Short-term Osteoclastic Activity Induced by Locally High Concentrations of Recombinant Human Bone Morphogenetic Protein–2 in a Cancellous Bone Environment

Study Design. An experimental study investigating osteoclastic activity induced by rhBMP-2 in sheep. Objective. To examine the effects of increasing local rhBMP-2 concentration on osteoclastic response and peri-implant bone resorption. Summary of Background Data. Level I clinical studies have established the safe and effective volume and concentration of rhBMP-2 delivered on an absorbable collagen sponge. However, peri-implant bone resorption appearing as decreased mineral density has been observed radiographically in rare instances after implantation of rhBMP-2 on an absorbable collagen sponge (rhBMP-2/ACS). Methods. Bilateral corticocancellous defects were created in the distal femora of 30 adult sheep. Combinations of rhBMP-2/ACS implant volume (V) (1V = normal fill or 2V = overfilled) and rhBMP-2 solution concentration (⤫) (1 ⤫ normal concentration or 3.5 ⤫ = hyperconcentrated) resulted in local rhBMP-2 concentrations of 0⤫, 1⤫, 2⤫, 3.5⤫, and 7⤫ the estimated effective concentration for this model. Faxitron radiography, quantitative CT, histology, and quantitative histomorphometry were conducted in a blinded fashion to analyze the effect of the treatments. Results. At 1 week, the normal fill-normal concentration implants (1⤫) produced the least transient osteoclastic activity resulting in limited peri-implant resorption. Overfilledhyperconcentrated implants (2⤫, 3.5⤫) demonstrated moderate resorption zones. Overfilled-hyperconcentrated implants (7⤫) demonstrated extensive osteoclastic activity and marked resorption. Results at 4 and 8 weeks revealed dense osteoid and bone in the voids with progressive bony healing. Control defects showed no osteoclastic activity with little to no bony healing. Conclusion. Increasing the local rhBMP-2 concentration by overfilling the defect with rhBMP-2/ACS or hyper-concentrating the rhBMP-2 solution on the absorbable collagen sponge led to a concentration-dependent osteoclastic resorption of peri-implant bone. The osteoclastic effect was transient, and progressive healing took place over the 8-week survival period

The solvation and dissociation of 4-benzylaniline hydrochloride in chlorobenzene

A reaction scheme is proposed to account for the liberation of 4-benzylaniline from 4-benzylaniline hydrochloride, using chlorobenzene as a solvent at a temperature of 373 K. Two operational regimes are explored: “closed” reaction conditions correspond to the retention of evolved hydrogen chloride gas within the reaction medium, whereas an “open” system permits gaseous hydrogen chloride to be released from the reaction medium. The solution phase chemistry is analyzed by 1H NMR spectroscopy. Complete liberation of solvated 4-benzylaniline from solid 4-benzylaniline hydrochloride is possible under “open” conditions, with the entropically favored conversion of solvated hydrogen chloride to the gaseous phase thought to be the thermodynamic driver that effectively controls a series of interconnecting equilibria. A kinetic model is proposed to account for the observations of the open system

Protein-Signaled Guided Bone Regeneration Using Titanium Mesh and Rh-BMP2 in Oral Surgery: A Case Report Involving Left Mandibular Reconstruction after Tumor Resection

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein approved for use in oral and maxillofacial defect reconstruction. Growth factors act as mediators of cellular growth on morphogenesis and mythogenesis phases. Utilized as recombinant proteins, these growth factors need the presence of local target cells capable of obtaining the required results. This cell population may be present at the wound site or added to scaffolding material before implantation at the surgical site

Quantitative analysis of the anterolateral ossification mass in diffuse idiopathic skeletal hyperostosis of the thoracic spine

