Dilemma in pediatric mandible fractures: resorbable or metallic plates?

PubMed

Taylan Filinte, Gaye; Akan, İsmail Mithat; Ayçiçek Çardak, Gülçin Nujen; Özkaya Mutlu, Özay; Aköz, Tayfun

2015-12-01

The aim of this study was to compare the efficiency of resorbable and metallic plates in open reduction and internal fixation of mandible fractures in children. Thirty-one patients (mean age, 8.05 years; range 20 months-14 years) were operated on various fractures of the mandible (26 [60.4%] symphysis- parasymphysis, 12 [27.9%] condylar-subcondylar fractures, 5 [11.6%] angulus and ramus fractures). Twelve patients were treated with resorbable plates and 19 patients with metallic plates. Mean follow-up time was 41 months (11-74 months) in the metallic hardware group and was 22 months (8-35 months) in the resorbable plate group. Both groups were investigated for primary bone healing, complications, number of operations, and mandibular growth. The results were discussed below. Both groups demonstrated primary bone healing. Minor complications were similar in both groups. The metallic group involved secondary operations for plate removal. Mandibular growth was satisfactory in both groups. Resorbable plates cost more than the metallic ones; however, when the secondary operations are included in the total cost, resorbable plates were favourable. As mandibular growth and complication parameters are similar in both groups, resorbable plates are favored due to avoidance of potential odontogenic injury, elimination of long-term foreign body retention and provision of adequate stability for rapid bone healing. However, learning curve and concerns for decreased stability against heavy forces of mastication accompanied with the resorbable plates when compared to the metallic ones should be kept in mind.

Novel resorbable glass-ceramic scaffolds for hard tissue engineering: from the parent phosphate glass to its bone-like macroporous derivatives.

PubMed

Bretcanu, Oana; Baino, Francesco; Verné, Enrica; Vitale-Brovarone, Chiara

2014-05-01

One of the major challenges of hard tissue engineering research focuses on the development of scaffolds that can match the mechanical properties of the host bone and resorb at the same rate as the bone is repaired. The aim of this work was the synthesis and characterization of a resorbable phosphate glass, as well as its application for the fabrication of three dimensional (3-D) scaffolds for bone regeneration. The glass microstructure and behaviour upon heating were analysed by X-ray diffraction, differential scanning calorimetry and hot stage microscopy. The glass solubility was investigated according to relevant ISO standards using distilled water, simulated body fluid (SBF) and Tris-HCl as testing media. The glass underwent progressive dissolution over time in all three media but the formation of a hydroxyapatite-like layer was also observed on the samples soaked in SBF and Tris-HCl, which demonstrated the bioactivity of the material. The glass powder was used to fabricate 3-D macroporous bone-like glass-ceramic scaffolds by adopting polyethylene particles as pore formers: during thermal treatment, the polymer additive was removed and the sintering of glass particles was allowed. The obtained scaffolds exhibited high porosity (87 vol.%) and compressive strength around 1.5 MPa. After soaking for 4 months in SBF, the scaffolds mass loss was 76 wt.% and the pH of the solution did not exceed the 7.55 value, thereby remaining in a physiological range. The produced scaffolds, being resorbable, bioactive, architecturally similar to trabecular bone and exhibiting interesting mechanical properties, can be proposed as promising candidates for bone repair applications.

Vertical ridge augmentation with autogenous bone grafts 3 years after loading: resorbable barriers versus titanium-reinforced barriers. A randomized controlled clinical trial.

PubMed

Merli, Mauro; Lombardini, Francesco; Esposito, Marco

2010-01-01

To compare the efficacy of two different techniques for vertical bone regeneration at implant placement with particulated autogenous bone at 3 years after loading: resorbable collagen barriers supported by osteosynthesis plates and nonresorbable titanium-reinforced expanded polytetrafluoroethylene barriers. Twenty-two partially edentulous patients requiring vertical bone augmentation were randomly allocated to two treatment groups, each composed of 11 patients. Prosthetic and implant failures, complications, the amount of vertically regenerated bone, and peri-implant marginal bone levels were recorded by independent and blinded assessors. The implant site requiring the most vertical bone regeneration was selected in each patient for bone level assessment. The follow-up time ranged from provisional loading to 3 years after loading. Analysis of covariance and paired t tests were conducted to compare means at the .05 level of significance. No patient dropped out or was excluded at the 3-year follow-up. No prosthetic failures and no implant failures or complications occurred after loading. There was no statistically significant difference in bone loss between the two groups at either 1 year or 3 years. Both groups had gradually lost a statistically significant amount of peri-implant bone at 1 and 3 years (P < .05). After 3 years, patients treated with resorbable barriers had lost a mean of 0.55 mm of bone; patients who had received nonresorbable barriers showed a mean of 0.53 mm of bone loss. Up to 3 years after implant loading, no failures or complications occurred and peri-implant marginal bone loss was minimal. Vertically regenerated bone can be successfully maintained after functional loading.

A clinical evaluation of resorbable hydroxylapatite for the repair of human intra-osseous defects.

PubMed

Corsair, A

1990-01-01

One of the goals of periodontal therapy is actual hard- and soft-tissue regeneration or at least the functional repair of periodontal defects. Alloplastic materials used in the past included dense hydroxylapatite grafts which were non-resorbable and often exfoliated. A new resorbable hydroxylapatite biomaterial [OsteoGen (HA RESORB)] was used during flap surgery. After the usual initial therapy, full-thickness flaps were elevated. A through debridement of the roots and osseous defects was accomplished. The defects were measured and then filled with OsteoGen. The mean initial bone defect depth was 4.47 mm. These defects were re-evaluated by the probing of bone levels after a 4-6-month healing period. A mean of 2.26 mm of new bone fill was obtained. This represents an average fill of 51%. Seventeen of the 22 defects had 42% or more actual new bone fill. No foreign body reaction or exfoliation occurred.

Secondary closure of alveolar cleft with resorbable collagen membrane and a combination of intraoral autogenous bone graft and deproteinized anorganic bovine bone

PubMed Central

Aly, Lobna Abdel Aziz; Hammouda, Nelly

2016-01-01

Objects: Secondary alveolar bone grafting is a method that enables an excellent oral rehabilitation of the patients having alveolar cleft. The aim of this work is to report the closure of the alveolar cleft with the use of harvested autogenous bone graft combined with deproteinized anorganic bovine bone (Bio-Oss) under local anesthesia. Settings and Sample Population: Nine patients with age range, 8–11 years were consulted for their unilateral alveolar cleft. Materials and Methods: A combination of symphyseal bone and deproteinized bovine bone mineral (DBBM) was placed into the alveolar cleft defect. Clinical and radiographical assessments were performed at 1, 3, and 6 months postoperatively. Results: The healing period was uneventful in all cases, and no complications, such as membrane exposure, infection, or harvest site morbidity, were observed. All treated defect sites exhibited excellent bone formation, with an average of 5.45 mm (range, 2–9 mm; standard deviation 1.93 mm) of augmentation achieved overall. Conclusion: The treatment of vertically deficient alveolar ridges with guided bone regeneration using a mixture of autogenous bone and DBBM and resorbable collagen membrane can be considered successful, using this technique in an out-patient office setting. PMID:28299252

[Our experience about the use of resorbable plates in the treatment of craniostenosis].

PubMed

Grassiot, B; Delabar, V; Szathmari, A; Beuriat, P A; Paulus, C; Mottolese, C

2015-09-01

The use of resorbable plates increases for craniosynostosis surgery. This material, based on polymere (PLA, PGA) can replace steel wire and non resorbable plates. A few studies present surgical results about the use of this material with a long follow-up. We present our ten years experience of using resorbable material for craniosynostosis treatment in children. Between 2002 and 2012, we operated 283 craniosynostosis (98 scaphocephalies, 55 trigonocephalies, 79 plagiocephalies et 51 craniofaciostenoses). Among these surgeries, 211 were realized with resorbable material (plates and screws). Different criteria were observed: the esthetic result, the infection rate, the re-intervention, the bone defects and the inflammatory granuloma. Among the 211 craniosynostosis, we found 62 plagiocephalies, 66 scaphocephalies, 50 trigonocephalies, 33 craniofaciostenoses. All the reconstructions were realized with the same resorbable material (Macropore by Medtronic). The rate of complications was low: one scar infection without participation of material for two patients (0.9%), a pseudo-meningocele for two patients (0.9%), epilepsy for four children (1.8%) and bone defect for 15 (7%). We observed no granuloma for these patients. Our experience of ten years using resorbable material is very satisfactory. This material permits to realize solid and esthetic reconstructions with a low rate of infection without dangerous reaction for children in young age. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A Retrospective Tomographic and Histologic Analysis of Horizontal Bone Augmentation in Maxillary Atrophic Ridges Using Resorbable Membrane with Anorganic Bovine Bone-Derived Mineral and Plasma Rich in Growth Factors.

PubMed

Lorenzetti, Massimo; Vono, Maurizio; Lorenzetti, Virginia

2018-02-16

A total of six patients treated from 2010 to 2014, having a knife-edge ridge (Cawood-Howell Class IV resorbed ridges) and requiring an implant-prosthetic rehabilitation, were selected. Tomographic measurement of the edentulous ridges was performed before grafting and after implant placement. At 6 months postgraft, a total of 41 implants had been inserted, 17 in the posterior region, 12 in the central region, and 12 in the anterior region. No surgical or healing complications were recorded, and the prostheses were loaded 6 to 9 months after implant placement. The tomographic measurements demonstrated an increased area in all the sites where bone augmentation had been performed, corresponding to 11.1% in the anterior region, 94.7% in the central region, and 760.2% in the posterior region. Histology was performed in 2 patients, one at 1 year and the other at 5 years postgrafting, and demonstrated the presence of mature lamellar bone tissue and newly formed bone without morphologic signs of necrosis or inflammation and a reduction of 50% to 30% of the grafted material. Although this study included a small number of clinical cases, it demonstrated how management of the atrophic maxillary ridge, with the goal of implant placement, may be handled using a technique that requires a single anorganic bovine bone-derived mineral treatment combined with a plasma rich in growth factors and resorbable collagen membrane.

Osteoclasts prefer aged bone.

PubMed

Henriksen, K; Leeming, D J; Byrjalsen, I; Nielsen, R H; Sorensen, M G; Dziegiel, M H; Martin, T John; Christiansen, C; Qvist, P; Karsdal, M A

2007-06-01

We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of aged bones. Osteoclasts resorb aging bone in order to repair damage and maintain the quality of bone. The mechanism behind the targeting of aged bone for remodeling is not clear. We investigated whether bones endogenously possess the ability to control osteoclastic resorption. To biochemically distinguish aged and young bones; we measured the ratio between the age-isomerized betaCTX fragment and the non-isomerized alphaCTX fragment. By measurement of TRACP activity, CTX release, number of TRACP positive cells and pit area/pit number, we evaluated osteoclastogenesis as well as osteoclast resorption on aged and young bones. We found that the alphaCTX/betaCTX ratio is 3:1 in young compared to aged bones, and we found that both alpha and betaCTX are released by osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared to young bones, and the difference was enhanced under low serum conditions. We found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology. These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones.

Treatment of intrabony defects with resorbable materials, non-resorbable materials and flap debridement.

PubMed

Zybutz, M D; Laurell, L; Rapoport, D A; Persson, G R

2000-03-01

Different types of barriers are used in guided tissue regenerative procedures. This prospective study compared resorbable citric acid ester softened polylactic acid membranes (RM) and non-resorbable expanded polytetrafluoroethylene (ePTFE) barriers (NRM) in GTR treatment of intrabony defects. 29 subjects were randomly assigned to the RM group or NRM group. Each patient received one GTR procedure. An open flap debridement (FD) was performed at another site 2 weeks later to evaluate healing potential. Clinical treatment outcomes were finally evaluated 12 months after surgery for changes of pocket depth PD, probing attachment level PAL, and probing bone level PBL, and radiographically for bone change using standardised radiographs. No differences in healing patters after surgery were found between patients in the 2 study groups as evaluated from the FD surgical procedures. NRM treated sites showed less signs of post-surgical inflammation during the 1st 4 weeks of healing than did RM treated sites (p<0.05). GTR-treated defects in the RM group, initially 7.0+/-2.2 mm deep, showed PD reduction of 3.3+/-2.2 mm, PAL gain of 2.4+/-1.8 mm, PBL gain of 2.4+/-3.7 mm (28%) and a radiographic bone fill of 2.3+/-2.4 mm. Defects treated with the NRM exhibited PD reduction of 3.1+/-2.1 mm, PAL gain of 2.4+/-0.8 mm, PBL gain of 2.2+/-1.7 mm (25%) and a radiographic bone fill of 3.3+/-2.2 mm. All improvements were statistically significant (p<0.01) but there was no difference between RM and NRM treatments for any of the efficacy variables. The results of this study indicated that there was no clinically significant difference in treatment outcomes following GTR treatment of intrabony defects with citric acid ester softened polylactic acid membranes as compared to ePTFE barriers. The overall mean inter-proximal vertical bone defect fill at 12 months as assessed from intra-oral radiographs was 44% of the original mean defect depth. Thus, no clinically significant difference in

Resorbable versus titanium plates for orthognathic surgery.

PubMed

Fedorowicz, Z; Nasser, M; Newton, J T; Oliver, R J

2007-04-18

Recognition of some of the limitations of titanium plates and screws used for the fixation of bones has led to the development of plates manufactured from bioresorbable materials. Whilst resorbable plates appear to offer clinical advantages over metal plates in orthognathic surgery, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. To compare the effectiveness of bioresorbable fixation systems with titanium systems used during orthognathic surgery. We searched the following databases: Cochrane Oral Health Group Trials Register (to 26th January 2006); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 4); MEDLINE (without filter) (from 1966 to 26th January 2006); and EMBASE (without filter) (from 1980 to 26th January 2006). Randomised controlled trials comparing resorbable versus titanium fixation systems used for orthognathic surgery. Clinical heterogeneity between the included trials precluded pooling of data, and only a descriptive summary is presented. This review included two trials, involving 103 participants, one compared titanium with resorbable plates and screws and the other titanium with resorbable screws, both provided very limited data for the primary outcomes of this review. All patients in one trial suffered mild to moderate postoperative discomfort with no statistically significant difference between the two plating groups at different follow-up times. Mean scores of patient satisfaction were 7.43 to 8.63 (range 0 to 10) with no statistically significant difference between the two groups throughout follow up. Adverse effects reported in one study were two plate exposures in each group occurring between the third and ninth months. Plate exposures occurred mainly in the posterior maxillary region, except for one titanium plate exposure in the mandibular premolar region. Known causes of infection were associated

Resorbable versus titanium plates for orthognathic surgery.

PubMed

Agnihotry, Anirudha; Fedorowicz, Zbys; Nasser, Mona; Gill, Karanjot S

2017-10-04

Recognition of some of the limitations of titanium plates and screws used for the fixation of bones has led to the development of plates manufactured from bioresorbable materials. Whilst resorbable plates appear to offer clinical advantages over metal plates in orthognathic surgery, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. This review compares the use of titanium versus bioresorbable plates in orthognathic surgery and is an update of the Cochrane Review first published in 2007. To compare the effects of bioresorbable fixation systems with titanium systems used during orthognathic surgery. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 January 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched 20 January 2017); MEDLINE Ovid (1946 to 20 January 2017); and Embase Ovid (1980 to 20 January 2017). We searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 20 January 2017), and the World Health Organization International Clinical Trials Registry Platform (searched 20 January 2017) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing bioresorbable versus titanium fixation systems used for orthognathic surgery in adults. Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies. We resolved disagreement by discussion. Clinical heterogeneity between the included trials precluded pooling of data, and only a descriptive summary is presented. This review included two trials, involving 103 participants, one comparing titanium with resorbable plates and screws and

Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: A Histologic and Biomechanical Assessment.

PubMed

Ramalingam, Sundar; Basudan, Amani; Babay, Nadir; Al-Rasheed, Abdulaziz; Nooh, Nasser; Nagshbandi, Jafar; Aldahmash, Abdullah; Atteya, Muhammad; Al-Hezaimi, Khalid

2016-01-01

Guided bone regeneration (GBR) using a porcine-derived collagen matrix (Mucograft [MG], Geistlich) has not yet been reported. The aim of this histologic and biomechanical study was to compare the efficacy of MG versus resorbable collagen membranes (RCMs) in facilitating GBR around standardized rat calvarial defects. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A 4.6-mm-diameter standardized calvarial defect was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) MG group: the defect was covered with MG; (2) RCM group: the defect was covered with an RCM; (3) MG + bone group: the defect was filled with bone graft particles and covered by MG; and (4) RCM + bone group: the defect was filled with bone graft particles and covered by an RCM. Primary closure was achieved using interrupted resorbable sutures. The animals were sacrificed at 8 weeks after the surgical procedures. Qualitative histologic analysis and biomechanical assessment to identify hardness and elastic modulus of newly formed bone (NFB) were performed. Collected data were statistically analyzed using one-way analysis of variance. Histologic findings revealed NFB with fibrous connective tissue in all groups. The quantity of NFB was highest in the RCM + bone group. Statistically significant differences in the hardness (F = 567.69, dfN = 3, dfD = 36, P < .001) and elastic modulus (F = 294.19, dfN = 3, dfD = 36, P < .001) of NFB were found between the groups. Although the RCM + bone group had the highest mean ± standard deviation (SD) hardness of NFB (531.4 ± 24.9 MPa), the RCM group had the highest mean ± SD elastic modulus of NFB (18.63 ± 1.89 GPa). The present study demonstrated that RCMs are better than MG at enhancing new bone formation in standardized

Design and Optimization of Resorbable Silk Internal Fixation Devices

NASA Astrophysics Data System (ADS)

Haas, Dylan S.

Limitations of current material options for internal fracture fixation devices have resulted in a large gap between user needs and hardware function. Metal systems offer robust mechanical strength and ease of implantation but require secondary surgery for removal and/or result in long-term complications (infection, palpability, sensitivity, etc.). Current resorbable devices eliminate the need for second surgery and long-term complications but are still associated with negative host response as well as limited functionality and more difficult implantation. There is a definitive need for orthopedic hardware that is mechanically capable of immediate fracture stabilization and fracture fixation during healing, can safely biodegrade while allowing complete bone remodeling, can be resterilized for reuse, and is easily implantable (self-tapping). Previous work investigated the use of silk protein to produce resorbable orthopedic hardware for non- load bearing fracture fixation. In this study, silk orthopedic hardware was further investigated and optimized in order to better understand the ability of silk as a fracture fixation system and more closely meet the unfulfilled market needs. Solvent-based and aqueous-based silk processing formulations were cross-linked with methanol to induce beta sheet structure, dried, autoclaved and then machined to the desired device/geometry. Silk hardware was evaluated for dry, hydrated and fatigued (cyclic) mechanical properties, in vitro degradation, resterilization, functionalization with osteoinductive molecules and implantation technique for fracture fixation. Mechanical strength showed minor improvements from previous results, but remains comparable to current resorbable fixation systems with the advantages of self-tapping ability for ease of implantation, full degradation in 10 months, ability to be resterilized and reused, and ability to release molecules for osteoinudction. In vivo assessment confirmed biocompatibility, showed

Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets.

PubMed

Aruwajoye, Olumide O; Kim, Harry K W; Aswath, Pranesh B

2015-04-01

Ischemic osteonecrosis of the femoral head (IOFH) can lead to excessive resorption of the trabecular bone and collapse of the femoral head as a structure. A well-known mineral component to trabecular bone is hydroxyapatite, which can be present in many forms due to ionic substitution, thus altering chemical composition. Unfortunately, very little is known about the chemical changes to bone apatite following IOFH. We hypothesized that the apatite composition changes in necrotic bone possibly contribute to increased osteoclast resorption and structural collapse of the femoral head. The purpose of this study was to assess the macroscopic and local phosphate composition of actively resorbed necrotic trabecular bone to isolate differences between areas of increased osteoclast resorption and normal bone formation. A piglet model of IOFH was used. Scanning electron microscopy (SEM), histology, X-ray absorbance near edge structure (XANES), and Raman spectroscopy were performed on femoral heads to characterize normal and necrotic trabecular bone. Backscattered SEM, micro-computed tomography and histology showed deformity and active resorption of necrotic bone compared to normal. XANES and Raman spectroscopy obtained from actively resorbed necrotic bone and normal bone showed increased carbonate-to-phosphate content in the necrotic bone. The changes in the apatite composition due to carbonate substitution may play a role in the increased resorption of necrotic bone due to its increase in solubility. Indeed, a better understanding of the apatite composition of necrotic bone could shed light on osteoclast activity and potentially improve therapeutic treatments that target excessive resorption of bone.

[Development of fluorescent probes for bone imaging in vivo ~Fluorescent probes for intravital imaging of osteoclast activity~.

PubMed

Minoshima, Masafumi; Kikuchi, Kazuya

Fluorescent molecules are widely used as a tool to directly visualize target biomolecules in vivo. Fluorescent probes have the advantage that desired function can be rendered based on rational design. For bone-imaging fluorescent probes in vivo, they should be delivered to bone tissue upon administration. Recently, a fluorescent probe for detecting osteoclast activity was developed. The fluorescent probe has acid-sensitive fluorescence property, specific delivery to bone tissue, and durability against laser irradiation, which enabled real-time intravital imaging of bone-resorbing osteoclasts for a long period of time.

Use of resorbable plates and screws in pediatric facial fractures.

PubMed

Eppley, Barry L

2005-03-01

The use of resorbable plates and screws for fixation of pediatric facial fractures is both well tolerated and effective. It enables realignment and stable positioning of rapidly healing fracture segments while obviating any future issues secondary to long-term metal retention. Forty-four pediatric facial fractures were treated over a 10-year period at our institution using differing techniques of polymeric bone fixation. Twenty-nine mandible fractures in patients under the age of 10 (age range, 6 months to 8 years) were treated. Displaced fractures of the symphysis, parasymphysis, body, and ramus underwent open reduction and either 1.5-mm or 2.0-mm plate and screw fixation in 14 patients. Subcondylar fractures were treated by a short period of maxillomandibular fixation (3 weeks) achieved with suture ligation between resorbable screws placed at the zygoma and symphysis or a circummandibular suture attached to a zygomatic screw. Fifteen patients (age range, 4 to 11 years) with isolated frontal, supraorbital, intraorbital, or orbitozygomatic fractures were treated by open reduction and internal fixation with 1.5-mm resorbable plates, mesh, and screws. No long-term implant-related complications were seen in any of the treated patients. Resorbable polylactic and polyglycolic acid plates and screws can be an effective fixation method for facial fractures in children in the primary and secondary dentition periods.

A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease.

PubMed

Aimetti, Mario; Manavella, Valeria; Cricenti, Luca; Romano, Federica

2017-01-01

Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement.

A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease

PubMed Central

2017-01-01

Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement. PMID:28250998

Use of Resorbable Fixation System in Pediatric Facial Fractures.

PubMed

Wong, Frankie K; Adams, Saleigh; Hudson, Donald A; Ozaki, Wayne

2017-05-01

Resorbable fixation system (RFS) is an alternative to titanium in open reduction and internal fixation of pediatric facial fractures. This study retrospectively reviewed all medical records in a major metropolitan pediatric hospital in Cape Town, South Africa from September 2010 through May 2014. Inclusion criteria were children under the age of 13 with facial fractures who have undergone open reduction and internal fixation using RFS. Intraoperative and postoperative complications were reviewed. A total of 21 patients were included in this study. Twelve were males and 9 were females. Good dental occlusion was achieved in all patients and there were no complications intraoperatively. Three patients developed postoperative implanted-related complications: all 3 patients developed malocclusions and 1 developed an additional sterile abscess over the right zygomatic bone. For the latter, incision and drainage was performed and the problem resolved without additional operations. Resorbable fixation system is an alternative to titanium products in the setting of pediatric facial fractures without complications involving delayed union or malunion. The combination of intermaxillary fixation and RFS is not needed postoperatively for adequate fixation of mandible fractures. Resorbable fixation system is able to provide adequate internal fixation when both low-stress and high-stress craniofacial fractures occur simultaneously.

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

PubMed

Redini, Françoise; Heymann, Dominique

2015-01-01

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages.

PubMed

Kim, Yun-Ho; Kim, Jung-Lye; Lee, Eun-Jung; Park, Sin-Hye; Han, Seon-Young; Kang, Soon Ah; Kang, Young-Hee

2014-03-01

Osteoclastogenesis is comprised of several stage s including progenitor survival, differentiation to mononuclear preosteoclasts, cell fusion to multinuclear mature osteoclasts, and activation to osteoclasts with bone resorbing activity. Botanical antioxidants are now being increasingly investigated for their health-promoting effects on bone. This study investigated that fisetin, a flavonol found naturally in many fruits and vegetables, suppressed osteoclastogenesis by disturbing receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated signaling pathway and demoting osteoclastogenic protein induction. Nontoxic fisetin at ≤10 μM inhibited the induction of RANK, tumor necrosis factor receptor associated factor 6 (TRAF6) and the activation of NF-κB in RANKL-stimulated RAW 264.7 macrophages. In RANKL-differentiated osteoclasts cell fusion protein of E-cadherin was induced, which was dampened by fisetin. The formation of tartrate-resistance acid phosphatase-positive multinucleated osteoclasts was suppressed by adding fisetin to RANKL-exposed macrophages. It was also found that fisetin reduced actin ring formation and gelsolin induction of osteclasts enhanced by RANKL through disturbing c-Src-proline-rich tyrosine kinase 2 signaling. Fisetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton to seal the resorbing area and to secret protons for bone resorption. Consistently, the 5 day-treatment of fisetin diminished RANKL-induced cellular expression of carbonic anhydrase II and integrin β3 concurrently with a reduction of osteoclast bone-resorbing activity. Therefore, fisetin was a natural therapeutic agent retarding osteoclast fusion and cytoskeletal organization such as actin rings and ruffled boarder, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone. Copyright © 2014 Elsevier Inc. All rights reserved.

A hybrid technique for sinus floor elevation in the severely resorbed posterior maxilla

PubMed Central

Jung, Ui-Won; Hong, Ji-Youn; Lee, Jung-Seok; Kim, Chang-Sung; Cho, Kyoo-Sung

2010-01-01

Purpose This study aimed to evaluate the effectiveness of the modified sinus floor elevation technique described hereafter as a "hybrid technique," in 11 patients with severely resorbed posterior maxillae. Methods Eleven patients who received 22 implants in the maxillary premolar and molar areas by the hybrid technique were enrolled in this study. A slot-shaped osteotomy for access was prepared on the lateral wall along the lower border of the sinus floor. The Schneiderian membrane was fully reflected through the lateral slot. Following drilling with the membrane protected by a periosteal elevator, the bone was grafted. All implants were placed simultaneously with sinus augmentation. The cumulative success rate was calculated and clinical parameters were recorded. Radiographic measurements were performed. Results All implants were well maintained at last follow up (cumulative success rate=100%). The mean residual bone height, augmented bone height, crown-to-implant ratio, and marginal bone loss were 4.1±1.64 mm, 8.76±1.77 mm, 1.21±0.33 mm, and 0.34±0.72 mm, respectively. Conclusions Simultaneous implant placement with sinus augmentation by hybrid technique showed successful clinical results over a 2-year observation period and may be a reliable modality for reconstruction of a severely resorbed posterior maxilla. PMID:20498764

Gelatine modified monetite as a bone substitute material: An in vitro assessment of bone biocompatibility.

PubMed

Kruppke, Benjamin; Farack, Jana; Wagner, Alena-Svenja; Beckmann, Sarah; Heinemann, Christiane; Glenske, Kristina; Rößler, Sina; Wiesmann, Hans-Peter; Wenisch, Sabine; Hanke, Thomas

2016-03-01

Calcium phosphate phases are increasingly used for bone tissue substitution, and the load bearing properties of these inherently brittle biomaterials are increased by inclusion of organic components. Monetite prepared using mineralization of gelatine pre-structured through phosphate leads to a significantly increased biaxial strength and indirect tensile strength compared to gelatine-free monetite. Besides the mechanical properties, degradation in physiological solutions and osteoblast and osteoclast cell response were investigated. Human bone marrow stromal cells (hBMSCs) showed considerably higher proliferation rates on the gelatine modified monetite than on polystyrene reference material in calcium-free as well as standard cell culture medium (α-MEM). Osteogenic differentiation on the material was comparable to polystyrene in both medium types. Osteoclast-like cells derived from monocytes were able to actively resorb the biomaterial. Osteoblastic differentiation and perhaps even more important the cellular resorption of the biomaterial indicate that it can be actively involved in the bone remodeling process. Thus the behavior of osteoblasts and osteoclasts as well as the adequate degradation and mechanical properties are strong indicators for bone biocompatibility, although in vivo studies are still required to prove this. New and unique? A low temperature precipitationprocessforcalcium anhydrous hydrogen phosphateallows for the first time to produce monolithic compact composites of monetite and gelatine. The composite is degradable and resorbable. To prove that, the question arises: what is bone biocompatibility? The reaction of both mayor cell types of bone represents this biocompatibility. Therefore, human bone marrow stromal cells were seeded revealing the materials pro-osteogenic properties. Monocyte cultivation, becoming recently focus of interest, revealed the capability of the biomaterial to be actively resorbed by derived osteoclast-like cells. Not new

Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients.

PubMed

Alonso, Nivaldo; Tanikawa, Daniela Yukie Sakai; Freitas, Renato da Silva; Canan, Lady; Ozawa, Terumi Okada; Rocha, Diógenes Laércio

2010-10-01

A resorbable collagen matrix with recombinant human bone morphogenetic protein (rhBMP-2) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption. Sixteen patients with unilateral cleft lip and palate, aged 8 to 12 years, were selected and randomly assigned to group 1 (rhBMP-2) or group 2 (iliac crest bone graft). Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively. Bone height and defect volume were calculated through Osirix Dicom Viewer (Pixmeo, Apple Inc.). Overall morbidity was recorded. Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients. For group 1, final completion of the defect with a 65.0% mean bone height was detected 12 months postoperatively. For group 2, final completion of the defect with an 83.8% mean bone height was detected 6 months postoperatively. Dental eruption routinely occurred in both groups. Clinical complications included significant swelling in three group 1 patients (37.5%) and significant donor-site pain in seven group 2 patients (87.5%). For this select group of patients with immature skeleton, rhBMP-2 therapy resulted in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting.

