A comparison of commercially available demineralized bone matrix for spinal fusion

In an effort to augment the available grafting material as well as to increase spinal fusion rates, the utilization of a demineralized bone matrix (DBM) as a graft extender or replacement is common. There are several commercially available DBM substances available for use in spinal surgery, each with different amounts of DBM containing osteoinductive proteins. Each product may have different osteoinductivity potential due to different methods of preparation, storage, and donor specifications. The purpose of this study is to prospectively compare the osteoinductive potential of three different commercially available DBM substances in an athymic rodent spinal fusion model and to discuss the reasons of the variability in osteoinductivity. A posterolateral fusion was performed in 72 mature athymic nude female rats. Three groups of 18 rats were implanted with 1 of 3 DBMs (Osteofil, Grafton, and Dynagraft). A fourth group was implanted with rodent autogenous iliac crest bone graft. The rats were sacrificed at 2, 4, 6, and 8 weeks. A dose of 0.3 cm³ per side (0.6 cm³per animal) was used for each substance. Radiographs were taken at 2 weeks intervals until sacrifice. Fusion was determined by radiographs, manual palpation, and histological analysis. The Osteofil substance had the highest overall fusion rate (14/18), and the highest early 4 weeks fusion rate of (4/5). Grafton produced slightly lower fusion rates of (11/17) overall, and lower early 4 weeks fusion rate of (2/5). There was no statistically significant difference between the rate of fusion after implantation of Osteofil and Grafton. None of the sites implanted with Dynagraft fused at any time point (0/17), and there was a significantly lower fusion rate between the Dynagraft and the other two substances at the six-week-time point and for final fusion rate (P = 0.0001, Fischer’s exact test). None of the autogenous iliac crest animals fused at any time point. Non-decalcified histology confirmed the presence of a pseudarthrosis or the presence of a solid fusion, and the results were highly correlated with the manual testing. Although all products claim to have significant osteoinductive capabilities, this study demonstrates that there are significant differences between some of the tested products.     

Use of demineralized bone matrix in spinal fusion

Spinal fusion remains the gold-standard treatment for several pathological spine conditions. Although, autologous Iliac Crest Bone Grafting is considered the gold-standard graft choice to promote spinal fusion; however, it is associated with significant donor site morbidity and a limited graft quantity. Therefore, several bone graft alternatives have been developed, to augment arthrodesis. The purpose of this review is to present the results of clinical studies concerning the use of demineralized bone matrix (DBM), alone or as a composite graft, in the spinal fusion. A critical review of the English-language literature was conducted on Pubmed, using key word “demineralized bone matrix”, “DBM”, “spinal fusion”, and “scoliosis”. Results had been restricted to clinical studies. The majority of clinical trials demonstrate satisfactory fusion rates when DBM is employed as a graft extender or a graft enhancer. Limited number of prospective randomized controlled trials (4 studies), have been performed comparing DBM to autologous iliac crest bone graft in spine fusion. The majority of the clinical trials demonstrate comparable efficacy of DBM when it used as a graft extender in combination with autograft, but there is no clinical evidence to support its use as a standalone graft material. Additionally, high level of evidence studies are required, in order to optimize and clarify the indications of its use and the appropriate patient population that will benefit from DBM in spine arthrodesis.     

Evaluation of a new formulation of demineralized bone matrix putty in a rabbit posterolateral spinal fusion model

