补肾中药组方对去卵巢大鼠骨微结构的影响

目的研究补肾中药组方对去卵巢大鼠骨微结构的影响。方法通过卵巢摘除建立骨质疏松模型,研究不同剂量的补肾中药对去卵巢大鼠骨微结构的影响。结果光镜下观察高剂量补肾中药组方能改善去卵巢大鼠的骨小梁的分布、排列、之间的连接、厚度及间隙等组织学表现。组织计量学表明高、中剂量中药组能提高骨小梁TBV%和MTT(与OVX组比较P<0.05),这种功能与尼尔雌醇作用相当(P>0.05),低剂量中药组能提高骨小梁TBV%(与OVX组比较P<0.05)。结论补肾中药具有改善去势大鼠骨微结构的功能。     

Venous pressure and bone formation

We have studied the relationship of increased venous pressure to formation of periosteal new bone in growing dogs. The methods used were measurement of fluid spaces in bone by steady-state tracer techniques, measurement of venous pressure, and measurement of the rate of periosteal new bone formation by histomorphometry. The results of paired comparisons--test versus control tibia--show an increase in venous pressure, a decrease in vascular space, an increase in extracellular fluid space (sucrose space), and an increase in periosteal new bone formation on the side of increased venous pressure. The data support the hypothesis that an increase in venous pressure results in an increase in passage of fluid from capillary to bone matrix. Increased extravascular perfusion could be a factor in increasing periosteal bone formation. This flux of fluid may increase streaming potentials in bone and these act as a signal to bone cells to increase bone formation.     

Renal osteodystrophy and biochemical markers of bone turnover

Renal osteodystrophy which associates with high rates of morbidity in patients with chronic renal failure is not an uniform metabolic bone disease. Although bone histomorphometry is the most reliable diagnostic method, several biochemical markers have been proposed for evaluation of bone turnover in hemodialysis patients. This review assesses the value and the limitations of several serum markers of bone metabolism in patients with chronic renal failure.     

Salmon calcitonin prevents cyclosporin-A-induced high turnover bone loss

Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.     

Severe bone defects and reduced mineralization caused by massive metallosis after total knee arthroplasty: histopathologic and bone morphometric findings

We encountered a patient who developed metallosis after total knee arthroplasty (TKA), resulting in loosening of the implant, bone resorption, reduced bone formation, and fracture. The implant was replaced with a NexGen modular revision TKA system after autologous bone and hydroxyapatite granule grafting. Histopathologic examination showed accumulation of metallic debris and tartrate-resistant acid phosphatase-positive cells around the trabecular and cortical bone. Examination of hard tissue specimens showed a reduced bone volume (determined by bone histomorphometry) and an increase of all osteoid parameters, indicating disturbance of mineralization in addition to increased bone resorption.     

Bone mineral loss,bone histomorphometry and vitamin D metabolism in patients with rheumatoid arthritis on long-term glucocorticoid treatment

Summary Long-term glucocorticoid treatment might interfere with the vitamin D metabolism. The serum concentrations of 25-OHD were significantly reduced whereas the circulating levels of 1,25-(OH)₂D were normal in 50 patients with rheumatoid arthritis on long-term treatment with small doses of prednisone. The bone mineral content of the forearm was significantly reduced, but the degree of bone loss did not correlate with duration of treatment or dose of prednisone given. Quantitative bone histomorphometry was performed in 18 patients. Apart from a significant correlation between serum 25-OHD and the fractional trabecular bone volume, no relationships were observed between bone histomorphometry and vitamin D metabolites or serum iPTH. The results indicate that the bone loss was due to a decreased osteoblastic activity rather than to an impaired vitamin D metabolism.     