Recombinant VSV G proteins reveal a novel raft-dependent endocytic pathway in resorbing osteoclasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulari, Mika T.K.; Centre for Military Medicine, Research Department, Lahti; Nars, Martin

2008-05-01

Transcytotic membrane flow delivers degraded bone fragments from the ruffled border to the functional secretory domain, FSD, in bone resorbing osteoclasts. Here we show that there is also a FSD-to-ruffled border trafficking pathway that compensates for the membrane loss during the matrix uptake process and that rafts are essential for this ruffled border-targeted endosomal pathway. Replacing the cytoplasmic tail of the vesicular stomatitis virus G protein with that of CD4 resulted in partial insolubility in Triton X-100 and retargeting from the peripheral non-bone facing plasma membrane to the FSD. Recombinant G proteins were subsequently endosytosed and delivered from the FSDmore » to the peripheral fusion zone of the ruffled border, which were both rich in lipid rafts as suggested by viral protein transport analysis and visualizing the rafts with fluorescent recombinant cholera toxin. Cholesterol depletion by methyl-{beta}-cyclodextrin impaired the ruffled border-targeted vesicle trafficking pathway and inhibited bone resorption dose-dependently as quantified by measuring the CTX and TRACP 5b secreted to the culture medium and by measuring the resorbed area visualized with a bi-phasic labeling method using sulpho-NHS-biotin and WGA-lectin. Thus, rafts are vital for membrane recycling from the FSD to the late endosomal/lysosomal ruffled border and bone resorption.« less

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma

PubMed Central

Redini, Françoise; Heymann, Dominique

2015-01-01

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the “vicious cycle” concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable “niche” for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma. PMID:26779435

A synthetic bioactive resorbable graft for predictable implant reconstruction: part one.

PubMed

Valen, Maurice; Ganz, Scott D

2002-01-01

Animal studies were conducted to evaluate the cell response and chemical potentiality of a synthetic bioactive resorbable graft (SBRG) made of nonceramic cluster particulate of low-temperature HA material. The study evaluated bone-bridging of the SBRG particulates in 1-mm wide implant channels of 5 x 8 mm long roughened titanium interface in 6 dogs and compared results to the same implant channels left empty as controls at 6- and 12-week intervals. Resorption rate capacity and cell response were evaluated with an assessment of the chemical characterization of the synthetic nonceramic material next to the titanium implant interfaces. Results of the animal studies were compared with human histologic biopsies of the SBRG for bone quality, density, and bone growth into defect sites concurrent with resorption time of the graft. One human biopsy consisted of a graft mixture of the SBRG and dense bovine-derived HA, compared under the electron microscope, including histology by H and E staining. Part 1 of this paper presents evidence of the predictability and efficacy of the SBRG osteoconductive, particulate chemical potentiality to aid in the regeneration of lost bone anatomy next to titanium implant interfaces. Recent technological innovations in computer hardware and software have given clinicians the tools to determine 3-dimensional quality and density of bone, including anatomical discrepancies, which can aid in the diagnosis and treatment planning for grafting procedures. When teeth are extracted, the surrounding bone and soft tissue are challenged as a result of the natural resorptive process. The diminished structural foundation for prosthetic reconstruction, with or without implants, can be compromised. A synthetic bioactive resorbable graft material having osteoconductive biochemical and biomechanical qualities similar to the host bone provides the means to improve compromised bone topography for ridge preservation, ridge augmentation, or to enhance the bony site

Evidence that Resorption of Bone by Rat Peritoneal Macrophages Occurs in an Acidic Environment

NASA Technical Reports Server (NTRS)

Blair, H. C.

1985-01-01

Skeletal loss in space, like any form of osteoporosis, reflects a relative imbalance of the activities of cells resorbing (degrading) or forming bone. Consequently, prevention of weightlessness induced bone loss may theoretically be accomplished by (1) stimulating bone formation or (2) inhibiting bone resorption. This approach, however, requires fundamental understanding of the mechanisms by which cells form or degrade bone, information not yet at hand. An issue central to bone resorption is the pH at which resorption takes place. The pH dependent spectral shift of a fluorescent dye (fluorescein isothiocyanate) conjugated to bone matrix was used to determine the pH at the resorptive cell bone matrix interface. Devitalized rat bone was used as the substrate, and rat peritoneal macrophages were used as the bone resorbing cells. The results suggest that bone resorption is the result of generation of an acidic microenvironment at the cell matrix junction.

Evidence that failure of osteoid bone matrix resorption is caused by perturbation of osteoclast polarization.

PubMed

Yovich, S; Seydel, U; Papadimitriou, J M; Nicholson, G C; Wood, D J; Zheng, M H

1998-04-01

Osteoclasts resorb bone by a complex dynamic process that initially involves attachment, polarization and enzyme secretion, followed by their detachment and migration to new sites. In this study, we postulated that mineralized and osteoid bone matrix signal osteoclasts differently, resulting in the resorption of mineralized bone matrix only. We, therefore, compared the cytoplasmic distribution of cytoskeletal proteins F-actin and vinculin using confocal laser-scanning microscopy in osteoclasts cultured on mineralized and demineralized bone slices and correlated the observations with their functional activity. Our results have demonstrated significant differences in F-actin and vinculin staining patterns between osteoclasts cultured on mineralized bone matrix and those on demineralized bone matrix. In addition, the structural variations were accompanied by significant differences in bone resorbing activity between osteoclasts grown on mineralized bone matrix and those on demineralized bone matrix after 24 h of culture --resorption only occurring in mineralized bone but not in demineralized bone. These results indicated that failure of osteoid bone resorption is caused by perturbation of osteoclast polarization.

Choline kinase β mutant mice exhibit reduced phosphocholine, elevated osteoclast activity, and low bone mass.

PubMed

Kular, Jasreen; Tickner, Jennifer C; Pavlos, Nathan J; Viola, Helena M; Abel, Tamara; Lim, Bay Sie; Yang, Xiaohong; Chen, Honghui; Cook, Robert; Hool, Livia C; Zheng, Ming Hao; Xu, Jiake

2015-01-16

The maintenance of bone homeostasis requires tight coupling between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the precise molecular mechanism(s) underlying the differentiation and activities of these specialized cells are still largely unknown. Here, we identify choline kinase β (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase β mutant mice (flp/flp) exhibit a systemic low bone mass phenotype. Consistently, osteoclast numbers and activity are elevated in flp/flp mice. Interestingly, osteoclasts derived from flp/flp mice exhibit reduced sensitivity to excessive levels of extracellular calcium, which could account for the increased bone resorption. Conversely, supplementation of cytidine 5'-diphosphocholine in vivo and in vitro, a regimen that bypasses CHKB deficiency, restores osteoclast numbers to physiological levels. Finally, we demonstrate that, in addition to modulating osteoclast formation and function, loss of CHKB corresponds with a reduction in bone formation by osteoblasts. Taken together, these data posit CHKB as a new modulator of bone homeostasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Use of Antibiotic Impregnated Resorbable Beads Reduces Pressure Ulcer Recurrence: A Retrospective Analysis.

PubMed

Khansa, Ibrahim; Barker, Jenny C; Ghatak, Piya Das; Sen, Chandan K; Gordillo, Gayle M

2018-05-17

Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic- beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic-impregnated beads were compared to those who did not. 86 patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used, and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p=0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p=0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

Identification of Leukocyte Subpopulations Responsible for the Production of Osteoclast Activating Factor and their Role in Bone Resorption.

DTIC Science & Technology

1980-12-31

glandin E2, and active metabolites of Vitamin D (Luben, et al., 1974). Another report suggested that bone resorbing activity couTld be detected in... Vitamin B12 (1330 daltons) representing "big" OAF and "little" OAF, respectively, in a freely associating and disassociating, ionic strength dependent...dialysis would remove lower molecular weight compounds (򒮨 daltons) such as prostaglandins or vitamin D that might affect the assay. The results

Improvement of Implant Placement after Bone Augmentation of Severely Resorbed Maxillary Sinuses with 'Tent-Pole' Grafting Technique in Combination with rhBMP-2.

PubMed

Zhang, Qiao; Zhang, Li Li; Yang, Yang; Lin, Yi Zhen; Miron, Richard J; Zhang, Yu Feng

To study the clinical effect of short implant placement using osteotome sinus floor elevation technique and tent-pole grafting technique with recombinant human bone morphogenetic protein 2 (rhBMP-2) in severely resorbed maxillary area. Eleven patients with insufficient bone height in the posterior maxillary area were included. According to the native bone height and crown height space (CHS), the patients were divided into two groups: immediate placement of short implants with simultaneous bone augmentation (group A, 5 patients) and delayed dental implant placement (4 to 6 months) after bone augmentation. The rhBMP-2 was added into a deproteinised bovine bone mineral (DBBM) bone grafting material to shorten the treatment procedure and enhance the final effect of bone augmentation in both groups. Tent-pole grafting technique was applied for vertical bone augmentation in group B (6 patients). The success rate of the implants placed was 100% in both groups. In group A, the short implants treatment was successful, with a vertical gain of 1.5 to 6.4 mm in bone height after 4 to 6 months. In group B, the tent-pole grafting procedure in combination with DBBM and rhBMP-2 increased vertical bone height between 3.1 and 8.1 mm, an optimistic and adequate increase for implant placement. This bone increase was maintained following implant placement and final crown placement in the maxillary region (3.5 to 7.3 mm). The tent-pole grafting technique was a viable alternative choice to lateral sinus floor elevation in cases with excessive CHS. The application of rhBMP-2 with a shortened treatment time demonstrated positive outcomes in sinus floor augmentation procedures.

Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis.

PubMed

Mulvihill, Brianne M; McNamara, Laoise M; Prendergast, Patrick J

2008-10-06

Osteoporosis is characterized by rapid and irreversible loss of trabecular bone tissue leading to increased bone fragility. In this study, we hypothesize two causes for rapid loss of bone trabeculae; firstly, the perforation of trabeculae is caused by osteoclasts resorbing a cavity so deep that it cannot be refilled and, secondly, the increases in bone tissue elastic modulus lead to increased propensity for trabecular perforation. These hypotheses were tested using an algorithm that was based on two premises: (i) bone remodelling is a turnover process that repairs damaged bone tissue by resorbing and returning it to a homeostatic strain level and (ii) osteoblast attachment is under biochemical control. It was found that a mechano-biological algorithm based on these premises can simulate the remodelling cycle in a trabecular strut where damaged bone is resorbed to form a pit that is subsequently refilled with new bone. Furthermore, the simulation predicts that there is a depth of resorption cavity deeper than which refilling of the resorption pits is impossible and perforation inevitably occurs. However, perforation does not occur by a single fracture event but by continual removal of microdamage after it forms beneath the resorption pit. The simulation also predicts that perforations would occur more easily in trabeculae that are more highly mineralized (stiffer). Since both increased osteoclast activation rates and increased mineralization have been measured in osteoporotic bone, either or both may contribute to the rapid loss of trabecular bone mass observed in osteoporotic patients.

Osteoclast Progenitors Reside in the Peroxisome Proliferator-Activated Receptor γ-Expressing Bone Marrow Cell Population ▿

PubMed Central

Wei, Wei; Zeve, Daniel; Wang, Xueqian; Du, Yang; Tang, Wei; Dechow, Paul C.; Graff, Jonathan M.; Wan, Yihong

2011-01-01

Osteoclasts are bone-resorbing cells essential for skeletal development, homeostasis, and regeneration. They derive from hematopoietic progenitors in the monocyte/macrophage lineage and differentiate in response to RANKL. However, the precise nature of osteoclast progenitors is a longstanding and important question. Using inducible peroxisome proliferator-activated receptor γ (PPARγ)-tTA TRE-GFP (green fluorescent protein) reporter mice, we show that osteoclast progenitors reside specifically in the PPARγ-expressing hematopoietic bone marrow population and identify the quiescent PPARγ+ cells as osteoclast progenitors. Importantly, two PPARγ-tTA TRE-Cre-controlled genetic models provide compelling functional evidence. First, Notch activation in PPARγ+ cells causes high bone mass due to impaired osteoclast precursor proliferation. Second, selective ablation of PPARγ+ cells by diphtheria toxin also causes high bone mass due to decreased osteoclast numbers. Furthermore, PPARγ+ cells respond to both pathological and pharmacological resorption-enhancing stimuli. Mechanistically, PPARγ promotes osteoclast progenitors by activating GATA2 transcription. These findings not only identify the long-sought-after osteoclast progenitors but also establish unprecedented tools for their visualization, isolation, characterization, and genetic manipulation. PMID:21947280

WITHDRAWN: Resorbable versus titanium plates for facial fractures.

PubMed

Dorri, Mojtaba; Oliver, Richard

2018-05-23

Rigid internal fixation of the jaw bones is a routine procedure for the management of facial fractures. Titanium plates and screws are routinely used for this purpose. The limitations of this system has led to the development of plates manufactured from bioresorbable materials which, in some cases, omits the necessity for the second surgery. However, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. To compare the effectiveness of bioresorbable fixation systems with titanium systems for the management of facial fractures. We searched the following databases: The Cochrane Oral Health Group's Trials Register (to 20th August 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to 20th August 2008), EMBASE (from 1980 to 20th August 2008), http://www.clinicaltrials.gov/ and http://www.controlled-trials.com (to 20th August 2008). Randomised controlled trials comparing resorbable versus titanium fixation systems used for facial fractures. Retrieved studies were independently screened by two review authors. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated including both clinical and methodological factors. The search strategy retrieved 53 potentially eligible studies. None of the retrieved studies met our inclusion criteria and all were excluded from this review. One study is awaiting classification as we failed to obtain the full text copy. Three ongoing trials were retrieved, two of which were stopped before recruiting the planned number of participants. In one study, the excess complications in the resorbable arm was declared as the reason for stopping the trial. This review illustrates that there are no published randomised controlled clinical

Cell-specific paracrine actions of IL-6 family cytokines from bone, marrow and muscle that control bone formation and resorption.

PubMed

Sims, Natalie A

2016-10-01

Bone renews itself and changes shape throughout life to account for the changing needs of the body; this requires co-ordinated activities of bone resorbing cells (osteoclasts), bone forming cells (osteoblasts) and bone's internal cellular network (osteocytes). This review focuses on paracrine signaling by the IL-6 family of cytokines between bone cells, bone marrow, and skeletal muscle in normal physiology and in pathological states where their levels may be locally or systemically elevated. These functions include the support of osteoclast formation by osteoblast lineage cells in response to interleukin 6 (IL-6), interleukin 11 (IL-11), oncostatin M (OSM) and cardiotrophin 1 (CT-1). In addition it will discuss how bone-resorbing osteoclasts promote osteoblast activity by secreting CT-1, which acts as a "coupling factor" on osteocytes, osteoblasts, and their precursors to promote bone formation. OSM, produced by osteoblast lineage cells and macrophages, stimulates bone formation via osteocytes. IL-6 family cytokines also mediate actions of other bone formation stimuli like parathyroid hormone (PTH) and mechanical loading. CT-1, OSM and LIF suppress marrow adipogenesis by shifting commitment of pluripotent precursors towards osteoblast differentiation. Ciliary neurotrophic factor (CNTF) is released as a myokine from skeletal muscle and suppresses osteoblast differentiation and bone formation on the periosteum (outer bone surface in apposition to muscle). Finally, IL-6 acts directly on marrow-derived osteoclasts to stimulate release of "osteotransmitters" that act through the cortical osteocyte network to stimulate bone formation on the periosteum. Each will be discussed as illustrations of how the extended family of IL-6 cytokines acts within the skeleton in physiology and may be altered in pathological conditions or by targeted therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Guided bone regeneration: general survey].

PubMed

Cosyn, Jan; De Bruyn, Hugo

2009-01-01

The principle of 'guided bone regeneration' was first described in 1988 on the basis of animal-experimental data. Six weeks after transmandibular defects had been created and protected by non-resorbable teflonmembranes, complete bone regeneration was found. The technique was based on the selective repopulation of the wound: every infiltration of cells outside the neighbouring bone tissue was prevented by the application of the membrane. Additional animal experiments showed that guided bone regeneration was a viable treatment option for local bone defects surrounding dental implants. Clinical practice, however, showed that premature membrane exposure was a common complication, which was responsible for a tremendous reduction in regenerated bone volume. In addition, a second surgical intervention was always necessary to remove the membrane. As a result, resorbable alternatives were developed. Since these are less rigid, bone fillers are usually used simultaneously. These comprise autogenous bone chips and bone substitutes from allogenic or xenogenic origine. Also alloplastic materials could be used for this purpose. Based on their characteristics this article provides an overview of the biomaterials that could be considered for guided bone regeneration. Specific attention goes to their application in clinical practice.

Repair of tegmen defect using cranial particulate bone graft.

PubMed

Greene, Arin K; Poe, Dennis S

2015-01-01

Bone paté is used to repair cranial bone defects. This material contains bone-dust collected during the high-speed burring of the cranium. Clinical and experimental studies of bone dust, however, have shown that it does not have biological activity and is resorbed. We describe the use of bone paté using particulate bone graft. Particulate graft is harvested with a hand-driven brace and 16mm bit; it is not subjected to thermal injury and its large size resists resorption. Bone paté containing particulate graft is much more likely than bone dust to contain viable osteoblasts capable of producing new bone. Copyright © 2015 Elsevier Inc. All rights reserved.

Polymeric membranes for guided bone regeneration.

PubMed

Gentile, Piergiorgio; Chiono, Valeria; Tonda-Turo, Chiara; Ferreira, Ana M; Ciardelli, Gianluca

2011-10-01

In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acceleration of Alveolar Ridge Augmentation Using a Low Dose of Recombinant Human Bone Morphogenetic Protein-2 Loaded on a Resorbable Bioactive Ceramic.

PubMed

Fahmy, Rania A; Mahmoud, Naguiba; Soliman, Samia; Nouh, Samir R; Cunningham, Larry; El-Ghannam, Ahmed

2015-12-01

The aim of the present study was to evaluate the effect of a porous silica-calcium phosphate composite (SCPC50) loaded with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) on alveolar ridge augmentation in saddle-type defects. Micro-granules of SCPC50 resorbable bioactive ceramic were coated with rhBMP-2 10 mg and then implanted into a saddle-type defect (12 × 7 mm) in a dog mandible and covered with a collagen membrane. Control groups included defects grafted with SCPC50 granules without rhBMP-2 and un-grafted defects. Bone healing was evaluated at 8 and 16 weeks using histologic and histomorphometric techniques. The increase in bone height and total defect fill were assessed for each specimen using the ImageJ 1.46 program. The release kinetics of rhBMP-2 was determined in vitro. The height of the bone in the grafted defects and the total defect fill were statistically analyzed. SCPC50 enhanced alveolar ridge augmentation as indicated by the increased vertical bone height, bone surface area, and bone volume after 16 weeks. SCPC50-rhBMP-2 provided a sustained release profile of a low effective dose (BMP-2 4.6 ± 1.34 pg/mL per hour) during the 1- to 21-day period. The slow rate of release of rhBMP-2 from SCPC50 accelerated synchronized complete bone regeneration and graft material resorption in 8 weeks. Successful rapid reconstruction of the alveolar ridge by SCPC50 and SCPC50-rhBMP-2 occurred without any adverse excessive bone formation, inflammation, or fluid-filled voids. Results of this study suggest that SCPC50 is an effective graft material to preserve the alveolar ridge after tooth extraction. Coating SCPC50-rhBMP-2 further accelerated bone regeneration and a considerable increase in vertical bone height. These findings make SCPC50 the primary choice as a carrier for rhBMP-2. SCPC50-rhBMP-2 can serve as an alternative to autologous bone grafting. Published by Elsevier Inc.

Bone remodelling: its local regulation and the emergence of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2008-10-01

Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

A novel one-pot process for near-net-shape fabrication of open-porous resorbable hydroxyapatite/protein composites and in vivo assessment.

PubMed

Mueller, Berit; Koch, Dietmar; Lutz, Rainer; Schlegel, Karl A; Treccani, Laura; Rezwan, Kurosch

2014-09-01

We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

TRAF family member-associated NF-κB activator (TANK) is a negative regulator of osteoclastogenesis and bone formation.

PubMed

Maruyama, Kenta; Kawagoe, Tatsukata; Kondo, Takeshi; Akira, Shizuo; Takeuchi, Osamu

2012-08-17

The differentiation of bone-resorbing osteoclasts is induced by RANKL signaling, and leads to the activation of NF-κB via TRAF6 activation. TRAF family member-associated NF-κB activator (TANK) acts as a negative regulator of Toll-like receptors (TLRs) and B-cell receptor (BCR) signaling by inhibiting TRAF6 activation. Tank(-/-) mice spontaneously develop autoimmune glomerular nephritis in an IL-6-dependent manner. Despite its importance in the TCRs and BCR-activated TRAF6 inhibition, the involvement of TANK in RANKL signaling is poorly understood. Here, we report that TANK is a negative regulator of osteoclast differentiation. The expression levels of TANK mRNA and protein were up-regulated during RANKL-induced osteoclastogenesis, and overexpression of TANK in vitro led to a decrease in osteoclast formation. The in vitro osteoclastogenesis of Tank(-/-) cells was significantly increased, accompanied by increased ubiquitination of TRAF6 and enhanced canonical NF-κB activation in response to RANKL stimulation. Tank(-/-) mice showed severe trabecular bone loss, but increased cortical bone mineral density, because of enhanced bone erosion and formation. TANK mRNA expression was induced during osteoblast differentiation and Tank(-/-) osteoblasts exhibited enhaced NF-κB activation, IL-11 expression, and bone nodule formation than wild-type control cells. Finally, wild-type mice transplanted with bone marrow cells from Tank(-/-) mice showed trabecular bone loss analogous to that in Tank(-/-) mice. These findings demonstrate that TANK is critical for osteoclastogenesis by regulating NF-κB, and is also important for proper bone remodeling.

TRAF Family Member-associated NF-κB Activator (TANK) Is a Negative Regulator of Osteoclastogenesis and Bone Formation*

PubMed Central

Maruyama, Kenta; Kawagoe, Tatsukata; Kondo, Takeshi; Akira, Shizuo; Takeuchi, Osamu

2012-01-01

The differentiation of bone-resorbing osteoclasts is induced by RANKL signaling, and leads to the activation of NF-κB via TRAF6 activation. TRAF family member-associated NF-κB activator (TANK) acts as a negative regulator of Toll-like receptors (TLRs) and B-cell receptor (BCR) signaling by inhibiting TRAF6 activation. Tank−/− mice spontaneously develop autoimmune glomerular nephritis in an IL-6-dependent manner. Despite its importance in the TCRs and BCR-activated TRAF6 inhibition, the involvement of TANK in RANKL signaling is poorly understood. Here, we report that TANK is a negative regulator of osteoclast differentiation. The expression levels of TANK mRNA and protein were up-regulated during RANKL-induced osteoclastogenesis, and overexpression of TANK in vitro led to a decrease in osteoclast formation. The in vitro osteoclastogenesis of Tank−/− cells was significantly increased, accompanied by increased ubiquitination of TRAF6 and enhanced canonical NF-κB activation in response to RANKL stimulation. Tank−/− mice showed severe trabecular bone loss, but increased cortical bone mineral density, because of enhanced bone erosion and formation. TANK mRNA expression was induced during osteoblast differentiation and Tank−/− osteoblasts exhibited enhaced NF-κB activation, IL-11 expression, and bone nodule formation than wild-type control cells. Finally, wild-type mice transplanted with bone marrow cells from Tank−/− mice showed trabecular bone loss analogous to that in Tank−/− mice. These findings demonstrate that TANK is critical for osteoclastogenesis by regulating NF-κB, and is also important for proper bone remodeling. PMID:22773835

Comparison of Resorbable Plating Systems: Complications During Degradation.

PubMed

Nguyen, Dennis C; Woo, Albert S; Farber, Scott J; Skolnick, Gary B; Yu, Jenny; Naidoo, Sybill D; Patel, Kamlesh B

2017-01-01

Several bioresorbable plating systems have become standard in pediatric craniosynostosis reconstruction. A comparison of these systems is needed to aid surgeons in the preoperative planning process. The authors aim to evaluate 1 institution's experience using Resorb-X by KLS Martin and Delta Resorbable Fixation System by Stryker (Stryker Craniomaxillofacial, Kalamazoo, MI). A sample of patients with single-suture nonsyndromic craniosynostosis treated at St Louis Children's Hospital between 2007 and 2014 using either Resorb-X or Delta bioresorbable plating systems were reviewed. Only patients with preoperative, immediate, and long-term 3-dimensional photographic images or computed tomography scans were included. A comparison of plating system outcomes was performed to determine the need for clinic and emergency room visits, imaging obtained, and incidence of subsequent surgical procedures due to complications. Forty-six patients (24 Resorb-X and 22 Delta) underwent open repair with bioabsorbable plating for single suture craniosynostosis. The mean age at each imaging time point was similar between the 2 plating systems (P > 0.717). Deformity-specific measures for sagittal (cranial index), metopic (interfrontotemporale), and unicoronal (frontal asymmetry) synostosis were equivalent between the systems at all time points (0.05 < P < 0.904). A single Delta patient developed bilateral scalp cellulitis and abscesses and subsequently required operative intervention and antibiotics. Bioabsorbable plating for craniosynostosis in children is effective and has low morbidity. In our experience, the authors did not find a difference between the outcomes and safety profiles between Resorb-X and Delta.

The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling

PubMed Central

Razawy, Wida; van Driel, Marjolein

2018-01-01

Abstract The IL‐23/Th17 axis has been implicated in the development of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). RA and PsA are heterogeneous diseases with substantial burden on patients. Increasing evidence suggests that the IL‐23 signaling pathway may be involved in the development of autoimmunity and erosive joint damage. IL‐23 can act either directly or indirectly on bone forming osteoblasts as well as on bone resorbing osteoclasts. As IL‐23 regulates the activity of cells of the bone, it is conceivable that in addition to inflammation‐mediated joint erosion, IL‐23 may play a role in physiological bone remodeling. In this review, we focus on the role of IL‐23 in autoimmune arthritis in patients and murine models, and provide an overview of IL‐23 producing and responding cells in autoimmune arthritic joints. In addition, we discuss the role of IL‐23 on bone forming osteoblasts and bone resorbing osteoclasts regarding inflammation‐mediated joint damage and bone remodeling. At last, we briefly discuss the clinical implications of targeting this pathway for joint damage and systemic bone loss in autoimmune arthritis. PMID:29148561

Inflammatory foreign body reaction caused by resorbable materials used for orbital fractures repair

PubMed Central

He, Jie; Shi, Wodong

2017-01-01

Abstract Rationale: Resorbable materials have been recommended for orbital fractures repair. Many literatures reported the advantages of resorbable materials in clinical applications, but few reports about complications. Patient concerns: In this study, we encountered a 14-year-old boy treated for the orbital fracture by using resorbable plate, in whom inflammatory foreign body reaction was detected. In addition, this patient had repeated history of skin allergy and upper respiratory tract infection. Diagnoses: Intraoperative observation showed that the resorbable material near the orbital rim was covered by granulation and inflammatory tissues, without purulent secretions. The histological examination revealed inflammatory foreign body reaction to the resorbable plate. Interventions: Debridement was taken to remove the mass on the left lower eyelid. At the outpatient examination, a small amount of granulation tissue was found at the incision. Then, secondary surgery for exploration and removal of the resorbable material was carried, 9 months after the first surgery. Outcomes: One month after the surgery, the skin retraction, ectropion, and edema gradually improved. Lessons: Inadequate degradation of resorbable materials and patient's medical history of allergies may cause an inflammatory foreign body reaction. Therefore, it is prudent to choose resorbable materials for patients. PMID:29245243

Bone generation in the reconstruction of a critical size calvarial defect in an experimental model.

PubMed

Por, Yong-Chen; Barceló, C Raul; Salyer, Kenneth E; Genecov, David G; Troxel, Karen; Gendler, El; Elsalanty, Mohammed E; Opperman, Lynne A

2008-03-01

This study was designed to investigate the optimal combination of known osteogenic biomaterials with shape conforming struts to achieve calvarial vault reconstruction, using a canine model. Eighteen adolescent beagles were divided equally into 6 groups. A critical-size defect of 6 x 2 cm traversed the sagittal suture. The biomaterials used for calvarial reconstruction were demineralized perforated bone matrix (DBM), recombinant human bone morphogenetic protein 2 (rhBMP2), and autogenous platelet-rich plasma (PRP). The struts used were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1) DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM + rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable plate. Animals were killed at 3 months after surgery. There was no mortality or major complications. Analysis was performed macroscopically and histologically and with computed tomography. There was complete bony regeneration in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the defect edges and on the dural surface, a finding confirmed by computed tomographic scan and histology. Platelet-rich plasma did not enhance bone regeneration. Shape conformation was good with both metal and resorbable plate. rhBMP2, but not PRP, accelerated calvarial regeneration in 3 months. The DBMs in the rhBMP2 groups were substituted by new trabecular bone. Shape molding was good with both metal and resorbable plate.

Water extract of the fruits of Alpinia oxyphylla inhibits osteoclast differentiation and bone loss.

PubMed

Ha, Hyunil; Shim, Ki-Shuk; Kim, Taesoo; Lee, Chung-Jo; Park, Ji Hyung; Kim, Han Sung; Ma, Jin Yeul

2014-09-23

Excessive bone resorption by osteoclasts causes pathological bone destruction, seen in various bone diseases. There is accumulating evidence that certain herbal extracts have beneficial effects on bone metabolism. The fruits of Alpinia oxyphylla has been traditionally used for the treatment of diarrhea and enuresis. In this study, we investigated the effects of water extract of the fruits of Alpinia oxyphylla (WEAO) on osteoclast differentiation and osteoclast-mediated bone destruction. For osteoclast differentiation assay, mouse bone marrow-derived macrophages (BMMs) were cultured in the presence of RANKL and M-CSF. RANKL signaling pathways and gene expression of transcription factors regulating osteoclast differentiation were investigated by real-time PCR and Western blotting. A constitutively active form of NFATc1 was retrovirally transduced into BMMs. Bone resorbing activity of mature osteoclast was examined on a plate coated with an inorganic crystalline calcium phosphate. The in vivo effect against bone destruction was assessed in a murine model of RANKL-induced osteoporosis by micro-computed tomography and bone metabolism marker analyses. WEAO dose-dependently inhibited RANKL-induced osteoclast differentiation from BMMs by targeting the early stages of osteoclast differentiation. WEAO inhibited RANKL-induced expression of NFATc1, the master regulator of osteoclast differentiation. Overexpression of a constitutively active form of NFATc1 blunted the inhibitory effect of WEAO on osteoclast differentiation, suggesting that NFATc1 is a critical target of the inhibitory action of WEAO. WEAO inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1, by suppressing the classical NF-κB signaling pathway. WEAO also inhibited RANKL-induced down-regulation of Id2 and MafB, negative regulators of NFATc1. WEAO does not directly affect bone resorbing activity of mature osteoclasts. In accordance with the in vitro results, WEAO attenuated RANKL

Three-Dimensional Volumetric Changes in Severely Resorbed Alveolar Sockets After Ridge Augmentation with Bovine-Derived Xenograft and Resorbable Barrier: A Preliminary Study on CBCT Imaging.