Background contextAlternatives to autologous bone graft (ABG) with osteoconductive, osteoinductive, and osteogenic potential continue to prove elusive. Demineralized bone matrix (DBM) however, with its osteoconductive and osteoinductive potential remains a viable option to ABG in posterolateral spine fusion.PurposeTo compare the efficacy of a new formulation of DBM putty with that of ABG in a rabbit posterolateral spinal fusion model.Study designEfficacy of a new formulation of DBM was studied in an experimental animal posterolateral spinal fusion model.MethodsTwenty-four male New Zealand White rabbits underwent bilateral posterolateral spine arthrodesis of the L5–L6 intertransverse processes, using either ABG (control group, n=12) or DBM (DBM made from rabbit bone) putty (test group, n=12). The animals were killed 12 weeks after surgery and the lumbar spines were excised. Fusion success was evaluated by manual palpation, high resolution X-rays, microcomputed tomography imaging, biomechanical four-point bending tests, and histology.ResultsTwo animals were lost because of anesthetic related issues. Manual palpation to assess fusion success in the explanted lumbar spines showed no statistical significant difference in successful fusion in 81.8% (9/11) of DBM group and 72.7% (8/11) of ABG group (p=.99). Reliability of these assessments was measured between three independent observers and found near perfect agreement (intraclass correlation cofficient: 0.92 and 0.94, respectively). Fusion using high resolution X-rays was solid in 10 of the DBM group and 9 of the ABG group (p=.59). Biomechanical testing showed no significant difference in stiffness between the control and test groups on flexion, extension, and left lateral and right lateral bends, with p values accounting for .79, .42, .75, and .52, respectively. The bone volume/total volume was greater than 85% in the DBM treated fusion masses. Histologic evaluation revealed endochondral ossification in both groups, but the fusion masses were more mature in the DBM group.ConclusionsThe DBM putty achieved comparable fusion rates to ABG in the rabbit posterolateral spinal fusion model.     

Posterolateral lumbar spine fusion using a novel demineralized bone matrix: a controlled case pilot study

Introduction

Intertransverse posterolateral fusion along with instrumentation is a common technique used for spinal fusion. Iliac crest bone graft (ICBG) offers good fusion success rates with a low risk for disease transmission but is, however, linked with certain morbidity. In an effort to eliminate or reduce the amount of iliac graft needed, bone substitutes including demineralized bone matrix (DBM) have been developed. This study evaluates a novel DBM (Accell Connexus^®) used in one or two-level instrumented posterolateral lumbar fusion.

Materials and methods

A total of 59 consecutive patients were studied as two groups. Group 1 consisted of 33 patients having Accell Connexus^® used to augment either ICBG or local decompression material. Group 2 consisted of 26 consecutive patients, operated prior to the introduction of this novel DBM, having either ICBG alone or local decompression material. Fusion was assessed by two independent observers, blinded to graft material, using standardized criteria found in the literature. All adverse events were recorded prospectively.

Results

The results show no statistically significant differences between the two groups in fusion rates, complications, surgery duration, ODI, or pain on VAS. Logistical regression showed no relation between fusion and age, smoking status or comorbidities. Furthermore, no adverse events related to the use of the novel DBM were observed.

Conclusion

The results from this study demonstrate that the novel DBM presented performs equally as well as that of autologous bone, be it either ICBG or a local decompression material, and can therefore be used as a graft extender.

     

新型硫酸钙和脱钙骨基质混合物的临床应用

目的 评价新型硫酸钙和脱钙骨基质混合物作为骨移植替代物的临床应用效果. 方法 2005年2月至2008年2月采用新型人工骨移植治疗51例患者,按照植入物不同分为两组:人工骨与自体骨混合组21例,即植人硫酸钙和脱钙骨基质混合物加自体骨;单纯人工骨组30例,只植入硫酸钙和脱钙骨基质混合物.术后定期复查,观察人工骨吸收和新骨生长情况. 结果 51例切口一期愈合,无局部红肿、渗出.3例患者失访,48例随访6～36个月,平均16个月.单纯人工骨组术后4周可见人工骨部分吸收,颗粒形态模糊,术后8～12周(平均9.6周)完伞吸收,可见新生骨质,术后8～16周(平均11周)骨性愈合.人工骨与自体骨混和组术后8～12周(平均11.5周)人工骨颗粒完全吸收,骨折不愈合患者术后14～24周(平均19周)获骨性愈合,其余患者术后9～20周(平均13周)获骨性愈合. 结论 新型人工骨能够发挥增加移植物容量、促进骨生成的作用,无局部不良反应,是一种安全有效的骨移植替代物.     

