How can bone turnover modify bone strength independent of bone mass?

The amount of bone turnover in the skeleton has been identified as a predictor of fracture risk independent of areal bone mineral density (aBMD) and is increasingly cited as an explanation for discrepancies between areal bone mineral density and fracture risk. A number of mechanisms have been proposed to explain how bone turnover influences bone biomechanics, including regulation of tissue degree of mineralization, the disconnection or fenestration of individual trabeculae by remodeling cavities, and the ability of cavities formed during the remodeling process to act as stress risers. While these mechanisms can influence bone biomechanics, they also modify bone mass. If bone turnover is to explain any of the observed discrepancies between fracture risk and areal bone mineral density, however, it must not only modify bone strength, but must also modify bone strength in excess of what would be expected from the associated change in bone mass. This article summarizes biomechanical studies of how tissue mineralization, trabecular disconnection, and the presence of remodeling cavities might have an effect on cancellous bone strength independent of bone mass. Existing data support the idea that all of these factors may have a disproportionate effect on bone stiffness and/or strength, with the exception of average tissue degree of mineralization, which may not affect bone strength independent of aBMD. Disproportionate effects of mineral content on bone biomechanics may instead come from variation in tissue degree of mineralization at the micro-structural level. The biomechanical explanation for the relationship between bone turnover and fracture incidence remains to be determined, but must be examined not in terms of bone biomechanics, but in terms of bone biomechanics relative to bone mass.     

Radionuclide studies of bone metabolism: do bone uptake and bone plasma clearance provide equivalent measurements of bone turnover?

Quantitative radionuclide imaging using (18)F-fluoride positron emission tomography (18F-PET) or (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans provides a novel tool for studying regional and whole skeleton bone turnover that complements the information provided by biochemical markers. Radionuclide bone scans can be quantified by measuring either tracer uptake or, if blood sampling is performed, bone plasma clearance. This study examines whether these two methods provide equivalent information about bone turnover. We examined data from two clinical trials of the bone anabolic agent teriparatide. In Study 1 twenty osteoporotic women had 18F-PET scans of the lumbar spine at baseline and after 6 months treatment with teriparatide. Bone uptake in the lumbar spine was expressed as standardised uptake values (SUV) and blood samples taken to evaluate plasma clearance. In Study 2 ten women had (99m)Tc-MDP scans at baseline, 3 and 18 months after starting teriparatide. Blood samples were taken and whole skeleton plasma clearance and bone uptake calculated. In Study 1 spine plasma clearance increased by 23.8% after 6-months treatment (P=0.0003), whilst SUV increased by only 3.0% (P=0.84). In Study 2 whole skeleton plasma clearance increased by 37.1% after 18-months treatment (P=0.0002), whilst the 4-hour whole skeleton uptake increased by only 25.5% (P=0.0001). During treatment the 18F- plasma concentration decrease by 20% and (99m)Tc-MDP concentration by 13%, and these latter changes were sufficient to explain the differences between the uptake and plasma clearance results. Measurements of response to treatment using bone uptake and plasma clearance gave different results because the effects of teriparatide on bone resulted in a sufficiently increased demand for radionuclide tracer from the skeleton that the concentration in the circulation decreased. Similar effects may occur with other therapies that have a large enough effect on bone metabolism. In these circumstances changes in bone plasma clearance give a truer impression of response to treatment than those in SUV or uptake.     

Study of gelatinized marrow stroma osteoblasts and true bone ceramic active bone

Trueboneceramic(TBC)isacomparativelygoodframematerialinbonetissueengineeringbecauseofitsadvantagesofnaturalbonetrabeculestructure, easydegradation, nonimmunogenicity, easymanufacture, abundantresources, andlowcost, etc1.Owingtoitsfragileness, nonductility, andasmoothsurfaceunfitforseedcelladhesion, itisstilldifficultforwidespreadclinicaluse. Bytakingadvantageofthepeculiaritiesofsodiumalginatethatwilltransformfromliquidstateintogelatinationstateandproducelateralconjunctionwhencombiningwithbiva…     

Microcracks in cortical bone: How do they affect bone biology?

