异体骨与自体髂骨修复粉碎性骨折的初步实验研究

目的 对比观察兔自体髂骨与同种异体骨植骨对长管骨粉碎性骨折的修复效果。将新西兰大白兔双侧肱骨人工造成粉碎骨折，一侧取自体髂骨植入，另一侧取等量同种异体骨植入，不同阶段处死后行大体，X线片及组织学观察。结果 自体髂骨植骨与异体骨植骨的骨愈合过程基本相同，均通过软骨化骨，爬行替代而愈合。植骨术后1周，纤维结缔组织包绕植骨片，无炎性反应；2周时，成骨性肉芽组织包绕植骨片，有早期软骨性骨梁形成；3周时，新生的骨梁间可见崩解的植骨片，植骨周围软骨化骨活跃；4周时，植骨片消失，出现成熟骨梁，其边缘可见骨祖细胞成排排列；5周时，骨梁变粗，致密，基本为成熟骨；6周时，呈现致密的板层结构，哈佛氏系统完整。其中第3，4周利用图像分析系统处理，结果两侧无统计学意义（P＞0．05）。结论 同种异体骨具有良好的组织相容性及骨传导作用，可以取代自体髂骨植骨修复长管骨骨折。     

脱钙骨基质/磷酸钙复合骨水泥骨诱导活性观察

目的：观察磷酸钙骨水泥（CPC）中加入脱钙骨基质（DBM）后形成的复合骨水泥的成骨诱导活性。方法：将DBM/CPC复合骨水泥分别植入兔背肌肌袋内，于不同时间取材，通过组织学切片、ALP等手段观察异位诱导成骨情况。结果：术后2周，DBM/CPC复合骨水泥组可见间充质细胞增殖、聚集并包绕DBM骨粒。4周时，DBM已有部分吸收，并软骨样细胞和软骨样组织包裹。8周，DBM进一步吸收，软骨细胞和软骨组织逐渐成熟，新骨形成。12周，DBM吸收并被新骨组织部分或大部分代替且相互连接成片。ALP测定结果与组织学观察的新骨形成情况基本一致。结论：DBM/CPC复合骨水泥有较强的异位诱导成骨能力，诱导新骨的形成伴随着材料的降解，可以有效弥补单纯使用CPC时降解速度太慢和无骨诱导能力的不足。     

同种异体骨复合氨基胍对兔桡骨缺损愈合的影响

目的探讨同种异体松质骨和iNOS选择性抑制剂氨基胍(AG)复合物对兔桡骨中段骨缺损愈合的影响。材料和方法制备同种异体松质骨并和氨基胍复合。制备兔桡骨骨缺损动物模型。左侧前肢植入同种异体松质骨,右侧前肢植入氨基胍和同种异体松质骨复合物。术后2、4、8、12周,行肉眼观察、X线片、骨密度检查和组织学切片检查。术后12周,用材料性能试验机行三点弯曲试验。并与正常桡骨比较。结果氨基胍和同种异体松质骨复合物在骨缺损愈合过程中成骨量、成骨速度、时间均优于单纯同种异体松质骨。术后12周骨缺损基本得到修复。结论iNOS选择性抑制剂氨基胍可促进骨缺损愈合。     

