异种骨基质明胶(BMG)诱导成骨活性的实验研究

本文按着 Urist 方法制备了人、兔、猪和羊四种骨基质明胶(BMG),分别将其植入25只成年 SD 大鼠的胸部和股部肌肉,在手术的第2、4、6和8周后,通过光学显微镜观察各种 BMG 在肌肉内的免疫排斥反应和诱导成骨活性。结果表明:异种 BMG 具有一定的诱导成骨能力。但在 BMG 周围亦出现程度不同的排斥反应。本文认为,进一步降低 BMG 的抗原性,提高其诱导成骨活性,对于异种 BMG的临床应用将具有重要意义。     

Effect of 1α-hydroxyvitamin D3 on bone metabolic disorders in gastrectomized rats

The effect of 1α-hydroxyvitamin D₃ (1α(OH)D₃) on the metabolic bone disorders developed in gastrectomized rats were investigated biochemically and histomorphologically. 1α(OH)D₃ was suspended in 0.2 % Triton-X-100 aqueous solution after dissolving in a very small amount of ethanol, was given orally to the rats for 10 weeks. The sham operated animals and the gastrectomy control animals received the vehicle alone. Gastrectomy was followed by the development of the metabolic bone disorders after 10 weeks of observation. This was characterized by reduction in ash content of the femur and histologically by a disappearance of the trabecular bone in tibial metaphysis. Decrease Ca absorption from the intestines was demonstrated by a radiotracer technique. Biochemical studies showed significant decreases in serum 25(OH)D concentration in gastrectomized rats. These findings suggest that gastrectomy partially impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorders in rats. The administration of 1α(OH)D₃ increased dose-dependently serum calcium and Ca absorption from the intestine and prevented the development of bone metabolic disorders histomorphologically.     

Bony allografts and prosthetic replacement of the acetabular aspect of the hip

Summary 51 cases of repeat hip replacement have been reviewed, using allografts for acetabular bone loss, stages 2 and 3 (27 lyophilised and 24 deep-frozen). Mean follow-up was 4 years. Loosening was the reason for intervention; 14% of cases were septic. Massive grafts were used in 75% of cases and smaller grafts in 25% of cases. In addition a reinforcement ring was necessary in 75% of cases. Merle d'Aubigné's rating scale was used to assess results. The radiologic assessment score was that of Gross and De Lee.There was no difference between lyophilised and deep-frozen grafts. Clinical scores found 55% of excellent results; 11% were poor, the rest were good or fair. Stability was more troublesome than pain. Radiologic screening showed union between graft and host in 53% of cases but in 41% there was incomplete fusion. In the non-weight-bearing area bone lysis appeared in 14 cases out of 20. Five cases were complete failures; four of these were infected and were reoperated, the bone-graft acting as a foreign body.To date, we have no better bone replacement material than allografts. Fixation of the graft must be secure. An infected hip is not a good indication for this type of operation. Clinical results are satisfactory in more than 80% of cases, although 40% of grafts seem to be incompletely integrated.     

Decreased Bone Mass and Strength in Ovariectomized Cynomolgus Monkeys (Macaca fascicularis)

Agents for prevention or treatment of osteoporosis must now be tested in a large animal species that exhibits bone remodeling. Ovariectomized, nonhuman primates provide one such model, and they consistently develop osteopenia accompanied by high bone turnover rates. The goal of this study was to further characterize this model, and particularly to determine the effect of ovariectomy on bone strength in vertebrae and femoral necks. Longitudinal evaluations of spinal bone mass and serum markers of bone turnover were performed in 19 sham-ovariectomized (SHAM) and 18 ovariectomized (OVX), domestically reared cynomolgus monkeys, aged >9 years. OVX monkeys lost bone relative to both baseline values and SHAM controls. Serum markers of bone turnover were increased by OVX. After 72 weeks, both vertebral bone compressive strength and femoral neck breaking strength were significantly decreased in OVX animals compared with SHAM. Ovariectomized cynomolgus monkeys, like postmenopausal women, develop accelerated bone loss, increased bone turnover, and reduced bone strength, and provide a suitable large animal model for efficacy studies with agents for prevention or treatment of osteoporosis. Received: 24 June 1996 / Accepted: 3 September 1996     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

