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The reversibility of disuse osteoporosis. Studies of bone density, bone formation, and cell proliferation in bone tissue.

One hind leg of 80 adult rats of the Sprague-Dawley strain was made osteoporotic by immobilization for 9 weeks. Osteoporosis was noted in both the femur and the tibia when the hydrated gross bone density and the bone surface areas were measured. No signs of reversibility were observed during 10 weeks after the period of immobilization. Tetracycline and DCAF labelling failed to show significant signs of increased bone formation during the 10 weeks after remobilization. At the moment of remobilization and for some weeks thereafter, there were signs of depressed mitotic activity in the bone cells when expressed as the 3H-thymidine/DNA ratio. The conclusion was that neither the cell-proliferation rate nor the cellular activity increases sufficiently for restitution of the disuse osteoporosis.

Animals↗

Expression of vascular antigens by bone cells during bone regeneration in a membranous bone distraction system.

An in vivo system of membranous bone formation during distraction has been investigated in order to follow cells that express vascular markers with the objective of understanding the neovascularization process. Concomitantly, sustained proliferation of preskeletal cells was achieved through the application of mechanical force. New capillaries and leading edges that arose by angiogenesis from the periosteal and mucosal surfaces and invaded the central zone of the regenerating distraction tissue temporally preceded the growth of delicate woven bone trabeculae from both edges of the cut bone. Concentrically arranged 'onion-like' configurations were abundant in paracentral zones and in association with mesenchymal condensations, suggesting their de novo formation in situ. Vascular specific markers, the angiopoietin receptor Tie-2 and factor VIII-related antigen (FVIIIrAg), were localized immunohistochemically in order to follow cells of vascular origin. Endothelial cells of the new capillaries, centrally located cells of the concentric configurations, pericytes, and most of the adjacent polygonal mesenchymal cells stained positively with specific antibodies to both antigens. Moreover, preosteoblasts and osteoblasts that lie adjacent to or already embedded in the osteiod of the newly formed trabeculae were also FVIIIrAg and Tie-2 immunopositive. As the source of the bone-forming cells in regenerating tissue during distraction is not yet fully understood, this observation might support the possibility of their vascular origin.

Animals↗

Bone densitometry of proximal femur in Chinese subjects: gender differences in bone mass and bone areas.

Bone mineral content (BMC), bone areas (BA), and bone mineral density (BMD) of the proximal femur were measured in 202 healthy Chinese men and 507 healthy Chinese women, aged 21-70 years, to investigate gender differences in densitometry of the femur. Densitometric values measured at the femoral neck, trochanter, and Ward's triangle were generally greater in men than women of the same age, except at Ward's triangle. While BMD decreased with aging with similar slopes of -0.2 approximately -1% per year, the actual readings were 10%-15% lower than those of Caucasian subjects of the same age and gender for Chinese men and women. Furthermore, with increasing age, trochanteric BA increased in women but not in men, and femoral neck BA increased in men but not in women. These different trends of change in bone dimensions were independent of weight or height. They may reflect a structural difference at the proximal femur and imply differences in mechanical strength, and thus may have played some roles in the different incidence of hip fractures between the elderly men and women.

Absorptiometry, Photon↗

Bone density, bone markers and bone radiological features in mastocytosis.

We examined the association between severity of disease in mastocytosis and skeletal manifestation and bone markers in 16 patients varying in extent of mastocytosis as determined by the urine excretion of methylimidazoleacetic acid. Both osteoporosis and osteosclerosis were found. Bone density in the hip was significantly higher (p < 0.05) in both men and women with an enhanced histamine metabolite excretion. Patients with only moderately increased mast cell mass had low bone mineral density in the hip, osteoporosis and vertebral fractures. The different skeletal disease patterns in mastocytosis might be the effect on osteoblasts and osteoclasts of biologically active substances. Mast cells release a number of vasoactive substances, including histamine which promotes osteoblasts and heparin and prostaglandin D2 which induce bone resorption by activation of osteoclasts. Systemic mastocytosis is a rare disease characterized by multi-organ infiltration by mast cells and with varying skeletal manifestations including osteoporosis. Treatment with bisphosphonates may be beneficial in arresting osteoporosis in this disorder.

Acid Phosphatase↗

Clinical evaluation of freeze-dried bone allografts in periodontal osseous defects. Part III. Composite freeze-dried bone allografts with and without autogenous bone grafts.