Efficacy comparison of Accell Evo3 and Grafton demineralized bone matrix putties against autologous bone in a rat posterolateral spine fusion model

Background Context

Spinal fusion procedures are intended to stabilize the spinal column for a multitude of disorders including abnormal curvature, traumatic instability, degenerative instability, and damage from infections or tumors. As an aid in the bone healing response, bone graft materials are used to bridge joints for arthrodesis and promote unions in pseudoarthrosis. Currently, the gold standard for stabilizing fusion masses in spinal procedures involves using the osteogenic, osteoinductive, and osteoconductive properties of autologous iliac crest corticocancellous bone. However, considerable morbidity is associated with harvesting the autologous graft. Donor site complications including infection, large hematomas, and pain have been reported at rates as high as 50% (Boden and Jeffrey, 1995). Biologically, the rate of bone repair dictates the rate at which the fusion mass will unite under autologous graft conditions.

Effects of gamma irradiation on osteoinduction associated with demineralized bone matrix

Gamma irradiation is frequently used to sterilize implanted devices but has limitations when used on biologically active materials and composites. In this study, we have evaluated the changes of biological activity of demineralized bone matrix (DBM) in the dry state and in the presence of aqueous and non‐aqueous carriers while exposed to various levels of ionizing radiation. The activity of DBM in the dry state remains relatively stable with only a small loss of activity. Composites of DBM with a carrier such as lecithin, to which no water has been added, lose activity at approximately the same rate as DBM in the anhydrous form. In composites that contain water, the loss of activity occurs even at much lower levels of radiation exposure. Gamma irradiation does not change cell attachment to the DBM matrix but has an influence on both stem cell and osteoprecursor cell proliferation rates. Because of the limitations imposed by radiation, it seems most practical to handle DBM aseptically throughout the procedures of compositing pastes, putties, or suspensions, and only if necessary exposing the inert excipients to radiation sterilization prior to mixing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:75–82, 2008     

脱钙骨基质在四肢植骨中应用的有效性及安全性的系统评价与Meta分析

目的研究脱钙骨基质（DBM）在四肢植骨手术中的疗效,对所有已获得的数据进行系统综述和Meta分析,评价DBM在四肢植骨手术中作为骨移植替代物的有效性及安全性。 方法在PubMed、MEDLINE,EMBASE和Cochrane协作网图书馆中进行文献检索。检索DBM在四肢植骨手术中的应用,根据文献纳入标准进行选择。重点选择数据可以被提取以及能够进行Meta分析的文章。 结果44项研究符合纳入标准,其中随机对照试验3篇,病例系列研究27篇,病例-对照研究14篇。所有的研究报告均未报道DBM作为移植物,融合部位出现破坏或者移位。 结论1项病例系列研究认为,使用Allomatrix DBM作为自体骨移植的替代品,其极高的并发症风险是不可接受的。余下43项研究报告得出的结果均为DBM与自体骨和其他骨移植替代材料相比较具有非劣效性,根据患者的随访报告结果可以认为DBM作为骨移植替代材料的融合率和安全性是有保障的,但是这方面证据的数量和质量是非常有限的。     

一种高效制备工艺对脱钙骨基质性能的影响

目的 目前脱钙骨基质生产工艺耗时长效率低,浪费资源和成本.本研究在保存骨诱导活性的前提下,显著缩短了脱钙骨基质的工艺时间.方法 采用动态脱钙和二次换酸工艺制备脱钙骨基质,对pH值、钙含量进行评价.用裸鼠体内植入实验评价这种脱钙骨基质骨诱导活性.结果 材料的pH值为6.2±0.3,呈弱酸性.钙含量为(0.6±0.2)％,符合＜6％的标准.裸鼠体内植入后创面一期愈合,无不良反应发生.其骨诱导活性阳性,4周时可见大量的新生骨组织、骨髓样组织和软骨化成骨现象.结论 该工艺可以提高脱钙骨基质生产效率,不影响材料活性.     