PubMed

Manavella, Valeria; Romano, Federica; Corano, Lisa; Bignardi, Cristina; Aimetti, Mario

The primary aim of the study was to describe a novel technique to evaluate volumetric hard tissue dimensional changes after ridge augmentation procedures. The secondary aim was to apply this newly developed measuring method to compromised alveolar sockets grafted with a slowly resorbing biomaterial covered with a collagen membrane. Eleven patients (6 men and 5 women, mean age 52.7 ± 8.3 years) requiring extraction of one hopeless tooth for severe periodontitis in the maxillary anterior area were consecutively treated with a ridge augmentation procedure. All experimental sockets showed advanced buccal bone plate deficiency and were grafted with deproteinized bovine bone mineral with 10% collagen covered with a collagen membrane. Sockets healed by secondary intention. Three-dimensional volumetric alveolar bone changes were calculated by superimposing cone beam computed tomography scans obtained before and 12 months after the augmentation procedure. After 12 months, the alveolar mineralized tissue filled 91.20% ± 7.96% of the maximum volume for regeneration. The augmentation procedure appeared not only to compensate for bone remodeling in most alveolar regions but also to repair a significant portion of the buccal wall. The most significant ridge width changes occurred 1 mm apical to the bone crest (2.33 ± 1.46 mm, P < .001). Within present limitations, this radiographic measuring methodology can be a useful tool to evaluate changes in socket volume. A ridge preservation technique performed with collagenated bovine bone and a collagen membrane was able to improve ridge shape and dimensions in compromised alveolar sockets.

The role of IL-23 receptor signaling in inflammation-mediated erosive autoimmune arthritis and bone remodeling.

PubMed

Razawy, Wida; van Driel, Marjolein; Lubberts, Erik

2018-02-01

The IL-23/Th17 axis has been implicated in the development of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). RA and PsA are heterogeneous diseases with substantial burden on patients. Increasing evidence suggests that the IL-23 signaling pathway may be involved in the development of autoimmunity and erosive joint damage. IL-23 can act either directly or indirectly on bone forming osteoblasts as well as on bone resorbing osteoclasts. As IL-23 regulates the activity of cells of the bone, it is conceivable that in addition to inflammation-mediated joint erosion, IL-23 may play a role in physiological bone remodeling. In this review, we focus on the role of IL-23 in autoimmune arthritis in patients and murine models, and provide an overview of IL-23 producing and responding cells in autoimmune arthritic joints. In addition, we discuss the role of IL-23 on bone forming osteoblasts and bone resorbing osteoclasts regarding inflammation-mediated joint damage and bone remodeling. At last, we briefly discuss the clinical implications of targeting this pathway for joint damage and systemic bone loss in autoimmune arthritis. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resorbable poly(D,L)lactide plates and screws for osteosynthesis of condylar neck fractures in sheep.

PubMed

Rasse, Michael; Moser, Doris; Zahl, Christian; Gerlach, Klaus Louis; Eckelt, Uwe; Loukota, Richard

2007-01-01

We made osteotomies in the condylar neck in 12 adult sheep to simulate fractures, and joined the two ends with 2 poly(D,L)lactide (PDLLA) plates and 8 PDLLA screws 2mm in diameter. The animals were killed after 2, 6, and 12 months and bony healing was assessed macroscopically and histologically. The plates and screws remained intact and there was no displacement of the bony ends. The degrading plates, which were still visible in the specimens after 6 months, had been replaced by bone. At 12 months the PDLLA had been resorbed with no foreign body reaction and no resorption of underlying bone. The articular discs showed no signs of degeneration.

Absorption machine with desorber-resorber

DOEpatents

Biermann, Wendell J.

1985-01-01

An absorption refrigeration system utilizing a low temperature desorber and intermediate temperature resorber. The system operates at three temperatures and three pressures to increase the efficiency of the system and is capable of utilizing a lower generator temperature than previously used.

The effect of osteotomy dimension on osseointegration to resorbable media-treated implants: a study in the sheep.

PubMed

Galli, Silvia; Jimbo, Ryo; Tovar, Nick; Yoo, Daniel Y; Anchieta, Rodolfo B; Yamaguchi, Satoshi; Coelho, Paulo G

2015-03-01

The drilling technique and the surface characteristics are known to influence the healing times of oral implants. The influence of osteotomy dimension on osseointegration of microroughned implant surfaces treated with resorbable blasting media was tested in an in vivo model. Ninety-six implants (ø4.5 mm, 8 mm in length) with resorbable blasting media-treated surfaces were placed in the ileum of six sheep. The final osteotomy diameters were 4.6 mm (reamer), 4.1 mm (loose), 3.7 mm (medium), and 3.2 mm (tight). After three and six weeks of healing, the implants were biomechanically tested and histologically evaluated. Statistical analysis was performed using Page L trend test for ordered and paired sample and linear regression, with significance level at p < 0.05. An overall increase in all dependent variables was observed with the reduction of osteotomy diameter. In addition, all osseointegration scores increased over time. At three weeks, the retention was significantly higher for smaller osteotomies. The histological sections depicted intimate contact of bone with all the implant surfaces and osteoblast lines were visible in all sections. The resorbable blasting media microroughed surfaces achieved successful osseointegration for all the instrumentation procedures tested, with higher osseointegration scores for the high insertion torque group. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

PubMed

Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

2015-05-01

The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in

Dental rehabilitation using an implant-carrying plate system in a severely resorbed edentulous maxilla: a case report.

PubMed

Kurita, Hiroshi; Sakai, Hironori; Uehara, Shinobu; Kurashina, Kenji

2008-01-01

This clinical article describes a case of dental rehabilitation using an implant-carrying plate system (EPITEC) for a patient with severely resorbed edentulous maxilla and microstomia. In this case, the presence of microstomia prevented bone augmentation procedures through an intraoral approach. Treatment using 2 endosseous implants inserted in the canine regions and an implant-supported overdenture was planned. However, endosseous implants were not feasible on the right side because of insufficient available bone volume. An implant-carrying plate system was then utilized on the right side. Four months later, an implant-supported ball-attachment overdenture was fabricated. At the 2-year follow-up, the clinical course remained uneventful, and the patient remained satisfied with the treatment.

Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.

PubMed

Kim, A-Ram; Kim, Hyuk Soon; Lee, Jeong Min; Choi, Jung Ho; Kim, Se Na; Kim, Do Kyun; Kim, Ji Hyung; Mun, Se Hwan; Kim, Jie Wan; Jeon, Hyun Soo; Kim, Young Mi; Choi, Wahn Soo

2012-05-05

Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Midlife women, bone health, vegetables, herbs and fruit study. The Scarborough Fair study protocol.

PubMed

Gunn, Caroline A; Weber, Janet L; Kruger, Marlena C

2013-01-10

Bone loss is accelerated in middle aged women but increased fruit/vegetable intake positively affects bone health by provision of micronutrients essential for bone formation, buffer precursors which reduce acid load and phytochemicals affecting inflammation and oxidative stress. Animal studies demonstrated bone resorption inhibiting properties of specific vegetables, fruit and herbs a decade ago. To increase fruit/vegetable intake in post menopausal women to 9 servings/day using a food specific approach to significantly reduce dietary acid load and include specific vegetables, fruit and herbs with bone resorbing inhibiting properties to assess effect on bone turnover, metabolic and inflammatory markers. The Scarborough Fair Study is a randomised active comparator controlled multi centre trial. It aimed to increase fruit and vegetable intake in 100 post menopausal women from ≤ 5 servings/day to ≥ 9 servings/day for 3 months. The women in the dietary intervention were randomly assigned to one of the two arms of the study. Both groups consumed ≥ 9 servings/day of fruit/vegetables and selected herbs but the diet of each group emphasised different fruit/vegetables/herbs with one group (B) selecting from a range of vegetables, fruit and culinary herbs with bone resorbing inhibiting properties. 50 women formed a negative control group (Group C usual diet). Primary outcome variables were plasma bone markers assessed at baseline, 6 weeks and 12 weeks. Secondary outcome variables were plasma inflammation and metabolic markers and urinary electrolytes (calcium, magnesium, potassium and sodium) assessed at baseline and 12 weeks. Dietary intake and urine pH change also were outcome variables. The dietary change was calculated with 3 day diet diaries and a 24 hour recall. Intervention participants kept a twice weekly record of fruit, vegetable and herb intake and urine pH. This study will provide information on midlife women's bone health and how a dietary intervention

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nurmio, Mirja, E-mail: Mirja.Nurmio@utu.fi; Department of Pediatrics, University of Turku; Joki, Henna, E-mail: Henna.Joki@utu.fi

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bonemore » physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.« less

High biocompatibility and improved osteogenic potential of novel Ca-P/titania composite scaffolds designed for regeneration of load-bearing segmental bone defects.

PubMed

Cunha, Carla; Sprio, Simone; Panseri, Silvia; Dapporto, Massimiliano; Marcacci, Maurilio; Tampieri, Anna

2013-06-01

Regeneration of load-bearing bone segments is still an open challenge due to the lack of biomaterials mimicking natural bone with a suitable chemicophysical and mechanical performance. This study proposes ceramic bone scaffolds made of β-tricalcium phosphate (β-TCP) and titania (TiO2 ), developed from hydroxyapatite (HA) and TiO2 starting nanopowders, which exhibit high and interconnected macroporosity (>70 vol %). The scaffold composition was designed to achieve a synergistic effect of bioactivity/resorbability and mechanical properties suitable for load-bearing regenerative applications. The analysis of the morphology, structure, and mechanical strength of the scaffolds resulted in compression strength nearly twice that of commercially available HA bone grafts with similar structure (Engipore(®)). Biological characterization was carried out for human MG-63 osteoblast-like cells proliferation, activity, attachment, and viability. β-TCP/TiO2 scaffolds show high proliferation rate, high viability, and high colonization rates. Moreover, an increased activity of the osteogenic marker alkaline phosphatase (ALP) was found. These results demonstrate that β-TCP/TiO2 scaffolds have good potential as osteogenically active load-bearing scaffolds; moreover, given the high and interconnected macroporosity as well as the resorbability properties of β-TCP, these scaffolds may enhance in vivo osteointegration and promote the formation of new organized bone, thus resulting in very promising biomimetic scaffolds for long bone regeneration. Copyright © 2012 Wiley Periodicals, Inc.

[Scintigraphic detection of osteoblast activity after implantation of BAS-0 bioactive glass-ceramic material into long bone defects].

PubMed

Sponer, P; Urban, K; Urbanová, E

2006-06-01

The aim of the study was to demonstrate, by three-phase bone scintigraphy, radionuclide uptake at the site of defects in long bones filled with the non-resorbable bioactive glass-ceramic material BAS-0 at a long follow-up. Twenty patients, 14 men and 6 women, operated on between 1990 and 2000 for benign bone tumors or tumor-like lesions localized in the femur, tibia or humerus were comprised in the study. Their average age at the time of operation was 14 years (range, 8 to 24). The diagnoses based on histological examination included juvenile bone cysts in 11, aneurysmal bone cyst in five, non-ossifying fibroma in two, and fibrous dysplasia in two patients. The lesions were localized in the femur, humerus and tibia in 11, five and four patients, respectively. The metaphysis was affected in eight and the diaphysis in 12 patients. Clinical, radiological and scintigraphic examinations were carried out at 2 to 12 years (7 years on average) after surgery. The clinical evaluation included subjective complaints and objective findings. Radiographs were made in standard projections and the osteo-integration of glass-ceramic material was investigated. Three-phase bone scans were made and the healthy and the affected limbs in each patient were compared by means of an index. Radionuclide uptake was considered normal when the index value was equal to 1.0, mildly increased at an index value of 1.2, moderately increased at 1.2-1.5 and markedly increased at an index value higher than 1.5. The clinical evaluation showed that, in the patients with glass-ceramic filling of metaphyses, six had no subjective complaints and two reported transient pain. In the patients with implants in diaphyses, subjective complaints were recorded in nine and no complaints in three patients. No inflammatory changes in soft tissues were found. No restriction in weightbearing of the limb treated was reported by any of the patients. On radiography, 18 patients were free from any disease residue or

Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

PubMed Central

van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

2000-01-01

Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. PMID:10869429

Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia

PubMed Central

Tamma, Roberto; Sun, Li; Cuscito, Concetta; Lu, Ping; Corcelli, Michelangelo; Li, Jianhua; Colaianni, Graziana; Moonga, Surinder S.; Di Benedetto, Adriana; Grano, Maria; Colucci, Silvia; Yuen, Tony; New, Maria I.; Zallone, Alberta; Zaidi, Mone

2013-01-01

Although hyponatremia is known to be associated with osteoporosis and a high fracture risk, the mechanism through which bone loss ensues has remained unclear. As hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, we examined whether AVP can affect the skeleton directly as yet another component of the pituitary-bone axis. Here, we report that the two Avp receptors, Avpr1α and Avpr2, coupled to Erk activation, are expressed in osteoblasts and osteoclasts. AVP injected into wild-type mice enhanced and reduced, respectively, the formation of bone-resorbing osteoclasts and bone-forming osteoblasts. Conversely, the exposure of osteoblast precursors to Avpr1α or Avpr2 antagonists, namely SR49059 or ADAM, increased osteoblastogenesis, as did the genetic deletion of Avpr1α. In contrast, osteoclast formation and bone resorption were both reduced in Avpr1α−/− cultures. This process increased bone formation and reduced resorption resulted in a profound enhancement of bone mass in Avpr1α−/− mice and in wild-type mice injected with SR49059. Collectively, the data not only establish a primary role for Avp signaling in bone mass regulation, but also call for further studies on the skeletal actions of Avpr inhibitors used commonly in hyponatremic patients. PMID:24167258

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

PubMed

Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

2016-03-01

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

Sinus lift using a nanocrystalline hydroxyapatite silica gel in severely resorbed maxillae: histological preliminary study.

PubMed

Canullo, Luigi; Dellavia, Claudia

2009-10-01

The aim of this preliminary study was to evaluate histologically a nanocrystalline hydroxyapatite silica gel in maxillary sinus floor grafting in severely resorbed maxillae. A total of 16 consecutive patients scheduled for sinus lift were recruited during this study. Patients were randomly divided in two groups, eight patients each. In both groups, preoperative residual bone level ranged between 1 and 3 mm (mean value of 2.03 mm). No membrane was used to occlude the buccal window. Second surgery was carried out after a healing period of 3 months in Group 1 and 6 months in Group 2. Using a trephine bur, one bone specimen was harvested from each augmented sinus and underwent histological and histomorphometric analysis. Histological analysis showed significant new bone formation and remodeling of the grafted material. In the cores obtained at 6 months, regenerated bone, residual NanoBone, and bone marrow occupied respectively 48 +/- 4.63%, 28 +/- 5.33%, and 24 +/- 7.23% of the grafted volume. In the specimens taken 3 months after grafting, mean new bone was 8 +/- 3.34%, mean NanoBone was 45 +/- 5.10%, and mean bone marrow was 47 +/- 6.81% of the bioptical volume. Within the limits of this preliminary prospective study, it was concluded that grafting of maxillary sinus using nanostructured hydroxyapatite silica gel as only bone filler is a reliable procedure also in critical anatomic conditions and after early healing period.

Inflammatory foreign body reaction caused by resorbable materials used for orbital fractures repair: A case report.

PubMed

He, Jie; Shi, Wodong

2017-12-01

Resorbable materials have been recommended for orbital fractures repair. Many literatures reported the advantages of resorbable materials in clinical applications, but few reports about complications. In this study, we encountered a 14-year-old boy treated for the orbital fracture by using resorbable plate, in whom inflammatory foreign body reaction was detected. In addition, this patient had repeated history of skin allergy and upper respiratory tract infection. Intraoperative observation showed that the resorbable material near the orbital rim was covered by granulation and inflammatory tissues, without purulent secretions. The histological examination revealed inflammatory foreign body reaction to the resorbable plate. Debridement was taken to remove the mass on the left lower eyelid. At the outpatient examination, a small amount of granulation tissue was found at the incision. Then, secondary surgery for exploration and removal of the resorbable material was carried, 9 months after the first surgery. One month after the surgery, the skin retraction, ectropion, and edema gradually improved. Inadequate degradation of resorbable materials and patient's medical history of allergies may cause an inflammatory foreign body reaction. Therefore, it is prudent to choose resorbable materials for patients.

Single-stage cartilage repair in the knee with microfracture covered with a resorbable polymer-based matrix and autologous bone marrow concentrate.

PubMed

Enea, D; Cecconi, S; Calcagno, S; Busilacchi, A; Manzotti, S; Kaps, C; Gigante, A

2013-12-01

Different single-stage surgical approaches are currently under evaluation to repair focal cartilage lesions. This study aims to analyze the clinical and histological results after treatment of focal condylar articular lesions of the knee with microfracture and subsequent covering with a resorbable polyglycolic acid/hyaluronan (PGA -HA) matrix augmented with autologous bone marrow concentrate (BMC). Nine patients with focal lesions of the condylar articular cartilage were consecutively treated with arthroscopic PGA -HA-covered microfracture and bone marrow concentrate (PGA -HA-CMBMC). Patients were retrospectively assessed using standardized assessment tools and magnetic resonance imaging (MRI). Five patients consented to undergo second look arthroscopy and 2 consented biopsy harvest. All the patients but one showed improvement in clinical scoring from the pre-operative situation to the latest follow-up (average 22±2months). The mean IKDC subjective score, Lysholm score, VAS and the median Tegner score significantly increased from baseline to the latest follow-up. Cartilage macroscopic assessment at 12months revealed that one repair appeared normal, three almost normal and one appeared abnormal. Histological analysis proofed hyaline-like cartilage repair tissue formation in one case. MRI at 8 to 12months follow-up showed complete defect filling. The first clinical experience with single-stage treatment of focal cartilage defects of the knee with microfracture and covering with the PGA -HA matrix augmented with autologous BMC (PGA -HA-CMBMC) suggests that it is safe, it improves knee function and has the potential to regenerate hyaline-like cartilage. IV, case series. Copyright © 2013 Elsevier B.V. All rights reserved.

Histomorphologic findings on human bone samples six months after bone augmentation of the maxillary sinus with Algipore.

PubMed

Schopper, C; Moser, D; Wanschitz, F; Watzinger, F; Lagogiannis, G; Spassova, E; Ewers, R

1999-01-01

Sinus grafting, a popular and standard treatment for maxillary atrophy, uses a variety of grafting materials. In this study, specimens obtained 6 months after sinus grafting with Algipore were evaluated under light microscopy and showed osseoformation, xenograft degradation, and bone ingrowth into particles. Osteoblastic cells were embedded in the intracorpuscular bone matrix, which indicated that xenograft particles are an osseoconductive scaffold and stimulate matrix deposition. Acute inflammatory responses after insertion of Algipore did not occur. Particles were degraded during physiologic bone remodeling, and newly formed bone gradually replaced resorbed biomaterial.

Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption.

PubMed

Wilson, Susan R; Peters, Christoph; Saftig, Paul; Brömme, Dieter

2009-01-23

Cathepsin K is responsible for the degradation of type I collagen in osteoclast-mediated bone resorption. Collagen fragments are known to be biologically active in a number of cell types. Here, we investigate their potential to regulate osteoclast activity. Mature murine osteoclasts were seeded on type I collagen for actin ring assays or dentine discs for resorption assays. Cells were treated with cathepsins K-, L-, or MMP-1-predigested type I collagen or soluble bone fragments for 24 h. The presence of actin rings was determined fluorescently by staining for actin. We found that the percentage of osteoclasts displaying actin rings and the area of resorbed dentine decreased significantly on addition of cathepsin K-digested type I collagen or bone fragments, but not with cathepsin L or MMP-1 digests. Counterintuitively, actin ring formation was found to decrease in the presence of the cysteine proteinase inhibitor LHVS and in cathepsin K-deficient osteoclasts. However, cathepsin L deficiency or the general MMP inhibitor GM6001 had no effect on the presence of actin rings. Predigestion of the collagen matrix with cathepsin K, but not by cathepsin L or MMP-1 resulted in an increased actin ring presence in cathepsin K-deficient osteoclasts. These studies suggest that cathepsin K interaction with type I collagen is required for 1) the release of cryptic Arg-Gly-Asp motifs during the initial attachment of osteoclasts and 2) termination of resorption via the creation of autocrine signals originating from type I collagen degradation.

Laryngotracheal reconstruction with resorbable microplate buttressing.

PubMed

Javia, Luv R; Zur, Karen B

2012-04-01

In patients undergoing laryngotracheal reconstruction (LTR), malacic segments of trachea can pose challenges to successful reconstruction. Malacic segments may inadequately support cartilage grafts used in augmentation surgery, sometimes requiring cricotracheal or tracheal resections. We describe a novel technique of LTR with resorbable microplate buttressing of malacic lateral tracheal segments. Retrospective case series. Review of technique, treatment outcomes, and complications of seven children with subglottic stenosis and tracheomalacia requiring a microplate-augmented LTR technique. Seven infants ranging from 26 months to 9 years of age successfully underwent LTR for subglottic stenosis. Six children had a grade III subglottic stenosis. The seventh child had grade II subglottic stenosis, bilateral vocal fold paralysis, an elliptical cricoid, and an obstructing giant suprastomal fibroma. Five children underwent a double-stage LTR with resorbable microplates sutured bilaterally to support severely malacic lateral tracheal segments. A cricotracheal resection would not have been feasible in one child due to the resection length and inadequate tracheal mobilization. Two children underwent a single-stage LTR with unilateral application of a microplate. Six children were decannulated within 3 months and continue without airway symptoms or complications. One child, who is just over 2 months from reconstructive surgery, is being setup for decannulation. No complications were encountered. LTR with resorbable microplate buttressing of malacic lateral tracheal segments is technically feasible, safe, and can avoid more extensive surgery requiring tracheal resection. Further experience may support the use of this technique in challenging airway reconstructions. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Uranium in bone: metabolic and autoradiographic studies in the rat.

PubMed

Priest, N D; Howells, G R; Green, D; Haines, J W

1982-03-01

The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

Guided bone regeneration: A novel approach in the treatment of pediatric dentoalveolar trauma

PubMed Central

Murthy, Prashanth Sadashiva; Shivamallu, Avinash Bettahalli; Deshmukh, Seema; Nandlal, Bhojraj; Thotappa, Srilatha K.

2015-01-01

Traumatic injuries in the primary dentition pose major challenges for management. This emergency treatment requires proper planning so as to achieve favorable results. Trauma causing severe dentoalveolar injuries, especially in children, needs an interdisciplinary approach so as to retain normal functional anatomy for that age. This article describes a clinical innovative technique, which utilizes a resorbable membrane in management of pediatric dentoalveolar trauma. The membrane was shaped to cover the multiple alveolar bone fracture, thereby favoring the healing of the bone defects. The use of this resorbable membrane maintained a secluded space for the bone growth and prevented overgrowth of the soft tissue in the region of the defect. This resulted in uneventful healing leading to well-maintained functional bone contour, which further favored the esthetic rehabilitation as well as protected the underlying permanent tooth buds. PMID:26005471

Axial load-bearing capacity of an osteochondral autograft stabilized with a resorbable osteoconductive bone cement compared with a press-fit graft in a bovine model.

PubMed

Kiss, Marc-Olivier; Levasseur, Annie; Petit, Yvan; Lavigne, Patrick

2012-05-01

Osteochondral autografts in mosaicplasty are inserted in a press-fit fashion, and hence, patients are kept nonweightbearing for up to 2 months after surgery to allow bone healing and prevent complications. Very little has been published regarding alternative fixation techniques of those grafts. Osteochondral autografts stabilized with a resorbable osteoconductive bone cement would have a greater load-bearing capacity than standard press-fit grafts. Controlled laboratory study. Biomechanical testing was conducted on 8 pairs of cadaveric bovine distal femurs. For the first 4 pairs, 6 single osteochondral autografts were inserted in a press-fit fashion on one femur. On the contralateral femur, 6 grafts were stabilized with a calcium triglyceride osteoconductive bone cement. For the 4 remaining pairs of femurs, 4 groups of 3 adjacent press-fit grafts were inserted on one femur, whereas on the contralateral femur, grafts were cemented. After a maturation period of 48 hours, axial loading was applied on all single grafts and on the middle graft of each 3-in-a-row series. For the single-graft configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 281.87 N versus 345.56 N (P = .015) and 336.29 N versus 454.08 N (P = .018), respectively. For the 3-in-a-row configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 260.31 N versus 353.47 N (P = .035) and 384.83 N versus 455.68 N (P = .029), respectively. Fixation of osteochondral grafts using bone cement appears to improve immediate stability over the original mosaicplasty technique for both single- and multiple-graft configurations. Achieving greater primary stability of osteochondral grafts could potentially accelerate postoperative recovery, allowing early weightbearing and physical therapy.

Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

PubMed Central

Ros-Tárraga, Patricia; Mazón, Patricia; Rodríguez, Miguel A.; Meseguer-Olmo, Luis; De Aza, Piedad N.

2016-01-01

This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ) rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared). The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially) and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung) as a result of degradation products being released. PMID:28773906

Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.

PubMed

Kawatani, Makoto; Osada, Hiroyuki

2009-11-01

Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors.

Evaluation of novel resorbable membranes for bone augmentation in a rat model.

PubMed

Zeng, Ni; van Leeuwen, Anne; Yuan, Huipin; Bos, Ruud R M; Grijpma, Dirk W; Kuijer, Roel

2016-02-01

Our study compared two novel, biodegradable poly(trimethylene carbonate) (PTMC) barrier membranes to clinically applied barrier membranes in maintaining volume of block autologous bone grafts in a rat mandible model. Two hundred and forty rats were included in this study. Block autologous bone grafts of 5 mm in diameter were harvested from the mandibular angles and transplanted onto the contralateral side. The bone grafts were either covered with a membrane or left uncovered. The applied membranes included pure PTMC membranes, biphasic calcium phosphate (BCP) incorporated PTMC composite membranes, expanded poly(tetrafluoroethylene) (e-PTFE) membranes (Tex) and collagen membranes (Geistlich Bio-Gide). After 2, 4 and 12 weeks, the rat mandibles were retrieved and analysed by histological evaluation and μCT quantification. The histological evaluation revealed that in time the block autologous bone graft was well integrated to the recipient bone via gradually maturing newly formed bone and did not show signs of resorption, independent of membrane coverage or types of membrane. μCT quantification showed the volume of the bone graft and recipient bone together was maintained by new bone formation and recipient bone resorption. Our study showed that the use of PTMC membranes and PTMC-BCP composite membranes resulted in similar bone remodelling to the collagen membranes and e-PTFE membranes and that the use of barrier membranes did not interfere with bone remodelling of the bone grafts and recipient bones. However, the used barrier membranes seemed not to contribute in maintaining the volume of block autologous bone grafts. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteoclastic differentiation and resorption is modulated by bioactive metal ions Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements

PubMed Central

Bernhardt, Anne; Schamel, Martha; Gbureck, Uwe; Gelinsky, Michael

2017-01-01

Biologically active metal ions in low doses have the potential to accelerate bone defect healing. For successful remodelling the interaction of bone graft materials with both bone-forming osteoblasts and bone resorbing osteoclasts is crucial. In the present study brushite forming calcium phosphate cements (CPC) were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on osteoclast differentiation and activity was examined. Human osteoclasts were differentiated from human peripheral blood mononuclear cells (PBMC) both on the surface and in indirect contact to the materials on dentin discs. Release of calcium, phosphate and bioactive metal ions was determined using ICP-MS both in the presence and absence of the cells. While Co2+ and Cu2+ showed a burst release, Cr3+ was released steadily at very low concentrations (below 1 μM) and both calcium and phosphate release of the cements was considerably changed in the Cr3+ modified samples. Direct cultivation of PBMC/osteoclasts on Co2+ cements showed lower attached cell number compared to the reference but high activity of osteoclast specific enzymes tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (CAII) and cathepsin K (CTSK) and significantly increased gene expression of vitronectin receptor. Indirect cultivation with diluted Co2+ cement extracts revealed highest resorbed area compared to all other modifications and the reference. Cu2+ cements had cytotoxic effect on PBMC/osteoclasts during direct cultivation, while indirect cultivation with diluted extracts from Cu2+ cements did not provoke cytotoxic effects but a strictly inhibited resorption. Cr3+ doped cements did not show cytotoxic effects at all. Gene expression and enzyme activity of CTSK was significantly increased in direct culture. Indirect cultivation with Cr3+ doped cements revealed significantly higher resorbed area compared to the reference. In conclusion Cr3+ doped calcium phosphate cements are an innovative cement

Osteoclastic differentiation and resorption is modulated by bioactive metal ions Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements.

PubMed

Bernhardt, Anne; Schamel, Martha; Gbureck, Uwe; Gelinsky, Michael

2017-01-01

Biologically active metal ions in low doses have the potential to accelerate bone defect healing. For successful remodelling the interaction of bone graft materials with both bone-forming osteoblasts and bone resorbing osteoclasts is crucial. In the present study brushite forming calcium phosphate cements (CPC) were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on osteoclast differentiation and activity was examined. Human osteoclasts were differentiated from human peripheral blood mononuclear cells (PBMC) both on the surface and in indirect contact to the materials on dentin discs. Release of calcium, phosphate and bioactive metal ions was determined using ICP-MS both in the presence and absence of the cells. While Co2+ and Cu2+ showed a burst release, Cr3+ was released steadily at very low concentrations (below 1 μM) and both calcium and phosphate release of the cements was considerably changed in the Cr3+ modified samples. Direct cultivation of PBMC/osteoclasts on Co2+ cements showed lower attached cell number compared to the reference but high activity of osteoclast specific enzymes tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (CAII) and cathepsin K (CTSK) and significantly increased gene expression of vitronectin receptor. Indirect cultivation with diluted Co2+ cement extracts revealed highest resorbed area compared to all other modifications and the reference. Cu2+ cements had cytotoxic effect on PBMC/osteoclasts during direct cultivation, while indirect cultivation with diluted extracts from Cu2+ cements did not provoke cytotoxic effects but a strictly inhibited resorption. Cr3+ doped cements did not show cytotoxic effects at all. Gene expression and enzyme activity of CTSK was significantly increased in direct culture. Indirect cultivation with Cr3+ doped cements revealed significantly higher resorbed area compared to the reference. In conclusion Cr3+ doped calcium phosphate cements are an innovative cement

Mechanical and Histological Effects of Resorbable Blasting Media Surface Treatment on the Initial Stability of Orthodontic Mini-Implants

PubMed Central

2016-01-01

Introduction. This study aimed to evaluate the effects of resorbable blasting media (RBM) treatment on early stability of orthodontic mini-implants by mechanical, histomorphometric, and histological analyses. Methods. Ninety-six (64 for mechanical study and 32 for histological study and histomorphometric analysis) titanium orthodontic mini-implants (OMIs) with machined (machined group) or RBM-treated (CaP) surface (RBM group) were implanted in the tibiae of 24 rabbits. Maximum initial torque (MIT) was measured during insertion, and maximum removal torque (MRT) and removal angular momentum (RAM) were measured at 2 and 4 weeks after implantation. Bone-to-implant contact (BIC) and bone area (BA) were analyzed at 4 weeks after implantation. Results. RBM group exhibited significantly lower MIT and significantly higher MRT and RAM at 2 weeks than machined group. No significant difference in MRT, RAM, and BIC between the two groups was noted at 4 weeks, although BA was significantly higher in RBM group than in machined group. RBM group showed little bone resorption, whereas machined group showed new bone formation after bone resorption. Conclusions. RBM surface treatment can provide early stability of OMIs around 2 weeks after insertion, whereas stability of machined surface OMIs may decrease in early stages because of bone resorption, although it can subsequently recover by new bone apposition. PMID:26942200

The cell biology and role of resorptive cells in diseases: A review.

