Stress relaxation function of bone and bone collagen

Relaxation Young's and shear moduli of bovine bone and bone collagen were investigated. It was found that each relaxation process observed had two stages, which were referred to as process I and process II in order of time. Process II was described by a simple exponential decay while process I was not. The Kohlrausch-Williams-Watts (KWW) function, ψ(t) = exp[t/τ₁)^B] (0 < B < 1), was found to be suitable to describe process I. The normalized relaxation modulus, M_r(t), was expressed by the combination of the simple exponential type relaxation function and the KWW function

M_r=A₁exp[−(t/τ₁)^B]+A₂exp[(t/τ₁)](0<B1)

On the basis of this equation, the relaxation mechanism in bone and bone collagen was identified. According to the model proposed for the KWW relaxation function, the stress relaxation process in bone was considered to be governed by viscoelastic properties of matrix collagen fiber. The model for the KWW relaxation function requires the disordered glassy structure of collagen fiber, which is consistent with the results of the structural investigations.     

Neuropeptidergic regulation of bone resorption and bone formation

Immunohistochemical studies have revealed an extensive network of nerve fibers in the vicinity and within the skeleton, not only in the periosteum of bone but also in cortical and trabecular bone as well as in the bone marrow. Phenotyping of the skeletal nerve fibers have demonstrated the expression of a restrictive panel of different signalling molecules including neuropeptides, neurotransmitters and neurotrophins. In this review, the presence of receptors for the neuropeptides vasoactive intestinal peptide, calcitonin gene-related peptide and substance P on osteoblasts and osteoclasts and the capacity of these receptors to regulate bone formation, osteoclast formation and activity are described. These findings, together with data obtained by chemically and surgically targeted nerve deletion and observations made in paraplegic patients, strongly suggest that neuro-osteogenic interactions play an important role in skeletal function.     

High bone density and bone health

The aim of this paper is to review the main aspects related to high bone density (HBD) as well as to discuss the physiologic mechanisms involved in bone health. There are still no well-defined criteria for identification of individuals with HBD and there are few studies on the topic. Most studies demonstrate that overweight, male gender, black ethnic background, physical activity, calcium and fluoride intake and use of medications such as statins and thiazide diuretics play a relevant and positive role on bone mineral density. Moreover, it is known that individuals with certain diseases such as obesity, diabetes, estrogen receptor-positive breast or endometrial cancer have greater bone density than healthy individuals, as well as athletes having higher bone density than non-athletes does not necessarily mean that they have healthy bones. A better understanding of risk and protective factors may help in the management of patients with bone frailty and have applicability in the treatment and in the prevention of osteoporosis, especially intervening on non-modifiable risk factors.     

Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation.     

From bone biology to bone analysis

Bone development is one of the key processes characterizing childhood and adolescence. Understanding this process is not only important for physicians treating pediatric bone disorders, but also for clinicians and researchers dealing with postmenopausal and senile osteoporosis. Bone densitometry has great potential to enhance our understanding of bone development. The usefulness of densitometry in children and adolescents would be increased if the physiological mechanisms and structural features of bone were given more consideration in the design and interpretation of densitometric studies. This review gives an overview on the most relevant techniques of quantitative noninvasive bone analysis. Furthermore it describes the relationship between bone biology, selected surrogates describing the biological processes and the possibilities of measuring these surrogates specifically and precisely by the different devices. The overall recommendation for researchers in this field is to describe firstly the biological process to be analyzed (bone growth in length, remodeling or modeling, or all together), secondly the bone parameter which describes this process, and thirdly the reason for selecting a special device.     

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).     