Freeze-dried bone allografts (FDBAs) were evaluated alone and in combination with various types of autogenous bone in the treatment of periodontal osseous defects. A total of 381 defects were evaluated by surgical reentry approximately 1 year after grafting. Reentry data were compared with similar data obtained when the grafts were placed. Osseous regeneration and pocket reduction were rated as complete, greater than 50%, less than 50%, or failed. Complete or greater than 50% regeneration was considered successful. When compared with FDBAs, composite freeze-dried bone allografts/autogenous bone grafts (FDBA/ABGs) appear to offer significantly improved results in both osseous regeneration and pocket reduction. Use of composite FDBA/ABGs resulted in significant improvement in the treatment of combination one/two-wall defects and furcation involvements. A trend of improvement was seen with two-wall defects. The surgical data indicated that complete wound closure and the use of antibiotics enhanced graft success. The results also indicated that the presence of endodontically obturated teeth may be a consideration in the success or failure of the graft.

Adolescent↗

[Unrelated bone marrow transplantation b. Bone Marrow Donor Registry. Nagoya Bone Marrow Transplantation Group].

Tokai Bone Marrow Donor Registry was established to facilitate unrelated bone marrow transplantations in Japan. Although the basic structure was constructed, the number of donors must be expanded and financial problems must be solved. More bone marrow donor registries are likely to be established in the near future throughout Japan, and those will be anticipated to become a nationwide bone marrow donor registry. The HLA identity between unrelated individuals is unique in that it is only phenotypically identical and not genotypically identical. Therefore, for the HLA matching, not only serological typing of donors and recipients but molecular and biochemical methods would be employed to facilitate the analysis of the degree of the HLA identity to be more precise. Those methods include HLA-DP DNA typing and IEF analysis of HLA-class 1 antigens.

Bone Marrow Transplantation↗

Use of the "blue dot" in femoral bone plug of bone-patellar tendon-bone graft in anterior cruciate ligament reconstruction.

The advancement of the femoral bone plug, with proper orientation through the femoral tunnel is often one of the most difficult maneuvers in the reconstruction of the anterior cruciate ligament using a bone-patellar tendon-bone graft. The authors describe a modification to the procedure featuring the use of methylene blue marker (to make a ¿blue dot¿) to highlight the site of drill holes as well as the anterior bone-tendon junction. The ¿blue dot¿ aids the localization of the drill hole with a probe and thus the advancement of the femoral plug through the femoral tunnel.

Anterior Cruciate Ligament↗

Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation, osteoclast recruitment, and bone turnover.

Reconstruction of craniofacial defects presents a substantial biomedical burden, and requires complex surgery. Interestingly, children after age 2 years and adults are unable to heal large skull defects. This nonhealing paradigm provides an excellent model system for craniofacial skeletal tissueengineering strategies. Previous studies have documented the in vivo osteogenic potential of adipose-derived stromal (ADS) cells and bone marrow-derived stromal (BMS) cells. This study investigates the ability to accelerate in vivo osteogenesis on ex vivo recombinant human bone morphogenetic protein 2 (BMP-2) and retinoic acid stimulation. Mouse osteoblasts, ADS cells, and BMS cells were seeded onto apatite-coated PLGA scaffolds, stimulated with rhBMP-2 and retinoic acid ex vivo for 4 weeks, and subsequently implanted into critically sized (4 mm) calvarial defects. Samples were harvested after 2, 4, 8, and 12 weeks. Areas of complete bony bridging were noted as early as 2 weeks in vivo; however, osteoclasts were attracted to the scaffold as identified by calcitonin receptor staining and tartrate-resistant acid phosphatase activity staining. Although the optimal method of in vitro osteogenic priming for mesenchymal cells remains unknown, these results provide evidence that BMP-2 and retinoic acid stimulation of multipotent cells ex vivo can subsequently induce significant quantities of bone formation within a short time period in vivo.

Animals↗

[Morpho-functional correlations of the structure of bone cells and adjoining bone matrix in the developing bone].