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition leading to ossification of spinal ligaments and has been shown to behave similarly to ankylosing spondylitis (AS) often leading to unstable hyperextension fractures. Currently, no quantitative data are available on the spatial relationship between the bridging anterolateral ossification mass (ALOM) and the vertebral body/intervertebral disc to explain the propensity in DISH to fracture through the vertebral body instead of through the intervertebral disc as more often seen in AS. Furthermore, no reasonable explanation is available for the typical flowing wax morphology observed in DISH. In the current study, a quantitative analysis of computed tomography (CT) data from human cadaveric specimens with DISH was performed to better understand the newly formed osseous structures and fracture biomechanics. Additionally, the results were verified using computed tomography angiography data from ten patients with DISH and ten controls. Transverse CT images were analyzed to obtain ALOM area and centroid angle relative to the anteroposterior axis; intervertebral disc and adjacent cranial and caudal levels. The ALOM area at the mid-vertebral body level averaged 57.9 ± 50.0 mm2; at the mid-intervertebral disc space level it averaged 246.4 ± 95.9 mm2. The mean ALOM area at the adjacent level caudal to the mid-vertebral body level was 169.6 ± 81.3 mm2; at the adjacent cranial level, it was 161.7 ± 78.2 mm2. The main finding was the significant difference between mean ALOM area at the mid-vertebral body level and other three levels (p < 0.0001). The subsequent verification study showed the presence of vertebral segmental arteries at the mid-vertebral body level in nearly all images irrespective of the presence of DISH. A larger area of ALOM seemed associated with increased counter-clockwise rotation (away from the aorta) of the centroid relative to the anteroposterior axis. The results from the present study suggest a predisposition for fractures through the vertebral body and a role for the arterial system in the inhibition of soft tissue ossification

Agency theory and performance appraisal: how bad theory damages learning and contributes to bad management practice

Performance appraisal interviews remain central to how employees are scrutinised, rewarded and sometimes penalised by managers. But they are also often castigated as ineffective, or even harmful, to both individuals and organisations. Exploring this paradox, we highlight the influence of agency theory on the (mal)practice of performance appraisal. The performative nature of human resource management increasingly reflects an economic approach within which its practices are aligned with agency theory. Such theory assumes that actors are motivated mainly or only by economic self-interest. Close surveillance is required to eliminate the risk of shirking and other deviant behaviours. It is a pessimistic mind-set about people that undermines the supportive, co-operative and developmental rhetoric with which appraisal interviews are usually accompanied. Consequently, managers often practice appraisal interviews while holding onto two contradictory mind-sets, a state of Orwellian Doublethink that damages individual learning and organisational performance. We encourage researchers to adopt a more radical critique of appraisal practices that foregrounds issues of power, control and conflicted interests between actors beyond the analyses offered to date

Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome

<p>Abstract</p> <p>Background</p> <p>Autogenous Iliac Crest Bone Graft (ICBG) has been the "gold standard" for spinal fusion. However, bone graft harvest may lead to complications, such as chronic pain, numbness, and poor cosmesis. The long-term impact of these complications on patient function and well-being has not been established but is critical in determining the value of expensive bone graft substitutes such as recombinant bone morphogenic protein. We thus aimed to investigate the long-term complications of ICBG. Our second aim was to evaluate the psychometric properties of a new measure of ICBG morbidity that would be useful for appropriately gauging spinal surgery outcomes.</p> <p>Methods</p> <p>Prospective study of patients undergoing spinal fusion surgery with autologous ICBG. The SF-36v2, Oswestry Disability Index, and a new 14-item follow-up questionnaire addressing persistent pain, functional limitation, and cosmesis were administered with an 83% response rate. Multiple regression analyses examined the independent effect of ICBG complications on physical and mental health and disability.</p> <p>Results</p> <p>The study population included 170 patients with a mean age of 51.1 years (SD = 12.2) and balanced gender (48% male). Lumbar fusion patients predominated (lumbar = 148; cervical n = 22). At 3.5 years mean follow-up, 5% of patients reported being bothered by harvest site scar appearance, 24% reported harvest site numbness, and 13% reported the numbness as bothersome. Harvest site pain resulted in difficulty with household chores (19%), recreational activity (18%), walking (16%), sexual activity (16%), work activity (10%), and irritation from clothing (9%). Multivariate regression analyses revealed that persistent ICBG complications 3.5 years post-surgery were associated with significantly worse disability and showed a trend association with worse physical health, after adjusting for age, workers' compensation status, surgical site pain, and arm or leg pain. There was no association between ICBG complications and mental health in the multivariate model.</p> <p>Conclusion</p> <p>Chronic ICBG harvest site pain and discomfort is reported by a significant percentage of patients undergoing this procedure more than three years following surgery, and these complications are associated with worse patient-reported disability. Future studies should consider employing a control group that does not include autologous bone graft harvest, e.g., a group utilizing rhBMP, to determine whether eliminating harvest-site morbidity does indeed lead to observable improvement in clinical outcome sufficient to justify the increased cost of bone graft substitutes.</p