The pathophysiology of bone loss

Aging is associated with a decline in cancellous and cortical bone mass and with a deterioration of microarchitecture in both skeletal compartments. These changes are more marked in women than men and are exaggerated in patients with fracture. With the insight gained from histomorphometry, we are beginning to understand the cellular mechanisms that underlie these changes. We recognize that deterioration in microarchitecture contributes to fracture risk, independently of bone mass. Techniques to assess bone microarchitecture noninvasively in a clinical setting are currently under development; it is likely that advances in this area will improve our ability to identify and manage patients with osteoporosis in the not too distant future.     

Severe bone defects and reduced mineralization caused by massive metallosis after total knee arthroplasty: histopathologic and bone morphometric findings

Abstract

We encountered a patient who developed metallosis after total knee arthroplasty (TKA), resulting in loosening of the implant, bone resorption, reduced bone formation, and fracture. The implant was replaced with a NexGen modular revision TKA system after autologous bone and hydroxyapatite granule grafting. Histopathologic examination showed accumulation of metallic debris and tartrate-resistant acid phosphatase-positive cells around the trabecular and cortical bone. Examination of hard tissue specimens showed a reduced bone volume (determined by bone histomorphometry) and an increase of all osteoid parameters, indicating disturbance of mineralization in addition to increased bone resorption.     

Serum and urinary markers of bone remodeling: assessment of bone turnover

It appears that at present, serum BGP is the one bone protein that has the most promise for assisting in the diagnosis and management of high turnover metabolic bone disease states. If further studies confirm its usefulness in osteoporosis as a predictor of rapid bone loss without the need for bone biopsy, this serum marker will then not only allow early detection but also an appropriate choice of therapy in osteoporosis, i.e. the use of specific inhibitors of high turnover states such as estrogen, calcitonin, or bisphosphonates. In addition, it may also permit more accurate follow-up of patients suffering from diseases such as primary hyperparathyroidism after surgery. In low turnover osteoporosis, it may also serve a useful function to observe whether the osteoblast can be stimulated to enhance bone formation with therapies such as fluoride, anabolic steroids, PTH, etc. As yet, additional measurements, such as bone histomorphometry and other bone mineral markers, are required for definitive diagnosis. Hopefully, the availability of specific well-characterized antibodies against BGP may define its role more accurately. Recently, several other new bone proteins have been identified but at present they have very limited clinical application. Future studies into the structure-function relationship of these bone proteins may identify those markers which will be most relevant to the diagnosis and treatment of metabolic bone disease.     

Methods for assessing bone quality

Bony quality, such as trabecular architecture and bone turnover, has conventionally been estimated by histomorphometric analysis of bone biopsy specimen. In recent years, these information can be obtained noninvasively by using CT, MRI, and biochemical markers. In the examination of bone specimen, several physical methods are newly utilized to assess the bone quality, providing detailed information on bone mineral and matrix protein.     

Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice

Providing enough calcium for milk production stresses calcium homeostasis in lactating mammals. A universal response to these demands for calcium appears to be the mobilization of maternal skeletal reserves, and bone loss during lactation has been well documented. However, the regulation of calcium and skeletal metabolism during lactation remains enigmatic. Our study was designed to examine mineral and bone metabolism in lactating mice. We found that mice lose bone rapidly at all sites during lactation. Bone mineral density as determined by dual-energy x-ray absorptiometry was 20 to 30% lower at the spine, femur, and total body in lactating compared with either age-matched virgin or pregnant mice. The decrease in bone mineral density was accompanied by dramatic reductions in bone volume and changes in trabecular architecture. Bone loss was also accompanied by increases in bone turnover as determined by biochemical markers and histomorphometry. PTHrP levels were elevated during lactation and correlated positively with markers of bone resorption and negatively with bone mass at all sites. Estrogen levels were low during lactation and correlated negatively with bone resorption markers. Finally, estrogen and pamidronate treatment lowered rates of bone resorption to baseline virgin levels and mitigated, but did not prevent, bone loss. These data suggest that the combination of estrogen deficiency and elevations in circulating PTHrP during lactation act to stimulate bone resorption and promote bone loss.     

Mechanism of action of estrogen on intramembranous bone formation: regulation of osteoblast differentiation and activity.