The effects of demineralized bone matrix and direct current on an "in vivo" culture of bone marrow cells

Bone marrow cells (BMCs) from rabbit femora and tibiae were grown in diffusion chambers implanted in rabbit muscle. At 42 days 80% of the BMC chambers exhibited cartilage formation within them. Demineralized bone matrix added to the marrow cell suspension in the chamber accelerated the appearance and increased the number of chambers with cartilage. Mineralization of the cartilage also occurred earlier in the chambers with bone matrix. In a second experiment, a 5-microA direct current cathode in the bone marrow chamber increased the number of chambers containing cartilage from 50 to 80% at day 25. Mineralization also occurred earlier in the chambers with direct current.     

An update on bone substitutes for spinal fusion

With the current advances in spinal surgery, an understanding of the precise biological mechanism of each bone substitute is necessary for inducing successful spinal fusion. In this review, the categories of bone substitutes include allografts, ceramics, demineralized bone matrix, osteoinductive factors, autogenous platelet concentrate, mesenchymal stem cells, and gene therapy. Further, clinical studies have been evaluated by their levels of evidence in order to elucidate the precise effect of the bone substitute employed and to establish clinical guidance. This article will review both clinical studies based on evidence and basic research in current advances in order to avoid as far as possible any chances of failure in the future and to understand cellular biology in novel technologies.     

低温保存对人骨髓基质干细胞在脱钙骨上体外增殖及成骨能力的影响

目的研究低温保存对人骨髓基质干细胞(BMSCs)在脱钙骨(DBM)上生长特性及成骨能力的影响。方法取3例志愿者骨髓(3～5mL),密度梯度离心、差速贴壁法获得BMSCs。第3代BMSCs在-196℃下保存24h,37℃复苏,测定细胞成活率。低温保存前、后的BMSCs分别用成骨诱导液诱导培养,至90%融合时,收集细胞接种在DBM支架上,并测定细胞在DBM上的粘附率。DiI荧光染料标记BMSCs,例置相差显微镜、荧光显微镜和SEM观察低温保存前、后的BMSCs在DBM上的生长及基质分泌情况,MTT法测定细胞在DBM上的增殖活性。通过测定碱性磷酸酶(ALP)活性和骨钙素(OCN)含量观察细胞在DBM上的成骨能力。结果复苏细胞的存活率为(90．24±0．02)%。低温保存前、后的BMSCs在DBM上的粘附率分别为(97．25±1．17)%和(97．00±1．09)%。倒置相差显微镜及SEM观察显示低温保存前、后的BMSCs在DBM上粘附、生长良好,有大量细胞外基质分泌、沉积。低温保存前、后的BMSCs在DBM上MTT吸光度值和ALP活性的检测结果差异无显著性意义(P＞0．05)；体外培养12d时,MTT吸光度值及ALP活性同时达到峰值。低温保存前、后的BMSCs在DBM上分泌OCN的量差异无显著性意义(P＞0．05),OCN含量随着培养时间延长而不断上升,在观察期(16d)内未出现平台期。结论低温保存对人BMSCs在DBM上的体外增殖、粘附及成骨能力影响差异无显著性意义,低温保存的人BMSCs可作为组织工程骨的种子细胞。     

Decal bone matrix as a local antibiotic delivery vehicle in a MRSA-infected bone model: An experimental study

Background:

Polymethyl methacrylate (PMMA) antibiotic beads though have proved their utility as a local antibiotic delivery system, however, there are limitations. Decalcified bone matrix (DBM) as a vehicle of antibiotics can serve the purpose, provided a minimum inhibitory concentration is sustained. Healing of the defect and avoiding the second surgery is another advantage. We studied the DBM as the delivery vehicle for vancomycin in controlling the methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis as well as healing of the cavity simultaneously in an experimental study.

Materials and Methods:

An in vitro study was conducted to optimize vancomycin impregnation in the DBM. For the in vivo study, a unicortical defect was created in the metaphysis of the distal femur in 18 rabbits. After contaminating the defect with MRSA, rabbits were divided into three groups. Group I (eight limbs) received no graft. Defects in group II (11 limbs) were filled with plain DBM chips and in group III (14 limbs), cavities were implanted with vancomycin-impregnated decal bone chips. Rabbits were assessed by clinical, radiological, histological, gross examination and bacterial load assay. High Performance Liquid Chromatography HPLC analysis of vancomycin in group III was done to assess the concentration in DBM chips.