自固化磷酸钙复合BMP及同种异体骨修复兔股骨大段骨缺损

[目的] 观察一种新型自固化磷酸钙（CPC）复合BMP与同种异体骨修复兔股骨节段性骨缺损的效果，为临床复合应用大段同种异体骨移植提供参考。[方法] 54只新西兰大白兔随机分成3组，于一侧股骨中上段造成2cm长皮质骨缺损模型，分别进行：A组复合BMP与CPC的新鲜冷冻同种异体骨移植；B组单纯新鲜冷冻同种异体骨移植；C组自体大段骨移植。移植骨均用直径3mm三棱髓内针固定。于术后4、8、12周，进行影像学、组织学检查，对比各组移植骨愈合过程与修复效果。[结果] CPC复合BMP大段同种异体骨移植早期骨修复效果优于单纯异体骨移植（P〈0．01），与自体骨移植修复效果相似，至12周3组均达骨性愈合，以A组及C组骨修复塑形较好。CPC复合BMP组骨痂量较多，分布于移植骨与宿主骨结合部及移植骨周围，形成皮质骨外骨桥，并较早在异体骨外表面形成破骨与成骨，异体骨内哈佛氏管扩大，衬垫细胞、成骨细胞、破骨细胞及血细胞较其它组多。CPC随着新骨的形成及改建塑形逐步缓慢降解。[结论] CPC复合BMP对大段同种异体骨移植的愈合及替代有增强和促进作用。     

脱钙骨基质/磷酸钙复合骨水泥骨诱导活性观察

目的:观察磷酸钙骨水泥(CPC)中加入脱钙骨基质(DBM)后形成的复合骨水泥的成骨诱导活性.方法:将DBM/CPC复合骨水泥分别植入兔背肌肌袋内,于不同时间取材,通过组织学切片、ALP等手段观察异位诱导成骨情况.结果:术后2周,DBM/CPC复合骨水泥组可见间充质细胞增殖、聚集并包绕DBM骨粒.4周时,DBM已有部分吸收,并软骨样细胞和软骨样组织包裹.8周,DBM进一步吸收,软骨细胞和软骨组织逐渐成熟,新骨形成.12周,DBM吸收并被新骨组织部分或大部分代替且相互连接成片.ALP测定结果与组织学观察的新骨形成情况基本一致.结论:DBM/CPC复合骨水泥有较强的异位诱导成骨能力,诱导新骨的形成伴随着材料的降解,可以有效弥补单纯使用CPC时降解速度太慢和无骨诱导能力的不足.     

脱钙骨基质/磷酸钙复合骨水泥骨诱导活性观察

目的:观察磷酸钙骨水泥(CPC)中加入脱钙骨基质(DBM)后形成的复合骨水泥的成骨诱导活性。方法:将DBM/CPC复合骨水泥分别植入兔背肌肌袋内,于不同时间取材,通过组织学切片、ALP等手段观察异位诱导成骨情况。结果:术后2周,DBM/CPC复合骨水泥组可见间充质细胞增殖、聚集并包绕DBM骨粒。4周时,DBM已有部分吸收,并软骨样细胞和软骨样组织包裹。8周,DBM进一步吸收,软骨细胞和软骨组织逐渐成熟,新骨形成。12周,DBM吸收并被新骨组织部分或大部分代替且相互连接成片。ALP测定结果与组织学观察的新骨形成情况基本一致。结论:DBM/CPC复合骨水泥有较强的异位诱导成骨能力,诱导新骨的形成伴随着材料的降解,可以有效弥补单纯使用CPC时降解速度太慢和无骨诱导能力的不足。     

兔自体骨髓间充质干细胞体内复合移植的成骨研究

目的 观察兔自体骨髓间充质干细胞（MSCs)体内复合移植的成骨能力，以寻求理想的MSCs载体。方法将10只新西兰大白兔随机分成A、B两组，从自体骨髓中分离出MSCs，体外培养并扩增后分别与相同大小的小牛脱钙骨（DBCB），自固化磷酸钙人工骨（CPC）复合移植于两组大白兔左侧骶棘肌中，同时右侧骶棘肌分别植入相同大小的DBCB，CPC作空白对照；16周后取出标本，观察成骨情况并行组织学检查。结果 A组5例：MSCs DBCB侧均发现有新骨组织形成，单纯DBCB侧3例被完全吸收，降解，2例大部分吸收，降解；B组5例；MSCs CPC侧和单纯CPC侧均未见骨组织形成，植入物也无明显吸收，结论 自体骨髓MSCs在适合载体负载下可在体内自动分化成骨，DBCB是MSCs的良好载体之一。     