Enhanced bone screw fixation with biodegradable bone cement in osteoporotic bone model

Purpose: The purpose of this study was to study the potential of novel biodegradable PCL bone cement to improve bone screw fixation strength in osteoporotic bone. Methods: The biomechanical properties of bone cement (ε-polycaprolactone, PCL) and fixation strength were studied using biomechanical tests and bone screws fixed in an osteoporotic bone model. Removal torques and pullout strengths were assessed for cortical, self-tapping, and cancellous screws inserted in the osteoporotic bone model (polyurethane foam blocks with polycarbonate plate) with and without PCL bone cement. Open cell and cellular rigid foam blocks with a density of 0.12 g/cm3 were used in this model. Results: Removal torques were significantly (more than six-fold) improved with bone cement for cancellous screws. Furthermore, the bone cement improved pullout strengths three to 12 times over depending on the screw and model material.?Conclusions: Biodegradable bone cement turned out to be a very potential material to stabilize screw fixation in osteoporotic bone. The results warrant further research before safe clinical use, especially to clarify clinically relevant factors using real osteoporotic bone under human body conditions and dynamic fatigue testing for long-term performance.     

Stromal cells of the bone marrow in growing bone

By means of electron microscopy, cytochemistry and radioautography with 3H-thymidine, the bone marrow stromal cells have been studied in the zones of endochondral osteogenesis in the rabbit and rat femoral bones. In the stromal cells demonstrating a high alkaline phosphatase activity are distinguished: perivascular, reticular fibroblastic, osteogenic cells. Populations of the perivascular phosphatase-positive cells include poorly differentiated DNA-synthesizing forms, as well as cells with signs of differentiation into stromal fibroblasts. Cleft-like spaces in cytoplasm of the fibroblastic reticular cells are, probably, formed as a result of lymphocyte-like mononuclears passing through. Phagocyting stromal elements are presented by macrophages, having perivascular localization and including into composition of erythroblastic islets. Mononuclear macrophages are revealed also on the surface of osseous trabecules, where they participate in destruction of hemopoetic and osteogenic cells.     

Expression of bone morphogenetic proteins during membranous bone healing

For the reconstructive plastic surgeon, knowledge of the molecular biology underlying membranous fracture healing is becoming increasingly vital. Understanding the complex patterns of gene expression manifested during the course of membranous fracture repair will be crucial to designing therapies that augment poor fracture healing or that expedite normal osseous repair by strategic manipulation of the normal course of gene expression. In the current study, we present a rat model of membranous bone repair. This model has great utility because of its technical simplicity, reproducibility, and relatively low cost. Furthermore, it is a powerful tool for analysis of the molecular regulation of membranous bone repair by immunolocalization and/or in situ hybridization techniques. In this study, an osteotomy was made within the caudal half of the hemimandible, thus producing a stable bone defect without the need for external or internal fixation. The healing process was then catalogued histologically in 28 Sprague-Dawley rats that were serially killed at 1, 2, 3, 4, 5, 6, and 8 weeks after operation. Furthermore, using this novel model, we analyzed, within the context of membranous bone healing, the temporal and spatial expression patterns of several members of the bone morphogenetic protein (BMP) family, known to be critical regulators of cells of osteoblast lineage. Our data suggest that BMP-2/-4 and BMP-7, also known as osteogenic protein-1 (OP-1), are expressed by osteoblasts, osteoclasts, and other more primitive mesenchymal cells within the fracture callus during the early stages of membranous fracture healing. These proteins continue to be expressed during the process of bone remodeling, albeit less prominently. The return of BMP-2/-4 and OP-1 immunostaining to baseline intensity coincides with the histological appearance of mature lamellar bone. Taken together, these data underscore the potentially important regulatory role played by the bone morphogenetic proteins in the process of membranous bone repair.     