PubMed

Babaji, Prashant; Devanna, Raghu; Jagtap, Kiran; Chaurasia, Vishwajit Rampratap; Jerry, Jeethu John; Choudhury, Basanta Kumar; Duhan, Dinesh

2017-01-01

Resorptive cells are responsible for the resorption of mineralized matrix of hard tissues. Bone-resorbing cells are called osteoclasts; however, they can resorb mineralized dental tissues or calcified cartilage and then they are called odontoclasts and chondroclasts, respectively. Resorptive cells form when mononuclear precursors derived from a monocyte-macrophage cell lineage are attracted to certain mineralized surfaces and subsequently fuse and adhere onto them for exerting their resorbing activity. These cells are responsible for degradation of calcified extracellular matrix composed of organic molecules and hydroxyapatite. The activity of these cells can be observed in both physiological and pathological processes throughout life and their activity is mainly required in bone turnover and growth, spontaneous and induced (orthodontic) tooth movement, tooth eruption, and bone fracture healing, as well as in pathological conditions such as osteoporosis, osteoarthritis, and bone metastasis. In addition, they are responsible for daily control of calcium homeostasis. Clastic cells also resorb the primary teeth for shedding before the permanent teeth erupt into the oral cavity.

Diabetes mellitus related bone metabolism and periodontal disease

PubMed Central

Wu, Ying-Ying; Xiao, E; Graves, Dana T

2015-01-01

Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

Maintaining space in localized ridge augmentation using guided bone regeneration with tenting screw technology.

PubMed

Chasioti, Evdokia; Chiang, Tat Fai; Drew, Howard J

2013-01-01

Prosthetic guided implant surgery requires adequate ridge dimensions for proper implant placement. Various surgical procedures can be used to augment deficient alveolar ridges. Studies have examined new bone formation on deficient ridges, utilizing numerous surgical techniques and biomaterials. The goal is to develop time efficient techniques, which have low morbidity. A crucial factor for successful bone grafting procedures is space maintenance. The article discusses space maintenance tenting screws, used in conjunction with bone allografts and resorbable barrier membranes, to ensure uneventful guided bone regeneration (GBR) enabling optimal implant positioning. The technique utilized has been described in the literature to treat severely resorbed alveolar ridges and additionally can be considered in restoring the vertical and horizontal component of deficient extraction sites. Three cases are presented to illustrate the utilization and effectiveness of tenting screw technology in the treatment of atrophic extraction sockets and for deficient ridges.

Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

PubMed Central

Jeney, Viktória

2017-01-01

Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

A new biphasic osteoinductive calcium composite material with a negative Zeta potential for bone augmentation

PubMed Central

Smeets, Ralf; Kolk, Andreas; Gerressen, Marcus; Driemel, Oliver; Maciejewski, Oliver; Hermanns-Sachweh, Benita; Riediger, Dieter; Stein, Jamal M

2009-01-01

The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants. PMID:19523239

Gene Expression in Bone

NASA Astrophysics Data System (ADS)

D'Ambrogio, A.

Skeletal system has two main functions, to provide mechanical integrity for both locomotion and protection and to play an important role in mineral homeostasis. There is extensive evidence showing loss of bone mass during long-term Space-Flights. The loss is due to a break in the equilibrium between the activity of osteoblasts (the cells that forms bone) and the activity of osteoclasts (the cells that resorbs bone). Surprisingly, there is scanty information about the possible altered gene expression occurring in cells that form bone in microgravity.(Just 69 articles result from a "gene expression in microgravity" MedLine query.) Gene-chip or microarray technology allows to screen thousands of genes at the same time: the use of this technology on samples coming from cells exposed to microgravity could provide us with many important informations. For example, the identification of the molecules or structures which are the first sensors of the mechanical stress derived from lack of gravity, could help in understanding which is the first event leading to bone loss due to long-term exposure to microgravity. Consequently, this structure could become a target for a custom-designed drug. It is evident that bone mass loss, observed during long-time stay in Space, represents an accelerated model of what happens in aging osteoporosis. Therefore, the discovery and design of drugs able to interfere with the bone-loss process, could help also in preventing negative physiological processes normally observed on Earth. Considering the aims stated above, my research is designed to:

Dried plum diet protects from bone loss caused by ionizing radiation

PubMed Central

Schreurs, A.-S.; Shirazi-Fard, Y.; Shahnazari, M.; Alwood, J. S.; Truong, T. A.; Tahimic, C. G. T.; Limoli, C. L.; Turner, N. D.; Halloran, B.; Globus, R. K.

2016-01-01

Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth. PMID:26867002

Medium-Term Function of a 3D Printed TCP/HA Structure as a New Osteoconductive Scaffold for Vertical Bone Augmentation: A Simulation by BMP-2 Activation

PubMed Central

Moussa, Mira; Carrel, Jean-Pierre; Scherrer, Susanne; Cattani-Lorente, Maria; Wiskott, Anselm; Durual, Stéphane

2015-01-01

Introduction: A 3D-printed construct made of orthogonally layered strands of tricalcium phosphate (TCP) and hydroxyapatite has recently become available. The material provides excellent osteoconductivity. We simulated a medium-term experiment in a sheep calvarial model by priming the blocks with BMP-2. Vertical bone growth/maturation and material resorption were evaluated. Materials and methods: Titanium hemispherical caps were filled with either bare- or BMP-2 primed constructs and placed onto the calvaria of adult sheep (n = 8). Histomorphometry was performed after 8 and 16 weeks. Results: After 8 weeks, relative to bare constructs, BMP-2 stimulation led to a two-fold increase in bone volume (Bare: 22% ± 2.1%; BMP-2 primed: 50% ± 3%) and a 3-fold decrease in substitute volume (Bare: 47% ± 5%; BMP-2 primed: 18% ± 2%). These rates were still observed at 16 weeks. The new bone grew and matured to a haversian-like structure while the substitute material resorbed via cell- and chemical-mediation. Conclusion: By priming the 3D construct with BMP-2, bone metabolism was physiologically accelerated, that is, enhancing vertical bone growth and maturation as well as material bioresorption. The scaffolding function of the block was maintained, leaving time for the bone to grow and mature to a haversian-like structure. In parallel, the material resorbed via cell-mediated and chemical processes. These promising results must be confirmed in clinical tests.

Effects of polyglactin mesh combined with resorbable calcium carbonate or replamineform hydroxyapatite on periodontal repair in dogs.

PubMed

Moon, I S; Chai, J K; Cho, K S; Wikesjö, U M; Kim, C K

1996-10-01

This study evaluates periodontal repair and biomaterial reaction following implantation of a polyglactin mesh with or without porous resorbable calcium carbonate (RCC) or porous replamineform hydroxyapatite (RHA) in conjunction with reconstructive surgery. Ligature- and surgically-induced interproximal periodontal defects of left and right mandibular premolar teeth in 7 dogs were used. Bilaterally, mesial defects of the 2nd, 3rd and 4th premolar teeth were treated with polyglactin mesh, polyglactin mesh and RHA, or polyglactin mesh and RCC, respectively. The polyglactin mesh, shaped according to the contour of the defect, was adapted to the experimental teeth; its coronal margin positioned immediately apical to the cemento-enamel junction. Gingival flap margins were adapted and sutured to cover the polyglactin mesh completely. Clinical healing was generally uneventful. The dogs were sacrificed to provide block sections for histologic evaluation at 1, 3, 6, 12, 26, 32 and 56 weeks following wound closure. Generally, cementum regeneration was observed beginning at week 6 in all groups. Bone regeneration was observed from week 3 in polyglactin mesh-treated groups, and from week 6 in polyglactin mesh+RCC or polyglactin mesh+RHA treated groups. Bone regeneration appeared enhanced in polyglactin mesh+RCC or polyglactin mesh+RHA treated defects at week 12 and 26, with little difference between the three experimental conditions at week 56. Polyglactin mesh degradation was observed at week 3 and appeared complete at week 12. The RHA did not appear to resorb, while the RCC was gradually replaced by bone from week 3. Within limitations of the study conditions, periodontal regeneration was observed following implantation of a polyglactin mesh with or without RCC or RHA in conjunction with reconstructive surgery. As a conclusion, there seems to be no significant difference in periodontal regeneration after 12 months of healing between the group treated with the membrane only

Protective Effects of Selected Botanical Agents on Bone.

PubMed

Jolly, James Jam; Chin, Kok-Yong; Alias, Ekram; Chua, Kien Hui; Soelaiman, Ima Nirwana

2018-05-11

Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.

Protective Effects of Selected Botanical Agents on Bone

PubMed Central

Jolly, James Jam; Alias, Ekram; Chua, Kien Hui; Soelaiman, Ima Nirwana

2018-01-01

Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis. PMID:29751644

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma

PubMed Central

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W.; Novane, Nora; Shah, Jatin J.; Davis, Richard E.; Hou, Jian; Gagel, Robert F.; Yang, Jing

2016-01-01

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP upregulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP upregulated the methylation of IRF8, thereby enhanced expression of NFATc1, leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2DDR. Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K/Akt signaling, and increased DNMT3A expression, resulting in hypermethylation of RUNX2, osterix, and IRF8. This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. As TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. PMID:27559096

Peripheral cannabinoid receptor, CB2, regulates bone mass

PubMed Central

Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

2006-01-01

The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss.

PubMed

Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc; Moriarty, Tara J

2017-02-01

Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption. Copyright © 2017 Tang et al.

Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo.

PubMed

Roelofs, Anke J; Stewart, Charlotte A; Sun, Shuting; Błażewska, Katarzyna M; Kashemirov, Boris A; McKenna, Charles E; Russell, R Graham G; Rogers, Michael J; Lundy, Mark W; Ebetino, Frank H; Coxon, Fraser P

2012-04-01

Bisphosphonates are widely used antiresorptive drugs that bind to calcium. It has become evident that these drugs have differing affinities for bone mineral; however, it is unclear whether such differences affect their distribution on mineral surfaces. In this study, fluorescent conjugates of risedronate, and its lower-affinity analogues deoxy-risedronate and 3-PEHPC, were used to compare the localization of compounds with differing mineral affinities in vivo. Binding to dentine in vitro confirmed differences in mineral binding between compounds, which was influenced predominantly by the characteristics of the parent compound but also by the choice of fluorescent tag. In growing rats, all compounds preferentially bound to forming endocortical as opposed to resorbing periosteal surfaces in cortical bone, 1 day after administration. At resorbing surfaces, lower-affinity compounds showed preferential binding to resorption lacunae, whereas the highest-affinity compound showed more uniform labeling. At forming surfaces, penetration into the mineralizing osteoid was found to inversely correlate with mineral affinity. These differences in distribution at resorbing and forming surfaces were not observed at quiescent surfaces. Lower-affinity compounds also showed a relatively higher degree of labeling of osteocyte lacunar walls and labeled lacunae deeper within cortical bone, indicating increased penetration of the osteocyte canalicular network. Similar differences in mineralizing surface and osteocyte network penetration between high- and low-affinity compounds were evident 7 days after administration, with fluorescent conjugates at forming surfaces buried under a new layer of bone. Fluorescent compounds were incorporated into these areas of newly formed bone, indicating that "recycling" had occurred, albeit at very low levels. Taken together, these findings indicate that the bone mineral affinity of bisphosphonates is likely to influence their distribution within the

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma.

PubMed

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W; Novane, Nora; Shah, Jatin J; Davis, Richard E; Hou, Jian; Gagel, Robert F; Yang, Jing

2016-08-24

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. Copyright © 2016, American Association for the Advancement of Science.

Histologic analysis of resorbable blasting media surface implants retrieved from humans: a report of two cases

PubMed Central

2016-01-01

The purpose of this study is to evaluate the degree of osseointegration of resorbable blasting media (RBM) surface implants retrieved from humans. Three implants in the mandibular molar region that were surface-treated with RBM were retrieved from two patients. The implants were used to manufacture specimens in order to measure the bone-implant contact (BIC) ratio. The BIC ratios of the three implants were found to be an average of 69.0%±9.1%. In conclusion, that RBM surface implants are integrated into the host environment with histological significance and the BIC ratio of the RBM surface-treated implant was not significantly different from that of other surface-treated implants. PMID:26904493

Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation.

PubMed

Joshi, Nayana; Reverte-Vinaixa, Mercè; Díaz-Ferreiro, Eugenio Wenceslao; Domínguez-Oronoz, Rosa

2012-06-01

Surgical management of patellar cartilage defects remains controversial. The ideal technique to regenerate hyaline cartilage is not yet defined. However, a synthetic resorbable osteochondral scaffold plug (TruFit CB) seems to offer a treatment option with good results at short-term follow-up, at least in the condylar setting. A synthetic implant provides a simple and efficacious means of treating the cartilage defects of the patellofemoral joint in young patients. Case series; Level of evidence, 4. A study was designed to evaluate prospectively short- and medium-term results in patients with osteochondral patellar defects treated with synthetic reabsorbable scaffolds. Patient outcome scores (Short Form 36 [SF-36] and Knee injury and Osteoarthritis Outcome Score [KOOS]), demographics, prior surgeries, and data from a physical examination were collected at baseline (before implantation) and at 6, 12, and 24 months after surgery. Defect characteristics were collected during implantation. Diagnosis and monitoring were performed by magnetic resonance imaging. Ten patients with a mean age of 33.3 years (range, 16-49 years) were evaluated prospectively at 24 months' follow-up. The number of plugs used for each patient ranged from 1 to 4. At 1-year follow-up, the results were satisfactory in 8 of 10 patients, and poor in 2, according to clinical assessment (KOOS, visual analog scale, and SF-36). At 18 months of follow-up, all patients except one complained of pain and knee swelling. Reoperation rate for implant failure at final follow-up was 70%. Magnetic resonance imaging at final follow-up showed a cylindrical cavity of fibrous tissue instead of subchondral bone restoration. A synthetic implant can improve symptoms and joint function, especially for small lesions, only for a short period of time. However, 2 years of monitoring has shown its failure in restoring the subchondral bone despite the formation of predominant hyaline cartilage from synthetic resorbable scaffolds

Histomorphometric Study of New Bone Formation Comparing Defect Healing with Three Bone Grafting Materials: The Effect of Osteoporosis on Graft Consolidation.

PubMed

Zhang, Qiao; Jing, Dai; Zhang, Yufeng; Miron, Richard J

Bone grafting materials are frequently utilized in oral surgery and periodontology to fill bone defects and augment lost or missing bone. The purpose of this study was to compare new bone formation in bone defects created in both normal and osteoporotic animals loaded with three types of bone grafts from different origins. Forty-eight female Wistar rats were equally divided into control normal and ovariectomized animals. Bilateral 2.5-mm femur defects were created and filled with an equal weight of (1) natural bone mineral (NBM, BioOss) of bovine origin, (2) demineralized freeze-dried bone allograft (DFDBA, LifeNet), or (3) biphasic calcium phosphate (BCP, Vivoss). Following 3 and 6 weeks of healing, hematoxylin and eosin and TRAP staining was performed to determine new bone formation, material degradation, and osteoclast activity. All bone substitutes demonstrated osteoconductive potential at 3 and 6 weeks with higher osteoclast numbers observed in all ovariectomized animals. NBM displayed continual new bone formation with little to no sign of particle degradation, even in osteoporotic animals. DFDBA particles showed similar levels of new bone formation but rapid particle degradation rates with lower levels of mineralized tissue. BCP bone grafts demonstrated significantly higher new bone formation when compared with both NBM and DFDBA particles; however, the material was associated with higher osteoclast activity and particle degradation. Interestingly, in osteoporotic animals, BCP displayed synergistically and markedly more rapid rates of particle degradation. Recent modifications to synthetically fabricated materials were shown to be equally or more osteopromotive than NBM and DFDBA. However, the current BCP utilized demonstrated much faster resorption properties in osteoporotic animals associated with a decrease in total bone volume when compared with the slowly/nonresorbing NBM. The results from this study point to the clinical relevance of minimizing fast-resorbing

Osteointegration of porous absorbable bone substitutes: A systematic review of the literature.

PubMed

Paulo, Maria Júlia Escanhoela; Dos Santos, Mariana Avelino; Cimatti, Bruno; Gava, Nelson Fabrício; Riberto, Marcelo; Engel, Edgard Eduard

2017-07-01

Biomaterials' structural characteristics and the addition of osteoinductors influence the osteointegration capacity of bone substitutes. This study aims to identify the characteristics of porous and resorbable bone substitutes that influence new bone formation. An Internet search for studies reporting new bone formation rates in bone defects filled with porous and resorbable substitutes was performed in duplicate using the PubMed, Web of Science, Scielo, and University of São Paulo Digital Library databases. Metaphyseal or calvarial bone defects 4 to 10 mm in diameter from various animal models were selected. New bone formation rates were collected from the histomorphometry or micro-CT data. The following variables were analyzed: animal model, bone region, defect diameter, follow-up time after implantation, basic substitute material, osteoinductor addition, pore size and porosity. Of 3,266 initially identified articles, 15 articles describing 32 experimental groups met the inclusion criteria. There were no differences between the groups in the experimental model characteristics, except for the follow-up time, which showed a very weak to moderate correlation with the rate of new bone formation. In terms of the biomaterial and structural characteristics, only porosity showed a significant influence on the rate of new bone formation. Higher porosity is related to higher new bone formation rates. The influence of other characteristics could not be identified, possibly due to the large variety of experimental models and methodologies used to estimate new bone formation rates. We suggest the inclusion of standard control groups in future experimental studies to compare biomaterials.

Osteointegration of porous absorbable bone substitutes: A systematic review of the literature

PubMed Central

Paulo, Maria Júlia Escanhoela; dos Santos, Mariana Avelino; Cimatti, Bruno; Gava, Nelson Fabrício; Riberto, Marcelo; Engel, Edgard Eduard

2017-01-01

Biomaterials’ structural characteristics and the addition of osteoinductors influence the osteointegration capacity of bone substitutes. This study aims to identify the characteristics of porous and resorbable bone substitutes that influence new bone formation. An Internet search for studies reporting new bone formation rates in bone defects filled with porous and resorbable substitutes was performed in duplicate using the PubMed, Web of Science, Scielo, and University of São Paulo Digital Library databases. Metaphyseal or calvarial bone defects 4 to 10 mm in diameter from various animal models were selected. New bone formation rates were collected from the histomorphometry or micro-CT data. The following variables were analyzed: animal model, bone region, defect diameter, follow-up time after implantation, basic substitute material, osteoinductor addition, pore size and porosity. Of 3,266 initially identified articles, 15 articles describing 32 experimental groups met the inclusion criteria. There were no differences between the groups in the experimental model characteristics, except for the follow-up time, which showed a very weak to moderate correlation with the rate of new bone formation. In terms of the biomaterial and structural characteristics, only porosity showed a significant influence on the rate of new bone formation. Higher porosity is related to higher new bone formation rates. The influence of other characteristics could not be identified, possibly due to the large variety of experimental models and methodologies used to estimate new bone formation rates. We suggest the inclusion of standard control groups in future experimental studies to compare biomaterials. PMID:28793006

Dried plum diet protects from bone loss caused by ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreurs, A. -S.; Shirazi-Fard, Y.; Shahnazari, M.

Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss.more » Dried plum was most effective in reducing the expression of genes related to bone resorption ( Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.« less

Dried plum diet protects from bone loss caused by ionizing radiation

DOE PAGES

Schreurs, A. -S.; Shirazi-Fard, Y.; Shahnazari, M.; ...

2016-02-11

Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss.more » Dried plum was most effective in reducing the expression of genes related to bone resorption ( Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.« less

Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts*

PubMed Central

Takegahara, Noriko; Kim, Hyunsoo; Mizuno, Hiroki; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Tomura, Michio; Kanagawa, Osami; Ishii, Masaru; Choi, Yongwon

2016-01-01

Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. PMID:26670608

Comparison of morphological changes in efferent lymph nodes after implantation of resorbable and non-resorbable implants in rabbits

PubMed Central

2011-01-01

Background Magnesium alloys as biodegradable implant materials received much interest in recent years. It is known that products of implant degradation can induce several types of immune response. Hence, the aim of this study was to examine the morphological changes of efferent lymph nodes after implantation of different resorbable magnesium alloys (MgCa0.8, LAE442) in comparison to commercially available resorbable (PLA) and non-resorbable (titanium) implant materials as well as control groups without implant material. Methods The different implant materials were inserted intramedullary into the rabbit tibia. After postoperative observation periods of three and six months, popliteal lymph nodes were examined histologically and immunhistologically and compared to lymph nodes of sham operated animals and animals without surgery. Haematoxylin and eosin staining was performed for cell differentiation. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection, mouse anti-CD68 primary antibodies for macrophage detection. Evaluation of all sections was performed applying a semi quantitative score. Results The histological evaluation demonstrated low and moderate levels of morphological changes for both magnesium alloys (LAE442 and MgCa0.8). Higher than moderate values were reached for titanium in sinus histiocytosis and histiocytic apoptosis (3 months) and for PLA in histiocytic apoptosis (3 and 6 months). The immune response to all investigated implants had a non-specific character and predominantly was a foreign-body reaction. LAE442 provoked the lowest changes which might be due to a lower degradation rate in comparison to MgCa0.8. Therewith it is a promising candidate for implants with low immunogenic potential. Conclusion Both examined magnesium alloys did not cause significantly increased morphological changes in efferent lymph nodes in comparison to the widely used implant materials titanium and PLA. LAE442

"Ruffled border" formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over.

PubMed

Merolli, Antonio; Fung, Stephanie; Murthy, N Sanjeeva; Pashuck, E Thomas; Mao, Yong; Wu, Xiaohuan; Steele, Joseph A M; Martin, Daniel; Moghe, Prabhas V; Bromage, Timothy; Kohn, Joachim

2018-03-21

Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the "actin ring" and the "ruffled border", which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior.

The parathyroid hormone, its fragments and analogues--potent bone-builders for treating osteoporosis.

PubMed

Whitfield, J; Morley, P; Willick, G

2000-06-01

As populations age a rising number of men and women, but especially women during the first decade after menopause, become victims of a severe, accelerated loss of bone with crippling fractures known as osteoporosis. This often results in costly, prolonged hospitalisation and perhaps indirectly, death. Osteoporosis in women is caused by the menopausal oestrogen decline, which removes several key restraints on the generation, longevity and activity of bone-resorbing osteoclasts. Although there are many antiresorptive drugs on or coming onto the market (calcitonin, bisphosphonates, oestrogen and SERMS) that can slow or stop further bone loss, there are none that can restore lost bone mechanical strength by directly stimulating osteoblast activity and bone growth. However, there is a family of potent bone-building peptides, namely the 84 amino acid parathyroid hormone (PTH). Its 31 to 38 amino acid N-terminal fragments are currently in or about to enter clinical trials. We can predict that these peptides will be effective therapeutics for osteoporosis especially when supplemented with bisphosphonates or SERMs to protect the new bone from osteoclasts. These peptides should also accelerate the healing of fractures in persons of all ages and restore lost bone mass and mechanical strength to astronauts following their return to earth after long voyages in space.

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Transglutaminases factor XIII-A and TG2 regulate resorption, adipogenesis and plasma fibronectin homeostasis in bone and bone marrow

PubMed Central

Mousa, Aisha; Cui, Cui; Song, Aimei; Myneni, Vamsee D; Sun, Huifang; Li, Jin Jin; Murshed, Monzur; Melino, Gerry; Kaartinen, Mari T

2017-01-01

Appropriate bone mass is maintained by bone-forming osteoblast and bone-resorbing osteoclasts. Mesenchymal stem cell (MSC) lineage cells control osteoclastogenesis via expression of RANKL and OPG (receptor activator of nuclear factor κB ligand and osteoprotegerin), which promote and inhibit bone resorption, respectively. Protein crosslinking enzymes transglutaminase 2 (TG2) and Factor XIII-A (FXIII-A) have been linked to activity of myeloid and MSC lineage cells; however, in vivo evidence has been lacking to support their function. In this study, we show in mice that TG2 and FXIII-A control monocyte-macrophage cell differentiation into osteoclasts as well as RANKL production in MSCs and in adipocytes. Long bones of mice lacking TG2 and FXIII-A transglutaminases, show compromised biomechanical properties and trabecular bone loss in axial and appendicular skeleton. This was caused by increased osteoclastogenesis, a cellular phenotype that persists in vitro. The increased potential of TG2 and FXIII-A deficient monocytes to form osteoclasts was reversed by chemical inhibition of TG activity, which revealed the presence of TG1 in osteoclasts and assigned different roles for the TGs as regulators of osteoclastogenesis. TG2- and FXIII-A-deficient mice had normal osteoblast activity, but increased bone marrow adipogenesis, MSCs lacking TG2 and FXIII-A showed high adipogenic potential and significantly increased RANKL expression as well as upregulated TG1 expression. Chemical inhibition of TG activity in the null cells further increased adipogenic potential and RANKL production. Altered differentiation of TG2 and FXIII-A null MSCs was associated with plasma fibronectin (FN) assembly defect in cultures and FN retention in serum and marrow in vivo instead of assembly into bone. Our findings provide new functions for TG2, FXIII-A and TG1 in bone cells and identify them as novel regulators of bone mass, plasma FN homeostasis, RANKL production and myeloid and MSC cell

Correlation between gamma glutamyltransferase fractions and bone quality.

PubMed

Franzini, M; Nesti, A; Panetta, D; Fierabracci, V; Marchetti, S; Parchi, P D; Caponi, L; Paolicchi, A; Musetti, V; Salvadori, P; Edmin, M; Pucci, A; Bonicoli, E; Scaglione, M; Piolanti, N

Gamma-glutamyltransferase (GGT) has been recently identified as a bone-resorbing factor. The aim of this study was to investigate the association between plasma GGT fractions levels and bone quality. Plasma GGT fractions were analysed by gel-filtration chromatography. Bone quality was established quantitatively by two micro-CT derived microarchitectural parameters: the BV/TV (mineralised bone volume/total volume), and the SMI (structure model index) that describes the rod-like (low resistant) or plate-like (high-resistant) shape of bone trabeculae. We enrolled 93 patients hospitalised for elective total hip replacement (group Arthrosis, n=46) or for proximal femoral fracture (group Fracture, n=47). Patients within the first quartile of BV/TV (Q1, osteoporotic patients, n=6) showed higher levels of b-GGT fraction [median (min-max): 3.37 (1.42–6.81)] compared to patients with normal bone density (fourth quartile Q4, n=10; 1.40 (0.83–4.36); p=0.0393]. Also, according to SMI, b-GGT value was higher in the subgroup with bone fragility [Q1, n=8: 1.36 (0.43–4.36); Q4, n=8: 5.10 (1.4 –7.60); p=0.0117]. In conclusion, patients characterised by fragile bone structure showed specifically higher levels of plasma b-GGT activity thus suggesting fractional GGT analysis as a possible biomarker in the diagnosis of osteoporosis.

The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts.

PubMed

Huang, Su; Eleniste, Pierre P; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A; Mains, Richard E; Allen, Matthew R; Bruzzaniti, Angela

2014-03-01

Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and found that it was expressed in osteoclasts and osteoblasts. Furthermore, micro-CT analyses of the distal femur of global Kalirin knockout (Kal-KO) mice revealed significantly reduced trabecular and cortical bone parameters in Kal-KO mice, compared to WT mice, with significantly reduced bone mass in 8, 14 and 36week-old female Kal-KO mice. Male mice also exhibited a decrease in bone parameters but not to the level seen in female mice. Histomorphometric analyses also revealed decreased bone formation rate in 14week-old female Kal-KO mice, as well as decreased osteoblast number/bone surface and increased osteoclast surface/bone surface. Consistent with our in vivo findings, the bone resorbing activity and differentiation of Kal-KO osteoclasts was increased in vitro. Although alkaline phosphatase activity by Kal-KO osteoblasts was increased in vitro, Kal-KO osteoblasts showed decreased mineralizing activity, as well as decreased secretion of OPG, which was inversely correlated with ERK activity. Taken together, our findings suggest that deletion of Kalirin directly affects osteoclast and osteoblast activity, leading to decreased OPG secretion by osteoblasts which is likely to alter the RANKL/OPG ratio and promote osteoclastogenesis. Therefore, Kalirin may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass. Copyright © 2013 Elsevier Inc. All rights reserved.

The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts

PubMed Central

Huang, Su; Eleniste, Pierre P.; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A.; Mains, Richard E.; Allen, Matthew R.; Bruzzaniti, Angela

2014-01-01

Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and found that it was expressed in osteoclasts and osteoblasts. Furthermore, micro-CT analyses of the distal femur of global Kalirin knockout (Kal-KO) mice revealed significantly reduced trabecular and cortical bone parameters in Kal-KO mice, compared to WT mice, with significantly reduced bone mass in 8, 14 and 36 week-old female Kal-KO mice. Male mice also exhibited a decrease in bone parameters but not to the level seen in female mice. Histomorphometric analyses also revealed decreased bone formation rate in 14 week-old female Kal-KO mice, as well as decreased osteoblast number/bone surface and increased osteoclast surface/bone surface. Consistent with our in vivo findings, the bone resorbing activity and differentiation of Kal-KO osteoclasts was increased in vitro. Although alkaline phosphatase activity by Kal-KO osteoblasts was increased in vitro, Kal-KO osteoblasts showed decreased mineralizing activity, as well as decreased secretion of OPG, which was inversely correlated with ERK activity. Taken together, our findings suggest that deletion of Kalirin directly affects osteoclast and osteoblast activity, leading to decreased OPG secretion by osteoblasts which is likely to alter the RANKL/OPG ratio and promote osteoclastogenesis. Therefore, Kalirin may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass. PMID:24380811

So You Want to Go to Mars: Bones and Matters of the Heart

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Globus, Ruth; Torres, Samantha; Steczina, Sonette

2017-01-01

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Collectively, our research team aims to understand the molecular mechanisms underlying the responses of mammalian tissue to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent tissue decrements induced by spaceflight and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will provide an overview of skeletal and cardiovascular responses to spaceflight and will highlight our research progress on understanding the role of reactive oxygen species (ROS) signaling in skeletal responses to radiation and simulated weightlessness.

[Engineering a bone free flap for maxillofacial reconstruction: technical restrictions].