椎体成形术或后凸成形术生物活性充填材料的体内降解

目的 观察磷酸钙骨水泥(CPC)和硫酸钙骨水泥(CSC)在椎体内的演变过程,为椎体成形术或后凸成形术中寻找更为合适的充填材料.方法 对24只成年雌性绵羊的L2～L5椎体制作骨缺损,随机注入CPC、CSC和聚甲基丙烯酸甲酯(PMMA),其中剩余的椎体作为空白对照,并以L6椎体作正常对照.术后2周、12周和24周分别随机处死其中8只绵羊,进行大体观察、生物力学测试、不脱钙组织学分析.结果 CSC组和CPC组椎体被填充材料明显增强,但CSC组椎体力学性能自2～12周呈现下降趋势,而到24周时又出现回升.CPC组椎体力学性能自2～24周呈上升趋势.12周时3组新骨形成量差异不明显,CSC已被大部分吸收;植入24周时新骨形成量CSC组＞空白组＞CPC组,CPC出现了明显的吸收,而CSC仅有少量残留.结论 CSC与CPC初期均能明显增强椎体;随着时间的推移,CSC在体内降解迅速,而CPC在体内降解缓慢.     

微小颗粒骨磷酸钙复合物作为骨组织工程支架材料的实验研究

目的探讨使用同种异体微小颗粒骨磷酸钙骨水泥（CPC）复合物作为骨组织工程支架材料的方法。方法采用同种异体微小颗粒骨CPC复合物作为支架材料，将rh—BMP与CPC液相混合，再与兔骨膜成骨细胞及毛细血管内皮细胞复合培养，制成组织工程化人工骨。将人工骨移植到兔骶棘肌肌袋内，于术后4、8、12周进行Masson三色法组织学观察、扫描及透射电镜观察，观察其骨化及血管化情况。再将兔的桡骨制成骨缺损模型，用组织工程人工骨进行修复，于术后4、8、12周摄X线片检查、苏木精-伊红染色，观察骨缺损修复情况。结果肌袋内成骨实验，除4周时A组与B组的新骨形成面积百分比无显著性差异（P〉0．05）外，其余时间段两组的新生骨面积及新生血管面积相比具有显著性差异（P〈0．05）。修复骨缺损实验，A组新骨形成的速度、质量均明显优于B组。结论同种异体微小颗粒骨CPC复合物是一种良好的骨组织工程支架材料，有利于组织工程骨快速完成骨化及血管化。     

