Cavity Of Long Bones Research Articles

Progressive skeletal defects caused by Kindlin3 deficiency, a model of autosomal recessive osteopetrosis in humans.

The cellular and molecular mechanisms of bone development and homeostasis are clinically important, but not fully understood. Mutations in integrins and Kindlin3 in humans known as Leukocyte adhesion deficiencies (LAD) cause a wide spectrum of complications, including osteopetrosis. Yet, the rarity, frequent misdiagnosis, and lethality of LAD preclude mechanistic analysis of skeletal abnormalities in these patients. Here, using inducible and constitutive tissue-specific Kindlin3 knockout (K3KO) mice, we show that the constitutive lack of embryonic-Kindlin3 in myeloid lineage cells causes growth retardation, edentulism, and skull deformity indicative of hydrocephaly. Micro-CT analysis revealed craniosynostosis, choanal stenosis, and micrognathia along with other skeletal abnormalities characteristic of osteopetrosis. A marked progression of osteosclerosis occurs in mature to middle-aged adults, resulting in the narrowing of cranial nerve foramina and bone marrow cavities of long bones. However, postnatal-Kindlin3 is less critical for bone remodeling and architecture. Thus, myeloid Kindlin3 is essential for skeletal development and its deficiency leads to autosomal recessive osteopetrosis (ARO). The study will aid in the diagnosis, management, and treatment choices for patients with LAD-III and ARO.

Bone Marrow Niches and Tumour Cells: Lights and Shadows of a Mutual Relationship.

The bone marrow (BM) niche is the spatial structure within the intra-trabecular spaces of spongious bones and of the cavity of long bones where adult haematopoietic stem cells (HSCs) maintain their undifferentiated and cellular self-renewal state through the intervention of vascular and nervous networks, metabolic pathways, transcriptional and epigenetic regulators, and humoral signals. Within the niche, HSCs interact with various cell types such as osteoblasts, endothelial cells, macrophages, and mesenchymal stromal cells (MSCs), which maintain HSCs in a quiescent state or sustain their proliferation, differentiation, and trafficking, depending on body needs. In physiological conditions, the BM niche permits the daily production of all the blood and immune cells and their admittance/ingress/progression into the bloodstream. However, disruption of this delicate microenvironment promotes the initiation and progression of malignancies such as those included in the spectrum of myeloid neoplasms, also favouring resistance to pharmacological therapies. Alterations in the MSC population and in the crosstalk with HSCs owing to tumour-derived factors contribute to the formation of a malignant niche. On the other hand, cells of the BM microenvironment cooperate in creating a unique milieu favouring metastasization of distant tumours into the bone. In this framework, the pro-tumorigenic role of MSCs is well-documented, and few evidence suggest also an anti-tumorigenic effect. Here we will review recent advances regarding the BM niche composition and functionality in normal and in malignant conditions, as well as the therapeutic implications of the interplay between its diverse cellular components and malignant cells.

Enchondroma Protuberans of the Transverse Process of D8 Vertebra Extending to the 7th and 8th Ribs: A Rare Case Report.

Enchondroma protuberans (EP) is rare, benign cartilaginous bone tumor arising from the intramedullary cavity of long bones and usually protrudes beyond the cortex with an exophytic growth pattern resembling osteochondroma. This study reports on a rare case of EP arising from the transverse process of the D8 vertebra and extending to the adjacent 7th and 8th ribs and the paraspinal tissues. A 45-year-old female patient came in with complaints of upper back pain radiating up to the left costal margin for the past 6 months. There were no parasthesias, and there was no history of any sensory or motor symptoms. On physical examination there was midline and left paraspinal tenderness over the D6 to D8 region. Anteroposterior and lateral X-ray images revealed a well-defined oval ossific mass lesion over the lateral aspect of the D8 vertebra, extending to the 7th and 8th ribs on the left side, and multiple bridging osteophytes were noted. Computed tomography scan showed an ossific mass lesion arising from the D8 transverse process with extension to the adjacent 7th and 8th ribs; its margins were well defined, with no periosteal reaction. Magnetic resonance imaging showed a well-defined expansile mass lesion arising from the transverse process of the D8 vertebra matrix; it was was isointense with adjacent marrow and had no evidence of calcifications or vascular flow voids and no encroachment into the spinal canal. Complete resection of the mass lesion with the adjacent part of the 7th and 8th ribs and with intramedullary curettage was performed and sent for histopathologic examination. Histopathology showed bony trabeculae with normal mucosal elements, and a mild hypercellularity with binucleation. Chondrocytes in the myxoid matrix located in round lacunae were compatible with enchondroma, with no evidence of atypia. The postoperative period was uneventful, and after 12 months there were no signs of recurrence noted in computed tomography scan. EP is a rare presentation in the dorsal spine; it should be considered in the differential diagnosis of osteochondroma, enchondroma, chondrosarcoma, and periosteal chondroid tumors.

