical test at 12 months of treatment, ultimate load of lumbar vertebral bodies and mid femur in the OVX-control group was decreased compared to the sham group. Minodronic acid prevented the reduction in bone strength at both sites. In particular, in the mid femur, treatment with 0.03 and 0.15 mg/kg minodronic acid increased bone strength to sham levels or greater. In conclusion, minodronic acid suppressed increased bone turnover, plus prevented the decrease in BMD, deterioration of bone microarchitecture and reduction in bone strength in OVX rats with established osteopenia. These results suggest that minodronic acid may be clinically useful for treatment of osteoporosis.