兔关节软骨下骨缺损骨移植后移植骨组织学变化实验研究

目的观察兔关节软骨下骨缺损后行骨水泥+自体骨或骨水泥+同种异体骨修复术后不同时间点移植骨组织学变化情况。方法选取30只成年健康新西兰大白兔,随机分为自体骨和同种异体骨组,每组各15只。模拟临床骨巨细胞瘤病灶刮除术,建立关节软骨下骨缺损动物模型,分别填充不同材料修复骨缺损。自体骨组填充骨水泥+自体骨,同种异体骨组填充骨水泥+同种异体骨,分别于术后4、6、8周取出植入骨。先行大体观察,然后通过HE染色切片观察其组织学变化。两组术后4、6、8周植入骨内成骨细胞和破骨细胞数量比较采用两因素方差分析,组间两两比较采用LSD法。P0.05为差异有统计学意义。结果术后4周自体骨组植入骨骨小梁开始吸收,植骨周围存在部分新生毛细血管和少量中性粒细胞,移植骨与宿主骨相邻的骨基质内可见少量骨细胞和破骨细胞,骨再生现象形成;同种异体骨组植入骨骨小梁未见明显吸收,植骨区可见肉芽组织,骨再生现象不明显。术后6周自体骨组植入骨骨小梁大部分被吸收,骨基质边缘新生毛细血管和新生成骨细胞增多,移植骨周边可见多核破骨细胞和排列不规则的编织骨,为成骨初期;同种异体骨组植入骨可见散在骨小梁及纤维结缔组织包绕死骨,存在溶骨现象,骨基质边缘可见少量新生毛细血管,破骨细胞及成骨细胞数量极少,无编织骨形成。术后第8周自体骨组植入骨骨小梁被吸收,可见大量新生骨、新生毛细血管和板层骨,骨基质边缘有排列较密集的成骨细胞,编织骨较术后6周时体积变小且排列逐步规整;同种异体骨组植入骨周围可见少量新生毛细血管,部分区域钙盐沉积较明显,少量新生骨小梁形成,其周围可见少量成骨细胞和破骨细胞,部分坏死钙化区内有板成骨形成。同种异体骨组术后第4、6、8周成骨细胞数量及术后第4、8周破骨细胞数量均低于自体骨组(P均0.05)。自体骨组和同种异体骨组术后第6、8周成骨细胞数量均高于术后第4周(P均0.05),自体骨组术后第8周成骨细胞数量高于术后第6周(P0.05)。自体骨组术后第8周破骨细胞数量均高于术后第4、6周(P均0.05),同种异体骨组术后第6周破骨细胞数量高于术后第4、8周(P均0.05)。结论关节软骨下骨缺损填充骨水泥+自体骨较填充骨水泥+同种异体骨植入骨区骨融合率高,成骨效能较好,术后不同时间点自体骨成骨细胞和破骨细胞表达较同种异体骨活跃。     

绝经后骨质疏松患者的缺钙和补钙的作用

２４例绝经后骨质疏松症患者分两组进行了钙平衡试验，年龄５６．３１±２．９９和５８．６６±４．２６，绝经年限１２．５±７．１１和１０．７７±４．５６，该组妇女平均食物钙摄入４２２．６ｍｇ／日，未补钙者平均负钙平衡１２．８８ｍｇ／日，补钙５００ｍｇ／日者平均正钙平衡３１８．２２ｍｇ／日，摄入钙的利用率占３３％，经２年单纯补钙，ＱＣＴ腰椎骨密度增高１３％，低钙摄入的妇女单纯补钙有一定预防骨质疏松的作用。     

Calcium supplements: Practical considerations

The preferable source of calcium is a balanced diet, but medicinal supplements are sometimes necessary if patients are to reach desired intakes. A divided dose regimen (4×/d; i.e., with meals and at bedtime) results in substantially greater absorption of a supplement than does l×/d dosing. However, differences in chemical solubility between supplement preparations are of little importance, with calcium carbonate preparations, for example, being absorbed as well or better than some much more highly soluble salts. Gastric acid is not necessary for absorption of even poorly soluble preparations, so long as they are taken with meals. Because typical patients exhibit a wide range of absorption efficiencies, it is desirable to assess absorption fraction before beginning a supplement regimen. (Some patients will need three times as large a dose as others to absorb the same amount of calcium.) Calcium intakes up to at least 62.5 mmol (2500 mg) are safe for virtually all patients.     

Comparison of calcium kinetics in man and the rat

The disappearance from the blood of intravenously-injected radiocalcium in man and the rat can be formally described by a two-termed exponential equation, which may be thought to have been generated by a two-compartment system in dynamic equilibrium with the environment. This paper reports an evaluation and comparison of the rate constants of such a system.In people over the age of 16, the mean system constant was 0.239 day^–1 (SE: 0.009) and the mean skeletal constant was 0.148 (SE: 0.008). The corresponding constants were 0.496 day^–1 (SE: 0.023) and 0.428 (SE: 0.019) for 4-month-old female Sprague Dawley rats and 0.744 (SE: 0.038) and 0.351 (SE: 0.021) for 10-month-old rats. All of the constants of the rats were significantly higher than those of man. There were no significant changes in man after the age of 16 years, whereas in the rat these constants changed with age.Differences in the constants can be explained by known differences in calcium metabolism and in the growth rates of the two species. Hence, a formal comparison of calcium kinetics in man and the rat yields information consistent with the interpretation that the two systems are comparable.Rate constants may prove useful for interspecies comparisons, as well as for studies of the regulation of calcium metabolism.These studies were supported in part by the National Institutes of Health (Grant No. AM 07983) and the National Dairy Council.     