OP-28 - The role of the adipocytic lineages in the development of age-related metabolic disorders

Obesity is a significant challenge to medical care systems worldwide. Thus, adequate treatment strategies are needed to counter overweight and its associated metabolic disorders. Aging exacerbates the onset and progression of many of these complications, including the development of insulin resistance and the ectopic accumulation of adipocytes in atypical anatomical sites, such as the marrow cavities of long bones. These processes are thought to contribute to the impairment of normal tissue maintenance and also to inhibit regenerative tissue repair after injury. An important goal of current research is therefore to decipher the cellular lineages involved in regeneration. Tissue-resident adult stem and progenitor cell populations that can give rise to mature fat cells are considered to be of the mesenchymal stem cell type, and their heterogeneous composition has not been assessed in much detail. We were recently able to show that mesenchymal cells of the bone marrow cavity are functionally diverse and give rise to ectopic fat but may at the same time contribute to the regulation of regenerative processes. These findings suggest that age-dependent changes of the cellular heterogeneity of the mesenchymal lineages may negatively affect tissue regeneration and health in aged individuals.

Sarcomas With Complex Genetic Changes

Sarcomas With Complex Genetic Changes

Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity.

Skeletal muscle and bone share common embryological origins from mesodermal cell populations and also display common growth trajectories early in life. Moreover, muscle and bone are both mechanoresponsive tissues, and the mass and strength of both tissues decline with age. The decline in muscle and bone strength that occurs with aging is accompanied in both cases by an accumulation of adipose tissue. In bone, adipocyte (AC) accumulation occurs in the marrow cavities of long bones and is known to increase with estrogen deficiency, mechanical unloading, and exposure to glucocorticoids. The factors leading to accumulation of intra- and intermuscular fat (myosteatosis) are less well understood, but recent evidence indicates that increases in intramuscular fat are associated with disuse, altered leptin signaling, sex steroid deficiency, and glucocorticoid treatment, factors that are also implicated in bone marrow adipogenesis. Importantly, accumulation of ACs in skeletal muscle and accumulation of intramyocellular lipid are linked to loss of muscle strength, reduced insulin sensitivity, and increased mortality among the elderly. Resistance exercise and whole body vibration can prevent fatty infiltration in skeletal muscle and also improve muscle strength. Therapeutic strategies to prevent myosteatosis may improve muscle function and reduce fall risk in the elderly, potentially impacting the incidence of bone fracture.

The Evolution of Free Vascularized Bone Transfer: A 40-Year Experience.