PubMed

Raoul, G; Myon, L; Chai, F; Blanchemain, N; Ferri, J

2011-09-01

Vascularisation is a key for success in bone tissue engineering. Creating a functional vascular network is an important concern so as to ensure vitality in regenerated tissues. Many strategies were developed to achieve this goal. One of these is cellular growth technique by perfusion bioreactor chamber. These new technical requirements came along with improved media and chamber receptacles: bioreactors (chapter 2). Some bone tissue engineering processes already have clinical applications but for volumes limited by the lack of vascularisation. Resorbable or non-resorbable membranes are an example. They are used separately or in association with bone grafts and they protect the graft during the revascularization process. Potentiated osseous regeneration uses molecular or cellular adjuvants (BMPs and autologous stem cells) to improve osseous healing. Significant improvements were made: integration of specific sequences, which may guide and enhance cells differentiation in scaffold; nano- or micro-patterned cell containing scaffolds. Finally, some authors consider the patient body as an ideal bioreactor to induce vascularisation in large volumes of grafted tissues. "Endocultivation", i.e., cellular culture inside the human body was proven to be feasible and safe. The properties of regenerated bone in the long run remain to be assessed. The objective to reach remains the engineering of an "in vitro" osseous free flap without morbidity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

PubMed

Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

2006-06-01

Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts.

PubMed

Takegahara, Noriko; Kim, Hyunsoo; Mizuno, Hiroki; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Tomura, Michio; Kanagawa, Osami; Ishii, Masaru; Choi, Yongwon

2016-02-12

Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Histone Deacetylases in Bone Development and Skeletal Disorders

PubMed Central

Bradley, Elizabeth W.; Carpio, Lomeli R.; van Wijnen, Andre J.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.

2015-01-01

Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn2+ for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2+. Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of

Skeletal lipidomics: regulation of bone metabolism by fatty acid amide family.

PubMed

Bab, Itai; Smoum, Reem; Bradshaw, Heather; Mechoulam, Raphael

2011-08-01

There is increasing evidence demonstrating that fatty acid derivatives play a key regulatory role in a variety of tissues. However, the study of skeletal lipidomics is just emerging and global strategies, such as targeted lipidomics, have not been applied to bone tissue. Such strategies hold great promises as in the case of genomics and proteomics. A partial profile of endocannabinoids and endocannabinoid-like compounds has demonstrated the presence of several long-chain fatty acid amides (FAAs), some of which displaying potent effects on osteoblasts, the bone forming cells and osteoclasts, the bone resorbing cells. In the skeleton, the FAAs activate the CB(1) cannabinoid receptor present in sympathetic nerve terminals as well as CB(2) cannabinoid receptor, the Gi-protein coupled receptor GPR55, and the transient receptor potential vanilloid type ion channel expressed by osteoblasts and/or osteoclasts. This review on the skeletal FAA system focuses on the production of FAAs in the skeleton and their net bone anabolic and anti-catabolic activity resulting from the stimulation of bone formation and inhibition of bone resorption. As the FAA family holds great promise as a basis for the treatment of osteoporosis and other diseases involving bone, further studies should aim towards the complete profiling of these lipids and their receptors in bone tissue, followed by elucidation of their function and mechanism of action. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

A crucial role for thiol antioxidants in estrogen-deficiency bone loss

PubMed Central

Lean, Jenny M.; Davies, Julie T.; Fuller, Karen; Jagger, Christopher J.; Kirstein, Barrie; Partington, Geoffrey A.; Urry, Zoë L.; Chambers, Timothy J.

2003-01-01

The mechanisms through which estrogen prevents bone loss are uncertain. Elsewhere, estrogen exerts beneficial actions by suppression of reactive oxygen species (ROS). ROS stimulate osteoclasts, the cells that resorb bone. Thus, estrogen might prevent bone loss by enhancing oxidant defenses in bone. We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-β estradiol. Moreover, administration of N-acetyl cysteine (NAC) or ascorbate, antioxidants that increase tissue glutathione levels, abolished ovariectomy-induced bone loss, while L-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis, caused substantial bone loss. The 17-β estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro. Furthermore, in vitro NAC prevented osteoclast formation and NF-κB activation. BSO and hydrogen peroxide did the opposite. Expression of TNF-α, a target for NF-κB and a cytokine strongly implicated in estrogen-deficiency bone loss, was suppressed in osteoclasts by 17-β estradiol and NAC. These observations strongly suggest that estrogen deficiency causes bone loss by lowering thiol antioxidants in osteoclasts. This directly sensitizes osteoclasts to osteoclastogenic signals and entrains ROS-enhanced expression of cytokines that promote osteoclastic bone resorption. PMID:12975476

Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-α-induced osteoclast formation in vivo.

PubMed

Sakai, Eiko; Aoki, Yuri; Yoshimatsu, Masako; Nishishita, Kazuhisa; Iwatake, Mayumi; Fukuma, Yutaka; Okamoto, Kuniaki; Tanaka, Takashi; Tsukuba, Takayuki

2016-07-15

Osteoclasts are multinucleated bone-resorbing cells that differentiate in response to receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). Enhanced osteoclastogenesis contributes to bone diseases, such as osteoporosis and rheumatoid arthritis. Rubus parvifolius L. is traditionally used as an herbal medicine for rheumatism; however, its detailed chemical composition and the molecular mechanisms responsible for its biological action have not been elucidated. To investigate the mechanisms by which R. parvifolius L. extract and its major constituent sanguiin H-6, inhibit osteoclastogenesis and bone resorption. Cell proliferation, cell differentiation, and bone resorption were detected in vitro. Inhibition of signaling pathways, marker protein expression, and protein nuclear translocation were evaluated by western blot analysis. Tumor necrosis factor-α (TNF-α)-mediated osteoclastogenesis was examined in vivo. R. parvifolius L. extract inhibited the bone-resorption activity of osteoclasts. In addition, sanguiin H-6 markedly inhibited RANKL-induced osteoclast differentiation and bone resorption, reduced reactive oxygen species production, and inhibited the phosphorylation of inhibitor of NF-κB alpha (IκBα) and p38 mitogen-activated protein kinase. Sanguiin H-6 also decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), cathepsin K, and c-Src. Moreover, sanguiin H-6 inhibited the nuclear translocation of NFATc1, c-Fos, and NF-κB in vitro, as well as TNF-α-mediated osteoclastogenesis in vivo. Our data revealed that R. parvifolius L. has anti-bone resorption activity and suggest that its constituent, sanguiin H-6, can potentially be used for the prevention and treatment of bone diseases associated with excessive osteoclast formation and subsequent bone destruction. Copyright © 2016 Elsevier GmbH. All rights reserved.

In vivo visualisation of different modes of action of biological DMARDs inhibiting osteoclastic bone resorption.

PubMed

Matsuura, Yoshinobu; Kikuta, Junichi; Kishi, Yuika; Hasegawa, Tetsuo; Okuzaki, Daisuke; Hirano, Toru; Minoshima, Masafumi; Kikuchi, Kazuya; Kumanogoh, Atsushi; Ishii, Masaru

2018-04-28

Osteoclasts play critical roles in inflammatory bone destruction. Precursor cell migration, cell differentiation, and functional cell activation are all in play. Biological disease-modifying antirheumatic drugs (DMARDs) have been shown to significantly inhibit both bone erosion as well as synovitis, although how such agents reduce osteoclastic bone destruction in vivo has not been fully explained. Here, we used an intravital time-lapse imaging technique to directly visualise mature osteoclasts and their precursors, and explored how different biological DMARDs acted in vivo . Lipopolysaccharide (LPS) was injected into the calvarial periosteum of fluorescent reporter mice to induce inflammatory bone destruction. Time-lapse imaging was performed via intravital multiphoton microscopy 5 days after LPS injection. Biological DMARDs, including monoclonal antibodies (mAbs) against the interleukin (IL) 6 receptor (IL-6R) and tumour necrosis factor α (TNFα), or cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-Ig, were intraperitoneally administered at the time of LPS injection. We determined CD80/86 expression levels in mature osteoclasts and their precursors by flow cytometry, quantitative PCR and immunohistochemistry. Of the biologicals tested, anti-IL-6R and anti-TNFα mAbs affected mature osteoclasts and switched bone-resorbing osteoclasts to non-resorbing cells. CTLA4-Ig had no action on mature osteoclasts but mobilised osteoclast precursors, eliminating their firm attachment to bone surfaces. In agreement with these results, CD80/86 (the target molecules of CTLA4-Ig) were prominently expressed only in osteoclast precursor cells, being suppressed during osteoclast maturation. Intravital imaging revealed that various biological DMARDs acted at specific therapeutic time points during osteoclastic bone destruction, with different efficacies. These results enable us to grasp the real modes of action of drugs, optimising the usage of drug regimens. © Article author

Space Maintenance and New Bone Formation with Polyurethane Biocomposites in a Canine Saddle Defect

DTIC Science & Technology

2014-05-01

Vanderbilt University, Nashville, TN 2. Medtronic Spinal and Biologics, Memphis, TN 3. US Army Institute of Surgical Research, Fort Sam Houston, TX...and 15% hydroxyapatite (HA) that is similar in mineral content to natural bone.3 45S5 Bioactive glass (BG) is a resorbable material that has been... used effectively in a variety of bone regeneration applications.4 In the present study, we investigated the ability of injectable PUR/MG and PUR/BG

Resorbable Self-Locking Implant for Lung Lobectomy Through Video-Assisted Thoracoscopic Surgery: First Live Animal Application.

PubMed

Guedes, Rogério Luizari; Höglund, Odd Viking; Brum, Juliana Sperotto; Borg, Niklas; Dornbusch, Peterson Triches

2018-04-01

The aim of this pilot test was to test a new self-locking resorbable implant for hilum occlusion during a video-assisted thoracoscopic lung lobectomy in a surviving pig model. Once the thoracic cavity was assessed and structures identified, the right middle lobe and its respective hilum were exposed. The implant was introduced with a semiclosed loop through a working channel and positioned around the pulmonary lobe. Occlusion was performed with a conventional Crile forceps and a laparoscopic Kelly forceps. Lobe section was done with laparoscopic Metzenbaum scissors and tissue removal through the dorsal access. No signs of pneumothorax or bleeding were observed during a 60-day follow-up. Necropsy findings showed minimal pleuritis in caudal access and in the lobar stump. A granulomatous formation was found around a dense, amorphous material, which was identified as remains of a small part of the implant. Histopathological findings showed signs of a chronic healing process without other alterations. The resorbable implant LigaTie appears to exhibit similar handling and application characteristics during surgery as nonsurgical tie wraps. The resorbable implant avoids the uncontrolled substances not suitable for implants of conventional ties. The results of this pilot test suggested the resorbable implant's mechanical properties provided effective tissue support to complete the healing of the pulmonary hilum.

Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption.

PubMed

Yang, Xiao; Gandhi, Chintan; Rahman, Md Mizanur; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

2015-12-01

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th day, respectively, to assess temporal changes in the number of differentiated osteoclasts, the number and size of osteoclastic resorption pits, the amount of bone resorbed, as well as the amount of matrix AGEs released in the medium by resorption. In addition, the in situ concentration of matrix AGEs at each resorption pit was also estimated based on its AGEs autofluorescent intensity. The results indicated that (1) osteoclastic resorption activities were significantly correlated with the donor age, showing larger but shallower resorption pits on the elderly bone substrates than on the younger ones; (2) osteoclast resorption activities were not significantly dependent on the in situ AGEs concentration in bone matrix, and (3) a correlation was observed between osteoclast activities and the concentration of AGEs released by the resorption. These results suggest that osteoclasts tend to migrate away from initial anchoring sites on elderly bone substrate during resorption compared to younger bone substrates. However, such behavior is not directly related to the in situ concentration of AGEs in bone matrix at the resorption sites.

Nutritional factors affecting poultry bone health.

PubMed

Fleming, Robert H

2008-05-01

Outlined are two main current research concerns relating to skeletal disorders in poultry: (a) osteoporosis in egg-laying hens; (b) leg problems caused by rapid bone growth in broiler chickens. Surveys indicate that 30% of caged laying hens suffer at least one lifetime fracture (a severe welfare issue). Modern hybrids produce one egg per d for 50 weeks. For this period 'normal' bone turnover ceases; only medullary bone (MB) is formed, a woven bone type of limited structural value. MB is resorbed for eggshell formation alongside structural bone, leading to increased fracture risk. Avian osteoporosis is reduced by activity and genetic selection but nutrition is also important. Fluoride and vitamin K are beneficial but the timing of nutritional intervention is important. Ca, inorganic P and vitamin D must be adequate and the form of Ca is critical. Limestone fed as particulates benefits skeletal and eggshell quality. In hens fed particulate limestone compared with flour-fed hens the tibiotarsus breaking strength and radiographic density are increased at 56 weeks of age (P<0.01 and P<0.001 respectively) and the number of tartrate-resistant acid phosphatase-positive stained active osteoclasts (mean number per microscopic field) is decreased (P<0.001). In broiler (meat) chickens selection for rapid growth from approximately 50 g to 3 kg in 42 d has inadvertently produced skeletal disorders such as tibial dyschondroplasia, rickets and associated valgus-varus deformities leading to lameness. The beneficial skeletal effects during growth of increased dietary n-3 PUFA:n-6 PUFA (utilising salmon oil) have been demonstrated. Experiments simulating daylight UVB levels have produced beneficial skeletal effects in Ca- and vitamin D-deficient chicks.

The Multifaceted Osteoclast; Far and Beyond Bone Resorption.

PubMed

Drissi, Hicham; Sanjay, Archana

2016-08-01

The accepted function of the bone resorbing cell, osteoclast, has been linked to bone remodeling and pathological osteolysis. Emerging evidence points to novel functions of osteoclasts in controlling bone formation and angiogenesis. Thus, while the concept of a "clastokine" with the potential to regulate osteogenesis during remodeling did not come as a surprise, new evidence provided unique insight into the mechanisms underlying osteoclastic control of bone formation. The question still remains as to whether osteoclast precursors or a unique trap positive mononuclear cell, can govern any aspect of bone formation. The novel paradigm eloquently proposed by leaders in the field brings together the concept of clastokines and osteoclast precursor-mediated bone formation, potentially though enhanced angiogenesis. These fascinating advances in osteoclast biology have motivated this short review, in which we discuss these new roles of osteoclasts. J. Cell. Biochem. 117: 1753-1756, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Skeletal lipidomics: regulation of bone metabolism by fatty acid amide family

PubMed Central

Bab, Itai; Smoum, Reem; Bradshaw, Heather; Mechoulam, Raphael

2011-01-01

There is increasing evidence demonstrating that fatty acid derivatives play a key regulatory role in a variety of tissues. However, the study of skeletal lipidomics is just emerging and global strategies, such as targeted lipidomics, have not been applied to bone tissue. Such strategies hold great promises as in the case of genomics and proteomics. A partial profile of endocannabinoids and endocannabinoid-like compounds has demonstrated the presence of several long-chain fatty acid amides (FAAs), some of which displaying potent effects on osteoblasts, the bone forming cells and osteoclasts, the bone resorbing cells. In the skeleton, the FAAs activate the CB1 cannabinoid receptor present in sympathetic nerve terminals as well as CB2 cannabinoid receptor, the Gi-protein coupled receptor GPR55, and the transient receptor potential vanilloid type ion channel expressed by osteoblasts and/or osteoclasts. This review on the skeletal FAA system focuses on the production of FAAs in the skeleton and their net bone anabolic and anti-catabolic activity resulting from the stimulation of bone formation and inhibition of bone resorption. As the FAA family holds great promise as a basis for the treatment of osteoporosis and other diseases involving bone, further studies should aim towards the complete profiling of these lipids and their receptors in bone tissue, followed by elucidation of their function and mechanism of action. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21557736

Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

PubMed

Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

2016-01-15

Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts. Copyright © 2015 Elsevier Inc. All rights reserved.

Computer-assisted virtual technology in intracapsular condylar fracture with two resorbable long-screws.

PubMed

Wang, W H; Deng, J Y; Zhu, J; Li, M; Xia, B; Xu, B

2013-03-01

Our aim was to fix intracapsular condylar fractures (ICF) with two resorbable long screws using preoperative computer-assisted virtual technology. From February 2008 to July 2011, 19 patients with ICF were treated with two resorbable long screws. Preoperatively we took panoramic radiographs and spiral computed tomography (CT). Depending on their digital imaging and communications in medicine (DICOM) data, the dislocated condylar segments were restored using the SimPlant Pro™ software, version 11.04. The mean (SD) widths of the condylar head and neck from lateral to medial were 19.01 (1.28)mm and 13.84 (1.13)mm, respectively. In all patients, the mandibles and the ICF seen intraoperatively corresponded with the preoperative three-dimensional and virtual reposition. All patients were followed up for 6-46 months (mean 21). Occlusion and mouth opening had been restored completely in all but one patient, and absolute anatomical reduction was also achieved in most cases. Computer-assisted virtual technology plays an important part in the diagnosis of ICF, as well as in its preoperative design. Fixation with only two resorbable long screws is an effective and reliable method for fixing ICF. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Journey into Bone Models: A Review

PubMed Central

Scheinpflug, Julia; Pfeiffenberger, Moritz; Damerau, Alexandra; Schwarz, Franziska; Textor, Martin; Lang, Annemarie

2018-01-01

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed. PMID:29748516

Journey into Bone Models: A Review.

PubMed

Scheinpflug, Julia; Pfeiffenberger, Moritz; Damerau, Alexandra; Schwarz, Franziska; Textor, Martin; Lang, Annemarie; Schulze, Frank

2018-05-10

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed.

Skeletal stability in bimaxillary orthognathic surgery: P(L/DL)LA-resorbable versus titanium osteofixation.

PubMed

Landes, Constantin A; Ballon, Alexander

2006-09-01

be as reliable as titanium, but as the study and control groups were not matched, the results have to be interpreted as preliminary. Resorbable materials permitted clinically faster occlusal and condylar settling than standard titanium osteosyntheses, as bone segments showed slight clinical mobility up to 6 weeks postoperatively.

Dietary isoflavones act on bone marrow osteoprogenitor cells and stimulate ovary development before influencing bone mass in pre-pubertal piglets.

PubMed

De Wilde, Anne; Maria Rassi, Claudia; Cournot, Giulia; Colin, Colette; Lacroix, Herminie C; Chaumaz, Gilles; Coxam, Veronique; Bennetau-Pelissero, Catherine; Pointillart, Alain; Lieberherr, Michele

2007-07-01

Food containing soybeans provide isoflavone phytoestrogens that can preserve bone mass in postmenopausal women, and prevent bone loss in ovariectomized rats. But their effects on bone remain unclear, particularly on bone formation during growth. Two groups of eight pre-pubertal piglets were fed a basal or an isoflavone-enriched (S800) diet for 6 weeks. The S800 diet contained 800 mg SoyLifetrade mark/kg, providing 2.8 mg isoflavones/kg body weight/day. Several bones were collected and tested for bone strength and density. Bone marrow was collected from humeri together with blood samples and genital tracts. The plasma concentrations of isoflavones were increased in the pigs fed S800, but growth rate, body weight, plasma bone markers, bone mineral density, and strength were all unaffected. In contrast, cultured stromal cells from S800 pigs had more alkaline phosphatase-rich cells and mineralized nodules, secreted more osteocalcin, osteoprotegerin and RANK-L, synthesized more osteoprotegerin, and RANK-L. Cultured mononucleated nonadherent bone marrow cells from S800 pigs developed fewer tartrate-resistant acid phosphatase mononucleated cells (osteoclast progenitors) when cultured with 1,25(OH)(2)D(3), and resorbed a smaller area of dentine slices. Freshly isolated bone marrow osteoclast progenitors from S800 pigs had more caspase-3 cleavage activity, and synthesized less RANK. Both osteoclast and osteoblast progenitors had ERalpha and ERbeta, whose syntheses were stimulated by the S800 diet. The S800 piglets had heavier ovaries with more follicles, but their uterus weight was unaffected. We conclude that dietary isoflavones have no detectable effect on the bone mass of growing female piglets, but act on bone marrow osteoprogenitors via ERs--mainly ERbeta, and stimulate ovary development.

In Vivo Performance of Bilayer Hydroxyapatite Scaffolds for Bone Tissue Regeneration in the Rabbit Radius

DTIC Science & Technology

2011-02-02

no treatments and the pres- ence of periosteal callus-like layer surrounding defects with scaffold implantation were observed after 8 weeks post...vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model. Biomaterials. 2004; 25(20):5037–44. 20. Lu JX, Gallur A, Flautre

Physical activity effects on bone metabolism.

PubMed

Smith, E L; Gilligan, C

1991-01-01

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

Behavior of POP-calcium carbonate hydrogel as bone substitute with controlled release capability: a study in rat.

PubMed

Dewi, Anne Handrini; Ana, Ika Dewi; Wolke, Joop; Jansen, John

2015-10-01

Gypsum or calcium sulfate (CS) or plaster of Paris (POP) is considered as a fast degradable material that usually resorbs before the bone defect area is completely filled by new bone. In this study, the incorporation of CaCO3 hydrogel into POP in different compositions was proposed to enhance the bone biological activity of POP and to decrease its degradability. The mechanical and degradation properties of the various materials were characterized by in vitro analysis. Subsequently, the materials were inserted into cylindrically sized bone defects as created into the femoral condyle of rats and left in situ for 1, 4, and 8 weeks. Histological analysis of the retrieved specimens indicated that the addition of CaCO3 hydrogel into POP increased bone formation, angiogenesis and collagen density and resulted into faster bone formation and maturation. It was also confirmed that the degradation rate of the POP decreased by the addition of CaCO3 hydrogel. The in vivo findings did corroborate with the in vitro analysis. In conclusion, the incorporation of CaCO3 hydrogel provides a promising technology to improve the properties of POP, the oldest biomaterial used for bone grafting. © 2015 Wiley Periodicals, Inc.

Identification, characterization and isolation of a common progenitor for osteoclasts, macrophages and dendritic cells from murine bone marrow and periphery

PubMed Central

Jacome-Galarza, Christian E.; Lee, Sun-Kyeong; Lorenzo, Joseph A.; LeonardoAguila, Hector

2012-01-01

Osteoclasts are specialized bone resorbing cells that derive from monocyte precursors. We have identified three populations of cells with high osteoclastogenic potential in murine bone marrow, which expressed the phenotype: B220−CD3−CD11b−/low CD115+ and either CD117hi, CD117intermediate or CD117low. We have evaluated these populations for their ability to also generate macrophages and dendritic cells. At a single cell level, the population expressing higher CD117 levels was able to generate bone-resorbing osteoclasts, phagocytic macrophages and antigen-presenting dendritic cells in vitro with efficiencies of over 90 percent, indicating that there exists a common developmental pathway for these cell types. Cells with osteoclastogenic potential also exist in blood and peripheral hematopoietic organs. Their functional meaning and/or their relationship with bone marrow progenitors is not well established. Hence, we characterized murine peripheral cell populations for their ability to form osteoclasts, macrophages and dendritic cells in vitro. The spleen and peripheral blood monocyte progenitors share phenotypic markers with bone marrow progenitors, but differ in their expression of CD11b, which was low in bone marrow but high in periphery. We propose that circulating monocyte progenitors are derived from a common bone marrow osteoclasts/macrophage/dendritic cell progenitor (OcMDC), which we have now characterized at a clonal level. However, the lineage relationship between the bone marrow and peripheral monocyte progenitors has yet to be defined. PMID:23165930

Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts.

PubMed

Amiable, Nathalie; Tat, Steeve Kwan; Lajeunesse, Daniel; Duval, Nicolas; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Boileau, Christelle

2009-06-01

In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts. PAR-2 expression and production were determined by real-time PCR and flow cytometry, respectively. PAR-2 modulation was investigated in OA subchondral bone osteoblasts treated with IL-1 beta (100 pg/ml), TNF-alpha (5 ng/ml), TGF-beta1 (10 ng/ml), PGE(2) (500 nM), IL-6 (10 ng/ml) and IL-17 (10 ng/ml). Membranous RANKL protein was assessed by flow cytometry, and OPG, MMP-1, MMP-9, MMP-13, IL-6 and intracellular signalling pathways by specific ELISAs. Bone resorptive activity was measured by using a co-culture model of human PBMC and OA subchondral bone osteoblasts. PAR-2 expression and production (p<0.05) were markedly increased when human OA subchondral bone osteoblasts were compared to normal. On OA osteoblasts, PAR-2 production was significantly increased by IL-1 beta, TNF-alpha and PGE(2). Activation of PAR-2 with a specific agonist, SLIGKV-NH(2), induced a significant up-regulation of MMP-1, MMP-9, IL-6, and membranous RANKL, but had no effect on MMP-13 or OPG production. Interestingly, bone resorptive activity was also significantly enhanced following PAR-2 activation. The PAR-2 effect was mediated by activation of the MAP kinases Erk1/2 and JNK. This study is the first to demonstrate that PAR-2 activation plays a role in OA subchondral bone resorption via an up-regulation of major bone remodelling factors. These results shed new light on the potential of PAR-2 as a therapeutic target in OA.

In vivo study of magnesium plate and screw degradation and bone fracture healing.

PubMed

Chaya, Amy; Yoshizawa, Sayuri; Verdelis, Kostas; Myers, Nicole; Costello, Bernard J; Chou, Da-Tren; Pal, Siladitya; Maiti, Spandan; Kumta, Prashant N; Sfeir, Charles

2015-05-01

Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bone bonding at natural and biomaterial surfaces.

PubMed

Davies, John E

2007-12-01

Bone bonding is occurring in each of us and all other terrestrial vertebrates throughout life at bony remodeling sites. The surface created by the bone-resorbing osteoclast provides a three-dimensionally complex surface with which the cement line, the first matrix elaborated during de novo bone formation, interdigitates and is interlocked. The structure and composition of this interfacial bony matrix has been conserved during evolution across species; and we have known for over a decade that this interfacial matrix can be recapitulated at a biomaterial surface implanted in bone, given appropriate healing conditions. No evidence has emerged to suggest that bone bonding to artificial materials is any different from this natural biological process. Given this understanding it is now possible to explain why bone-bonding biomaterials are not restricted to the calcium-phosphate-based bioactive materials as was once thought. Indeed, in the absence of surface porosity, calcium phosphate biomaterials are not bone bonding. On the contrary, non-bonding materials can be rendered bone bonding by modifying their surface topography. This paper argues that the driving force for bone bonding is bone formation by contact osteogenesis, but that this has to occur on a sufficiently stable recipient surface which has micron-scale surface topography with undercuts in the sub-micron scale-range.

Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages

PubMed Central

Kiviranta, Riku; Yamana, Kei; Saito, Hiroaki; Ho, Daniel K.; Laine, Julius; Tarkkonen, Kati; Nieminen-Pihala, Vappu; Hesse, Eric; Correa, Diego; Määttä, Jorma; Tessarollo, Lino; Rosen, Evan D.; Horne, William C.; Jenkins, Nancy A.; Copeland, Neal G.; Warming, Soren

2013-01-01

Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) and the transcriptional coregulator Zfp521 as components of the machinery that regulates bone homeostasis through coordinated effects in both lineages. Deletion of Zfp521 in OBs led to impaired bone formation and increased OB-dependent osteoclastogenesis (OC-genesis), and deletion in hematopoietic cells revealed a strong cell-autonomous role for Zfp521 in OC progenitors. In adult mice, the effects of Zfp521 were largely caused by repression of Ebf1, and the bone phenotype of Zfp521+/− mice was rescued in Zfp521+/−:Ebf1+/− mice. Zfp521 interacted with Ebf1 and repressed its transcriptional activity. Accordingly, deletion of Zfp521 led to increased Ebf1 activity in OBs and OCs. In vivo, Ebf1 overexpression in OBs resulted in suppressed bone formation, similar to the phenotype seen after OB-targeted deletion of Zfp521. Conversely, Ebf1 deletion led to cell-autonomous defects in both OB-dependent and cell-intrinsic OC-genesis, a phenotype opposite to that of the Zfp521 knockout. Thus, we have identified the interplay between Zfp521 and Ebf1 as a novel rheostat for bone homeostasis. PMID:23569325

Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Pagliaro, Umberto; Raffaelli, Eugenia; Nieri, Michele

2015-01-01

The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure β-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were

Application of Resorbable Poly(Lactide-co-Glycolide) with Entangled Hyaluronic Acid as an Autograft Extender for Posterolateral Intertransverse Lumbar Fusion in Rabbits

PubMed Central

Oliver, Rema A.; Gage, Gary; Yu, Yan; Bell, David; Bellemore, Jeremy; Adkisson, Huston Davis

2011-01-01

Facilitating fusion between bony segments in a reliable and reproducible manner using a synthetic bone graft material has a number of benefits for the surgeon as well as the patient. Although autograft remains the gold standard, associated comorbidities continue to drive the development of new biomaterials for use in spinal fusion. The ability of autograft alone and autograft combined with a radiolucent biomaterial composed of resorbable osteoconductive poly(lactide-co-glycolide) with entangled hyaluronic acid to facilitate fusion was examined in a single-level noninstrumented posterolateral intertransverse lumbar fusion model in New Zealand White rabbits. Progressive bone formation was demonstrated radiographically for the extender group (synthetic biomaterial plus autograft) between 3 and 6 months. Computed tomography revealed a new cortical shell in the fusion mass at 3 and 6 months for both study groups. Tensile testing at 6 months demonstrated that the quality of bone formed between the intertransverse space was equivalent for both study groups. Histologic evaluation of the fusion mass revealed new bone on and adjacent to the transverse processes with the synthetic biomaterial group that extended laterally, supporting the osteoconductive nature of the material. Histological evidence of endochondral bone growth in the intertransverse space was observed for the autograft plus synthetic biomaterial group. Bone remodeling, new marrow spaces, and peripheral cortices were observed for each study group at 3 months that matured by 6 months. These findings support the use of a radiolucent biosynthetic material comprising poly(lactide-co-glycolide) with integrated hyaluronic acid as an autograft extender for lumbar intertransverse fusion. PMID:20712417

Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration.

PubMed

Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio

2016-03-01

The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

Role of Oxidative Damage in Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

2014-01-01

During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats.

PubMed

Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

2016-03-30

The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical "lock" between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy.

Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats

PubMed Central

2012-01-01

Background Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling. PMID:22443362

Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report

PubMed Central

Blume, Oliver; Hoffmann, Lisa; Donkiewicz, Phil; Wenisch, Sabine; Back, Michael; Franke, Jörg; Schnettler, Reinhard

2017-01-01

The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR) procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept. PMID:29065477

Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report.

PubMed

Blume, Oliver; Hoffmann, Lisa; Donkiewicz, Phil; Wenisch, Sabine; Back, Michael; Franke, Jörg; Schnettler, Reinhard; Barbeck, Mike

2017-10-21

The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR) procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

Characterization of a resorbable poly(ester urethane) with biodegradable hard segments.