In vitro dissolution of calcium carbonate preparations

Summary Calcium supplements are widely used for the treatment of osteoporosis. The bioavailability of these preparations is unknown. Because poor tablet dissolution accounts for a majority of drug bioavailability problems, we determined thein vitro dissolution at 30, 60, and 90 minutes of 27 commercially available calcium carbonate supplements using the method of the U.S. Pharmacopoiea. At 30 minutes, five preparations (18%) were more than 75% dissolved, four (15%) between 33 and 74%, and the remaining 18 (67%) were less than 33% dissolved. After 90 minutes, 17 (63%) of the preparations were less than 50% dissolved. Dissolution correlated negatively with the weight of filler (noncalcium carbonate material in the tablet) (r_s=−0.51,P<0.01) but not with tablet hardness or cost. Simila to previous studies, we also found no correlation of dissolution with the stated calcium content, chemical source of calcium carbonate (oyster shell or chemical precipitate), or retail source. We conclude that there is a wide range ofin vitro dissolution among the calcium carbonate preparations tested, and that the filler is an important determinant of the dissolution of these tablets. These results raise concern about the bioavailability of the calcium in these preparations and may have important implications for the therapeutic use of the various calcium carbonate supplements. This work was presented in part at the Tenth Annual Scientific Meeting of the American Society for Bone and Mineral Research, June 1988.     

Influence of accompanying anion on intestinal radiocalcium absorption

Summary To assess directly the effect of ionic dissociation on the bioavailability of calcium, we used the double isotope inverse convolution method to compare the absorption of calcium gluconate and calcium pyrrolidone carboxylate, an organic, highly dissociated salt. Two tests were performed at a 2 day interval, using in random sequence either salt as a carrier. Forty-eight subjects of various age and clinical condition were studied. The use of the more dissociated salt consistently and significantly increased fractional absorption in a rather constant ratio. Moreover, it slowed absorption in normal subjects whatever their age, and accelerated it in patients with chronic renal failure or osteoporosis, leading to inferences on the alteration of calcium absorption in these conditions.     

Classification of idiopathic hypercalciuric patients by isotopic calcium absorption: A comparison with oral calcium tolerance test

Summary To test the accuracy of calcium tolerance test in estimating calcium absorption, we have measured the radioactive calcium absorption (expressed as Fx) in 27 patients with IH and renal calcium stones. The results of this test were compared with those of a standard oral calcium tolerance test. Although only seven of nine AH patients displayed normal fasting calcium excretion, they all displayed Fx values above normal and a normal parathyroid activity. Conversely, only 5 of our 18 RH patients demonstrated a hyperabsorption of radioactive calcium and an elevation in iPTH and cAMP above normal limits, yet all of them showed an increased calciuric response to an oral calcium challenge. Calcium absorption was inversely related to iPTH (r=−082;P<0.001) and cAMP (r=−064P<0.05) in AH, but directly proportional to these parameters (r=0.62P<0.001 andr=0.46P<0.05, respectively) in RH patients. In view of these results, two ratios, iPTH/Fx and cAMP/Fx were used to discriminate between the two groups of patients. Both ratios were over normal limits in all RH patients and within normal range in all but one AH patient. Furthermore, no overlap was found between the two groups. Conversely, we were unable to completely separate AH from RH subjects on the basis of the oral calcium tolerance test, since in both groups the fasting and the absolute (or percentage) changes in urinary calcium, cAMP and blood iPTH levels following oral calcium loading, overlapped in each instance. The result of this study indicates that two indices, iPTH/Fx and cAMP/Fx, may prove particularly useful in differentiating AH from RH patients. Furthermore, since only a subgroup of patients with an abnormal calciuric response to an oral calcium load manifest an increase in calcium absorption, it is concluded that the calcium tolerance test overestimates calcium absorption in IH. Supported in part by Grant No. 5T32 AM0703310     