The first successful free vascularized bone flap was performed on June 1, 1974 (and reported in 1975), using the fibula. This was followed by the iliac crest based on the superficial circumflex iliac artery in 1975 and then the deep circumflex iliac artery in 1978. A total of 384 transfers using fibula (n = 198), iliac crest (n = 180), radius (n = 4), rib (n = 1), and metatarsal (n = 1) were used between June of 1974 and June of 2014 for reconstruction of the mandible (n = 267), maxilla (n = 20), clavicle (n = 1), humerus (n = 8), radius and ulna (n = 21), carpus (n = 3), pelvis (n = 2), femur (n = 11), tibia (n = 47), and foot bones (n = 4). Indications were tumor ablation (n = 286), trauma (n = 84), osteomyelitis (n = 2), and the congenital deformities hemifacial microsomia (n = 2) and pseudarthrosis of the tibia (n = 9) and ulna (n = 1). Successful transfer was achieved in 95 percent of patients. Union varied with the recipient bone, from 6 to 8 weeks in the jaw, 2 to 3 months in the upper limb, and 3 to 4 months in the femur and tibia. Union was fastest with iliac crest. The fibula provided easier dissection; it could be raised on either peroneal or anterior tibial vessels; the skin flap could be designed distally; it could be placed centrally in the medullary cavity of long bones; and hairline stress fracture in the lower limb frequently preceded rapid subperiosteal hypertrophy. The fibula lacks sufficient height for osseointegration, whereas iliac crest is ideal. Osteotomies of either bone are possible to straighten or increase curvature. The fibula is best for long bone or angle-to-angle jaw reconstruction, especially in edentulous patients. Iliac crest is best for hemimandible, curved bones (pelvis, carpus, and metacarpus), and as an alternative for short, straight, 6- to 8-cm-long bone defects.

La fracturation osseuse : du fait technique à l’essai d’interprétation sociétale : l’exemple de l’antilope saïga du gisement magdalénien de Saint-Germain-la-Rivière (Gironde)

La fracturation osseuse est une pratique couramment observée sur les gisements paléolithiques, celle-ci intervenant dans diverses chaînes opératoires de transformation et d’utilisation des ressources animales, notamment alimentaires. La moelle osseuse, contenue dans la cavité médullaire des os longs, est une ressource alimentaire non négligeable pour de nombreux groupes humains, en particulier dans les zones périglaciaires, tels les Nunamiuts d’Alaska ou les Koriaks de Sibérie. Différents procédés sont mis en oeuvre pour sa récupération ; leur variabilité s’explique en partie par l’existence de traditions techniques et de modes de consommation de la moelle, propres aux différents groupes. Ces traditions entraînent souvent une standardisation des procédés de fracturation à l’intérieur de chaque groupe. De tels schémas récurrents sont-ils perceptibles dans le registre paléolithique ? Si oui, est-il possible de mettre en évidence une transmission des gestes relatifs à la récupération de la moelle ? Afin d’apporter des éléments de réponse à ces questions nous proposons dans le cadre de cet article, une étude détaillée des traces de percussion observées sur les os longs d’antilope saïga (Saiga tatarica), provenant de l’ensemble supérieur Magdalénien moyen de Saint-Germain-la-Rivière (Gironde). Les schémas observés ont ensuite été comparés à ceux décrits dans la littérature afin d’apprécier leurs spécificités et de discuter des paramètres ayant pu influer sur cette répartition des traces. Les vestiges fauniques de Saint-Germain-la-Rivière sont intensément fracturés et présentent de nombreuses traces de percussion d’origine anthropique attribuables à cette activité de fracturation de l’os. Des récurrences dans la localisation des traces de percussion ont pu être mises en évidence. Celles-ci varient selon les éléments squelettiques considérés et sont plus ou moins marquées. L’existence de telles récurrences tend à prouver que la disposition des points d’impact dépend d’un choix délibéré. Ces choix ne semblent pas être dictés exclusivement par l’existence de contraintes mécaniques (e. g. la structure osseuse) ou ergonomiques spécifiques aux éléments squelettiques. Par ailleurs, l’existence d’une variabilité inter-et intra-spécifique, observable d''après les données de la littérature laisse à penser qu’il s’agit de choix dictés en partie par un facteur culturel. L’analyse des traces de percussion a également permis de mettre en évidence, dans certains cas, la présence de plusieurs points d’impact sur une surface réduite. L’une des hypothèses que l’on peut émettre ici serait qu’il y ait eu plusieurs tentatives pour fracturer l’os. Ces pièces posent alors la question de l’acharnement et de la maîtrise du geste et pourraient évoquer des os fracturés par des novices.

Intramedullary fat globules related to bone trauma: a new MR imaging finding.