Microcrack accumulation in cortical bone has been implicated in skeletal fragility and stress fractures. These cracks have also been shown to affect the mechanical and material properties of cortical bone. Their growth has been linked to osteocyte apoptosis and the initiation of the remodeling process, which also has a role in their repair. Clinically, osteoporosis is diagnosed using dual energy x-ray absorptiometry. However, evidence now indicates that bone mass alone is insufficient to satisfactorily explain the skeletal fragility of osteoporosis and consideration needs to be given to bone quality in the diagnosis and treatment of the disease. Bone quality includes parameters such as trabecular and cortical microarchitecture, morphology, bone turnover, degree of mineralization of the bone matrix, and significantly, the amount of microdamage present in the bone. Current clinical treatments concentrate on the inhibition of osteoclast activity to maintain bone mass in osteoporotic patients. However, these cells have a major role in removing existing microcracks from the bone matrix, and hence the use of bone resorption-inhibiting drugs may lead to insufficient bone repair and therefore an increase in microdamage accumulation and loss of bone quality.     

Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice

onemorphogenetic proteins (BMPs)haveapowerfulcapacitytoelicitnewboneformation .ThereareseveraldeliverymethodsofBMPsintreatingbonedefects ,oneofwhichisgenetherapy .Retrovirus,adenovirusandadeno associatedvirushavebeenutilizedtodeliverBMPgene .1,2 Sincethedirectuseofthesevectorshasseveraldisadvantages ,wehavedevelopedexvivo genetherapytechniquewhichinvolvestheisolationandcultivationofautologousbonemarrow derivedmesenchymalstemcells (MSCs) ,transfectionofthecellsinvitroandimplantationofthesec…     

Does early PTH treatment compromise bone strength? The balance between remodeling,porosity, bone mineral,and bone size

The treatment of osteoporotic women with recombinant human parathyroid hormone (rhPTH[1-34]) increases bone mineral density and reduces fracture risk. However, there has been concern that the initiation of therapy in women with low bone mass may cause an early and transient increased fracture risk because PTH stimulates bone remodeling, which in its first phase is associated with bone resorption. Animal and human studies suggest, however, that the stimulation of remodeling caused by rhPTH(1–34) does not lead to a deterioration of bone’s mechanical properties or to an increased fracture risk even early in the treatment. There are several reasons for this. Bone biomarkers associated with formation rise earlier than those associated with resorption, suggesting that there is an initial period prior to the stimulation of remodeling during which bone formation occurs on surfaces without prior resorption. This initial period of formation may protect the patient from the later small and transient losses that occur through remodeling. Moreover, the increased remodeling occurs on cancellous surfaces or close to the endosteal surface of bone, where its mechanical effect is minimal. Additionally, these transient losses may be compensated by periosteal apposition that maintains the overall strength of the bone. Thus, the early stimulation of bone formation without prior resorption, and the redistribution of bone from cancellous and endocortical surfaces to the periosteal surface combine to prevent the mechanical deterioration that could otherwise occur with a transient acceleration of bone remodeling in a patient with low bone mass.     

The role of radioisotopes for the palliation of bone pain from bone metastases

Bone metastasis occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequences occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. Pain associated with osseous metastasis is thought to be distinct from neuropathic or inflammatory pain. Several mechanisms, such as invasion of tumor cells, spinal cord astrogliosis, and sensitization of nervous system, have been postulated to cause pain. Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates. These drugs are associated with side effects, and tolerance to these agents necessitates treatment with other modalities. Bisphosphonates act by inhibiting osteoclast-mediated resorption and have been increasingly used in treatment of painful bone metastasis. While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions, bone-seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. ^32p has been used for over 3 decades in the treatment of multiple osseous metastases. The myelosuppression caused by this agent has led to the development of other bone-seeking radiopharmaceuticals, including ^89SrCl, and ^153Sm-ethylenediaminetetramethylene phosphonic acid （^153Sm-EDTMP）. ^89Sr is a bone-seeking radionuclide, whereas ^153Sm-EDTMP is a bone-seeking tetraphosphonate; both have been approved by the Food and Drug Administration for the treatment of painful osseous metastases. While both agents have been shown to have efficacy in the treatment of painful osseous metastases from prostate cancer, they may also have utility in the treatment of painful osseous metastases from breast cancer and perhaps from non-small cell lung cancer. This article illustrates the salient features of these radiopharmaceuticals, including the approved dose, method of administration, and indications for use.     