Results:

In group I, the infection persisted throughout the period of the study. Group II showed the fulminated infection at the grafted site with DBM chips sequestrating out. Vancomycin-impregnated decal chips in group III did not show any sign of infection and eventually incorporated. The bacterial load study showed a progressive load change and HPLC revealed an effective antibiotic concentration up to 3 weeks in both in vitro and in vivo.

Conclusion:

Decal bone chips were effective as the local antibiotic delivery vehicle in preventing the MRSA osteomyelitis model. It eluted vancomycin significantly and the graft uptake was also excellent. Allogeneic decal grafts eliminated the need for second surgery and acted as an excellent delivery vehicle for antibiotics.     

The use of demineralized bone matrix for anterior cruciate ligament reconstruction: a radiographic,histologic, and immunohistochemical study in rabbits

Tendon-bone healing is crucial in success of anterior cruciate ligament (ACL) reconstruction surgery. Demineralized bone matrix (DBM) is a physiological component that has the inherent potential of bone regeneration. We hypothesized that the alternative bone substitute can affect the structural properties of tendon graft in tibial tunnel healing. Five 12-week-old New Zealand white rabbits in study group underwent unilateral ACL reconstructions plus the application of 0.5 cc DBM in the tibial tunnel. The assessment included radiological assessment and histologic and immunohistochemical analyses. Radiological examination revealed that DBM group had the least displacement of tendon in tibial tunnel (0.4 ± 0.12; P = 0.03). Histologic examination showed significantly better integration between tendon and bone in DBM group (77.62 ± 2.08; P = 0.001). On immunohistochemical analysis, the DBM group showed significantly higher expressions of bone morphogenetic protein-2 and vascular endothelial growth factor than control group (51.98 ± 3.02, 84.06 ± 1.86; P = 0.001, P < 0.001). DBM enhances the tendon-bone healing in ACL reconstruction. DBM has the potential use in ACL surgery.     

A systematic review of comparative studies on bone graft alternatives for common spine fusion procedures

Background

The increased prevalence of spinal fusion surgery has created an industry focus on bone graft alternatives. While autologous bone graft remains the gold standard, the complications and morbidity from harvesting autologous bone drives the search for reliable and safe bone graft substitutes. With the recent information about the adverse events related to bone morhogenetic protein use, it is appropriate to review the literature about the numerous products that are not solely bone morphogenetic protein.

Purpose

The purpose of this literature review is to determine the recommendations for use of non-bone morphogenetic protein bone graft alternatives in the most common spine procedures based on a quantifiable grading system.

Study design

Systematic literature review.

Methods

A literature search of MEDLINE (1946–2012), CINAHL (1937–2012), and the Cochrane Central Register of Controlled Trials (1940–April 2012) was performed, and this was supplemented by a hand search. The studies were then evaluated based on the Guyatt criteria for quality of the research to determine the strength of the recommendation.

Results

In this review, more than one hundred various studies on the ability of bone graft substitutes to create solid fusions and good patient outcomes are detailed.

Conclusion

The recommendations for use of bone graft substitutes and bone graft extenders are based on the strength of the studies and given a grade.     

The effects of doxorubicin (adriamycin) on spinal fusion: an experimental model of posterolateral lumbar spinal arthrodesis