The purpose of this study is to describe intraosseous fat globules related to bone trauma that are detectable with magnetic resonance imaging (MRI), to define the relationship of this finding to fracture and bone contusion, to establish the frequency and associated findings. A proposed pathogenesis is presented. We retrospectively reviewed 419 knee MRI examinations in patients with a history of recent injury and MRI findings of fracture or bone contusion. As a control population, 268 knee MRI examinations in patients without MRI findings of recent bone injury were also reviewed. Eight of 419 (1.9%) patients with acute or subacute knee injury with positive findings of osseous trauma on MRI demonstrated intraosseous fat globules. The mean age of patients with fat globules was greater than that of those without fat globules, and the finding was more commonly seen in women. Fat globules were hyperintense to the normal fatty marrow present elsewhere in the bone on TI-weighted imaging and had a surrounding halo of high signal intensity on fluid-sensitive imaging. Intramedullary fat globules related to bone injury visible on MRI are thought to be due to coalesced fat released by the necrosis of fatty marrow cells. The pathogenesis is supported by histologic studies of fat globules related to osteomyelitis, bone contusions and fractures. As the medullary cavity of long bones in older patients contains more fat than hematopoetic bone marrow, it is likely that this finding is more common with advancing age.

Fully automated shape model positioning for bone segmentation in whole-body CT scans

Analysing osteolytic and osteoblastic bone lesions in systematically affected skeletons, e.g. in multiple myeloma or bone metastasis, is a complex task. Quantification of the degree of bone destruction needs segmentation of all lesions but cannot be managed manually. Automatic bone lesion detection is necessary. Our future objective is comparing modified bones with healthy shape models. For applying model based strategies successfully, identification and position information of single bones is necessary. A solution to these requirements based on bone medullary cavities is presented in this paper.Medullary cavities are useful for shape model positioning since they have similar position and orientation as the bone itself but can be separated more easily. Skeleton segmentation is done by simple thresholding. Inside the skeleton medullary cavities are segmented by a flood filling algorithm. The filled regions are considered as medullary cavity objects. To provide automatic shape model selection, medullary cavity objects are assigned to bone structures with pattern recognition. To get a good starting position for shape models, principal component analysis of medullary cavities is performed. Bone identification was tested on 14 whole-body low-dose CT scans of multiple myeloma patients.Random forest classification assigns medullary cavities of long bones to the corresponding bone (overall accuracy 90%). Centroid and first principal component of medullary cavity are sufficiently similar to those of bone (mean centroid difference 21.7 mm, mean difference angle 1.54° for all long bones of one example patient) and therefore suitable for shape model initialization.This method enables locating long bone structures in whole-body CT scans and provides useful information for a reasonable shape model initialization.

High abundance of CD271+ multipotential stromal cells (MSCs) in intramedullary cavities of long bones

Aspiration of iliac crest bone marrow (ICBM) remains the most frequent technique used in harvesting multipotential stromal cells (MSCs) for bone regeneration. Although this tissue type is easily accessed by a surgeon, it has a low frequency of MSCs, which is significant given the high cell numbers required for bone regeneration strategies. Lipoaspirates possess higher MSC frequencies, albeit cells with a differentiation profile less suited to orthopaedic interventions. Intra-medullary cavities of long bones have previously been shown to harbour MSCs in animals, however evaluation of their frequency, differentiation capacity and phenotype in humans had not previously been performed.Long bone fatty bone marrow (LBFBM) was collected prior to harvesting bone graft. Basic cellular compositions of donor-matched LBFBM and ICBM aspirates, including the numbers of CD34+ hematopoietic stem cells and CD31+ endothelial cells, were similar. MSCs were enumerated using colony-forming-unit-fibroblast assays and flow cytometry for the presence of a resident LBFBM CD45−/low CD271+ MSC population and revealed a trend for higher MSC numbers (average 5 fold, n=6) per millilitre of LBFBM compared to donor-matched ICBM. Functional characteristics of resident MSCs, including their growth rates, differentiation potentials and surface phenotypes (CD73+CD105+CD90+) before and after culture-amplification, were similar. Enhanced numbers of MSCs could be recovered following brief enzymatic treatment of solid fragments of LBFBM.Our findings therefore reveal that the intramedullary cavity of the human femur is a depot of MSCs, which, although closely associated with fat, have a differentiation profile equivalent to ICBM. This anatomical site is frequently accessed by the orthopaedic/trauma surgeon and aspiration of the intramedullary cavity represents a ‘low-tech’ method of harvesting potentially large numbers of MSCs for regenerative therapies and research.This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.