PubMed

Dempsey, David K; Robinson, Jennifer L; Iyer, Ananth V; Parakka, James P; Bezwada, Rao S; Cosgriff-Hernandez, Elizabeth M

2014-01-01

The rapid growth of regenerative medicine and drug delivery fields has generated a strong need for improved polymeric materials that degrade at a controlled rate into safe, non-cytotoxic by-products. Polyurethane thermoplastic elastomers offer several advantages over other polymeric materials including tunable mechanical properties, excellent fatigue strength, and versatile processing. The variable segmental chemistry in developing resorbable polyurethanes also enables fine control over the degradation profile as well as the mechanical properties. Linear aliphatic isocyanates are most commonly used in biodegradable polyurethane formulations; however, these aliphatic polyurethanes do not match the mechanical properties of their aromatic counterparts. In this study, a novel poly(ester urethane) (PEsU) synthesized with biodegradable aromatic isocyanates based on glycolic acid was characterized for potential use as a new resorbable material in medical devices. Infrared spectral analysis confirmed the aromatic and phase-separated nature of the PEsU. Uniaxial tensile testing displayed stress-strain behavior typical of a semi-crystalline polymer above its Tg, in agreement with calorimetric findings. PEsU outperformed aliphatic PCL-based polyurethanes likely due to the enhanced cohesion of the aromatic hard domains. Accelerated degradation of the PEsU using 0.1 M sodium hydroxide resulted in hydrolysis of the polyester soft segment on the surface, reduced molecular weight, surface cracking, and a 30% mass loss after four weeks. Calorimetric studies indicated a disruption of the soft segment crystallinity after incubation which corresponded with a drop in initial modulus of the PEsU. Finally, cytocompatibility testing with 3T3 mouse fibroblasts exhibited cell viability on PEsU films comparable to a commercial poly(ether urethane urea) after 24 h followed by 85% cell viability at 72 h. Overall, this new resorbable polyurethane shows strong potential for use in wide

Histologic effect of pure-phase beta-tricalcium phosphate on bone regeneration in human artificial jawbone defects.

PubMed

Trisi, Paolo; Rao, Walter; Rebaudi, Alberto; Fiore, Peter

2003-02-01

The effect of the pure-phase beta-tricalcium phosphate (beta-TCP) Cerasorb on bone regeneration was evaluated in hollow titanium cylinders implanted in the posterior jaws of five volunteers. Beta-TCP particles were inserted inside the cylinders and harvested 6 months after placement. The density of the newly formed bone inside the bone-growing chambers measured 27.84% +/- 24.67% in test and 17.90% +/- 4.28% in control subjects, without a statistically significant difference. Analysis of the histologic specimens revealed that the density of the regenerated bone was related to the density of the surrounding bone. The present study demonstrates the spontaneous healing of infrabony artificial defects, 2.5 mm diameter, in the jaw. The pure beta-TCP was resorbed simultaneously with new bone formation, without interference with the bone matrix formation.

Efficacy of combination therapy using anorganic bovine bone graft with resorbable GTR membrane vs. open flap debridement alone in the management of grade II furcation defects in mandibular molars – A comparative study

PubMed Central

Kannan, Anitha Logaranjani; Bose, Buvaneshwari Birla; Muthu, Jananni; Perumalsamy, Rajapriya; Pushparajan, Saravanan; Namasivayam, Ambalavanan

2014-01-01

Context: Invasion of the bifurcation and trifurcation of the multi-rooted teeth resulting in furcation involvement is one of the serious complications of periodontitis. Aim: The purpose of the study was to evaluate the efficacy of combination therapy using anorganic bovine bone graft and resorbable guided tissue regeneration (GTR) membrane versus open flap debridement alone in the management of Grade II furcation defects in mandibular molars. Materials and Methods: The study included a total number of 20 sites in 10 patients with bilateral mandibular furcation defects, out of which 10 sites were treated as test group and 10 as control group. The test group was treated with combination therapy and the control group with open flap debridement alone. The parameters were recorded on 0 day (baseline), 90th day, and 180th day, which included vertical probing depth and horizontal probing depth of the furcation defect, clinical attachment level, and defect fill. Statistical Analysis Used: Mean and standard deviation were calculated for different variables in each study group at different time points. Mean values were compared by using Wilcoxon signed ranks test, after adjusting the P values for multiple comparison by using Bonferroni correction method. Results: Both the test and control groups showed a definitive improvement in clinical parameters, which was statistically significant. On comparison, the vertical probing depth showed significant reduction in the test group with a mean reduction of 3.1 ± 0.7 mm, when compared to the control group which showed a mean reduction of 1.5 ± 0.5 mm. The horizontal probing depth of furcation defects was also significantly reduced in the test group with a mean reduction of 2.2 ± 0.6 mm, when compared to the control group in which the mean reduction was 0.9 ± 0.3 mm. There was also significant gain in attachment level in the test group which showed a mean gain of 3.2 ± 0.6 mm, when compared to the control group which showed a

Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?

PubMed

Miron, Richard J; Zohdi, Hamoon; Fujioka-Kobayashi, Masako; Bosshardt, Dieter D

2016-12-01

Recently accumulating evidence has put into question the role of large multinucleated giant cells (MNGCs) around bone biomaterials. While cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials, it was originally thought that specifically in bone tissues, all giant cells were bone-resorbing osteoclasts whereas foreign body giant cells (FBGCs) were found associated with a connective tissue foreign body reaction resulting in fibrous encapsulation and/or material rejection. Despite the great majority of bone grafting materials routinely found with large osteoclasts, a special subclass of bone biomaterials has more recently been found surrounded by large giant cells virtually incapable of resorbing bone grafts even years after their implantation. While original hypotheses believed that a 'foreign body reaction' may be taking place, histological data retrieved from human samples years after their implantation have put these original hypotheses into question by demonstrating better and more stable long-term bone volume around certain bone grafts. Exactly how or why this 'special' subclass of giant cells is capable of maintaining long-term bone volume, or methods to scientifically distinguish them from osteoclasts remains extremely poorly studied. The aim of this review article was to gather the current available literature on giant cell markers and differences in expression patterns between osteoclasts and MNGCs utilizing 19 specific markers including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. This review article presents 19 specific cell-surface markers to distinguish between osteoclasts and MNGCs including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (often

Fracture bone healing and biodegradation of AZ31 implant in rats.

PubMed

Iglesias, C; Bodelón, O G; Montoya, R; Clemente, C; Garcia-Alonso, M C; Rubio, J C; Escudero, M L

2015-04-17

The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material.

Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement.

PubMed

Tao, Hu; Hwang, Suk-Won; Marelli, Benedetto; An, Bo; Moreau, Jodie E; Yang, Miaomiao; Brenckle, Mark A; Kim, Stanley; Kaplan, David L; Rogers, John A; Omenetto, Fiorenzo G

2014-12-09

A paradigm shift for implantable medical devices lies at the confluence between regenerative medicine, where materials remodel and integrate in the biological milieu, and technology, through the use of recently developed material platforms based on biomaterials and bioresorbable technologies such as optics and electronics. The union of materials and technology in this context enables a class of biomedical devices that can be optically or electronically functional and yet harmlessly degrade once their use is complete. We present here a fully degradable, remotely controlled, implantable therapeutic device operating in vivo to counter a Staphylococcus aureus infection that disappears once its function is complete. This class of device provides fully resorbable packaging and electronics that can be turned on remotely, after implantation, to provide the necessary thermal therapy or trigger drug delivery. Such externally controllable, resorbable devices not only obviate the need for secondary surgeries and retrieval, but also have extended utility as therapeutic devices that can be left behind at a surgical or suturing site, following intervention, and can be externally controlled to allow for infection management by either thermal treatment or by remote triggering of drug release when there is retardation of antibiotic diffusion, deep infections are present, or when systemic antibiotic treatment alone is insufficient due to the emergence of antibiotic-resistant strains. After completion of function, the device is safely resorbed into the body, within a programmable period.

The effects of Cosmos caudatus (Ulam Raja) supplementation on bone biochemical parameters in ovariectomized rats.

PubMed

Mohamed, Norazlina; Yin, Chai Mei; Shuid, Ahmad Nazrun; Muhammad, Norliza; Babji, Abdul Salam; Soelaiman, Ima Nirwana

2013-09-01

Cosmos caudatus (ulam raja) contains high mineral content and possesses high antioxidant activity which may be beneficial in bone disorder such as postmenopausal osteoporosis. The effects of C. caudatus on bone metabolism biomarkers in ovariectomized rats were studied. 48 Sprague-Dawley rats aged three months were divided into 6 groups. One group of rats was sham-operated while the remaining rats were ovariectomized. The ovariectomized rats were further divided into 5 groups: the control, three groups force-fed with C. caudatus at the doses of 100mg/kg, 200mg/kg or 300mg/kg and another group supplemented with calcium 1% ad libitum. Treatments were given 6 days per week for a period of eight weeks. Blood samples were collected twice; before and after treatment. Parameters measured were bone resorbing cytokine; interleukin-1 and the bone biomarkers; osteocalcin and pyridinoline. Serum IL-1 and pyridinoline levels were significantly increased in ovariectomized rats. Supplementation of C. caudatus was able to prevent the increase of IL-1 and pyridinoline in ovariectomized rats. Besides that, C. caudatus showed the same effect as calcium 1% on biochemical parameters of bone metabolism in ovariectomized rats. In conclusion, Cosmos caudatus was as effective as calcium in preventing the increase in bone resorption in ovariectomized rats.

Quickening: Translational design of resorbable synthetic vascular grafts.

PubMed

Stowell, Chelsea E T; Wang, Yadong

2018-08-01

Traditional tissue-engineered vascular grafts have yet to gain wide clinical use. The difficulty of scaling production of these cell- or biologic-based products has hindered commercialization. In situ tissue engineering bypasses such logistical challenges by using acellular resorbable scaffolds. Upon implant, the scaffolds become remodeled by host cells. This review describes the scientific and translational advantages of acellular, synthetic vascular grafts. It surveys in vivo results obtained with acellular synthetics over their fifty years of technological development. Finally, it discusses emerging principles, highlights strategic considerations for designers, and identifies questions needing additional research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Can physical activity improve peak bone mass?

PubMed

Specker, Bonny; Minett, Maggie

2013-09-01

The pediatric origin of osteoporosis has led many investigators to focus on determining factors that influence bone gain during growth and methods for optimizing this gain. Bone responds to bone loading activities by increasing mass or size. Overall, pediatric studies have found a positive effect of bone loading on bone size and accrual, but the types of loads necessary for a bone response have only recently been investigated in human studies. Findings indicate that responses vary by sex, maturational status, and are site-specific. Estrogen status, body composition, and nutritional status also may influence the bone response to loading. Despite the complex interrelationships among these various factors, it is prudent to conclude that increased physical activity throughout life is likely to optimize bone health.

Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Ryosuke; Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Kayamori, Kou

Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and themore » bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

Clinical use of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in post-extraction socket for maintaining the alveolar height: A prospective study.

PubMed

Hoda, Nadeemul; Saifi, Aamir Malick; Giraddi, Girish B

2016-01-01

A common sequel of tooth extraction is alveolar bone resorption. It makes the placement of dental implants difficult and creates an esthetic problem for the fabrication of conventional prostheses. Therefore, alveolar bone following tooth extraction should be preserved. The present prospective study was conducted to evaluate the efficacy of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in maintaining the alveolar height in post-extraction socket. 20 patients were selected based on inclusion and exclusion criteria and were randomly divided into two groups: cases and control comprising of 10 patients each. Atraumatic tooth extraction was done in all patients. PLGA bioscaffold was placed in cases and socket was closed with 3-0 vicryl. In control group, socket was directly closed with 3-0 vicryl. The patients were kept on follow-up and complications such as dry socket, pain, and swelling were recorded. IOPA were taken at 1st, 4th, 12th, and 24th week to record changes in the height of alveolar bone. The radiographic measurements were compared and the differences were statistically analyzed. Reduction in alveolar bone height after placement of PLGA bioscaffold was significantly less in cases as compared to controls at 4th, 12th, and 24th week following extraction. No complications were observed throughout the follow-up period. PLGA scaffold significantly reduces bone resorption. Application is very simple and can be easily performed in a dental setup. However, PLGA scaffold adds significantly to the cost of treatment.

Alveolar distraction osteogenesis: revive and restore the native bone.

PubMed

Sant, Sumedha; Jagtap, Amit

2009-12-01

In prosthodontics, knife-edge bony alveolar ridges can cause a problem in their rehabilitation. The distraction osteogenesis process raises the medullary component of the alveolus, allowing the labial plate of the existing natural bone to be displaced. This process involves mobilization, transport, and fixation of a healthy segment of bone adjacent to the deficient site. It entails use of the gradual controlled displacement of surgically created fractures, which results in simultaneous expansion of soft tissue and bone volume. A mechanical device, the alveolar distraction device, is used for this purpose. This modality of treatment can be used in implant dentistry cases for rehabilitation of resorbed ridges. The objective of this overview is to explain this procedure wherein the alveolar housing, including the osseous and soft-tissue components, is enlarged in a single, simultaneous process, which makes creation of an appropriate alveolar morphology possible.

In vivo bone regeneration using a novel porous bioactive composite

NASA Astrophysics Data System (ADS)

Xie, En; Hu, Yunyu; Chen, Xiaofeng; Bai, Xuedong; Li, Dan; Ren, Li; Zhang, Ziru

2008-11-01

Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

Zygomatic Implants: The Impact of Zygoma Bone Support on Biomechanics.

PubMed

Romeed, Shihab; Malik, Raheel; Dunne, Stephen

2012-03-20

Abstract Maxillectomy and severely resorbed maxilla are challenging to restore with provision of removable prostheses. Dental implants are essential to restore aesthetics and function and subsequently quality of life in such group of patients. Zygomatic implants reduce the complications associated with bone grafting procedures and simplify the rehabilitation of atrophic maxilla and maxillectomy. The purpose of this study was to compare, by means of three-dimensional finite element analysis, the impact of different zygomatic bone support (10, 15, and 20mm) on the biomechanics of zygomatic implants. Results indicated maximum stresses within the fixture were increased by three times, when bone support decreased from 20 to 10mm, and concentrated at fixture/bone interface. However, stresses within the abutment screw and abutment itself were not significantly different regardless of the bone support level. Supporting bone at 10mm suffered double the stresses of 15 and 20mm. Fixture's deflection was decreased by two to three times when bone level support increased to 15mm and 20mm respectively. It was concluded that zygomatic bone support should not be less than 15mm and abutment screw is not at risk of fracture regardless of the zygomatic bone support.

Randomized clinical study assessing two membranes for guided bone regeneration of peri-implant bone defects: clinical and histological outcomes at 6 months.

PubMed

Naenni, Nadja; Schneider, David; Jung, Ronald E; Hüsler, Jürg; Hämmerle, Christoph H F; Thoma, Daniel S

2017-10-01

To test whether or not one of two membranes is superior for peri-implant-guided bone regeneration in terms of clinical and histologic outcomes. In 27 patients, 27 two-piece dental implants were placed in single-tooth gaps in the esthetic area. Buccal dehiscence and/or fenestration-type defects were regenerated using demineralized bovine bone mineral and randomly covered with either a resorbable membrane (RES) or a titanium-reinforced non-resorbable membrane (N-RES). Clinical measurements included vertical defect resolution and the horizontal thickness of regenerated bone at implant placement and at 6 months. Statistics were performed by means of nonparametric testing. The remaining mean vertical defect measured 4 mm (±2.07) (RES) and 2.36 mm (±2.09) (N-RES) (P = 0.044) at baseline and 0.77 mm (±0.85) (RES) and 0.21 mm (±0.80) (N-RES) (P = 0.021) at re-entry. This translated into a defect resolution of 85% (RES) and 90.7% (N-RES) (P = 0.10). The horizontal thickness after augmentation measured 3.46 mm (±0.52) (RES) and 2.82 mm (±0.50) (N-RES) (P = 0.004). The mean loss in horizontal thickness from baseline to re-entry measured 2.23 mm (SD ±1.21) (RES) and 0.14 mm (±0.79) (N-RES) (P = 0.017). The horizontal changes in thickness at the implant shoulder level were statistically significant between the groups (P = 0.0001). Both treatment modalities were clinically effective in regenerating bone as demonstrated by a similar horizontal thickness and vertical defect fill at 6 months. The N-RES group exhibited significantly less horizontal bone thickness reduction from baseline to follow-up. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

PubMed

Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

2014-12-01

Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Mouse fibroblasts homozygous for c-Src oncogene disruption shows dramatic suppression of expression of the gene encoding osteopontin, and adhesive phosphoprotein implicated in bone differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chackalaparampil, I.; Mukherjee, B.B.; Peri, A.

1994-09-01

Osteopetrosis, affecting mice and humans alike, arises from reduced or impaired bone resorption, causing abnormally dense bone formation. Normal bone differentiation requires continuous resorption and remodeling by osteoclasts which are derived from monocyte/macrophage lineage in the bone marrow. It has been reported that targeted homozygous disruption of c-src proto-oncogene in mice results in the development of osteopetrosis due to impaired bone-resorbing function of osteoclast cells. However, the molecular mechanism(s) which leads to osteoclast dysfunction in c-src deficient (src{sup -/-}) mice remains unclear. Here, we report that in embryonic fibroblasts derived from homozygous Src{sup -/-} mice, the expression of the genemore » coding for osteopontin (OP), a phosphorylated glycoprotein involved in bone differentiation, is drastically repressed. OP gene expression is not, however, affected in the heterozygous (Src{sup +/-}) mutant cells of identical origin, or in the c-src expression and OP production. Moreover, OP expression in c-src-deficient cells could be rescued upon treatment with 12-0-tetradecanoyl phorbol-13-myristate-acetate or okadaic acid. These observations indicate that OP expression is regulated via an src-mediated protein kinase C signaling pathway. Since it is known that OP mediates osteoclast adherence to the bone matrix, a key event in bone differentiation, our data is most significant in that they strongly suggest that drastic inhibition of synthesis of OP prevents osteoclasts in Src{sup -/-} mice from anchoring to the bone matrix. Consequently, this disruption of osteoclast adherence impairs their ability to form bone-resorbing ruffled border, causing osteopetrosis.« less

Long-term results of bone-retinaculum-bone autograft for scapholunate instability.

PubMed

Soong, Maximillian; Merrell, Gregory A; Ortmann, Fred; Weiss, Arnold-Peter C

2013-03-01

To report long-term follow-up of scapholunate interosseous ligament reconstruction with bone-retinaculum-bone autograft in patients with dynamic scapholunate instability. Of the 14 patients from the previously reported cohort who had bone-retinaculum-bone autograft for dynamic instability, 6 returned for clinical examination and radiographs, 3 were reached by telephone, and 2 were lost to follow-up. The remaining 3 had salvage procedures (2 total wrist arthrodeses and 1 proximal row carpectomy) between the prior report and the current study and thus reached an endpoint, at 2 to 4 years. For the 6 who returned, outcome measurements included scapholunate angle and gap, radiographic evidence of secondary arthritis, wrist extension and flexion, grip strength, and Mayo wrist score. Follow-up averaged 11.9 years (range, 10.7-14.1 y). Clinical and radiographic outcomes deteriorated moderately from the prior report. Mayo wrist score averaged 83. There were 3 failures, resulting in 1 proximal row carpectomy and 2 total wrist arthrodeses. Findings at repeat surgery in the failed group included an intact graft without any apparent abnormalities, a partially ruptured graft (after a subsequent re-injury), and a completely resorbed graft. Bone-retinaculum-bone autograft reconstruction is a viable treatment option for dynamic scapholunate instability in which the scaphoid and lunate can be reduced. Results may deteriorate but are similar to those reported previously from other techniques. Problems with graft strength or stiffness may necessitate further surgery. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

How Does Physical Activity Help Build Healthy Bones?

MedlinePlus

... Share Facebook Twitter Pinterest Email Print How does physical activity help build healthy bones? Bones are living tissue. Weight-bearing physical activity causes new bone tissue to form, and this ...

Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement

PubMed Central

Tao, Hu; Hwang, Suk-Won; Marelli, Benedetto; An, Bo; Moreau, Jodie E.; Yang, Miaomiao; Brenckle, Mark A.; Kim, Stanley; Kaplan, David L.; Rogers, John A.; Omenetto, Fiorenzo G.

2014-01-01

A paradigm shift for implantable medical devices lies at the confluence between regenerative medicine, where materials remodel and integrate in the biological milieu, and technology, through the use of recently developed material platforms based on biomaterials and bioresorbable technologies such as optics and electronics. The union of materials and technology in this context enables a class of biomedical devices that can be optically or electronically functional and yet harmlessly degrade once their use is complete. We present here a fully degradable, remotely controlled, implantable therapeutic device operating in vivo to counter a Staphylococcus aureus infection that disappears once its function is complete. This class of device provides fully resorbable packaging and electronics that can be turned on remotely, after implantation, to provide the necessary thermal therapy or trigger drug delivery. Such externally controllable, resorbable devices not only obviate the need for secondary surgeries and retrieval, but also have extended utility as therapeutic devices that can be left behind at a surgical or suturing site, following intervention, and can be externally controlled to allow for infection management by either thermal treatment or by remote triggering of drug release when there is retardation of antibiotic diffusion, deep infections are present, or when systemic antibiotic treatment alone is insufficient due to the emergence of antibiotic-resistant strains. After completion of function, the device is safely resorbed into the body, within a programmable period. PMID:25422476

Cancer-associated bone disease.

PubMed

Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

2013-12-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

Cancer-associated bone disease

PubMed Central

Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

2016-01-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

Cherubism Mice Also Deficient in c-Fos Exhibit Inflammatory Bone Destruction Executed by Macrophages That Express MMP14 Despite the Absence of TRAP+ Osteoclasts.

PubMed

Kittaka, Mizuho; Mayahara, Kotoe; Mukai, Tomoyuki; Yoshimoto, Tetsuya; Yoshitaka, Teruhito; Gorski, Jeffrey P; Ueki, Yasuyoshi

2018-01-01

Currently, it is believed that osteoclasts positive for tartrate-resistant acid phosphatase (TRAP+) are the exclusive bone-resorbing cells responsible for focal bone destruction in inflammatory arthritis. Recently, a mouse model of cherubism (Sh3bp2 KI/KI ) with a homozygous gain-of-function mutation in the SH3-domain binding protein 2 (SH3BP2) was shown to develop auto-inflammatory joint destruction. Here, we demonstrate that Sh3bp2 KI/KI mice also deficient in the FBJ osteosarcoma oncogene (c-Fos) still exhibit noticeable bone erosion at the distal tibia even in the absence of osteoclasts at 12 weeks old. Levels of serum collagen I C-terminal telopeptide (ICTP), a marker of bone resorption generated by matrix metalloproteinases (MMPs), were elevated, whereas levels of serum cross-linked C-telopeptide (CTX), another resorption marker produced by cathepsin K, were not increased. Collagenolytic MMP levels were increased in the inflamed joints of the Sh3bp2 KI/KI mice deficient in c-Fos. Resorption pits contained a large number of F4/80+ macrophages and genetic depletion of macrophages rescued these erosive changes. Importantly, administration of NSC405020, an MMP14 inhibitor targeted to the hemopexin (PEX) domain, suppressed bone erosion in c-Fos-deficient Sh3bp2 KI/KI mice. After activation of the NF-κB pathway, macrophage colony-stimulating factor (M-CSF)-dependent macrophages from c-Fos-deficient Sh3bp2 KI/KI mice expressed increased amounts of MMP14 compared with wild-type macrophages. Interestingly, receptor activator of NF-κB ligand (RANKL)-deficient Sh3bp2 KI/KI mice failed to show notable bone erosion, whereas c-Fos deletion did restore bone erosion to the RANKL-deficient Sh3bp2 KI/KI mice, suggesting that osteolytic transformation of macrophages requires both loss-of-function of c-Fos and gain-of-function of SH3BP2 in this model. These data provide the first genetic evidence that cells other than osteoclasts can cause focal bone destruction in

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

PubMed

Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Transgenic medaka fish as models to analyze bone homeostasis under micro-gravity conditions in vivo

NASA Astrophysics Data System (ADS)

Winkler, C.; Wagner, T.; Renn, J.; Goerlich, R.; Schartl, M.

Long-term space flight and microgravity results in bone loss that can be explained by reduced activity of bone-forming osteoblast cells and/or an increase in activity of bone resorbing osteoclast cells. Osteoprotegerin (OPG), a secreted protein of 401 amino acids, has been shown to regulate the balance between osteoblast and osteoclast formation and thereby warrants constant bone mass under normal gravitational conditions. Consistent with this, earlier reports using transgenic mice have shown that increased activation of OPG leads to exc essive bone formation (osteopetrosis), while inactivation of OPG leads to bone loss (osteoporosis). Importantly, it has recently been reported that expression of murine OPG is regulated by vector averaged gravity (Kanematsu et al., 2002, Bone 30, p553). The small bony fish medaka (Oryzias latipes ) has attracted increasing attention as genetic model system to study developmental and pathological processes. To analyze the molecular mechanisms of bone formation in this small vertebrate, we have isolated two related genes, opr-1 and opr -2, from medaka. Our phylogenetic analysis revealed that both genes originated from a common ancestor by fish-specific gene duplication and represent the orthologs of the mammalian OPG gene. Both opr genes are differentially expressed during embryonic and larval development, in adult tissues and in cultured primary osteoblast cells. We have characterized their promoter regions and identified consensus binding sites for transcription factors of the bone-morphogenetic-protein (BMP) p thway and for core-binding-factor-1Aa (cbfa1). Cbfa1 has been shown to be the key regulator of OPG expression during several steps of osteoblast differentiation in mammals. This opens the possibility that the mechanisms controlling bone formation in teleost fish and higher vertebrates are regulated by related mechanisms. We are currently generating transgenic medakafish expressing a GFP reporter gene under control of the

A resorbable and rapid method for maxillomandibular fixation in pediatric mandible fractures.

PubMed

Eppley, B L

2000-05-01

Maxillomandibular immobilization in pediatric mandible fractures is accomplished through a resorbable screw placed into the zygomatic body to which is attached a large, monofilament, circummandibular suture. Although the screw must be placed intraoperatively, this method of jaw immobilization is rapid, secure, does not damage the teeth, and can be removed in the office in the older child.

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

PubMed Central

Addadi, Lia; Geiger, Benjamin

2017-01-01

Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. It is commonly assumed that the structure and dynamic properties of the SZ depend on the physical and chemical properties of the substrate. Considering the unique complex structure of native bone, elucidation of the relevant parameters affecting SZ formation and stability is challenging. In this study, we examined in detail the dynamic response of the SZ to the microtopography of devitalized bone surfaces, taken from the same area in cattle femur. We show that there is a significant enrichment in large and stable SZs (diameter larger than 14 µm; lifespan of hours) in cells cultured on rough bone surfaces, compared with small and fast turning over SZ rings (diameter below 7 µm; lifespan approx. 7 min) formed on smooth bone surfaces. Based on these results, we propose that the surface roughness of the physiologically relevant substrate of osteoclasts, namely bone, affects primarily the local stability of growing SZs. PMID:28202594

Effects of Polymethoxyflavonoids on Bone Loss Induced by Estrogen Deficiency and by LPS-Dependent Inflammation in Mice.

PubMed

Matsumoto, Shigeru; Tominari, Tsukasa; Matsumoto, Chiho; Yoshinouchi, Shosei; Ichimaru, Ryota; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

2018-01-20

Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone (TMF) in citrus fruits. PMFs have shown various biological functions, including anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF all inhibited interleukin (IL)-1-mediated osteoclast differentiation via the inhibition of prostaglandin E2 synthesis. In this study, we created an original mixture of PMFs (nobiletin, tangeretin, HMF, and TMF) and examined whether or not PMFs exhibit co-operative inhibitory effects on osteoclastogenesis and bone resorption. In a coculture of bone marrow cells and osteoblasts, PMFs dose-dependently inhibited IL-1-induced osteoclast differentiation and bone resorption. The optimum concentration of PMFs was lower than that of nobiletin alone in the suppression of osteoclast differentiation, suggesting that the potency of PMFs was stronger than that of nobiletin in vitro. The oral administration of PMFs recovered the femoral bone loss induced by estrogen deficiency in ovariectomized mice. We further tested the effects of PMFs on lipopolysaccharide-induced bone resorption in mouse alveolar bone. In an ex vivo experimental model for periodontitis, PMFs significantly suppressed the bone-resorbing activity in organ cultures of mouse alveolar bone. These results indicate that a mixture of purified nobiletin, tangeretin, HMF, and TMF exhibits a co-operative inhibitory effect for the protection against bone loss in a mouse model of bone disease, suggesting that PMFs may be potential candidates for the prevention of bone resorption diseases, such as osteoporosis and periodontitis.

New mechanisms and targets in the treatment of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2007-01-01

Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with

Do pregnant lizards resorb or abort inviable eggs and embryos? Morphological evidence from an Australian skink, Pseudemoia pagenstecheri.

PubMed

Blackburn, Daniel G; Weaber, Kera K; Stewart, James R; Thompson, Michael B

2003-05-01

Although pregnant viviparous squamates are sometimes claimed to be able to resorb inviable eggs and embryos from the uterus, definitive evidence for such resorption is not available. After placing pregnant female Pseudemoia pagenstecheri into conditions under which embryonic development is terminated, we periodically harvested the gravid oviducts and examined them histologically. Females contained abnormal and degenerating eggs and embryos that had died in various stages of development. Dead embryos had undergone extensive cytolysis, dissolution, and aseptic necrosis and vitelline masses showed signs of deterioration and passage down the oviduct. The uterine mucosa lay in direct contact with the vitelline material, with no intact shell membrane intervening between them. Yolk was sometimes displaced into the exocoelom and allantoic cavity due to rupture of the extraembryonic membranes. Histological examination revealed no evidence of the uptake of yolk by the uterine epithelium or its accumulation in the subepithelial connective tissue. In many specimens, the uterine epithelium showed minuscule, apical granules. The position, appearance, and staining properties of the granules suggests them to be secretory, a manifestation of placentotrophy. Our observations indicate that P. pagenstecheri females retain dead eggs and embryos for several weeks or longer, yet do not resorb them during that period. This lizard is the second placentotrophic skink species in which resorption has been suspected, but in which abortive eggs appear to be retained or extruded instead of being resorbed by the oviducts. Researchers should not assume that squamates can digest and resorb oviductal eggs without definitive morphological evidence. Copyright 2003 Wiley-Liss, Inc.

Osteoprotegerin in bone metastases: mathematical solution to the puzzle.

PubMed

Ryser, Marc D; Qu, Yiding; Komarova, Svetlana V

2012-01-01

Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG) is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes.

Design of biocomposite materials for bone tissue regeneration.

