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Vascularized bone transfer for tibial pseudarthrosis. Part II: Vascularized bone and muscle transfers. Exclusive free fibular bone graft.

The techniques of vascularized transfer of a bone segment, or of revascularization of a conventional bone autograft by a pedicle or a microsurgical muscular flap represent one of the most significant advances made during the last years for the treatment of large bone defects of the tibia with associated skin injury. The authors present their experience with 16 cases, including 5 microsurgical transfers.

Adult↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Tartrate-resistant acid phosphatase (TRACP)].

Tartrate-resistant acid phosphatase (TRACP) is a well-known marker for bone resorption, but it is not enough for clinical use in specificity of bone and instability in serum. Tartrate-resistant acid phosphatase type 5b (TRACP-5b) is an osteoclast-produced enzyme and was reported the clinical performance of a novel fragments absorbed immunocapture enzyme assay. TRACP-5b have smaller day-to-day and diurnal variation than those of urinary bone resorption markers and show the usefulness as promising markers in monitoring the treatment for osteoporosis.

Acid Phosphatase↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Receptor activator of NF-kappaB ligand (RANKL)].

Identification of RANKL (receptor activator of NF-kappaB ligand), RANK (receptor activator of NF-kappaB) and OPG (osteoprotegerin) revealed the mechanisms regulating osteoclast differentiation and function. RANKL-RANK signaling is essential for the physiological osteoclast development and plays a major role in the pathological bone destruction. RANKL is a transmembrane protein, but soluble form (sRANKL) is circulated in blood stream. Change of sRANKL concentration was observed in several bone diseases. This paper reviews the potential of sRANKL measurement as a marker of bone diseases.

Biomarkers↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Osteocalcin (OC)].

Osteocalcin is produced by mature osteoblasts and primarily deposited in the extracellular matrix of skeletal tissue. It has been shown that serum osteocalcin is a marker of osteoblastic activity, and the levels reflect the rate of bone formation. The first osteocalcin assays were competitive radioimmunoassays using bovine osteocalcin as a standard, and a new generation of assays was developed to measure the major circulating forms of the protein, which is the intact and the large N-terminal fragment. Since osteocalcin binds to hydroxyapatite crystal after gamma-carboxylation at three residues, increased amounts of immature undercarboxylated osteocalcin might reflect risks for fractures. However, at present, measurement of osteocalcin does not substitute for bone mass measurement and only provide limited clinical values on evaluation of patients with osteoporosis or metabolic bone diseases.

Biomarkers↗

Will reducing adopogenesis in bone increase bone mass?: PPARgamma2 as a key target in the treatment of age-related bone loss.

There are several mechanisms that explain the pathophysiology of senile osteoporosis. One of them is the increasing levels of adipogenesis in bone marrow that are seen during the aging process. It is known that mesenchymal stem cells expressing a ligand-activated transcription factor known as peroxisome proliferator-activated receptor gamma(2) (PPARgamma(2)) are committed to differentiate into adipocytes. The regulation of PPARgamma(2) activation may play a role in the control of adipogenic differentiation of mesenchymal stem cells and thus contribute to their differentiation into osteoblasts in order to form new bone. In this review we describe the characteristics of the orphan receptor family of PPARs, with emphasis on PPARgamma(2), its structural and functional characteristics and its potential as a therapeutic target for the treatment of senile osteoporosis.

Adipocytes↗

[Bone and joint transplantation. Alternatives to bridging segmental bone defects and a model for allogenic bone transplantation].

Fresh allogeneic diaphyseal bone segments were transplanted into 12 dogs. We attempted to improve the immunogenity and incorporation of the bone segments through "graft manipulation" with and without immunosuppression. Through clinical and radiological study during the 20-week experimental period, we observed transplant healing with differing structural phenomena. After autologous knee joint replantation in 4 dogs and allogeneic transplantation in 2 dogs (with and without revascularization and immunomodulation with Cyclosporin A) we present a canine model to investigate all open questions about the transplantation of allogeneic, fresh joints (i.e. transplant biology, immunology, and vitality).

Animals↗

[The production of IL-1, IL-3 and CSA by bone marrow nuclear elements during the recovery of bone marrow hematopoiesis after lethal irradiation and the transplantation of syngeneic bone marrow].

The production of haemopoietic factors (IL-1, IL-3, CSA) by adherent and nonadherent cells of lethally irradiated CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoietic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by nonadherent bone marrow elements was realised in a late terms of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells.

Animals↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Regulatory mechanisms of osteoclast differentiation and function].