BACKGROUND CONTEXT: Malignant spinal lesions may require surgical excision and segmental stabilization. The decision to perform a concomitant fusion procedure is influenced in part by the need for adjunctive chemotherapy as well as the patient's anticipated survival. Although some evidence exists that suggests that chemotherapy may inhibit bony healing, no information exists regarding the effect of chemotherapy on spinal fusion healing. PURPOSE: To determine the effect of a frequently used chemotherapeutic agent, doxorubicin, on posterolateral spinal fusion rates. STUDY DESIGN/SETTING: Prospective animal model of posterolateral lumbar fusion. OUTCOME MEASURES: Determination of spinal fusion by manual palpation of excised spines. Plain radiographic evaluation of denuded spines to evaluate intertransverse bone formation. METHODS: Thirty-two New Zealand White rabbits underwent posterior intertransverse process fusion at L5-L6 with the use of iliac autograft bone. Rabbits randomly received either intravenous doxorubicin (2.5 mg/kg) by means of the central vein of the ear at the time of surgery (16 animals) or no treatment (16 animals; the control group). The animals were euthanized at 5 weeks, and the lumbar spines were excised. Spine fusion was assessed by manually palpating (by observers blinded to the treatment group) at the level of arthrodesis, and at the adjacent levels proximal and distal. This provided similar information to surgical fusion assessment by palpation in humans. Fusion was defined as the absence of palpable motion. Posteroanterior radiographs of the excised spines were graded in a blinded fashion using a five-point scoring system (0 to 4) devised to describe the amount of bone observed between the L5-L6 transverse processes. Power analysis conducted before initiation of the study indicated that an allocation of 16 animals to each group would permit detection of at least a 20% difference in fusion rates with statistical significance at p=.05. RESULTS: Eleven of the 16 spines (69%) in the control group and 6 of the 16 spines (38%) in the doxorubicin group fused. This difference was statistically significant (=.038). There was no significant correlation (p>.05) between the radiographic grade of bone formation (0 to 4) and fusion as determined by palpation. There were four wound infections in the control group and four in the doxorubicin group. However, solid fusions were palpated in three of these four spines in both the control and treatment groups. CONCLUSIONS: No significant differences in wound complications were noted with doxorubicin administration. A single dose of doxorubicin administered intravenously at the time of surgery appears to play a significant inhibitory role in the process of spinal fusion. If similar effects occur in humans, these data suggest that doxorubicin may be harmful to bone healing in a spine fusion if given during the perioperative period. Further investigation will be necessary to determine the effect of time to aid at determining whether doxorubicin administered several weeks pre- or postoperatively results in improved fusion rate, and whether bone morphogenetic proteins can overcome these inhibitory effects.     

A poly(propylene glycol-co-fumaric acid) based bone graft extender for lumbar spinal fusion: in vivo assessment in a rabbit model

Study design: An animal model of posterolateral intertransverse process lumbar spinal fusion compared fusion rates amongst autologous bone (group 1), a porous, bioabsorbable, scaffold based on the biopolymer, poly(propylene glycol-co-fumaric acid) (PPF) (group 2), and a combination of autograft and the bioabsorbable scaffold (group 3). Objectives: To evaluate the feasibility of augmenting spinal fusion with an osteoconductive and bioabsorbable scaffold as an alternative or as an adjunct, i.e., an extender, to autograft. Summary of background data: There is little preclinical data on applications of bioabsorable bone graft extenders in spinal fusion. Methods: New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were treated with one of three materials: autologous bone (group 1), a bioabsorable material based on PPF (group 2), and the PPF biopolymer scaffold with autologous bone graft (group 3). Animals were evaluated at 6 weeks, and fusion was evaluated by manual palpation, and radiographic, histologic, and histomorphometric analyses. Results: Radiographic and manual palpation showed evidence of fusion in all three groups. Histomorphometric measurement of bone ingrowth showed the highest quantity of new bone in group 3 (91%), followed by group 1 (72%) and group 2 (53%). Conclusions: Results of this study suggested that osteoconductive bioabsorbable scaffolds prepared from PPF might be used as an autograft extender when applied as an adjunct to spinal fusion.     

