Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (±standard deviation) age of the patients was 99 (±63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.     

Desmoplastic fibroma of bone. An ultrastructural study

The ultrastructure of three cases of desmoplastic fibroma of bone is presented. The lesion is principally characterized by myofibroblasts admixed with lesser numbers of fibroblasts and primitive mesenchymal cells. Thus, the cellular composition is similar to that described in a variety of nonneoplastic proliferative processes of soft tissue. It is postulated that the myofibroblastic proliferation develops in response to unknown factors acting on marrow fibroblasts or primitive mesenchymal cells.     

Erythropoietin resistance as a result of oxalosis in bone marrow

Anemia is an important cause of morbidity in patients suffering from chronic renal failure, and erythropoietin is a milestone of anemia treatment. Various factors may cause erythropoietin resistance. Herein, we describe the case of 32-year-old man who presented with anemia and weakness. He developed progressive renal failure secondary to recurrent kidney stones. One year before admission, he developed anemia for which he had been treated with erythropoietin. However, the anemia persisted. Examination of bone marrow biopsy specimen showed that the marrow was extensively replaced with oxalate crystals and fibrous connective tissue with severe decrease of hematopoietic cells. To the best of our knowledge, our patient represents the first case in the literature describing the association between the oxalate deposition and EPO resistance.     

Primary bone oxalosis: the roles of oxalate deposits and renal osteodystrophy

Primary oxalosis is a rare congenital disorder. The excessive oxalate biosynthesis induces deposits in many organs, particularly in kidney and bone. The late onset of primary oxalosis is reported in a 50-year-old man. His chronic renal failure was treated by maintenance hemodialysis for 3 years. He then developed a diffuse bone disease with osteosclerosis and roentgenographic features of hyperparathyroidism. A parathyroidectomy was performed, with debatable improvement of bone lesions. Laboratory results and histologic and histomorphometric studies before and after parathyroidectomy suggest a double histopathogenetic mechanism for this bone disease: renal osteodystrophy and massive bone oxalate deposits. Such deposits may induce both a heterogeneous osteosclerosis with dense metaphyseal bands and histologic bone lesions similar to those of hyperparathyroidism. The crystalline deposits induce in the bone tissue a granulomatous macrophagic reaction. These macrophages are unable to phagocytize the crystals and may be involved in active bone resorption. Bone lesions of oxalosis occur in patients with chronic renal failure, and hyperparathyroidism has a worsening role.     

Intimal hyperplasia and neointima: An ultrastructural analysis of thrombosed grafts in humans

The distal anastomoses of thrombosed saphenous vein (11), bovine (4), Dacron (7), and polytetrafluoroethylene (PTFE) (27) grafts removed en bloc during reoperation or amputation were studied with light microscopy, scanning electron microscopy, and transmission electron microscopy. Analysis of the ultrastructures of the distal anastomostic regions was done to characterize morphogenesis of intimal hyperplasia and neointimal proliferation. Complete reendothelialization occurred in all vein grafts. In bovine heterografts, there were isolated areas of endothelia. Thrombosed PTFE grafts were lined with gelatinous, proteinaceous material with no consistent organized cellular pattern. In contrast, laminated fibrous tissue produced by fibroblasts lined the Dacron grafts. Intimal hyperplasia was found in 6 of 11 vein grafts and in all prosthetic grafts examined. Regardless of the type of graft used, intimal hyperplasia was found predominantly at the heel of the graft and on the floor of the artery. Beneath the endothelia, collagenous ground substance and myofibroblasts mixed with smooth muscle cells were seen, characterized by pyknotic nuclei, reduced cytoplasm/nuclei ratio, and loss of cytoplasmic organelles. Endothelialization occurred exclusively in vein grafts. Prosthetic grafts lacked endothelia, with the neointima consisting of fibroblasts and fibrous matrix. In intimal hyperplasia, two forms of smooth muscle cell pathomorphogenesis were recognized. Formation of myofibroblasts induced medial fibroplasia, whereas degeneration of muscle cells progressed to medial necrosis. Smooth muscle cells seem to play a role not previously recognized in the pathogenesis of graft failure.     

Calcium oxalate deposition in growing bone: Anatomical and radiological study in a case of primary oxalosis

A combined radiological, histological, and crystallographical study of bone, primarily the inferior femur, taken at autopsy from a 9 year old female with primary oxalosis, is reported. The essential feature is the deposition of calcium oxalate monohydrate (whewellite) crystals, inducing a foreign body reaction and bone remodelling. Synovial and cartilage surfaces are not involved. The changes occur primarily at sites of previous or present growth and seem to be related to the reaction of tissue to the deposition of blood-borne crystals. The radiological changes may be explained in part by the deposition of crystals at Harris' lines of growth arrest. Cancellous bone also shows changes similar to those observed in renal osteodystrophy.     