By means of scanning and transmissive electron microscopy methods structure of the developing bone has been studied. Interconnection of the cell structure and spatial organization of the adjoining matrix has been demonstrated. On the surface of the growing bone not only forming areas have been revealed, where under osteoblasts at various functional states, osteoid layer is determined, but also areas of resorption and completed osteogenesis. This demonstrates an interrupted character of osteogenesis at modelling. At the same time for the remodelling process presence of erosive lacunae is specific; they are filled with a newly deposited collagenous matrix. Therefore, it is possible to suppose that formation of the bone as an organ during the postnatal development includes in itself both mechanisms supporting its form at outgrowth of the osseous matrix volume (modeling) and its continuous rearrangement and adaptation to real conditions of functioning (remodelling).

Animals↗

[Anterior cruciate ligament reconstruction by autogenous bone-patellar tendon-bone graft: correlation between bone-tunnel position and clinical results].

The authors evaluate correlation between bone-tunnel position and clinical results of 50 patients, aged 18-47 years, after anterior cruciate ligament reconstruction by bone-patellar tendon-bone autograft with half-tunnel technique. The evaluation comprises the femoral tunnel placement at the lateral femoral condyle, the angle of the tibial tunnel to the medial joint line of the tibia and paraarticular location of the tibial tunnel width clinical outcome within one to five years prior to operation. Bone-tunnel placement was based on radiograms done in anteroposterior and lateral view. Clinical evaluation was based on the International Knee Documentation Committee (IKDC) scale. Statistical analysis was performed by using Fisher exact test, Mann-Whitney test and chi 2 test with Yates correction. The results show that placement the femoral tunnel anteriorly to the line which was perpendicular to the Blumensaat line where it starts to curve posteriorly and tibial tunnel angle of 75 degrees or more is associated with statistically significant worsened of clinical outcome. Malalignment of femoral tunnel placement characterised much larger effects of qualitative and quantitative changes.

Adult↗

In search of the ideal bone morphogenetic protein delivery system: in vitro studies on demineralized bone matrix, purified, and recombinant bone morphogenetic protein.

The clinical use of recombinant bone morphogenetic protein (rBMP) is limited by the lack of a suitable delivery system. The bone morphogenetic protein (BMP) delivery system provided by nature is highly effective, and by studying purified BMP (BMP/NCP) and demineralized bone matrix (DBM), it may be possible to learn how to emulate nature's success. The current study used an in vitro muscle cell model to study the activity of BMP/NCP and DBM and the effects of extracellular matrix on BMP activity. C2C12 cells transiently exposed to recombinant human BMP-4 (rhBMP-4) rapidly increased their alkaline phosphatase (AP) activity to day 5, after which it steadily declined. Cells exposed to BMP/NCP or DBM continued to increase their AP activity over the 14-day culture. If BMP/NCP was treated to remove a 22-kd protein, it became water-soluble and exhibited a similar activity pattern to rhBMP-4. Cells cultured on collagen type I, fibronectin, and hyaluronic-coated surfaces demonstrated increased AP activity when exposed to rhBMP-4 or BMP/NCP compared with cells cultured on bovine serum albumin or poly-l-lysine. These results suggest that the natural BMP delivery system operates both by binding to the BMP molecule and slowly releasing it into the extracellular milieu and by interacting with the responding cells through cell-matrix receptors to enhance the cellular response to BMP.

Alkaline Phosphatase↗

Radiographic alveolar bone change as an outcome measure for therapies that inhibit bone loss or foster bone gain.

Periodontal clinical trials rely on signs of gingival inflammation, periodontal probing methods, and intra-oral radiographic methods to measure outcomes of therapies that inhibit bone loss or foster bone gain. A single radiograph can provide information on the accumulation of past disease, and sequential radiographs can determine regeneration or progression of periodontal destruction. However, the precision achieved with a radiograph is associated with the actual exposure of the film and the subsequent analysis. A film exposed using standardized geometry and standardized processing has many advantages over non-standardized conventional film. If the patient population for a study is a small, selective group, or if one needs to identify the smallest amount of bone loss in the shortest time, standardized films may be used. Conversely, in a large-scale trial, the use of standardized films may prove to be impractical. Since the advent of personal computer-based image-processing workstations, digital-image analysis has also become a practical tool for clinical trials. Digital subtraction radiography is a highly precise and accurate technique for assessing bony changes associated with periodontal disease. Therefore, advanced digital-imaging systems may be more cost-effective in a clinical trial because the level of precision will have an effect on study length and sample size.

Alveolar Bone Loss↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. DPD (total, free)].