Comparison between the fractional isotopic calcium absorption and an oral calcium tolerance test

Summary In 27 subjects with several disorders of calcium metabolism, the fractional intestinal absorption of⁴⁷CaCl₂ was rather poorly correlated with the urinary output of calcium or with the maximal increase of serum calcium after an oral calcium load. Conversely, a good correlation was observed with the product of these parameters. We propose that this product be used as an estimate of intestinal calcium absorption when a radioisotopic method is not available.     

Oral calcium loading test and response to diuretics in normal taiwanese school children

To investigate possible mechanisms of increased urinary calcium excretion and increased prevalence of urolithiasis in 16- to 20-year-old children, oral calcium loading and diuretic tests were performed in 120 normal children in three age groups (7–8, 12–13, and 17–18 years of age). Urinary calcium/creatinine ratios and 24-h urinary calcium excretion were significantly increased following the oral calcium loading test in 17- to 18-year-olds compared with the two younger age groups. Oral furosemide resulted in increased urinary calcium excretion in the 17- to 18-year age group, while hydrochlorothiazide was less effective in reducing urinary calcium excretion in this age group. These results suggest that increased intestinal calcium absorption and decreased renal tubular reabsorption of calcium in 17- to 18-year-olds may be contributing factors in the increased prevalence of nephrolithiasis in older Taiwanese children.     

Caffeine and the calcium economy revisited

We report an analysis of data from 560 calcium balance studies carried out on 190 women aged 34.8–69.3 years at the time of study. The main purposes were to confirm a previously observed association between caffeine intake and calcium balance, and to attribute the association, if possible, to specific component(s) of balance. We found a caffeine relationship such that for every 6 fl oz (177.5 ml) serving of caffeine-containing coffee, calcium balance was more negative by 0.114 mmol/day (4.6 mg/day) (P<0.001). The relationship was localized to the input side of the balance equation, and both of its components (i.e. calcium intake and calcium absorption efficiency) were independently and inversely associated with caffeine intake. There was no evidence that the putative caffeine effect is confined to, or is greater among, subjects with low calcium intakes or those who are older or estrogen-deprived. The magnitude of the negative effect of caffeine on calcium balance suggests that it can be offset by increasing calcium intake by about 1 mmol (40 mg) for every 177.5 ml serving of caffeine-containing coffee.     

Comparison of the effect of gluconate, lactose, and xylitol on bone recalcification in calcium-deficient rats

The therapeutic value of three calcium absorption promoting carbohydrates, lactose, gluconate and xylitol, in bone calcification was evaluated in 7-week-old male rats which were fed on a semisynthetic Ca-deficient diet for 3 weeks. Lactose + CaCO₃, xylitol + CaCO₃, Ca-gluconate, or CaCO₃ alone were administered to the Ca-deficient rats for 2 weeks; the carbohydrate and Ca contents of the diets were 5% and 0.5%, respectively. The Ca-deficient rats showed a decrease in serum total Ca and ionized Ca²⁺ and in tibial Ca, Mg, P and density, with a concomitant increase in bone hydroxyproline concentration. Bone and serum tartrateresistant acid phosphatase activities were increased 2-fold and the serum 1,25(OH)₂D₃ level 5-fold. Smaller increases were found in serum calcitonin, PTH, alkaline phosphatase and osteocalcin levels. These changes (except calcitonin) were reversed by the administration of Ca and the carbohydrates. It was observed that all three agents improved the recalcification of bones compared with the effect of CaCO₃ alone. The effect of lactose and xylitol was superior to that of gluconate. These results suggest advantages in the use of xylitol in Ca-supplements.