Scanning electron microscopy and X-ray diffraction studies of human bone oxalosis

Summary Postmortem scanning electron microscopy of human phalanges in a chronic uremic hemodialysis patient with hyperparathyroidism showed the presence of confluent abnormal rounded formations with a radial rosette-like crystalline pattern in the diaphysis as well as in the epiphyseal part of the bones. These fan-shaped configurations were found either as individual formations within bone trabeculae or as numerous aggregated crystalline deposits replacing large parts of the bone structure. The microdissected content of such large areas submitted to X-ray diffraction analysis revealed the predominant presence of calcium oxalate monohydrate or whewellite with some traces of hydroxyapatite. Oxalate titration analysis indicated the presence of 25% of oxalate, corresponding to 45% in weight of whewellite.     

Bone regeneration 6 years after impaction bone grafting: a PET analysis

BACKGROUND: Impacted morselized bone allograft in revision total hip arthroplasty for prosthetic loosening has gained widespread clinical use during the last decades. The clinical results are good but little is known about the bone regeneration in the graft. PATIENTS AND METHODS: 5 patients were revised with impaction of morselized frozen allograft and a cemented total hip arthroplasty (THA) due to loosening and osteolysis of a primary THA. We used positron emission tomography ([18F]-fluoride PET) to produce quantitative images of new bone formation in the allograft surrounding the femur stem 6 years after surgery. RESULTS: The 5 patients had previously been analyzed by [18F]-fluoride PET during the first year after surgery (S?rensen et al. 2003). During the first year, bone formation proceeded through the graft layer and reached the cement layer surrounding the femoral stems. The clinical and radiographic results were excellent at 6 years. PET analyses at 6 years showed that the bone metabolism was significantly reduced in most areas of the proximal femur, compared to the elevated activity during the first year after surgery, and also normalized compared to the contralateral healthy femur. Graft bone metabolism distal to the stem tip remained slightly increased. Small patchy areas of increased uptake remained along the proximal femoral stem, probably reflecting small volumes of fibrous healing. INTERPRETATION: The metabolism of the allografted bone had normalized compared to native bone, indicating full regeneration throughout the graft--and a good long-term prognosis for implant fixation.     

Secondary alveolar bone grafting: An outcome analysis

OBJECTIVE

To review the outcome of secondary alveolar bone grafting in unilateral and bilateral cleft lip and palate.

DESIGN

A surgeon’s experience, by retrospective chart review, of 70 consecutive patients at a tertiary care centre.

OUTCOME MEASURE

Periapical radiographs were taken at least six months after secondary alveolar bone grafting. The Enemark grading system was used to stratify graft-take.

RESULTS

In unilateral clefts, 33% were level 1, 36% were level 2, 20% were level 3 and 11% were level 4. In bilateral clefts, 29% were level 1, 50% were level 2, 14% were level 3 and 7% were level 4. There was no statistically significant difference between the level of take and the type of cleft. Complications encountered were infection (n=3), fistula (n=3), pain (n=4) and bone graft exposure that led to failure (n=2). Two patients required reoperation for bone grafting.

CONCLUSIONS

The iliac crest is a good donor site with excellent results and minimal morbidity.     

An ultrastructural analysis of vascular leiomyoma of the bladder

We report a case of vascular leiomyoma of the bladder in a 62-year-old man. To our knowledge, this is the first ultrastructural study published on vascular leiomyoma of the bladder. The tumoral cells reproduced the smooth muscle cells. The vascular structures corresponded to capillaries and arterioles. We consider that the vascular component is not tumoral and its origin is related to mast cells.     

Extracellular matrix mineralization in murine MC3T3-E1 osteoblast cultures: An ultrastructural,compositional and comparative analysis with mouse bone

Bone cell culture systems are essential tools for the study of the molecular mechanisms regulating extracellular matrix mineralization. MC3T3-E1 osteoblast cell cultures are the most commonly used in vitro model of bone matrix mineralization. Despite the widespread use of this cell line to study biomineralization, there is as yet no systematic characterization of the mineral phase produced in these cultures. Here we provide a comprehensive, multi-technique biophysical characterization of this cell culture mineral and extracellular matrix, and compare it to mouse bone and synthetic apatite mineral standards, to determine the suitability of MC3T3-E1 cultures for biomineralization studies. Elemental compositional analysis by energy-dispersive X-ray spectroscopy (EDS) showed calcium and phosphorus, and trace amounts of sodium and magnesium, in both biological samples. X-ray diffraction (XRD) on resin-embedded intact cultures demonstrated that similar to 1-month-old mouse bone, apatite crystals grew with preferential orientations along the (100), (101) and (111) mineral planes indicative of guided biogenic growth as opposed to dystrophic calcification. XRD of crystals isolated from the cultures revealed that the mineral phase was poorly crystalline hydroxyapatite with 10 to 20 nm-sized nanocrystallites. Consistent with the XRD observations, electron diffraction patterns indicated that culture mineral had low crystallinity typical of biological apatites. Fourier-transform infrared spectroscopy (FTIR) confirmed apatitic carbonate and phosphate within the biological samples. With all techniques utilized, cell culture mineral and mouse bone mineral were remarkably similar. Scanning (SEM) and transmission (TEM) electron microscopy showed that the cultures had a dense fibrillar collagen matrix with small, 100 nm-sized, collagen fibril-associated mineralization foci which coalesced to form larger mineral aggregates, and where mineralized sites showed the accumulation of the mineral-binding protein osteopontin. Light microscopy, confocal microscopy and three-dimensional reconstructions showed that some cells had dendritic processes and became embedded within the mineral in an osteocyte-like manner. In conclusion, we have documented characteristics of the mineral and matrix phases of MC3T3-E1 osteoblast cultures, and have determined that the structural and compositional properties of the mineral are highly similar to that of mouse bone.     