The role of radioisotopes for the palliation of bone pain flrOm bone metastases

~~The role of radioisotopes for the palliation of bone pain flrOm bone metastases[1]Neeta PT，Maria Batraki BS，Chaitanya RD．Radiopharmaceuticaltherapy for palliation of bone pain from osseous nK[astases Jotlr-nal of Nuclear Medicine．2004．45：l 358-136     

Growth factors and bone regeneration: how much bone can we expect?

A large body of research has investigated the use of growth factors for bone regeneration, as a potential alternative to autogenous bone grafting. The bone morphogenetic proteins (BMPs) represent the most extensively investigated growth factors to date, as potential therapeutic agents for bone regeneration. Despite decades of research, the ideal growth factor or combination of growth factors for bone regeneration remains undefined. This article reviews the current available evidence for the application of growth factors for bone regeneration, with a focus on the clinical evidence for BMP use. Emerging pre-clinical and clinical evidence for growth factors other than the BMPs is also discussed.     

BIO-OSS--a resorbable bone substitute?

BIO-OSS is an allergen-free bone substitute material of bovine origin, used to fill bone defects or to reconstruct ridge configurations. Seventy one patients (39 female, 32 male) received 126 BIO-OSS implantations. Some health parameters or habits were documented to eliminate possible risk factors of influence. The diameter of jaw defects filled with BIO-OSS was measured. There was a significant influence of the defect size on the healing result. In X-ray controls, BIO-OSS served to identify the surrounding native bone. The density of the BIO-OSS areas was higher than in control sites. These radiological results were supported by bone biopsies. Histologically, the permanency of the BIO-OSS was still recognizable after 6 years and longer. The ingrowth of newly formed bone in the BIO-OSS scaffold explained the increased density of the implanted regions. There were no clinical signs of BIO-OSS resorption. Therefore, we can assume that form corrections achieved by BIO-OSS insertions will last.     

Does bone mass equate with bone health? An argument for the negative.

This article argues that diagnosing osteopenias and osteoporoses by bone mass Z-scores, and viewing disorders detected in that way as diseases, fostered a belief that those scores evaluate whole-bone strength and bone health equally well (here, mass has its meaning in absorptiometry, not in physics). However, load-bearing bones normally adapt their strength to the past and present voluntary loads on them in ways that make strong muscles make strong bones, and make persistently weak muscles make weak bones. The resulting adaptations also make bones strong enough to keep voluntary mechanical usage from fracturing them. Such observations suggest a new criterion for a bone's health that would depend on the relationship among its strength, the size of the voluntary loads it carries, and any spontaneous fractures caused by those loads. Such a relationship could indicate a bone"s health independently of its mass. For example, mouse and horse femurs differ in strength more than 1000-fold, but they could be equally healthy if they were to satisfy that criterion in the animals from which they come. That idea would distinguish abnormal in a strictly statistical sense (which T- and Z-scores would evaluate) from unhealthy in the sense of both abnormal and diseased (which the above relationship would evaluate). Thus, a bone with a negative Z-score could still be healthy if voluntary loads do not fracture it. These ideas and some of their implications question some long-held views. This article presents the ideas, evidence they stand on, and some of their implications.     