Urinary deoxypyridinoline (DPD) shows a high specificity for bone, and the measurement of DPD is not influenced by newly collagens and dietary intake. The measurement of free DPD is available by Japanese health insurance. Free DPD excretion above the upper limit of the premenopausal range was associated with increased hip fracture and osteoporotic fracture risk with approximately 2-folds. Total DPD is good predictor of change bone mineral density (BMD) in bone antiresorptive drugs, however, free DPD is inferior to type I -collagen N-telopeptide (NTX).

Amino Acids↗

[Usefulness of assessing bone mineral content of cortical bone in patients with lingering imbalance of bone metabolism].

The CT numbers of cortex at the level of 20 cm (CT20) and of spongiosa in the lateral condyle at 2 cm (CT02) proximally from the distal end of the femur, and the bone mineral density of spongiosa in L3 body (BMD), were obtained by QCT. The study included 48 patients with rheumatoid arthritis or chronic renal failure as well as 10 healthy volunteers. The relationships of CT20 vs BMD in the regions above and below a critical value of BMD were quite different from each other. Similar relationships were observed in the plot of CT20 vs CT02. The results indicated that the demineralization of cortex was much less than that of spongiosa while the mineral content of spongiosa kept higher than a critical value, but the demineralization of cortex surpassed that of spongiosa once the mineral content of spongiosa had become lower than the critical value. It is necessary to assess bone mineral content of cortex especially in patients with lingering imbalance of bone metabolism.

Adult↗

MRI findings in the subchondral bone marrow: a discussion of conditions including transient osteoporosis, transient bone marrow edema syndrome, SONK, and shifting bone marrow edema of the knee.

Bone marrow edema signal can be seen in many settings ranging from trauma and arthritis to less common conditions including transient osteoporosis, transient bone marrow edema syndrome, true osteonecrosis, spontaneous osteonecrosis, and shifting bone marrow edema. Terms such as spontaneous osteonecrosis of the knee (SONK) appear frequently in the radiology and orthopedics literature but are rarely described on true, histologic basis. This article reviews the less frequently encountered and less well understood entities and explores their potential pathophysiologies and significance.

Bone Marrow↗

The effect of nasal hCT on bone turnover in Paget's disease of bone--implications for the treatment of other metabolic bone diseases.

Thirty pagetic patients were treated for 6 months with a daily nasal application of 2 mg of synthetic human calcitonin (hCT). Serum alkaline phosphatases (SAP) and urinary hydroxyproline/creatinine ratio (OH/Cr), reflecting bone turnover, were significantly reduced from the first month of treatment (mean +/- SEM: SAP, -13.9 +/- 2.2%; OH/Cr, -22.2 +/- 5.8%; both P less than 0.01) and until the end of the 6-month course (mean +/- SEM: SAP, -29.7 +/- 4.6%; OH/Cr, -22.5 +/- 5.9%; both P less than 0.01). Nasal hCT was perfectly tolerated both locally and systemically. These results allow us to consider nasal hCT for long-term trials in metabolic bone diseases characterized by a relative increase of bone resorption.

Administration, Intranasal↗

[Bone mineral density (BMD) of the calcaneus bone in 72 dialysis patients measured by ultrasonic bone absorptiometry].

BACKGROUND: To determine what factors contribute to and change BMD in dialysis patients. METHODS: Bone parameters, namely, osteosono-assessment index (calculated by speed of sound and transmission index) were measured at calcaneus bone by ultrasonic bone absorptiometry with an Aloka Acoustic Osteoscreener (Model AOS-100). Seventy two patients were 62. 8 +/- 10.5 years of age (mean +/- SD) (range 36-81) and 70.8% were males; the patients had received dialytic therapy for 52.7 +/- 41.7 months (range 2-205). The effects of sex, age, height, weight, postmenoposal years, dialysis duration, various blood parameters, oral phosphorus binding agent (CaCO3 dosage) and oral vitamin D3 treatment (D3 dosage) on BMD were assessed statistically. RESULT: BMD in male patients were significantly higher than those in female patients (Mann-Whitney test, p < 0.01). BMD showed significant correlations with age (Spearman's correlation coefficient r = -0.384, p < 0.01), height (r = 0.479, p < 0.00001), postmenoposal years (r = -0.692, p < 0.05), dialysis duration (r = 0.250, p < 0.01), blood Ca level (r = 0.292, p < 0.05) and CaCO3 dosage, postmenoposal years and dialysis duration were the variables that significantly correlated with the BMD (multiple correlation coefficient = 0.646).

Adult↗