Osteoclast differentiation is tightly regulated by osteoblasts. Osteoblasts express two cytokines, macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL), essential for osteoclast differentiation. Osteoclast precursors firstly differentiate into mononuclear osteoclasts in response to M-CSF and RANKL. Nuclear factor of activated T cells 1 (NFATc1) is a transcription factor, which is involved in the determination of osteoclast differentiation. The mononuclear osteoclast then fuses each other to form the multinucleated cell. Dendritic cell-specific transmembrane protein (DC-STAMP) plays an important role in the fusion of mononuclear osteoclasts. Osteoclasts recognize bone and form ruffled borders and clear zones on the bone surface (polarization). Polarizing osteoclasts construct active vascular transportation systems to resorb bone efficiently. RANK-TRAF6 (TNF receptor-associated factor 6) -mediated signals key roles in both osteoclast differentiation and function. In this article, I will review the recent findings on osteoclast differentiation and function.

Animals↗

Cortical bone loss and measurements of the second metacarpal bone: II. Hypodense bone in postwar Guamanian children.

Hand-wrist radiographs from 326 Guamanian children (180 boys and 146 girls) were evaluated for total width, medullary width, length, and combined cortical thickness of the second metacarpal. Bone measurements as well as standing height and weight were compared to similar published data from U.S. mainland black, white, and Mexican-American children. The results demonstrated that the second metacarpal bones of Guamanian boys and girls of all age groups (5-17 years) have narrower width and shorter length with less combined cortical thickness than any of the other groups. Guamanian children also weighed less and were of shorter stature than their black, white, or Mexican-American counterparts. These results agree closely with those comparisons between Guamanian and U.S. mainland white adults published earlier. It is not possible from the present data to ascertain whether these differences were due to genetic variability or nutritional deficiency.

Adolescent↗

Bone marrow aspiration before bone marrow core biopsy using the same bone marrow biopsy needle: a good or bad practice?

A single-needle single-site technique for bone marrow aspiration and core biopsy has been compared with a two-needle technique, using 30 randomly selected patients who required these two investigations. In addition, two single-needle techniques were compared, aspirating immediately after penetrating the cortex or, alternatively, aspirating after the needle (without the stilette) had been advanced 20-25 mm. The two-needle technique was found to be superior to either of the single-needle techniques, which often resulted in a biopsy specimen that was denuded of bone marrow cells.

Aged↗

Diurnal rhythms in Ca transfer into bone, Ca release from bone, and bone resorbing activity in serum of rats.

To characterize diurnal rhythms in calcium transfer in and out of bone, rats were adapted to a 12:12 h light-dark illumination program (with light from 0600 to 1800 h). For studies of deposition, rats were injected with 45CaCl2 at 0300, 0700, 1100, 1500, 1900 or 2300 h and killed with chloroform inhalation 60 min later, and radioactivity was determined in tibia and mandibular incisor. Peak deposition occurred at 2400 h, with a nadir at 1200 h. For studies of radionuclide release, rats were prelabeled with 45CaCl2 for 6 days and serum obtained from the tail at 4-h intervals. 45Ca and specific activity were maximal around 1200-1600 h and lowest late in the dark period. To determine the role of humoral factor(s), fetal rat limb bones were cultured in media prepared with sera from light-dark-adapted rats. Activity was maximal in serum collected at 0800 h and minimal at 1600 h. Heat inactivation at 100 degrees C for 5 min eliminated the difference between the peak and nadir. The results suggest that a heat-sensitive humoral factor(s) regulates diurnal rhythms in calcium metabolism.

Animals↗

[A histopathological study of bone marrow in acute myeloid leukemia. Bone marrow biopsy changes before chemotherapy and comparison with bone marrow smears].

Histopathological changes of pretreatment bone marrow biopsy from 42 cases with acute myeloid leukemia (AML) were described. A considerable difference was shown between the results of aspirate smears and the findings of plastic embedded biopsy sections, particularly in bone marrow cellularity such as infiltration of inflammatory cells and presence of residual hemopoietic cells, qualitative and quantitative abnormalities of megakaryocytes suggestive of myelodysplastic features were more accurately assessed in the sections of marrow biopsy than in the aspirate smears. In three cases there was considerable infiltration of maturing but dysplastic granulocytic cells and erythroid precursors in the sections, but not in the aspirate smears. Our study shows that plastic embedded biopsy sections provide more information than aspiration smears for the diagnosis of AML.

Adolescent↗

Bone- and non-bone-derived growth factors and effects on bone healing.

In the future, it may be possible to manipulate the fracture site with exogenous growth factors to allow successful union of the bone ends without additional surgery. The complex interaction of growth factors, the timing of their appearance and disappearance at the wound site, and the concentrations necessary to achieve specific effects must be studied more thoroughly. For growth factors to find widespread clinical use, there must be evidence that healing is enhanced. It may be difficult to enhance the healing of fresh fractures in normal animals, and it may also be difficult to demonstrate the healing of nonunion fractures. Because of the great variability in fractures of clinical patients, studies designed to determine the effect of growth factors on bone healing must be carefully designed with appropriate attention given to randomizing patients based on the risk of delayed healing and other patient characteristics.