Hematopoietic stem cell development, aging and functional failure

Hematopoietic stem cells (HSCs) are found in yolk sac, fetal liver, umbilical cord blood, placenta, and amniotic fluid during mammalian embryonic development. In adults, HSCs reside in marrow cavity of long bones where they self-renew and differentiate to replenish short-lived mature blood cells. HSCs exist in very low frequencies within specific "niches" where they interact with the surrounding environment through molecular associations. Overall HSC function can last much longer than a normal lifetime, but HSCs do show functional senescence with characteristic features of decreased self-renewal, reduced clonal stability, reduced homing and engraftment, and biased lineage commitment. The progressive shortening of telomeres with increasing age, especially under conditions with specific mutations in the telomerase gene complex, could predispose patients to HSC dysfunction and bone marrow failure diseases. Continuous investigation into HSC biology should facilitate the utilization of HSCs as a therapeutic modality and helps to prevent HSC malfunction.

Sonographic Evaluation of Enchondroma With Soft Tissue Extension in the Setting of Ollier Disease

Enchondroma is a benign cartilaginous neoplasm that arises after entrapment of a physeal rest of cartilage within the intramedullary cavity of long bones. 1 Ollier disease is a rare sporadic developmental abnormality that results in multiple intramedullary and intracortical enchondromas. 2 Clinical problems caused by enchondromas in Oflier disease include skeletal deformities, fractures, limb length discrepancy, and a risk of malignant transformation to chondrosarcoma. 3 Enchondroma protuberans is a chondromatous lesion that arises in the intramedullary cavity of bone, protrudes through adjacent cortex, and forms a prominent exophytic mass in the adjacent soft tissues. 4 This entity can be seen in the setting of multiple enchondromatosis or solitary enchondroma and should be distinguished from osteochondroma and chondrosarcoma. 5 To this date, characterization of enchondroma protuberans and enchondromatosis has relied on radiography and magnetic resonance imaging (MRI). 5-10 We recently performed a functional evaluation of a patient with a deformity of the hand related to long-standing Ollier disease using sonography to characterize the cause of pain in the patient's index finger and a clicking sensation in the middle finger.

Extraction of high numbers of mesenchymal stem cells (MSCs) from intramedullary cavities of long bones

Extraction of high numbers of mesenchymal stem cells (MSCs) from intramedullary cavities of long bones

Evidence for the expression of estrogen receptors in osteogenic cells isolated from hen medullary bone

Medullary bone is a unique tissue in female birds and forms in the cavity of long bones. This bone displays rapid remodeling in response to circulating estrogen levels, suggesting that the osteoblasts in this bone are highly sensitive to estrogen. The present study examined expression of two estrogen receptor (ER) mRNAs in osteogenic cells of medullary bone of white Leghorn hens in vitro. At day 3, isolated cells from the hen medullary bone expressed alkaline phosphatase activity. Using immunocytochemistry, ER protein was demonstrated in the nuclei of these cells. RT-PCR analysis revealed that ER-alpha mRNA was constantly expressed from day 3 to day 15 of culture, while ER-beta mRNA was not detected throughout the culture period. These results indicate that estrogen may act via ER-alpha, but not ER-beta, on osteogenic cells of the avian medullary bone.

Periosteal Ewing Sarcoma Family of Tumors of the Femur Confirmed by Molecular Detection of EWS-FLI1 Fusion Gene Transcripts

Ewing sarcoma family of tumors (ESFT) comprise common sarcomas in children and young adults. Such tumors usually occur in the medullary cavity of long bones and directly invade cortical bone and circumferential soft tissue, including periosteum. Periosteal ESFT is extremely rare and only a small numbers of cases, including cases not confirmed by molecular detection of chimeric fusion gene, have been reported. We describe herein a case of periosteal ESFT of the femur in a 13-year-old boy harboring EWS-FLI1 chimeric fusion gene transcripts detected by reverse transcription-polymerase chain reaction analysis. This report may provide an opportunity for further evaluation of the EWS-FLI1 type 1 fusion gene and detection of prognostic significance in periosteal ESFT.