Dynamic bone histomorphometry, [3H]thymidine radioautography, and Northern analysis for bone matrix proteins and insulin-like growth factor-I (IGF-I) were performed in calvariae of ovariectomized (OVX) and estrogen-treated OVX rats. Treatment of OVX rats with diethylstilbestrol (DES) for 2 weeks reduced the periosteal mineral apposition rate, osteoblast number, and osteoblast size in calvarial periosteum. DES treatment also reduced the number of preosteoblasts in the S phase of the cell cycle, suggesting that the decrease in osteoblast number was due in part to inhibition of proliferation of osteoprogenitor cells. One week after ovariectomy, there were small increases in mRNA levels for pre pro-alpha 2 (I) subunit of type I collagen (collagen), osteocalcin, and osteonectin and a large increase in the mRNA level for IGF-I. DES treatment resulted in rapid decreases (3 h) in the mRNA levels for osteonectin, osteocalcin, and IGF-I. In contrast, mRNA levels for collagen were virtually unchanged after short term DES treatment. Uterus and liver served as positive and negative control tissues, respectively, for the effects of DES on IGF-I mRNA levels in OVX rats; mRNA levels were increased in uterus and decreased in liver after hormone treatment. We conclude from these studies that estrogen reduces periosteal bone formation by inhibiting both the differentiation and activity of osteoblasts. Furthermore, down-regulation of mRNA levels for IGF-I and bone matrix proteins precedes the changes in dynamic bone histomorphometry.     

Effects of growth hormones on bone formation and resorption in rainbow trout (Oncorhynchus mykiss), as examined by histomorphometry of the pharyngeal bone.

Effects of salmon and eel growth hormones (GHs) on bone metabolism in rainbow trout (Oncorhynchus mykiss) were studied using histomorphometry of their pharyngeal bones. When salmon GH (sGH) was injected intraperitoneally at a dose of 0.01 or 0.1 microgram/g/week for 10 times into fed trout, body growth in both length and weight was accelerated. Formation and resorption of bone were enhanced only by the higher dose of sGH. When a cholesterol pellet containing recombinant eel GH (reGH-pellet) was implanted subcutaneously into starved trout for 1 week (37 micrograms reGH/18 g fish), formation and resorption of bone increased, although activity of bone formation was low. The results indicate that the GHs increased both formation and resorption of bone, regardless of the nutritional status of the fish.     

Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings

BACKGROUND: The process of bone remodelling is disturbed in the development of osteoporosis. OBJECTIVE: To investigate if proteins in osteoporotic bone are modified by advanced glycation end products (AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings. METHODS: Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and N(epsilon)-carboxymethyllysine. RESULTS: Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs. CONCLUSIONS: It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling.     

去卵巢大鼠骨形成参数和血清碱性磷酸酶的相关性研究

目的　观察去卵巢大鼠骨组织形态计量学参数和血清碱性磷酸酶 (ALP)之间的相关性。方法　 4个半月龄 SD大鼠双侧卵巢去除术后预防用药 90 d。用骨组织形态计量学方法测定大鼠胫骨组织近端松质骨形态计量学参数 ,并测定血清 ALP含量。结果　去卵巢组大鼠血清 ALP含量增加 ,骨形成参数增加 (P<0 .0 5)。去卵巢组和预防用药组骨形成参数与 ALP测量值之间有相关性 (P<0 .0 5)。去卵巢组的骨组织形态计量学参数与 ALP测量值之间的相关系数大于预防用药组。结论　去卵巢大鼠血清 ALP与骨形成参数之间存在相关性 ,这种相关性在给药后下降。     