骨与关节肿瘤和瘤样病变1084例统计分析

目的：分析青海高原地区骨与关节肿瘤及瘤样病变的发病情况。方法：对１９６３～１９９５年１０月的１０８４例骨与关节肿瘤及瘤样病变进行了统计分析。结果：良性骨肿瘤７２２例（６６．６１％），恶性骨与关节肿瘤２４９例（２２．９７％），瘤样病变１１３例（１０．４２％），良、恶性肿瘤之比为２．９∶１，男女之比为１．２２∶１，好发年龄为１１～３０岁，好发部位为胫骨（２７．３％），其次为股骨（２１．８％）。良性骨肿瘤以骨软骨瘤（５４．４３％）、软骨瘤（２１．１９％）、骨巨细胞瘤（９．９７％）多见。原发恶性骨肿瘤以骨肉瘤（３３．３％）、软骨肉瘤（１０．８５％）、骨髓瘤（１０．０５％）多见。瘤样病变则以孤立性骨囊肿（４６．０１％）和骨纤维结构不良（３０．９７％）多见。结论：本组结果与国内文献对比有许多相似之处，但良性骨肿瘤与恶性骨肿瘤之比与国内文献有较大不同，可能与高原环境有关。     

MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration

 Objective: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. Design and patients: The patients consisted of two groups: group 1 comprised 94 healthy adults (18–86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n=20) or breast carcinoma (n=10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n=20) and clinical parameters (n=10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/α: 68 ms/6 ms 75°) were performed in 10 controls with normal bone marrow. Results and conclusion: Contrast material enhancement in healthy persons can vary greatly (range 3–59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson’s correlation, P<0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20–50 vol%) and high-grade (biopsy >50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P<0.001). Low-grade (biopsy <20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.     

人骨髓间充质干细胞体外分化为雪旺样细胞的方法

目的 :建立人骨髓间充质干细胞体外向雪旺样细胞定向诱导分化的方法。方法 :取健康人骨髓血标本 ,利用percoll(密度为 1.0 73 g·ml-1)分离骨髓单个核细胞 ,在DMEM LG + 10 % (体积分数 )FBS中培养 ,通过流式细胞术对培养细胞进行表型测定 ,对第 2、3、5、8代间充质干细胞进行定向诱导分化 ,用单抗S 10 0、神经胶质纤维酸性蛋白 (glialfibrillargacidicprotein ,GFAP) ,通过免疫组化方法对诱导的细胞进行鉴定。 结果 :经 percoll分离的间充质干细胞可传 16代 ,细胞数增加了大约 6× 10 7倍。流式细胞术结果显示 :percoll分离出来的未经培养的细胞 ,其CD2 9+CD4 4 +CD3 4 -CD4 5 -细胞数为 3 2 .4 7%± 3 .4 9% ,而培养后贴壁细胞中CD2 9+CD4 4 +CD3 4 -CD4 5 -细胞数为 94 .3 8%± 1.5 0 %。诱导后免疫组化染色结果显示 :由 β ME +bFGF预诱导、β ME +bFGF诱导的S 10 0阳性细胞最多 ,可达 90 %± 4 % ,GFAP阳性细胞为 2 1%± 5 %。结论 :人骨髓中间充质干细胞能定向诱导分化成雪旺样细胞。     

应力松弛接骨板对骨几何形态和力学性能影响的实验观察

作者采用粘弹性材料制成垫圈置于接骨板螺孔与螺丝钉之间，构成应力松弛接骨板系统。实验证实，有垫与无垫接骨板在固定早期对模拟骨的应力遮挡作用相同，固定８周后垫圈出现明显变形和破坏，使有垫接骨板的应力遮挡率从第１０周起明显低于无垫接骨板。有垫接骨板固定的胫骨骨质疏松明显轻于无垫组，固定２０周后，有垫组的胫骨髓腔径明显小于无垫组，骨皮质厚度和胫骨抗弯强度均明显大于无垫组（Ｐ＜０．０５～０．０１）。说明应力松弛接骨板系统早期具有与坚强接骨板相同的固定作用，后期其应力遮挡效应可逐渐减小，避免严重的骨质疏松和骨力学性能下降。     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997