How tough is bone? Application of elastic–plastic fracture mechanics to bone

Bone, with a hierarchical structure that spans from the nano-scale to the macro-scale and a composite design composed of nano-sized mineral crystals embedded in an organic matrix, has been shown to have several toughening mechanisms that increases its toughness. These mechanisms can stop, slow, or deflect crack propagation and cause bone to have a moderate amount of apparent plastic deformation before fracture. In addition, bone contains a high volumetric percentage of organics and water that makes it behave nonlinearly before fracture. Many researchers used strength or critical stress intensity factor (fracture toughness) to characterize the mechanical property of bone. However, these parameters do not account for the energy spent in plastic deformation before bone fracture. To accurately describe the mechanical characteristics of bone, we applied elastic-plastic fracture mechanics to study bone's fracture toughness. The J integral, a parameter that estimates both the energies consumed in the elastic and plastic deformations, was used to quantify the total energy spent before bone fracture. Twenty cortical bone specimens were cut from the mid-diaphysis of bovine femurs. Ten of them were prepared to undergo transverse fracture and the other 10 were prepared to undergo longitudinal fracture. The specimens were prepared following the apparatus suggested in ASTM E1820 and tested in distilled water at 37 degrees C. The average J integral of the transverse-fractured specimens was found to be 6.6 kPa m, which is 187% greater than that of longitudinal-fractured specimens (2.3 kPa m). The energy spent in the plastic deformation of the longitudinal-fractured and transverse-fractured bovine specimens was found to be 3.6-4.1 times the energy spent in the elastic deformation. This study shows that the toughness of bone estimated using the J integral is much greater than the toughness measured using the critical stress intensity factor. We suggest that the J integral method is a better technique in estimating the toughness of bone.     

Loading-related reorientation of bone proteoglycan in vivo. Strain memory in bone tissue?

The load-carrying capacity of the skeleton is achieved and maintained as the result of a continued functional stimulus to the cell populations responsible for bone remodeling. Although some bone cells have been assumed to be influenced by the load-induced changes in strain throughout the matrix, no evidence is available to indicate which cells are susceptible to such strain change or how such transient events provide a sustained influence on cell behaviour. In the present study, we showed that a short period of dynamic loading in vivo affects the orientation of proteoglycan within bone tissue. This reorientation declines only slowly, thus providing a persistent record of the tissue's recent strain history. Such a record has the ability not only to "capture" strain transients but also to "update" and "average" them. In this way, the bone cells could be presented with a sustained and coherent stimulus directly related to dynamic strain transients. These transients are the tissue's principal function variable.     

Hybrid grafting of post-traumatic bone defects using β-tricalcium phosphate and demineralized bone matrix

Objectives

Management of post-traumatic bone defects continues to be a substantial clinical challenge in orthopaedic trauma. This retrospective study evaluates the results of primary hybrid grafting of residual bone defects or voids, in displaced and comminuted long-bone fractures treated by plate fixation, using β-tricalcium phosphate and demineralized bone matrix.

Materials and Methods

Fifty-four patients having 62 fractures were included. Their mean age was 40.7 ± 10.7 years; femoral and tibial fractures were the commonest (70.9 %) in this study. Eight fractures (12.9 %) were open injuries; 13 fractures had critical-sized defects that averaged 3.4 ± 0.9 cm. Cortical bone defects occurred in 51 cases, and cancellous bone voids in eleven. Eleven patients (20 %) were polytraumatized. Tobramycin powder was added to the graft in all open fractures. The functional outcome was evaluated according to a modified Karlström and Olerud criteria.

Results

All fractures (100 %) had solid union without any implant failure. There was a significant delayed union (P < 0.001) in all critical-sized defects. The mean healing time showed a highly significant difference (P < 0.001) between closed and open fractures. The functional outcome was excellent in 28 fractures, good in 21 fractures, fair in nine fractures and poor in four fractures.

Conclusions

We believe that the ideal bone graft substitute for all situations does not exist; however, this hybrid grafting is a very good alternative to autogenous grafts especially in polytraumatized patients and when massive bone grafting is needed to reconstruct more than one bone in absence of segmental defects.     