BMP‐2 delivered via sucrose acetate isobutyrate (SAIB) improves bone repair in a rat open fracture model

Human bone morphogenetic proteins (BMPs) are an alternative to bone graft for the treatment of high‐energy open fractures. The standard delivery system for BMP‐2 is a porous collagen sponge, but we have previously found that the biocompatible, high viscosity carrier, Sucrose acetate isobutyrate (SAIB) is an effective and potentially less invasive alternative. The efficacy of SAIB as a BMP‐2 delivery system was examined in an open fracture model featuring a femoral osteotomy with periosteal stripping in 9‐week‐old male Sprague Dawley rats. SAIB containing BMP‐2 (SAIB/BMP‐2) was delivered into the fracture site during surgery and an additional group was further co‐treated with zoledronic acid and hydroxyapatite nanoparticles (SAIB/BMP‐2/HA/ZA). These were compared to untreated fractures and SAIB carrier alone (negative controls), and BMP‐2 loaded collagen sponge (positive control). The rate of radiographic union and the biomechanical properties of the healed fractures were compared after 6–week. Untreated and SAIB‐treated fractures showed poor repair, with 53% and 64%, respectively, not bridged at 6 week. In contrast, collagen/BMP‐2, SAIB/BMP‐2, and SAIB/BMP‐2/HA/ZA showed significantly increased union (100%, 100%, and 94%, respectively, p < 0.05). Four‐point bend testing revealed that collagen/BMP‐2 and SAIB/BMP‐2/HA/ZA restored the strength of fractured femora to that of intact femora by 6 week, whereas untreated and SAIB remained less than intact controls by 60% and 67%, respectively (p < 0.05). Overall, the SAIB/BMP‐2/HA/ZA formulation was comparable to BMP‐2 infused collagen sponge in terms of promoting open fractures repair, but with the additional potential for less invasive delivery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1168–1176, 2016.     

Mandibular bone loss in an animal model of male osteoporosis (orchidectomized rat): a radiographic and densitometric study

In humans, hypogonadism is associated with osteoporosis and can be studied by densitometry (DXA) on the vertebrae or long bones. There is some controversy about the relationships between bone loss in these sites and in the mandible. Osteoporosis has been suggested as a risk factor for dental problems. In the rat, orchidectomy (ORX) is associated with an increased bone resorption resulting in bone loss. We have studied the time effects of ORX on the alveolar bone in the rat. Forty-eight male Wistar rats were divided into four groups and studied over 2, 4, 8 and 16 weeks. In each group, six rats were ORX and six sham-operated (SHAM) animals were used as control. The mandible of each rat was dissected. Numeric radiographs, centered on the molar region, were obtained. Bone loss was observed qualitatively at 16 weeks in ORX animals. Quantitative modifications were confirmed by texture analysis of numeric radiographs using the run-length technique. The bone mineral content (BMC) and density (BMD) of the hemimandible and in a region centered on the molars were measured by DXA. The coefficient of variation (CV) for BMC was poor on the whole bone and no differences could be observed even at 16 weeks. For BMC of the molar region, the CV was improved and significant bone loss occurred in the ORX group at 16 weeks (P<0.016). This study confirms that in the male rat, the reduction of sex hormones induced by ORX is associated with a decrease in bone mass in the mandible.     

Tendon to bone tunnel healing—A study on the time‐dependent changes in biomechanics,bone remodeling,and histology in a rat model

Tendons and ligaments attach to bone through a transitional connective tissue with complex biomechanical properties. This unique tissue is not regenerated during healing, and surgical reattachment therefore often fails. The present study was designed to evaluate tendon healing in a bone tunnel and to evaluate the utilized rat model. Wistar rats (n = 61) were operated with the Achilles tendon through a bone tunnel in the distal tibia. Healing was evaluated at 2, 3, 4, and 12 weeks by biomechanical testing, bone mineral density and histology. After 2 weeks median (interquartile range) pull‐out force was 2.2 N (1.9). The pull‐out force increased chronologically, by 12 weeks fivefold to 11.2 N (11.4). Energy absorption, stiffness, and bone mineral density increased similarly. The histological analyses showed inflammation at early stages with increasing callus by time. Our data showed a slow healing response the first 4 weeks followed by an accelerated healing period, favoring that most of the gain in mechanical strength occurred later than 4 weeks postoperatively. These findings support the concern of a vulnerable tendon bone tunnel interface in the early stages of healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:216–223, 2015.