Atmospheric pressure as a force that fills developing bones with marrow and air

Many theories try to explain the existence and function of paranasal sinuses. This paper is an attempt to correlate process of paranasal sinus development in human with bone pneumatization processes in animals. It is here proposed that this mechanism starts in utero and continues after birth. During endochondral development, a solid hyaline cartilage model transforms into long bones. Central chondrocytes hypertrophy and their lacunae become confluent. Dissolving of the cartilage intercellular matrix forms a primitive marrow cavity. It is soon invaded by the periostal bud. Once circulation is established in the developing bone, the dissolved hyaline matrix can be slowly washed away from the bone cavity. Circulation in the bone cavity can develop slight subatmospheric pressures, similar to negative interstitial pressures in subcutaneous tissues. The amniotic fluid conducts atmospheric pressure to the fetal body. The pressure is trying to fill enlarging bone cavities through the existing vascular openings, or to create new openings. Bone walls of developing paranasal bones are to weak to resist the pressure gradient on their walls. New openings form on the weakest spots allowing airway mucosa to form initial paranasal sinuses. The enlarging cavities of long bones that are remote from the body surface and airway also develop a slightly subatmospheric pressure that fills them with cellular elements. These elements enter bone through the feeding vessels and form bone marrow. During after birth skeletal growth, bone remodeling shapes paranasal sinuses in a process of slow evolution that do not require measurable pressure gradients. When two sinuses come in vicinity, their growth rate declines, since the remaining thin and fragile bone lamella between them does not retract anymore.

Radiogrammetric Study of Width, Area of Cortex and Medullary Cavity of Long Bones of Macaca Mulatta From Juvenile to Adult Stages

Radiogrammetric Study of Width, Area of Cortex and Medullary Cavity of Long Bones of Macaca Mulatta From Juvenile to Adult Stages

Catheterization of the Medullary Cavity of Long Bones.

Vascular catheterization techniques were used in bones to allow access to the entire medullary cavity through a minimal percutaneous approach. The study was carried out on human and animal anatomical specimens and in living sheep. After oblique penetration at an angle of approximately 40û to the surface of the cortical bone, we attempted to pass in the bone shaft using various types of guides and catheters. Different types of instrumentation currently available were compared for ease of advancement in the shaft and quantity of bone marrow that could be aspirated. Once the metaphysis was reached, a variety of techniques were studied to penetrate the cancellous bone and to introduce a catheter. A percutaneous approach to any part of a long bone through a cortical pathway from a remote entry site is feasible in certain diagnostic or therapeutic indications, when direct approach to pathological sites in long bones is dangerous or impossible.

Osteoblasts develop from isolated fetal mouse chondrocytes when co-cultured in high density with brain tissue.

Chondrocytes from the hypertrophic and proliferative zones of 16-day-old fetal murine metatarsal bones were enzymatically dissociated and cultured in a high-density type of culture, exposed to the gas phase. We ascertained that no cells of the perichondrium were included in the cell suspension. Control cultures formed a solid cartilaginous mass, of which all the chondrocytes were alkaline phosphatase positive and the matrix started to calcify after 4 days. After 6 days, nearly the entire matrix was calcified. When co-cultured with pieces of cerebral tissue, some chondrocytes had transdifferentiated into osteoblasts after 4 days. They had started to form osteoid. After 6 and 11 days part of the cartilage had been replaced by bone, especially in the periphery of the cultures, but also in areas in the center. The bone matrix was partly calcified. Osteoblasts and bone matrix were identified as such electron microscopically. The nature of the bone matrix was also confirmed by immunohistochemical demonstration of collagen type I and osteocalcin. These results show that enzymatically isolated chondrocytes are able to become osteoblasts when properly stimulated. This supports the concept of chondrocytes being responsible for (part of) the endochondral bone formation in the marrow cavity of long bones.