Your diagnosis? Aneurysmal bone cyst

The etiology of aneurysmal bone cysts is uncertain, but they may originate as a localized arteriovenous malformation. These benign lesions can be primary or occur secondary to an underlying lesion. The majority of patients who present with aneurysmal bone cysts are younger than age 20 years. One half of lesions occur within the long bones and one third involve the spine. Most flat bone lesions, approximately 10%, occur in the pelvis. Fluid-fluid levels are common on CT and MRI but are not pathognomonic. Although aneurysmal bone cyst is benign, there may be aggressive clinical and imaging features. Treatment for aneurysmal bone cyst is surgical curettage, intraoperative adjuvant therapy, and bone grafting of the lesion. The prognosis following treatment is very good, although 10% to 20% of cases are reported to recur.     

Temporal bone fracture and its complications

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The effect of bone porosity on the shear strength of the bone–cement interface

This study investigated the relationship of bone porosity and bone–cement interface shear strength. One hundred forty-six samples were taken from the distal metaphysis of 20 bovine femora. After cementation, the shear strength of the bone–cement interface was tested. According to the porosity, the samples were divided into four groups. Group I (porosity <80%) had a median interface shear strength of 4.03 MPa, group II (80% ≤porosity <85%) 7.06 MPa, group III (85% ≤porosity <90%) 9.44 MPa, and group IV (porosity ≥90%) 14.85 MPa. The differences between the four groups were statistically significant. Greater porosity yielded a stronger bone–cement interface shear strength under the identical cementation technique. The optimum porosity of cancellous bone is more than 90% which can be found by reaming or drilling to deeper bone in cemented acetabular fixation.

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Résumé  L’objet de cette étude est d’apprécier les relations entre la porosité osseuse et l’interface ciment-os. 146 échantillons osseux prélevés sur la métaphyse distale de 20 fémurs bovins ont permis de tester l’interface ciment-os après cimentation. suivant leur degré de porosité, les échantillons ont été divisés en 4 groupes. Groupe I porosité < 80% avec des forces, au niveau de l’interface de 4,03 MPa, groupe II porosité comprise entre 80 et 85% (7,06 MPa), groupe III porosité comprise entre 85 et 90% (9,44 MPa) et groupe IV porosité inférieure à 90% (14,85 MPa). Les différences entre ces 4 groupes sont statistiquement significatives. une plus grande porosité permet l’application de forces plus importantes au niveau de l’interface ciment-os après cimentation. La porosité optimum au niveau de l’os spongieux doit être supérieur à 90% et cette porosité peut être augmentée par l’alésage et les trous d’ancrages au niveau de la zone de fixation acétabulaire.

     

Are bone autografts still necessary in 2006? A three-year retrospective study of bone grafting

Autograft is considered as the gold standard in bone grafting. However, the development of tissue banks has allowed for a wider use of bone allografts, with good results. Demineralised Bone Matrix (DBM) and recombinant human Bone Morphogenetic Proteins (rh-BMP's) were also introduced to replace the time-honoured autograft. Is there currently still a place for bone autograft? The authors reviewed the orthopaedic surgical activity in their institution during the period 2003-2005, and traced all the surgical procedures in which bone grafting was performed. Tracking forms from the tissue bank were reviewed to assess the surgical indications. Between 2003 and 2005, the use of autografts decreased from 1.3% to 0.9% of all surgical interventions, particularly owing to their decreased use in primary fusions, while the use of allografts increased from 10.7% to 12.7%. Indications for allografts covered all fields of orthopaedic surgery, including nonunions. Processed allografts represented 90% of all grafts used. DBM and rh-BMP were used on an exceptional basis. There is currently a trend for surgeons to use allografts as substitutes for autografts, as processing of the allografts increases their safety while preserving most of their biological and mechanical properties. Autografting is now limited to revision operations after failed fusions, and to combined use at the junction with massive allografts. DBM and rh-BMP are still controversial but they might replace autografts, even in their currently remaining indications, if their cost effectiveness and efficiency are established.