雌激素对老年雄性大鼠植入骨新形成的影响

目的　研究雌激素对老年雄性哺乳动物的植入骨的新生骨骨面积及对全身骨代谢的影响。方法　骨基质骨片植入老年雄性大鼠 ,观察注射雌激素组、雄激素组和对照组骨组织计量学、骨生物力学、尿脱氧吡啶啉 /肌酐 (Dpd/Cr)比值 ,以及血和尿的钙、磷等的变化。结果 ( 1)新生骨骨面积 :雌激素组和雄激素组均比对照组明显增高 (P <0 0 5 ) ,雌激素组和雄激素组之间差异无显著性。 ( 2 )破骨细胞数 :雌激素组 ( 5 5± 3)个 /mm2 和雄激素组 ( 5 3± 3)个 /mm2 均显著高于对照组 ( 40± 3)个 /mm2 (P≤ 0 0 0 2 ) ,雌激素组和雄激素组之间差异无显著性。 ( 3)尿Dpd/Cr比值 (mmol/mol) :注药后5周 ,对照组 (注射溶剂 )比注药前明显升高 ( 198± 2 0vs 10 4± 7) ,雌激素组 ( 114± 16 )和雄激素组 ( 118± 19)均比对照组 ( 198± 2 0 )明显减低 ,与注药前无明显差异 ,雌激素和雄激素组之间差异无显著性。结论　雌激素和雄激素不仅能刺激老年雄性大白鼠植入骨的新生骨骨面积增加 ,也能抑制全身骨骼的骨吸收速率。本实验条件下 ,这两方面的影响 ,雌激素和雄激素组之间未见明显差异     

Metabolic bone disease in asymptomatic men after partial gastrectomy with Billroth II anastomosis

We sought to determine whether gastric surgery might be associated with metabolic bone disease in a well-characterized population, and if so to explore its etiology. Sixteen asymptomatic middle-aged men who had had partial gastrectomy with Billroth II anastomosis but no other risk factors for metabolic bone disease were compared with unoperated healthy controls. Studies included a dietary survey, biochemical tests of bone and mineral metabolism, radiographs of the spine, determinations of bone mineral content, and bone histomorphometry. The gastric surgery subjects exhibited frequent vertebral fractures and an unusual constellation of bone abnormalities characterized by decreased bone mineral content and hyperosteoidosis without evidence of osteomalacia. Although serum immunoreactive parathyroid hormone and 25-hydroxyvitamin D levels were not different, 1,25-dihydroxyvitamin D levels were significantly higher (p = 0.037), and 24,25-dihydroxyvitamin D levels were significantly lower (p less than 0.0001) in subjects than in controls. Partial gastrectomy with Billroth II anastomosis may be associated with asymptomatic but clinically important metabolic bone disease. The pathophysiology is uncertain, but appears to involve alterations in vitamin D metabolism.     

雌激素对大鼠去卵巢后白细胞介素-6介导的骨吸收的影响

目的观察雌激素对去卵巢大鼠骨髓细胞白细胞介素6(IL6)、IL6受体、gp130基因表达以及骨髓源性破骨细胞形成的影响。方法健康3月龄雌性SD大鼠72只,随机平均分为假手术对照组、去卵巢组和雌激素组(苯甲酸雌二醇02mg/kg,皮下注射,每周1次)。分别于术后2、4、6、12周每组各取6只大鼠骨髓细胞作细胞培养和提取RNA。培养第6天计数破骨细胞数,第12周取左侧胫骨作骨形态计量学检测。结果骨形态学显示去卵巢后出现骨吸收亢进,雌激素对其有抑制作用。去卵巢后2周,去卵巢组破骨细胞形成数即多于对照组(1450±169对901±141,P<005),骨髓细胞IL6和IL6受体mRNA表达均显著升高(P<005,P<001),第4～6周,上述改变达高峰,至第12周仍呈有意义增高;从2～12周,上述各指标雌激素组均明显低于去卵巢组(P<005,P<001)。各组未见gp130基因表达水平有明显变化。结论雌激素可以抑制大鼠去卵巢后骨髓源性破骨细胞的生成,这一效应可能与其抑制骨髓细胞在去卵巢后过度表达IL6、IL6受体基因有关。