PubMed

Yunus Basha, Rubaiya; Sampath Kumar, T S; Doble, Mukesh

2015-12-01

Several synthetic scaffolds are being developed using polymers, ceramics and their composites to overcome the limitations of auto- and allografts. Polymer-ceramic composites appear to be the most promising bone graft substitute since the natural bone itself is a composite of collagen and hydroxyapatite. Ceramics provide strength and osteoconductivity to the scaffold while polymers impart flexibility and resorbability. Natural polymers have an edge over synthetic polymers because of their biocompatibility and biological recognition property. But, very few natural polymer-ceramic composites are available as commercial products, and those few are predominantly based on type I collagen. Disadvantages of using collagen include allergic reactions and pathogen transmission. The commercial products also lack sufficient mechanical properties. This review summarizes the recent developments of biocomposite materials as bone scaffolds to overcome these drawbacks. Their characteristics, in vitro and in vivo performance are discussed with emphasis on their mechanical properties and ways to improve their performance. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of Bruton’s tyrosine kinase in myeloma cell migration and induction of bone disease

PubMed Central

Bam, Rakesh; Ling, Wen; Khan, Sharmin; Pennisi, Angela; Venkateshaiah, Sathisha Upparahalli; Li, Xin; van Rhee, Frits; Usmani, Saad; Barlogie, Bart; Shaughnessy, John; Epstein, Joshua; Yaccoby, Shmuel

2014-01-01

Myeloma cells typically grow in bone, recruit osteoclast precursors and induce their differentiation and activity in areas adjacent to tumor foci. Bruton’s tyrosine kinase (BTK), of the TEC family, is expressed in hematopoietic cells and is particularly involved in B-lymphocyte function and osteoclastogenesis. We demonstrated BTK expression in clinical myeloma plasma cells, interleukin (IL) –6– or stroma–dependent cell lines and osteoclasts. SDF-1 induced BTK activation in myeloma cells and BTK inhibition by small hairpin RNA or the small molecule inhibitor, LFM-A13, reduced their migration toward stromal cell-derived factor-1 (SDF-1). Pretreatment with LFM-A13 also reduced in vivo homing of myeloma cells to bone using bioluminescence imaging in the SCID-rab model. Enforced expression of BTK in myeloma cell line enhanced cell migration toward SDF-1 but had no effect on short-term growth. BTK expression was correlated with cell-surface CXCR4 expression in myeloma cells (n = 33, r = 0.81, P < 0.0001), and BTK gene and protein expression was more profound in cell-surface CXCR4-expressing myeloma cells. BTK was not upregulated by IL-6 while its inhibition had no effect on IL-6 signaling in myeloma cells. Human osteoclast precursors also expressed BTK and cell-surface CXCR4 and migrated toward SDF-1. LFM-A13 suppressed migration and differentiation of osteoclast precursors as well as bone-resorbing activity of mature osteoclasts. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibited osteoclast activity, prevented myeloma-induced bone resorption and moderately suppressed myeloma growth. These data demonstrate BTK and cell-surface CXCR4 association in myeloma cells and that BTK plays a role in myeloma cell homing to bone and myeloma-induced bone disease. PMID:23456977

Zygomatic implants: the impact of zygoma bone support on biomechanics.

PubMed

Romeed, Shihab A; Malik, Raheel; Dunne, Stephen M

2014-06-01

Maxillectomy and severely resorbed maxilla are challenging to restore with provision of removable prostheses. Dental implants are essential to restore esthetics and function and subsequently quality of life in such group of patients. Zygomatic implants reduce the complications associated with bone grafting procedures and simplify the rehabilitation of atrophic maxilla and maxillectomy. The purpose of this study was to compare, by means of 3-dimensional finite element analysis, the impact of different zygomatic bone support (10, 15, and 20 mm) on the biomechanics of zygomatic implants. Results indicated that maximum stresses within the fixture were increased by 3 times when bone support decreased from 20 to 10 mm and were concentrated at the fixture/bone interface. However, stresses within the abutment screw and the abutment itself were not significantly different regardless of the bone support level. Supporting bone at 10 mm sustained double the stresses of 15 and 20 mm. Fixture's deflection was decreased by 2 to 3 times when bone support level increased to 15 mm and 20 mm, respectively. It was concluded that zygomatic bone support should not be less than 15 mm, and abutment screw is not at risk of fracture regardless of the zygomatic bone support.

The BPAQ: a bone-specific physical activity assessment instrument.

PubMed

Weeks, B K; Beck, B R

2008-11-01

A newly developed bone-specific physical activity questionnaire (BPAQ) was compared with other common measures of physical activity for its ability to predict parameters of bone strength in healthy, young adults. The BPAQ predicted indices of bone strength at clinically relevant sites in both men and women, while other measures did not. Only certain types of physical activity (PA) are notably osteogenic. Most methods to quantify levels of PA fail to account for bone relevant loading. Our aim was to examine the ability of several methods of PA assessment and a new bone-specific measure to predict parameters of bone strength in healthy adults. We recruited 40 men and women (mean age 24.5). Subjects completed the modifiable activity questionnaire, Bouchard 3-day activity record, a recently published bone loading history questionnaire (BLHQ), and wore a pedometer for 14 days. We also administered our bone-specific physical activity questionnaire (BPAQ). Calcaneal broadband ultrasound attenuation (BUA) (QUS-2, Quidel) and densitometric measures (XR-36, Norland) were examined. Multiple regression and correlation analyses were performed on the data. The current activity component of BPAQ was a significant predictor of variance in femoral neck bone mineral density (BMD), lumbar spine BMD, and whole body BMD (R(2) = 0.36-0.68, p < 0.01) for men, while the past activity component of BPAQ predicted calcaneal BUA (R(2) = 0.48, p = 0.001) for women. The BPAQ predicted indices of bone strength at skeletal sites at risk of osteoporotic fracture while other PA measurement tools did not.

New predictive model for monitoring bone remodeling.

PubMed

Bougherara, Habiba; Klika, Václav; Marsík, Frantisek; Marík, Ivo A; Yahia, L'hocine

2010-10-01

The aim of this article was to present a new thermodynamic-based model for bone remodeling which is able to predict the functional adaptation of bone in response to changes in both mechanical and biochemical environments. The model was based on chemical kinetics and irreversible thermodynamic principles, in which bone is considered as a self-organizing system that exchanges matter, energy and entropy with its surroundings. The governing equations of the mathematical model have been numerically solved using Matlab software and implemented in ANSYS software using the Finite Element Method. With the aid of this model, the whole inner structure of bone was elucidated. The current model suggested that bone remodeling was a dynamic process which was driven by mechanical loading, metabolic factors and other external contributions. The model clearly indicated that in the absence of mechanical stimulus, the bone was not completely resorbed and reaches a new steady state after about 50% of bone loss. This finding agreed with previous clinical studies. Furthermore, results of virtual computations of bone density in a composite femur showed the development of a dense cortical bone around the medullary canal and a dense trabeculae bone between the femoral head and the calcar region of the medial cortex due to compressive stresses. The comparison of the predicted bone density with the structure of the proximal femur obtained from X-rays and using strain energy density gave credibility to the current model. Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

PubMed

Rougraff, Bruce T; Kling, Thomas J

2002-06-01

The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.

PubMed

Shinohara, Masahiro; Chang, Betty Y; Buggy, Joseph J; Nagai, Yusuke; Kodama, Tatsuhiko; Asahara, Hiroshi; Takayanagi, Hiroshi

2014-03-01

Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as well as in various bone disorders such as osteoporosis and rheumatoid arthritis. Previously we showed that the Tec family of tyrosine kinases is essential for the differentiation of osteoclasts and the inhibition of Btk is a promising strategy for the prevention of the bone loss in osteoclast-associated bone disorders. Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function. Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts. In addition, genome-wide screening revealed that Btk regulates the expression of the genes involved in osteoclast differentiation and function in both an NFATc1-dependent and -independent manner. Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests ibrutinib to be a promising therapeutic agent for osteoclast-associated bone diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

The use of resorbable hardware for fixation of pediatric mandible fracture. Case report.

PubMed

Poore, Matthew C; Penna, Kevin J

2008-01-01

The diagnosis and management of mandible fractures in the pediatric patient population can pose multiple challenges to the oral and maxillofacial surgeon. Resorbable plates and screws for fixation in this population are both well tolerated and effective. They enable realignment and stable positioning of rapidly healing fracture segments, while obviating any potential impediments to long-term metal retention.

Applications of Metals for Bone Regeneration.

PubMed

Glenske, Kristina; Donkiewicz, Phil; Köwitsch, Alexander; Milosevic-Oljaca, Nada; Rider, Patrick; Rofall, Sven; Franke, Jörg; Jung, Ole; Smeets, Ralf; Schnettler, Reinhard; Wenisch, Sabine; Barbeck, Mike

2018-03-12

The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum . In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

Applications of Metals for Bone Regeneration

PubMed Central

Glenske, Kristina; Donkiewicz, Phil; Köwitsch, Alexander; Milosevic-Oljaca, Nada; Rider, Patrick; Rofall, Sven; Franke, Jörg; Jung, Ole; Smeets, Ralf; Schnettler, Reinhard; Wenisch, Sabine

2018-01-01

The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration. PMID:29534546

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulatedmore » with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. �

Jolkinolide B inhibits RANKL-induced osteoclastogenesis by suppressing the activation NF-κB and MAPK signaling pathways.

PubMed

Ma, Xiaojun; Liu, Yupeng; Zhang, Yao; Yu, Xiaobing; Wang, Weiming; Zhao, Dewei

2014-03-07

Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. The unique function and ability of osteoclasts to resorb bone makes them critical in both normal bone homeostasis and pathologic bone diseases such as osteoporosis and rheumatoid arthritis. Thus, new compounds that may inhibit osteoclastogenesis and osteoclast function may be of great value in the treatment of osteoclast-related diseases. In the present study, we examined the effect of jolkinolide B (JB), isolated from the root of Euphorbia fischeriana Steud on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. We found that JB inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages (BMMs) without cytotoxicity. Furthermore, the expression of osteoclastic marker genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CtsK), and calcitonin receptor (CTR), was significantly inhibited. JB inhibited RANKL-induced activation of NF-κB by suppressing RANKL-mediated IκBα degradation. Moreover, JB inhibited RANKL-induced phosphorylation of mitogen-activated protein kinases (p38, JNK, and ERK). This study thus identifies JB as an inhibitor of osteoclast formation and provides evidence that JB might be an alternative medicine for preventing and treating osteolysis. Copyright © 2014 Elsevier Inc. All rights reserved.

Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

NASA Astrophysics Data System (ADS)

Zhang, Haifeng; Mao, Xiyuan; Du, Zijing; Jiang, Wenbo; Han, Xiuguo; Zhao, Danyang; Han, Dong; Li, Qingfeng

2016-01-01

We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo. The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model.

PubMed

Zhang, Haifeng; Mao, Xiyuan; Du, Zijing; Jiang, Wenbo; Han, Xiuguo; Zhao, Danyang; Han, Dong; Li, Qingfeng

2016-01-01

We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo . The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy

PubMed Central

Adapala, Naga Suresh; Holland, Danielle; Piccuillo, Vanessa; Barbe, Mary F.; Langdon, Wallace Y.; Tsygankov, Alexander Y.; Lorenzo, Joseph A.; Sanjay, Archana

2014-01-01

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl−/− mice have delayed bone development due to decreased osteoclast migration. Cbl-b−/− mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl−/− and Cbl-b−/− mice showed significant bone loss in tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. PMID:24994594

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.

PubMed

Adapala, Naga Suresh; Holland, Danielle; Scanlon, Vanessa; Barbe, Mary F; Langdon, Wallace Y; Tsygankov, Alexander Y; Lorenzo, Joseph A; Sanjay, Archana

2014-10-01

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl-/- mice have delayed bone development due to decreased osteoclast migration. Cbl-b-/- mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl-/- and Cbl-b-/- mice showed significant bone loss in the tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Imaging of Alkaline Phosphatase Activity in Bone Tissue

PubMed Central

Gade, Terence P.; Motley, Matthew W.; Beattie, Bradley J.; Bhakta, Roshni; Boskey, Adele L.; Koutcher, Jason A.; Mayer-Kuckuk, Philipp

2011-01-01

The purpose of this study was to develop a paradigm for quantitative molecular imaging of bone cell activity. We hypothesized the feasibility of non-invasive imaging of the osteoblast enzyme alkaline phosphatase (ALP) using a small imaging molecule in combination with 19Flourine magnetic resonance spectroscopic imaging (19FMRSI). 6, 8-difluoro-4-methylumbelliferyl phosphate (DiFMUP), a fluorinated ALP substrate that is activatable to a fluorescent hydrolysis product was utilized as a prototype small imaging molecule. The molecular structure of DiFMUP includes two Fluorine atoms adjacent to a phosphate group allowing it and its hydrolysis product to be distinguished using 19Fluorine magnetic resonance spectroscopy (19FMRS) and 19FMRSI. ALP-mediated hydrolysis of DiFMUP was tested on osteoblastic cells and bone tissue, using serial measurements of fluorescence activity. Extracellular activation of DiFMUP on ALP-positive mouse bone precursor cells was observed. Concurringly, DiFMUP was also activated on bone derived from rat tibia. Marked inhibition of the cell and tissue activation of DiFMUP was detected after the addition of the ALP inhibitor levamisole. 19FMRS and 19FMRSI were applied for the non-invasive measurement of DiFMUP hydrolysis. 19FMRS revealed a two-peak spectrum representing DiFMUP with an associated chemical shift for the hydrolysis product. Activation of DiFMUP by ALP yielded a characteristic pharmacokinetic profile, which was quantifiable using non-localized 19FMRS and enabled the development of a pharmacokinetic model of ALP activity. Application of 19FMRSI facilitated anatomically accurate, non-invasive imaging of ALP concentration and activity in rat bone. Thus, 19FMRSI represents a promising approach for the quantitative imaging of bone cell activity during bone formation with potential for both preclinical and clinical applications. PMID:21799916

Active multilayered capsules for in vivo bone formation

PubMed Central

Facca, S.; Cortez, C.; Mendoza-Palomares, C.; Messadeq, N.; Dierich, A.; Johnston, A. P. R.; Mainard, D.; Voegel, J.-C.; Caruso, F.; Benkirane-Jessel, N.

2010-01-01

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled. PMID:20160118

[Clinical usefulness of bone turnover markers in the management of osteoporosis].

PubMed

Yano, Shozo

2013-09-01

Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future.

Bioactive scaffold for bone tissue engineering: An in vivo study

NASA Astrophysics Data System (ADS)

Livingston, Treena Lynne

Massive bone loss of the proximal femur is a common problem in revision cases of total hip implants. Allograft is typically used to reconstruct the site for insertion of the new prosthesis. However, for long term fixation and function, it is desirable that the allograft becomes fully replaced by bone tissue and aids in the regeneration of bone to that site. However, allograft use is typically associated with delayed incorporation and poor remodeling. Due to these profound limitations, alternative approaches are needed. Tissue engineering is an attractive approach to designing improved graft materials. By combining osteogenic activity with a resorbable scaffold, bone formation can be stimulated while providing structure and stability to the limb during incorporation and remodeling of the scaffold. Porous, surface modified bioactive ceramic scaffolds (pSMC) have been developed which stimulate the expression of the osteoblastic phenotype and production of bone-like tissue in vitro. The scaffold and two tissue-engineered constructs, osteoprogenitor cells seeded onto scaffolds or cells expanded in culture to form bone tissue on the scaffolds prior to implantation, were investigated in a long bone defect model. The rate of incorporation was assessed. Both tissue-engineered constructs stimulated bone formation and comparable repair at 2 weeks. In a rat femoral window defect model, bone formation increased over time for all groups in concert with scaffold resorption, leading to a 40% increase in bone and 40% reduction of the scaffold in the defect by 12 weeks. Both tissue-engineered constructs enhanced the rate of mechanical repair of long bones due to better bony union with the host cortex. Long bones treated with tissue engineered constructs demonstrated a return in normal torsional properties by 4 weeks as compared to 12 weeks for long bones treated with pSMC. Culture expansion of cells to produce bone tissue in vitro did not accelerate incorporation over the treatment

Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

PubMed

Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

2009-12-15

The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

Reduced energy availability: implications for bone health in physically active populations.

PubMed

Papageorgiou, Maria; Dolan, Eimear; Elliott-Sale, Kirsty J; Sale, Craig

2018-04-01

The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Osteoclasts on bone and dentin in vitro: mechanism of trail formation and comparison of resorption behavior.

PubMed

Rumpler, M; Würger, T; Roschger, P; Zwettler, E; Sturmlechner, I; Altmann, P; Fratzl, P; Rogers, M J; Klaushofer, K

2013-12-01

The main function of osteoclasts in vivo is the resorption of bone matrix, leaving behind typical resorption traces consisting of pits and trails. The mechanism of pit formation is well described, but less is known about trail formation. Pit-forming osteoclasts possess round actin rings. In this study we show that trail-forming osteoclasts have crescent-shaped actin rings and provide a model that describes the detailed mechanism. To generate a trail, the actin ring of the resorption organelle attaches with one side outside the existing trail margin. The other side of the ring attaches to the wall inside the trail, thus sealing that narrow part to be resorbed next (3–21 lm). This 3D configuration allows vertical resorption layer-by-layer from the surface to a depth in combination with horizontal cell movement. Thus, trails are not just traces of a horizontal translation of osteoclasts during resorption. Additionally, we compared osteoclastic resorption on bone and dentin since the latter is the most frequently used in vitro model and data are extrapolated to bone. Histomorphometric analyses revealed a material-dependent effect reflected by an 11-fold higher resorption area and a sevenfold higher number of pits per square centimeter on dentin compared to bone. An important material-independent aspect was reflected by comparable mean pit area (μm²) and podosome patterns. Hence, dentin promotes the generation of resorbing osteoclasts, but once resorption has started, it proceeds independently of material properties. Thus, dentin is a suitable model substrate for data acquisition as long as osteoclast generation is not part of the analyses.

Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer

PubMed Central

Liu, Jin; Li, Defang; Dang, Lei; Liang, Chao; Guo, Baosheng; Lu, Cheng; He, Xiaojuan; Cheung, Hilda Y. S.; He, Bing; Liu, Biao; Li, Fangfei; Lu, Jun; Wang, Luyao; Shaikh, Atik Badshah; Jiang, Feng; Lu, Changwei; Peng, Songlin; Zhang, Zongkang; Zhang, Bao-Ting; Pan, Xiaohua; Xiao, Lianbo; Lu, Aiping; Zhang, Ge

2017-01-01

The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3′UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p. PMID:28071724

Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results

PubMed Central

Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F.; Kirkpatrick, Charles J.; Sader, Robert A.

2013-01-01

Background: The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Materials and Methods: Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Results: Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Conclusions: Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer. PMID:24205471

Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results.

PubMed

Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F; Kirkpatrick, Charles J; Sader, Robert A

2013-07-01

The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.

Localized tissue mineralization regulated by bone remodelling: A computational approach

PubMed Central

Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

2017-01-01

Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

Effects of directly autotransplanted tibial bone marrow aspirates on bone regeneration and osseointegration of dental implants.

PubMed

Payer, Michael; Lohberger, Birgit; Strunk, Dirk; Reich, Karoline M; Acham, Stephan; Jakse, Norbert

2014-04-01

Aim of the pilot trial was to evaluate applicability and effects of directly autotransplanted tibial bone marrow (BM) aspirates on the incorporation of porous bovine bone mineral in a sinus lift model and on the osseointegration of dental implants. Six edentulous patients with bilaterally severely resorbed maxillae requiring sinus augmentation and implant treatment were included. During surgery, tibial BM was harvested and added to bone substitute material (Bio-Oss(®) ) at the randomly selected test site. At control sites, augmentation was performed with Bio-Oss(®) alone. The cellular content of each BM aspirate was checked for multipotency and surface antigen expression as quality control. Histomorphometric analysis of biopsies from the augmented sites after 3 and 6 months (during implantation) was used to evaluate effects on bone regeneration. Osseointegration of implants was evaluated with Periotest(®) and radiographic means. Multipotent cellular content in tibial BM aspirates was comparable to that in punctures from the iliac crest. No significant difference in amount of new bone formation and the integration of bone substitute particles was detected histomorphometrically. Periotest(®) values and radiographs showed successful osseointegration of inserted implants at all sites. Directly autotransplanted tibial BM aspirates did not show beneficial regenerative effects in the small study population (N = 6) of the present pilot trial. However, the proximal tibia proved to be a potential donor site for small quantities of BM. Future trials should clarify whether concentration of tibial BM aspirates could effect higher regenerative potency. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate

PubMed Central

Pederson, Larry; Ruan, Ming; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

2008-01-01

Under most conditions, resorbed bone is nearly precisely replaced in location and amount by new bone. Thus, it has long been recognized that bone loss through osteoclast-mediated bone resorption and bone replacement through osteoblast-mediated bone formation are tightly coupled processes. Abundant data conclusively demonstrate that osteoblasts direct osteoclast differentiation. Key questions remain, however, as to how osteoblasts are recruited to the resorption site and how the amount of bone produced is so precisely controlled. We hypothesized that osteoclasts play a crucial role in the promotion of bone formation. We found that osteoclast conditioned medium stimulates human mesenchymal stem (hMS) cell migration and differentiation toward the osteoblast lineage as measured by mineralized nodule formation in vitro. We identified candidate osteoclast-derived coupling factors using the Affymetrix microarray. We observed significant induction of sphingosine kinase 1 (SPHK1), which catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (S1P), in mature multinucleated osteoclasts as compared with preosteoclasts. S1P induces osteoblast precursor recruitment and promotes mature cell survival. Wnt10b and BMP6 also were significantly increased in mature osteoclasts, whereas sclerostin levels decreased during differentiation. Stimulation of hMS cell nodule formation by osteoclast conditioned media was attenuated by the Wnt antagonist Dkk1, a BMP6-neutralizing antibody, and by a S1P antagonist. BMP6 antibodies and the S1P antagonist, but not Dkk1, reduced osteoclast conditioned media-induced hMS chemokinesis. In summary, our findings indicate that osteoclasts may recruit osteoprogenitors to the site of bone remodeling through SIP and BMP6 and stimulate bone formation through increased activation of Wnt/BMP pathways. PMID:19075223

Physical Activity and Bone Density in Women

NASA Technical Reports Server (NTRS)

Bowley, Susan M.; Whalen, R. T.

2000-01-01

A mathematical model of bone density regulation as a function of the daily tissue "effective" stress has been derived. Using the model, the influence of daily activity in the form of a daily loading history has been related to bone density of the calcaneus. The theory incorporates a stress exponent m to account for differences in the importance of magnitude and number of load cycles experienced during daily activity. We have derived a parameter from the model, the "Bone Density Index" (BDI). We have developed a method of collecting daily habitual loading histories using an insole force sensor interfaced to a portable digital data logger carried in a fanny pack. Our goal for this study was to determine a stress exponent, m, relating GRFz history to Calcaneal Bone Mineral Density (CBMD).

Incorporation of RANKL promotes osteoclast formation and osteoclast activity on β-TCP ceramics.

PubMed

Choy, John; Albers, Christoph E; Siebenrock, Klaus A; Dolder, Silvia; Hofstetter, Wilhelm; Klenke, Frank M

2014-12-01

β-Tricalcium phosphate (β-TCP) ceramics are approved for the repair of osseous defects. In large defects, however, the substitution of the material by authentic bone is inadequate to provide sufficient long-term mechanical stability. We aimed to develop composites of β-TCP ceramics and receptor activator of nuclear factor κ-B ligand (RANKL) to enhance the formation of osteoclasts and promote cell mediated calcium phosphate resorption. RANKL was adsorbed superficially onto β-TCP ceramics or incorporated into a crystalline layer of calcium phosphate by the use of a co-precipitation technique. Murine osteoclast precursors were seeded onto the ceramics. After 15 days, the formation of osteoclasts was quantified cytologically and colorimetrically with tartrate-resistant acidic phosphatase (TRAP) staining and TRAP activity measurements, respectively. Additionally, the expression of transcripts encoding the osteoclast gene products cathepsin K, calcitonin receptor, and of the sodium/hydrogen exchanger NHA2 were quantified by real-time PCR. The activity of newly formed osteoclasts was evaluated by means of a calcium phosphate resorption assay. Superficially adsorbed RANKL did not induce the formation of osteoclasts on β-TCP ceramics. When co-precipitated onto β-TCP ceramics RANKL supported the formation of mature osteoclasts. The development of osteoclast lineage cells was further confirmed by the increased expression of cathepsin K, calcitonin receptor, and NHA2. Incorporated RANKL stimulated the cells to resorb crystalline calcium phosphate. Our in vitro study shows that RANKL incorporated into β-TCP ceramics induces the formation of active, resorbing osteoclasts on the material surface. Once formed, osteoclasts mediate the release of RANKL thereby perpetuating their differentiation and activation. In vivo, the stimulation of osteoclast-mediated resorption may contribute to a coordinated sequence of material resorption and bone formation. Further in vivo studies

Continuous Digital Light Processing (cDLP): Highly Accurate Additive Manufacturing of Tissue Engineered Bone Scaffolds.

PubMed

Dean, David; Jonathan, Wallace; Siblani, Ali; Wang, Martha O; Kim, Kyobum; Mikos, Antonios G; Fisher, John P

2012-03-01

Highly accurate rendering of the external and internal geometry of bone tissue engineering scaffolds effects fit at the defect site, loading of internal pore spaces with cells, bioreactor-delivered nutrient and growth factor circulation, and scaffold resorption. It may be necessary to render resorbable polymer scaffolds with 50 μm or less accuracy to achieve these goals. This level of accuracy is available using Continuous Digital Light processing (cDLP) which utilizes a DLP(®) (Texas Instruments, Dallas, TX) chip. One such additive manufacturing device is the envisionTEC (Ferndale, MI) Perfactory(®). To use cDLP we integrate a photo-crosslinkable polymer, a photo-initiator, and a biocompatible dye. The dye attenuates light, thereby limiting the depth of polymerization. In this study we fabricated scaffolds using the well-studied resorbable polymer, poly(propylene fumarate) (PPF), titanium dioxide (TiO(2)) as a dye, Irgacure(®) 819 (BASF [Ciba], Florham Park, NJ) as an initiator, and diethyl fumarate as a solvent to control viscosity.

Implantation of tetrapod-shaped granular artificial bones or β-tricalcium phosphate granules in a canine large bone-defect model.

PubMed

Choi, Sungjin; Liu, I-Li; Yamamoto, Kenichi; Honnami, Muneki; Sakai, Takamasa; Ohba, Shinsuke; Echigo, Ryosuke; Suzuki, Shigeki; Nishimura, Ryouhei; Chung, Ung-Il; Sasaki, Nobuo; Mochizuki, Manabu

2014-03-01

We investigated biodegradability and new bone formation after implantation of tetrapod-shaped granular artificial bone (Tetrabone®) or β-tricalcium phosphate granules (β-TCP) in experimental critical-size defects in dogs, which were created through medial and lateral femoral condyles. The defect was packed with Tetrabone® (Tetrabone group) or β-TCP (β-TCP group) or received no implant (control group). Computed tomography (CT) was performed at 0, 4 and 8 weeks after implantation. Micro-CT and histological analysis were conducted to measure the non-osseous tissue rate and the area and distribution of new bone tissue in the defect at 8 weeks after implantation. On CT, β-TCP was gradually resorbed, while Tetrabone® showed minimal resorption at 8 weeks after implantation. On micro-CT, non-osseous tissue rate of the control group was significantly higher compared with the β-TCP and Tetrabone groups (P<0.01), and that of the β-TCP group was significantly higher compared with the Tetrabone group (P<0.05). On histology, area of new bone tissue of the β-TCP group was significantly greater than those of the Tetrabone and control groups (P<0.05), and new bone distribution of the Tetrabone group was significantly greater than those of the β-TCP and control groups (P<0.05). These results indicate differences in biodegradability and connectivity of intergranule pore structure between study samples. In conclusion, Tetrabone® may be superior for the repair of large bone defects in dogs.

A Bone Anabolic Effect of RANKL in a Murine Model of Osteoporosis mediated through FoxP3+ CD8 T-cells

PubMed Central

Buchwald, Zachary S.; Yang, Chang; Nellore, Suman; Shashkova, Elena V.; Davis, Jennifer L.; Cline, Anna; Ko, Je; Novack, Deborah V.; DiPaolo, Richard; Aurora, Rajeev

2015-01-01

TNFα and IL-17 secreted by proinflammatory T-cells (TEFF) promote bone erosion by activating osteoclasts. We previously demonstrated that in addition to bone resorption, osteoclasts act as antigen presenting cells to induce FoxP3 in CD8 T-cells (TcREG). The osteoclast-induced regulatory CD8 T-cells limit bone resorption in ovariectomized mice (a murine model of postmenopausal osteoporosis). Here we show that while low-dose RANKL maximally induces TcREG via Notch signaling pathway to limit bone resorption, high-dose RANKL promotes bone resorption. In vitro, both TNFα and IL-17, cytokines that are abundant in ovariectomized animals, suppress TcREG induction by osteoclasts by repressing Notch ligand expression in osteoclasts but this effect can be counteracted by addition of RANKL. Ovariectomized mice treated with low-dose RANKL induced TcREG that suppressed bone resorption, decreased TEFF levels and increased bone formation. High dose RANKL had the expected osteolytic effect. Low dose RANKL administration in ovariectomized mice lacking CD8 T-cells was also osteolytic, confirming that TcREG mediate this bone anabolic effect. Our results show that while RANKL directly stimulates osteoclasts to resorb bone, it also controls the osteoclasts’ ability to induce regulatory T-cells, engaging an important negative feedback loop. In addition to the conceivable clinical relevance to treatment of osteoporosis, these observations have potential relevance to induction of tolerance and autoimmune diseases. PMID:25656537

[Homeostasis and Disorder of Musculoskeletal System.Cellular dynamics in musculoskeletal system visualized by intravital imaging techniques.

PubMed

Kikuta, Junichi; Ishii, Masaru

Bone is continually remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. Although it has long been believed that bone homeostasis is tightly regulated by communication between osteoclasts and osteoblasts, the fundamental process and dynamics have remained elusive. We originally established an advanced imaging system to visualize living bone tissues using intravital two-photon microscopy. By means of this system, we revealed the in vivo behavior of bone-resorbing osteoclasts and bone-forming osteoblasts in bone tissues. This approach facilitates investigation of cellular dynamics in the pathogenesis of musculoskeletal disorders, and would thus be useful for evaluating the efficacy of novel therapeutic agents.

Bone microarchitecture and estimated bone strength in men with active acromegaly.