An ultrastructural study of bone cells: The occurrence of microtubules,microfilaments and tight junctions

Bone cells of calvaria from young mice were studied at the ultrastructural level. Microtubules were demonstrated in both osteoblasts and osteocytes in the cell body, but not in the cell processes. Instead, the cytoplasm of cell processes is filled with bundles of 50 to 70 Å microfilaments, running parallel to the long axis of the process. Where two cell processes meet, the cell membranes form a tight junction. These junctions are found between osteocytes, between osteocytes and osteoblasts, and between bodies of osteoblasts on the cell surface. The cell processes usually meet side-to-side, thus forming an extended tight junction. The junctions between osteoblasts are short and are believed to be spot-like. Inside the bone scarcely any extracellular space is visible. The likelihood of intracellular transport is discussed.     

Bone hyperresorption in bone metastases

MECHANISMS OF BONE LOSS: In patients with bone metastases, bone loss is the consequence of a dissociated process combining excessive bone resorption and inhibited bone formation. This destructive process occurs in response to soluble factors secreted by metastatic cells (PTH-rP, cytokines) which activate osteoclasts. These cells also secrete proteases (cathepsin K, metalloprotease MMP-9) which degrade the bone's collagen network. Excessive bone resorption is also favored by direct interaction between the metastatic cells and stromal cells in the bone marrow in response to the activation of membrane receptors (integrins a4 beta 1 and a4 beta 7). Finally, metastatic cells secrete non-identified soluble factors capable of inhibiting osteoblast proliferation in vitro. EFFECT OF BONE LOSS ON THE METASTASIS: Bone is a major reservoir of growth factors (mainly TGF beta and IGF-1). Positive feedback mechanism operates at the site of osteolysis where TGF beta released by bone tissue induces a paracrine stimulation of PTH-rP production by metastatic cells. IGF-1 released by the bone favors grow of metastatic cells present in the marrow. In addition, IGF-1 as well as collagen proteolytic fragments may stimulate recruitment of new metastatic cells at the site of the bone metastasis. This creates a vicious circle of mutual stimulation between bone destruction and tumor proliferation.     

纳米羟基磷灰石修复兔颌骨缺损的骨密度分析

目的 研究纳米羟基磷灰石修复颌骨缺损的可行性.方法 将24只健康的中国哈尔滨大白兔随机分为实验组及对照组.在下颌骨体部制作面积为1.5 cm×1.5 cm的骨缺损,实验组以纳米羟基磷灰石修复,对照组以普通羟基磷灰石修复,于修复后第1、4、8、12周分别处死,X线拍片,采用图像分析处理程序进行骨密度分析,并进行统计学处理.结果 骨缺损修复后,实验组骨密度随时间的延长逐渐增大,直至与正常的骨密度接近并趋于稳定;对照组骨密度随时间的延长逐渐减小.实验组与对照组比较,差异有显著意义(P＜0.01).结论 纳米羟基磷灰石修复骨缺损,骨成熟较快,是修复骨缺损的良好材料.     

富血小板血浆修复犬牙种植体周围骨缺损的骨密度分析

目的 研究富血小板血浆(PRP)修复犬牙种植体周围骨缺损的可行性.方法 Beagle犬4只,拔除单侧下颌1、2、4前磨牙.3个月后植入种植体,制备种植体周围骨缺损并植入相应的骨移植材料:实验组植入PRP/磷酸三钙(TCP);对照组植入TCP.分别于种植术后8、16周处死动物,对种植部位行大体及X线观察,并测量种植体周围的骨密度.采用SPSS 13.0软件对所有数据进行t检验.结果 大体及X线观察显示,实验组修复效果明显优于对照组;16周时,实验组骨密度显著高于对照组(P＜0.05).结论 PRP/TCP可以作为修复牙种植体周围骨缺损的骨移植材料.     

纳米羟基磷灰石修复兔颌骨缺损的骨密度分析

目的研究纳米羟基磷灰石修复颌骨缺损的可行性。方法将24只健康的中国哈尔滨大白兔随机分为实验组及对照组。在下颌骨体部制作面积为1.5cm×1.5cm的骨缺损,实验组以纳米羟基磷灰石修复,对照组以普通羟基磷灰石修复,于修复后第1、4、8、12周分别处死,X线拍片,采用图像分析处理程序进行骨密度分析,并进行统计学处理。结果骨缺损修复后,实验组骨密度随时间的延长逐渐增大,直至与正常的骨密度接近并趋于稳定;对照组骨密度随时间的延长逐渐减小。实验组与对照组比较,差异有显著意义(P<0.01)。结论纳米羟基磷灰石修复骨缺损,骨成熟较快,是修复骨缺损的良好材料。