Extracts of bone contain a potent regulator of bone formation

We prepared aqueous extracts of whole femorae and tibiae of embryonic chicks. An amount of extract containing 25 μg of protein resulted in a 500% increase in DNA synthesis in calvarial cell cultures, and significant effects were detected with 5 μg (55%). The time course for stimulation of DNA synthesis showed a peak occurring 16–20 h after addition of the extract. This matrix factor is nondialyzable, and fractionation on a column of Sephadex G-100 indicated a molecular weight of 60–80 000. At the maximum dose used, [³H]proline incorporation into total protein of calvarial cells was increased by 55%, and thus far, all fractions active in promoting DNA synthesis have been found to increase collagen synthesis in culture chick tibiae. These data are consistent with an effect on osteoblasts as well as bone precursor cells. Extracts prepared from tibiae of 2-day-old chicks, from which the marrow had been removed, also stimulated DNA synthesis (280% increase), thus ruling out the possibility that the factor is a relatively nonspecific mitogen from the hematopoietic cell line. We conclude that bone matrix contains a substance which could regulate bone formation in vitro by control of mitosis in osteogenic precursors and/or stimulation of osteoblast activity.     

The bone pencil and the bone surgeon

While helpful for preoperative skin markings, methylene blue is washed away by irrigation and tissue fluids during bony reconstruction. The bone pencil is an ideal marker for hard tissue because it is indelible to irrigation. Further, the surgeon may draw with ease in areas of limited access (i.e., sagittal split and intraoral vertical ramus osteotomies). The pencil can be obtained from most art suppliers. No adverse effects from use of the pencil have been noted in any of our patients.     

Repair of bone defects using dynamic fabricated tissue-engineered bone based on a bio-derived porous bone scaffold

Fabrication and transplantation of tissue-engineered bones in a rotating wall vessel bioreactor (RWVB) was studied in the present study aiming to repair segmental bone defects. Osteoblasts were transfected with green fluorescent protein prior to seeding on bio-derived porous bone scaffolds at a density of 1?×?10⁶?cells/mL and cultured in an RWVB for one week. For comparison, constructs were also cultured in a static condition. Morphology and structure of fabricated bones were examined using an inverted microscope, scanning electron microscope and histology analysis via hematoxylin–eosin and toluidine blue staining. Moreover, an animal model for repairing segmental bone defects of a Zelanian rabbit was used to assess the efficacy and biosafety of fabricated bones. In conclusion, tissue-engineered bones grew favorably in RWVB. In animal study, a preliminary repair of bone defects was noticed only in the experimental group after 4 weeks of implantation. Using RWVB, the fabricated tissue-engineered bone constructs were approved with better bio-capability in repairing the segmental bone defect.     

A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease

Background  

Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease.     

肿瘤细胞和骨微环境在骨转移中的作用

随着肿瘤治疗水平的提高,肿瘤患者的生存期显著延长,转移性骨肿瘤的发生率呈增长趋势.骨转移引起的剧烈的临床症状和其较长的潜伏期,以及缺乏有效的治疗方法,极大降低了患者的生活质量.本文主要综述了骨转移相关的细胞特征及骨微环境在骨转移中的作用,并分析了影响骨转移形成的相关分子因素,为骨转移的定向分子治疗提供进一步的理论依据.     

Impact of bone events on survival in solitary bone plasmacytoma

BackgroundAlthough much studied in multiple myeloma, bone events (BE) can also cause important morbidity in bone plasmacytoma patients. To our knowledge, the effect of BE on overall survival (OS) and progression to multiple myeloma free-survival (MPFS) also has never been studied.Patients and MethodsFifty-nine patients treated from 2008 to 2017 were retrospectively assessed. All patients had histological proof of disease and were treated with radical radiotherapy (RT). Available clinical information for at least 6 months follow-up or until death had to be available. BE were described as one of the following events in the index bone: fractures, osteomyelitis, chronic pain, surgery or loss of limb function after RT.ResultsMean age at diagnosis was 57.3 years (18–80); most male (67.8%). Mean OS, bone event free-survival (BEFS), local progression-free survival (LPFS) and MPFS were 41, 36, 37 and 19 months, respectively. There were 15 deaths. BEFS (p = 0.008) and age>55y (p = 0.044) were associated with MPFS. Only BEFS correlated with OS (p = 0.029). BE was independently associated with both MPFS and OS in multivariate analysis.ConclusionBE and survival end-points were correlated. BE should be investigated in prospective trials.