Animals↗

Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: avoiding second site autologous bone harvest.

Mineralization and integrity of the bone graft mass were evaluated among patients having posterolateral fusion. Grafting consisted of a composite of Grafton and "local" autologous bone (n=56) or iliac crest autograft alone (n=52). Mineralization was rated radiographically at baseline and at 3, 6, 12, and 24 months. Integrity was judged as fused or not fused. Mineralization ratings did not differ significantly between groups at any postoperative interval (P values of .25-1.00). The percentage of patients fused was similar in both groups (60% and 56% for Grafton and controls, respectively; P=.83). Fifteen control patients reported donor site pain. These findings warrant further evaluation of this composite.

Adult↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Structure and metabolisms of collagen].

Collagens are the most abundant proteins in mammals. They are the major structural proteins in bone as well as other organs. The synthesis of collagens is regulated by numerous growth factors, cytokines and hormones. The higher structure of collagen is derived from the series of biosynthesis including its characteristic primary amino acid structure and post-translational modifications. The degradation products of collagen have been utilized as markers for bone turnover.

Collagen↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Measurement of PICP and PINP in the evaluation of pharmaceutical treatment efficacy for osteoporosis].

Propeptides of type I procollagen are generated during the process of collagen formation in bone matrix. Among them measurements of circulating N-terminal propeptide (PINP) has been recognized as one of promising metabolic bone markers in the assessment of efficacy of pharmaceutical intervention for osteoporosis. Recently assays of PINP have been established to be supplied as measurement kits following those of C-terminal propeptide (PICP) and clinical data on usefulness of PINP in the evaluation of teriparatide an anabolic agent as well as various anti-catabolic agents have accumulated. Therefore, the measurement of PINP must be an essential tool in Japan at the time when newer agents for osteoporosis are applied to clinical practice in the future.

Biomarkers↗

Application of serum-free liquid bone marrow cultures to bone marrow purging for autologous bone marrow transplantation in acute lymphoblastic leukemia.

We have previously established a serum-free (SF) culture medium which allows normal haematopoietic progenitor cells to be maintained for at least 4 weeks as in the conventional serum dependent SD) medium. In the present study we investigated the efficiency of the SF liquid system to sustain normal residual haemopoiesis to the detriment of the leukemic population in patients with ALL. Probes for a potential selective effect were brought through leukemic progenitor cell assay (CFU-ALL) and the polymerase chain reaction (PCR) study of the bcr/abl translocation. In 13 experiments done in 12 patients, morphological blast cells and the ALL-CFU were dramatically reduced within 3 weeks of incubation in both SF and SD cultures. In 5/5 experiments in SD conditions and 2/5 experiments in SF conditions, leukemic cells expressing the bcr/abl fusion gene also disappeared within the same period. There was no difference in the CFU-GM production between SF and SD mediums. Erythropoiesis exhibited a slower decline in conditions SF, compared to the conditions SD. These results indicate that the liquid marrow culture may selectively deplete the leukemic lymphoblastic cells and enable repopulation by residual normal hemopoietic cells. It may be useful to purge leukemic cells for clinical autologous bone marrow transplantation in patients with ALL.

Bone Marrow Cells↗

Human herpesvirus 6 (HHV-6) isolation from bone marrow: HHV-6-associated bone marrow suppression in bone marrow transplant patients.

These studies tested the hypothesis that human herpesvirus 6 (HHV-6) can cause posttransplant bone marrow (BM) suppression in BM transplant (BMT) patients. Fifteen adult patients who received T-lymphocyte-depleted, allogeneic BM transplants and who developed posttransplant BM suppression were studied. Detailed chart reviews were used to divide the patients into two groups: (1) those with diagnosed BM suppression (DBMS) and (2) those with idiopathic BM suppression (IBMS). BM aspirates obtained from the patients at the onset of BM suppression were subjected to an HHV-6 isolation procedure using mitogen-stimulated blood mononuclear cells. BM specimens obtained from another population of BMT patients solely to document engraftment irrespective of their BM function were also subjected to the HHV-6 isolation procedure as controls. HHV-6 was isolated from 6 of 15 BM samples from BMT patients with BM suppression. BM samples from patients with IBMS were more likely to be positive for HHV-6 than those from patients with DBMS (P < .01). Also, HHV-6-positive BM were significantly more likely (P < .05) to come from patients with suppression of more than one BM lineage than HHV-6-negative BM. Finally, samples of BM from an unselected series of BMT patients studied without regard to their BM function were less likely (P < .01) to be positive for HHV-6 than patients with IBMS.

Adult↗