The Incidence of Adjacent Segment Degeneration after Cervical Disc Arthroplasty (CDA): A Meta Analysis of Randomized Controlled Trials

Cervical disc arthroplasty is being used as an alternative degenerative disc disease treatment with fusion of the cervical spine in order to preserve motion. However, whether replacement arthoplasty in the spine achieves its primary patient centered objective of lowering the frequency of adjacent segment degeneration is not verified yet.We conducted a meta-analysis according to the guidelines of the Cochrane Collaboration using databases including PubMed, Cochrane Central Register of Controlled Trials and Embase. The inclusion criteria were: 1) Randomized, controlled study of degenerative disc disease of the cervical spine involving single segment or double segments using Cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) as controls; 2) A minimum of two-year follow-up using imaging and clinical analyses; 3) Definite diagnostic evidences for "adjacent segment degeneration" and "adjacent segment disease"; 4) At least a minimum of 30 patients per population. Two authors independently selected trials; assessed methodological quality, extracted data and the results were pooled.No study has specifically compared the results of adjacent segment degenerative; Two papers describing 140 patients with 162 symptomatic cervical segment disorders and compared the rate of postoperative adjacent segment disease development between CDA and ACDF treatments, three publications describing the rate of adjacent-segment surgery including 1273 patients with symptomatic cervical segments. The result of the meta-analysis indicates that there were fewer the rate of adjacent segment disease and the rate for adjacent-segment surgery comparing CDA with ACDF, but the difference was not statistically significant.Based on available evidence, it cannot be concluded, that CDA can significantly reduce the postoperative rate of the adjacent segment degenerative and adjacent segment disease. However, due to some limitations, the results of this meta-analysis should be cautiously accepted, and further studies are needed

Use of Carboxymethyl Cellulose and Collagen Carrier with Equine Bone Lyophilisate Suggests Late Onset Bone Regenerative Effect in a Humerus Drill Defect – A Pilot Study in Six Sheep

We assessed the use of a filler compound together with the osteoinductive demineralized bone matrix (DBM), Colloss E. The filler was comprised of carboxymethyl-cellulose and collagen type 1. The purpose of the study was to see if the filler compound would enhance the bone formation and distribute the osteoinductive stimulus throughout the bone defect. Six sheep underwent a bilateral humerus drill defect. The drill hole was filled with a compound consisting of 100 mg CMC, 100 mg collagen powder, and 1 ccm autologous full blood in one side, and a combination of this filler compound and 20 mg Colloss E in the other. The animals were divided into three groups of two animals and observed for 8, 12 and 16 weeks. Drill holes was evaluated using quantitative computed tomography (QCT), micro computed tomography (µCT) and histomorphometry. Mean total bone mineral density (BMD) of each implantation site was calculated with both QCT and µCT. Bone volume to total volume (BV/TV) was analyzed using µCT and histomorphometry. Although not statistically significant, results showed increased bone BMD after 16 weeks in µCT data and an increased BV/TV after 16 weeks in both µCT and histology. Correlation between QCT and µCT was R2 = 0.804. Correlation between histomorphometry and µCT BV/TV data was R2 = 0.8935 and with an average overrepresentation of 8.2% in histomorphometry. In conclusion the CMC-Collagen + Colloss E filler seems like a viable osteogenic bone filler mid- to long term. A correlation was found between the analytical methods used in this study