PubMed

Silva, Paula P B; Amlashi, Fatemeh G; Yu, Elaine W; Pulaski-Liebert, Karen J; Gerweck, Anu V; Fazeli, Pouneh K; Lawson, Elizabeth; Nachtigall, Lisa B; Biller, Beverly M K; Miller, Karen K; Klibanski, Anne; Bouxsein, Mary; Tritos, Nicholas A

2017-11-01

Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area ( P  < 0.0001), cortical thickness ( P  = 0.0038), cortical pore volume ( P  < 0.0001) and cortical porosity ( P  = 0.0008), but lower trabecular bone density ( P  = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density ( P  = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly. © 2017 European Society of Endocrinology.

Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal organization by protein-tyrosine phosphatase ϵ in osteoclasts.

PubMed

Levy-Apter, Einat; Finkelshtein, Eynat; Vemulapalli, Vidyasiri; Li, Shawn S-C; Bedford, Mark T; Elson, Ari

2014-12-26

The non-receptor isoform of protein-tyrosine phosphatase ϵ (cyt-PTPe) supports adhesion of bone-resorbing osteoclasts by activating Src downstream of integrins. Loss of cyt-PTPe reduces Src activity in osteoclasts, reduces resorption of mineralized matrix both in vivo and in cell culture, and induces mild osteopetrosis in young female PTPe KO mice. Activation of Src by cyt-PTPe is dependent upon this phosphatase undergoing phosphorylation at its C-terminal Tyr-638 by partially active Src. To understand how cyt-PTPe activates Src, we screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe. The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most prominently, whereas the Src SH2 domain did not bind at all, suggesting that GRB2 may link PTPe with downstream molecules. Further studies indicated that GRB2 is required for activation of Src by cyt-PTPe in osteoclast-like cells (OCLs) in culture. Overexpression of GRB2 in OCLs increased activating phosphorylation of Src at Tyr-416 and of cyt-PTPe at Tyr-638; opposite results were obtained when GRB2 expression was reduced by shRNA or by gene inactivation. Phosphorylation of cyt-PTPe at Tyr-683 and its association with GRB2 are integrin-driven processes in OCLs, and cyt-PTPe undergoes autodephosphorylation at Tyr-683, thus limiting Src activation by integrins. Reduced GRB2 expression also reduced the ability of bone marrow precursors to differentiate into OCLs and reduced the fraction of OCLs in which podosomal adhesion structures assume organization typical of active, resorbing cells. We conclude that GRB2 physically links cyt-PTPe with Src and enables cyt-PTPe to activate Src downstream of activated integrins in OCLs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

[Development, physiology, and cell activity of bone].

PubMed

de Baat, P; Heijboer, M P; de Baat, C

2005-07-01

Bones are of crucial importance for the human body, providing skeletal support, serving as a home for the formation of haematopoietic cells, and reservoiring calcium and phosphate. Long bones develop by endochondral ossification. Flat bones develop by intramembranous ossification. Bone tissue contains hydroxyapatite and various extracellular proteins, producing bone matrix. Two biological mechanisms, determining the strength of bone, are modelling and remodelling. Modelling can change bone shape and size through bone formation by osteoblasts at some sites and through bone destruction by osteoclasts at other sites. Remodelling is bone turnover, also performed by osteoclasts and osteoblasts. The processes of modelling and remodelling are induced by mechanical loads, predominantly muscle loads. Osteoblasts develop from mesenchymal stem cells. Many stimulating factors are known to activate the differentiation. Mature osteoblasts synthesize bone matrix and may further differentiate into osteocytes. Osteocytes maintain structural bone integrity and allow bone to adapt to any mechanical and chemical stimulus. Osteoclasts derive from haematopoietic stem cells. A number of transcription and growth factors have been identified essential for osteoclast differentiation and function. Finally, there is a complex interaction between osteoblasts and osteoclasts. Bone destruction starts by attachment of osteoclasts to the bone surface. Following this, osteoclasts undergo specific morphological changes. The process of bone destruction starts by acid dissolution of hydroxyapatite. After that osteoclasts start to destruct the organic matrix.

Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis

DOE PAGES

Fowler, Tristan W.; Acevedo, Claire; Mazur, Courtney M.; ...

2017-03-22

Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. We find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis. In glucocorticoid-treated mice, we find that glucocorticoids coordinately suppress expression of several proteases required for perilacunar remodeling while causingmore » degeneration of the osteocyte lacunocanalicular network, collagen disorganization, and matrix hypermineralization; all of which are apparent in human osteonecrotic lesions. Therefore, osteocyte-mediated perilacunar remodeling maintains bone homeostasis, is dysregulated in skeletal disease, and may represent an attractive therapeutic target for the treatment of osteonecrosis.« less

Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, Tristan W.; Acevedo, Claire; Mazur, Courtney M.

Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. We find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis. In glucocorticoid-treated mice, we find that glucocorticoids coordinately suppress expression of several proteases required for perilacunar remodeling while causingmore » degeneration of the osteocyte lacunocanalicular network, collagen disorganization, and matrix hypermineralization; all of which are apparent in human osteonecrotic lesions. Therefore, osteocyte-mediated perilacunar remodeling maintains bone homeostasis, is dysregulated in skeletal disease, and may represent an attractive therapeutic target for the treatment of osteonecrosis.« less

Leukemia inhibitory factor: a novel bone-active cytokine.

PubMed

Reid, L R; Lowe, C; Cornish, J; Skinner, S J; Hilton, D J; Willson, T A; Gearing, D P; Martin, T J

1990-03-01

A number of cytokines have been found to be potent regulators of bone resorption and to share the properties originally attributed to osteoclast-activating factor. One such activity, differentiation-inducing factor (DIF, D-factor) from mouse spleen cells, shares a number of biological and biochemical properties with the recently characterized and cloned leukemia inhibitory factor (LIF). We have assessed the effects of recombinant LIF on bone resorption and other parameters in neonatal mouse calvaria. Both recombinant murine and human (h) LIFs stimulated 45Ca release from prelabeled calvaria in a dose-dependent manner. The increase in bone resorption was associated with an increase in the number of osteoclasts per mm2 bone. The osteolytic effect of hLIF were blocked by 10(-7) M indomethacin. hLIF also stimulated incorporation of [3H] thymidine into calvaria, but the dose-response relationship was distinct from that for bone resorption, and this effect was not blocked by indomethacin. Similarly, hLIF increased [3H]phenylalanine incorporation into calvaria, and this was also not inhibited by indomethacin. It is concluded that LIF stimulates bone resorption by a mechanism involving prostaglandin production, but that a distinct mechanism is responsible for its stimulation of DNA and protein synthesis. The primary structure of LIF differs from that of other fully characterized, bone-active cytokines, and it, thus, represents a novel factor which may be involved in the normal regulation of bone cell function.

Anorganic bovine bone and a silicate-based synthetic bone activate different microRNAs.

PubMed

Annalisa, Palmieri; Furio, Pezzetti; Ilaria, Zollino; Anna, Avantaggiato; Luca, Scapoli; Marcella, Martinelli; Marzia, Arlotti; Elena, Masiero; Carinci, Francesco

2008-09-01

Bio-Oss (BO), composed of anorganic bovine bone, is widely used in several bone regeneration procedures in oral surgery. PerioGlas (PG) is an alloplastic material that has been used for grafting of periodontal osseous defects since the 1990s. However, how these biomaterials alter osteoblast activity to promote bone formation is poorly understood. We attempted to address this question by using microRNA microarray techniques to investigate differences in translational regulation in osteoblasts exposed to BO and PG. By using miRNA microarrays containing 329 probes designed from human miRNA sequences, we investigated miRNAs whose expression was significantly modified in an osteoblast-like cell line (MG-63) cultured with BO vs PG. Three up-regulated miRNAs (mir-337, mir-200b, mir-377) and 4 down-regulated miRNAs (mir-130a, mir-214, mir-27a, mir-93) were identified. Our results indicated that BO and PG act on different miRNAs. Globally, PG causes activation of bone-forming signaling, whereas BO also activates cartilage-related pathways.

ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

PubMed Central

Rentsch, C.; Rentsch, B.; Heinemann, S.; Bernhardt, R.; Bischoff, B.; Förster, Y.; Scharnweber, D.; Rammelt, S.

2014-01-01

Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

Localized ridge defect augmentation using human pericardium membrane and demineralized bone matrix.

PubMed

Vidyadharan, Arun Kumar; Ravindran, Anjana

2014-01-01

Patient wanted to restore her lost teeth with implants in the lower left first molar and second premolar region. Cone beam computerized tomography (CBCT) revealed inadequate bone width and height around future implant sites. The extraction socket of second premolar area revealed inadequate socket healing with sparse bone fill after 4 months of extraction. To evaluate the clinical feasibility of using a collagen physical resorbable barrier made of human pericardium (HP) to augment localized alveolar ridge defects for the subsequent placement of dental implants. Ridge augmentation was done in the compromised area using Puros® demineralized bone matrix (DBM) Putty with chips and an HP allograft membrane. Horizontal (width) and vertical hard tissue measurements with CBCT were recorded on the day of ridge augmentation surgery, 4 month and 7 months follow-up. Intra oral periapical taken 1 year after implant installation showed minimal crestal bone loss. Bone volume achieved through guided bone regeneration was a gain of 4.8 mm horizontally (width) and 6.8 mm vertically in the deficient ridge within a period of 7 months following the procedure. The results suggested that HP Allograft membrane may be a suitable component for augmentation of localized alveolar ridge defects in conjunction with DBM with bone chips.

[Bone marrow stromal damage mediated by immune response activity].

PubMed

Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

1994-01-01

The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

Experimental models for cancellous bone healing in the rat

PubMed Central

Bernhardsson, Magnus; Sandberg, Olof; Aspenberg, Per

2015-01-01

Background and purpose — Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods — Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results — The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation — The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model. PMID:26200395

Conception on the cell mechanisms of bone tissue loss under spase flight conditions

NASA Astrophysics Data System (ADS)

Rodionova, Natalia; Oganov, Victor; Kabitskaya, Olga

Basing on the analysis of available literature and the results of our own electron microscopic and radioautographic researches the data are presented about the morpho-functional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures under normal conditions and after exposure of animals (rats, monkeys, mice) to microgravity (SLS-2, Bion-11, BionM-1). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and surface osteocytes as well as to the bone-marrow stromal cells and to those lying on bone surfaces. As a response to the mechanical stimulus (microgravity) the system of stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, some of the osteoblasts undergo apoptosis. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts and bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn’t occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in these remodeling loci. These cell reactions are considered as adaptive-compensatory, but they don’t result

Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture.

PubMed

Sanz-Salvador, Lucía; García-Pérez, Miguel Ángel; Tarín, Juan J; Cano, Antonio

2015-02-01

Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use. © 2015 European Society of Endocrinology.

Physical activity benefits bone density and bone-related hormones in adult men with cervical spinal cord injury.

PubMed

Chain, Amina; Koury, Josely C; Bezerra, Flávia Fioruci

2012-09-01

Severe bone loss is a recognized complication of chronic spinal cord injury (SCI). Physical exercise contributes to bone health; however, its influence on bone mass of cervical SCI individuals has not been investigated. The aim of this study was to investigate the influence of physical activity on bone mass, bone metabolism, and vitamin D status in quadriplegics. Total, lumbar spine (L1-L4), femur and radius bone mineral density (BMD) were assessed in active (n = 15) and sedentary (n = 10) quadriplegic men by dual energy X-ray absorptiometry. Concentrations of 25-hydroxyvitamin D [25(OH)D], PTH, IGF1, osteocalcin and NTx were measured in serum. After adjustments for duration of injury, total body mass, and habitual calcium intake, bone indices were similar between groups, except for L1-L4 BMD Z score that was higher in the sedentary group (P < 0.05). Hours of physical exercise per week correlated positively with 25(OH)D (r = 0.59; P < 0.05) and negatively with PTH (r = -0.50; P < 0.05). Femur BMD was negatively associated with the number of months elapsed between the injury and the onset of physical activity (r = -0.60; P < 0.05). Moreover, in the active subjects, both L1-L4 BMD Z score (r = 0.72; P < 0.01) and radius BMD (r = 0.59; P < 0.05) were positively associated with calcium intake. In this cross-sectional study, both the onset of physical activity after injury and the number of hours dedicated to exercise were able to influence bone density and bone-related hormones in quadriplegic men. Our results also suggest a positive combined effect of exercise and calcium intake on bone health of quadriplegic individuals.

A histomorphometric study of adaptive responses of cancellous bone in different regions in the sheep mandibular condyle following experimental forward mandibular displacement.

PubMed

Ma, Bingkui; Sampson, Wayne; Wilson, David; Wiebkin, Ole; Fazzalari, Nicola

2002-07-01

Forward mandibular displacement in animal models is associated with faster and/or redirected condylar growth. Here the effect of forward displacement induced with an intraoral appliance on modelling/remodelling of the mandibular condyle was investigated in eight, 4-month-old, castrated male Merino sheep, randomly allocated to experimental and control groups (n=4 in each group). The study period was 15 weeks, during that time, (1). calcein, (2). tetracycline, and (3). alizarin red S fluorochromes were given to all animals from day 1. Midsagittal sections of the temporomandibular joints were selected for analysis. Dynamic variables of bone formation, static indices of bone-forming and -resorbing activity, and structural indices of trabecular bone were estimated histomorphometrically. The sampling site was divided into two regions for analysis: (a). a 'subchondral region' (2 and 3 labels only), believed to be the bone newly formed during the experimental period; (b). a 'central region' (labelled by all three fluorochromes), believed to be the bone that existed before the experiment. Regional differences in adaptive response were found. In the experimental group, the bone-volume fraction (BV/TV) of the subchondral regions had decreased, although the specific bone-surface and bone-formation rates had increased. This low BV/TV was associated with decreased trabecular thickness and increased trabecular separation. In the central condylar region of the experimental group, BV/TV was unchanged, but an increased osteoid surface was apparent when the eroded surface was taken into consideration. These adaptive condylar responses to forward mandibular displacement appeared to be the result of increased osteoblastic activity. Further studies are recommended to examine why the subchondral and central regions responded differently.

Novel bone substitute material in alveolar bone healing following tooth extraction: an experimental study in sheep.

PubMed

Liu, Jinyi; Schmidlin, Patrick R; Philipp, Alexander; Hild, Nora; Tawse-Smith, Andrew; Duncan, Warwick

2016-07-01

Electrospun cotton wool-like nanocomposite (ECWN) is a novel synthetic bone substitute that incorporates amorphous calcium phosphate nanoparticles into a biodegradable synthetic copolymer poly(lactide-co-glycolide). The objectives of this study were to develop a tooth extraction socket model in sheep for bone graft research and to compare ECWN and bovine-derived xenograft (BX) in this model. Sixteen cross-bred female sheep were used. Bilateral mandibular premolars were extracted atraumatically. Second and third premolar sockets were filled (Latin-square allocation) with BX, ECWN or left unfilled. Resorbable collagen membranes were placed over BX and selected ECWN grafted sockets. Eight sheep per time period were sacrificed after 8 and 16 weeks. Resin-embedded undemineralised sections were analysed for descriptive histology and histomorphometric analyses. At 8 weeks, there were with no distinct differences in healing among the different sites. At 16 weeks, osseous healing followed a fine trabecular pattern in ECWN sites. Non-grafted sites showed thick trabeculae separated by large areas of fibrovascular connective tissue. In BX grafted sites, xenograft particles were surrounded by newly formed bone or fibrovascular connective tissue. There were no statistically significant differences in bone formation across the four groups. However, ECWN sites had significantly less residual graft material than BX sites at 16 weeks (P = 0.048). This first description of a tooth extraction socket model in sheep supports the utility of this model for bone graft research. The results of this study suggested that the novel material ECWN did not impede bone ingrowth into sockets and showed evidence of material resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The use of resorbable plates in association with dental arch stabilization in the treatment of mandibular fractures in children.

PubMed

Li, Zhi; David, Ongodia; Li, Zu-Bing

2014-07-01

The purpose of this study was to investigate the effect of resorbable plate fixation in association with dental arch stabilization in the treatment of displaced mandibular fractures in children. Thirteen children (5 girls and 8 boys, age range 2 years 5 months to 12 years 2 months) with displaced mandibular fractures were included in this case series. Open reduction by intraoral approach was performed on these patients, and the fractures were fixed using resorbable plates and monocortical screws placed at the lower border of the mandible. At the same time, an arch bar or orthodontic wire splint was anchored using stainless steel wires or resin on the teeth to stabilize the whole mandibular dental arch. Postoperatively, follow-up was undertaken to evaluate the fracture healing, mandible movement, and mandible growth. Postoperatively, all patients achieved uneventful healing; premorbid occlusion restoration and wound healing were achieved, along with unimpaired function and normal growth and development of the mandible. Complications such as damage to tooth buds, infection, malunion, and nonunion were not encountered in these patients. Resorbable plates use in association with dental arch stabilization can provide good stabilization for mandibular fractures and is a promising approach for the treatment of displaced mandibular fractures in children. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

El Backly, Rania M.; IRCCS AOU San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova; Faculty of Dentistry, Alexandria University, Alexandria

The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX{sup ®}) membranemore » was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12–16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX{sup ®}) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute.« less

The Use of Polymer Design in Resorbable Colloids

NASA Astrophysics Data System (ADS)

Finne-Wistrand, Anna; Albertsson, Ann-Christine

2006-08-01

During the past decade, researchers in the field of polymer chemistry have developed a wide range of very powerful procedures for constructing ever-more-sophisticated polymers. These methods subsequently have been used in suitable systems to solve specific medical problems. This is complicated, and many key factors such as mechanical properties, biocompatibility, biodegradation, stability, and degradation profile must be considered. Colloid particle systems can be used to solve many biomedical- and pharmaceutical-related problems, and it is expected that nanotechnology can be used to develop these materials, devices, and systems even further. For example, an injectible scaffold system with a defined release and degradation profile has huge potential for the repair and regeneration of damaged tissues. This short, nonexhaustive review presents examples of polymer architecture in resorbable particles that have been compared and tested in biomedical applications. We also discuss the design of polymers for core-shell structures.

Evaluation of four biodegradable, injectable bone cements in an experimental drill hole model in sheep.

PubMed

von Rechenberg, Brigitte; Génot, Oliver R; Nuss, Katja; Galuppo, Larry; Fulmer, Mark; Jacobson, Evan; Kronen, Peter; Zlinszky, Kati; Auer, Jörg A

2013-09-01

Four cement applications were tested in this investigation. Two dicalcium phosphate dihydrate (DCPD-brushite) hydraulic cements, an apatite hydraulic fiber loaded cement, and a calcium sulfate cement (Plaster of Paris) were implanted in epiphyseal and metaphyseal cylindrical bone defects in sheep. The in vivo study was performed to assess the biocompatibility and bone remodeling of four cement formulations. After time periods of 2, 4, and 6 months, the cement samples were clinically and histologically evaluated. Histomorphometrically, the amount of new bone formation, fibrous tissue, and bone marrow and the area of remaining cement were measured. In all specimens, no signs of inflammation were detectable either macroscopically or microscopically. Cements differed mainly in their resorption time. Calcium sulfate was already completely resorbed at 2 months and showed a variable amount of new bone formation and/or fibrous tissue in the original drill hole over all time periods. The two DCPD cements in contrast were degraded to a large amount at 6 months, whereas the apatite was almost unchanged over all time periods. Copyright © 2013. Published by Elsevier B.V.

Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.

PubMed

Lee, Su-Ui; Park, Sang-Joon; Kwak, Han Bok; Oh, Jaemin; Min, Yong Ki; Kim, Seong Hwan

2008-01-01

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone mass and improve bone architecture. In this study, we demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances differentiation and mineralization of osteoblasts in vitro. We found that ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs), inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid in the late stage of osteoblast differentiation. Importantly, ursolic acid was shown to have bone-forming activity in vivo in a mouse calvarial bone formation model. A high proportion of positive immunostaining of BMP-2 was found in the nuclear region of woven bone formed by ursolic acid. These results suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation.

Bio resorbability of the modified hydroxyapatite in Tris-HCL buffer

NASA Astrophysics Data System (ADS)

Golovanova, O. A.; Izmailov, R. R.; Ghyngazov, S. A.

2016-02-01

The solubility of carbonated hydroxyapatite powders and granulated carbonated hydroxyapatite produced from the synovial biofluid model solution has been studied. The kinetic characteristics of dissolution were determined. It was found that the solubility of carbonated hydroxyapatite is higher as compared to that of hydroxyapatite. The impact of the organic matrix on the rate of sample dissolution was revealed. For HA-gelatin composites, as the gelatin concentration grows, the dissolution rate becomes greater, and a sample of 6.0 g / L concentration has higher resorbability. The results of the research can be used to study the kinetics of dissolution and the biocompatibility of ceramic materials for medicine, namely for reconstructive surgery, dentistry, and development of drug delivery systems.

Implantation of Tetrapod-Shaped Granular Artificial Bones or β-Tricalcium Phosphate Granules in a Canine Large Bone-Defect Model

PubMed Central

CHOI, Sungjin; LIU, I-Li; YAMAMOTO, Kenichi; HONNAMI, Muneki; SAKAI, Takamasa; OHBA, Shinsuke; ECHIGO, Ryosuke; SUZUKI, Shigeki; NISHIMURA, Ryouhei; CHUNG, Ung-il; SASAKI, Nobuo; MOCHIZUKI, Manabu

2013-01-01

ABSTRACT We investigated biodegradability and new bone formation after implantation of tetrapod-shaped granular artificial bone (Tetrabone®) or β-tricalcium phosphate granules (β-TCP) in experimental critical-size defects in dogs, which were created through medial and lateral femoral condyles. The defect was packed with Tetrabone® (Tetrabone group) or β-TCP (β-TCP group) or received no implant (control group). Computed tomography (CT) was performed at 0, 4 and 8 weeks after implantation. Micro-CT and histological analysis were conducted to measure the non-osseous tissue rate and the area and distribution of new bone tissue in the defect at 8 weeks after implantation. On CT, β-TCP was gradually resorbed, while Tetrabone® showed minimal resorption at 8 weeks after implantation. On micro-CT, non-osseous tissue rate of the control group was significantly higher compared with the β-TCP and Tetrabone groups (P<0.01), and that of the β-TCP group was significantly higher compared with the Tetrabone group (P<0.05). On histology, area of new bone tissue of the β-TCP group was significantly greater than those of the Tetrabone and control groups (P<0.05), and new bone distribution of the Tetrabone group was significantly greater than those of the β-TCP and control groups (P<0.05). These results indicate differences in biodegradability and connectivity of intergranule pore structure between study samples. In conclusion, Tetrabone® may be superior for the repair of large bone defects in dogs. PMID:24161964

Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

PubMed

Abdelkarem, Hala M; Fadda, Laila H; El-Sayed, Eman M; Radwan, Omyma K

2018-05-04

The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg - 1/day -1 ); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg - 1/day -1 ); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg - 1/day -1 ). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

Periosteal BMP2 activity drives bone graft healing.

PubMed

Chappuis, Vivianne; Gamer, Laura; Cox, Karen; Lowery, Jonathan W; Bosshardt, Dieter D; Rosen, Vicki

2012-10-01

Bone graft incorporation depends on the orchestrated activation of numerous growth factors and cytokines in both the host and the graft. Prominent in this signaling cascade is BMP2. Although BMP2 is dispensable for bone formation, it is required for the initiation of bone repair; thus understanding the cellular mechanisms underlying bone regeneration driven by BMP2 is essential for improving bone graft therapies. In the present study, we assessed the role of Bmp2 in bone graft incorporation using mice in which Bmp2 has been removed from the limb prior to skeletal formation (Bmp2(cKO)). When autograft transplantations were performed in Bmp2cKO mice, callus formation and bone healing were absent. Transplantation of either a vital wild type (WT) bone graft into a Bmp2(cKO) host or a vital Bmp2(cKO) graft into a WT host also resulted in the inhibition of bone graft incorporation. Histological analyses of these transplants show that in the absence of BMP2, periosteal progenitors remain quiescent and healing is not initiated. When we analyzed the expression of Sox9, a marker of chondrogenesis, on the graft surface, we found it significantly reduced when BMP2 was absent in either the graft itself or the host, suggesting that local BMP2 levels drive periosteal cell condensation and subsequent callus cell differentiation. The lack of integrated healing in the absence of BMP2 was not due to the inability of periosteal cells to respond to BMP2. Healing was achieved when grafts were pre-soaked in rhBMP2 protein, indicating that periosteal progenitors remain responsive in the absence of BMP2. In contrast to the requirement for BMP2 in periosteal progenitor activation in vital bone grafts, we found that bone matrix-derived BMP2 does not significantly enhance bone graft incorporation. Taken together, our data show that BMP2 signaling is not essential for the maintenance of periosteal progenitors, but is required for the activation of these progenitors and their subsequent

Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females.

PubMed

Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

2016-01-01

Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. In this cross sectional study postmenopausal females between 50-70 years of age were recruited and divided into two groups: Physically inactive (n=133) performing light physical activity and Physically active (n=34) performing moderate physical activity. Physical activity (in metabolic equivalents), bone mineral density and serum homocysteine levels were assessed. Spearman's rho correlation was applied to observe correlations. Two independent sample t test and Mann Whitney U test were applied to compare groups. P-value ≤ 0.05 was taken statistically significant. Parameters of bone profile were significantly higher and serum homocysteine levels were significantly lower in postmenopausal females performing moderate physical activity as compared to females performing light physical activity. Homocysteine was not significantly related to T-score and Z-score in both groups. Improving physical activity could be beneficial for improving the quality of bone, decreasing fracture risk and decreasing serum homocysteine levels.

The influence of collagen membrane and autogenous bone chips on bone augmentation in the anterior maxilla: a preclinical study.

PubMed

Janner, Simone F M; Bosshardt, Dieter D; Cochran, David L; Chappuis, Vivianne; Huynh-Ba, Guy; Jones, Archie A; Buser, Daniel

2017-11-01

To evaluate the effect of a resorbable collagen membrane and autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) on the healing of buccal dehiscence-type defects. The second incisors and the first premolars were extracted in the maxilla of eight mongrels. Reduced diameter, bone-level implants were placed 5 weeks later. Standardized buccal dehiscence-type defects were created and grafted at implant surgery. According to an allocation algorithm, the graft composition of each of the four maxillary sites was DBBM + membrane (group D + M), autogenous bone chips + DBBM + membrane (group A + D + M), DBBM alone (group D) or autogenous bone chips + DBBM (group A + D). Four animals were sacrificed after 3 weeks of healing and four animals after 12 weeks. Histological and histomorphometric analyses were performed on oro-facial sections. The pattern of bone formation and resorption within the grafted area showed high variability among the same group and healing time. The histomorphometric analysis of the 3-week specimens showed a positive effect of autogenous bone chips on both implant osseointegration and bone formation into the grafted region (P < 0.05). The presence of the collagen membrane correlated with greater bone formation around the DBBM particles and greater bone formation in the grafted region after 12 weeks of healing (P < 0.05). The oro-facial width of the augmented region at the level of the implant shoulder was significantly reduced in cases where damage of the protection splints occurred in the first week of healing (P < 0.05). The addition of autogenous bone chips and the presence of the collagen membrane increased bone formation around DBBM particles. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications

PubMed Central

2015-01-01

Bone remodeling relies on the coordinated functioning of osteoblasts, bone-forming cells, and osteoclasts, bone-resorbing cells. The effects of specific chemical and physical bone features on the osteoclast adhesive apparatus, the sealing zone ring, and their relation to resorption functionality are still not well-understood. We designed and implemented a correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscopy, and atomic force microscopy before, during, and after exposure to osteoclasts. We show that sealing zone rings preferentially develop around surface protrusions, with lateral dimensions of several micrometers, and ∼1 μm height. Direct overlay of sealing zone rings onto resorption pits on the bone surface shows that the rings adapt to pit morphology. The correlative procedure presented here is noninvasive and performed under ambient conditions, without the need for sample labeling. It can potentially be applied to study various aspects of cell-matrix interactions. PMID:26682493

Bone grafts utilized in dentistry: an analysis of patients' preferences.

PubMed

Fernández, Ramón Fuentes; Bucchi, Cristina; Navarro, Pablo; Beltrán, Víctor; Borie, Eduardo

2015-10-20

Many procedures currently require the use of bone grafts to replace or recover bone volume that has been resorbed. However, the patient's opinion and preferences must be taken into account before implementing any treatment. Researchers have focused primarily on assessing the effectiveness of bone grafts rather than on patients' perceptions. Thus, the aim of this study was to explore patients' opinions regarding the different types of bone grafts used in dental treatments. One hundred patients were randomly chosen participated in the study. A standardized survey of 10 questions was used to investigate their opinions regarding the different types of bone grafts used in dental treatments. Descriptive statistics were calculated for the different variables, and absolute frequencies and percentages were used as summary measures. A value of p <0.05 was selected as the threshold for statistical significance. The highest rate of refusal was observed for allografts and xenografts. The grafts with the lowest rates of refusal were autologous grafts (3 %) and alloplastics (2 %). No significant differences were found between the various types of bone grafts in the sociodemographic variables or the refusal/acceptance variable. Similarly, no significant relations were observed between a specific religious affiliation and the acceptance/refusal rates of the various types of graft. Allografts and xenografts elicited the highest refusal rates among the surveyed patients, and autologous bone and alloplastics were the most accepted bone grafts. Moreover, no differences were found in the sociodemographic variables or religious affiliations in terms of the acceptance/refusal rates of the different bone grafts.

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

PubMed

Kim, Beom-Jun; Kwak, Mi Kyung; Ahn, Seong Hee; Kim, Hyeonmok; Lee, Seung Hun; Song, Kee-Ho; Suh, Sunghwan; Kim, Jae Hyeon; Koh, Jung-Min

2017-08-01

Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. To clarify the link between the sympathetic nervous system and the skeleton in humans. Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption. Copyright © 2017 Endocrine Society

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation.

PubMed

Ghanaati, Shahram; Udeabor, Samuel E; Barbeck, Mike; Willershausen, Ines; Kuenzel, Oliver; Sader, Robert A; Kirkpatrick, C James

2013-01-04

Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.

Multiphysics of bone remodeling: A 2D mesoscale activation simulation.

PubMed

Spingarn, C; Wagner, D; Rémond, Y; George, D

2017-01-01

In this work, we present an evolutive trabecular model for bone remodeling based on a boundary detection algorithm accounting for both biology and applied mechanical forces, known to be an important factor in bone evolution. A finite element (FE) numerical model using the Abaqus/Standard® software was used with a UMAT subroutine to solve the governing coupled mechanical-biological non-linear differential equations of the bone evolution model. The simulations present cell activation on a simplified trabeculae configuration organization with trabecular thickness of 200µm. For this activation process, the results confirm that the trabeculae are mainly oriented in the active direction of the principal mechanical stresses and according to the principal applied mechanical load directions. The trabeculae surface activation is clearly identified and can provide understanding of the different bone cell activations in more complex geometries and load conditions.

Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice.

PubMed

Iacobini, Carla; Fantauzzi, Claudia Blasetti; Bedini, Rossella; Pecci, Raffaella; Bartolazzi, Armando; Amadio, Bruno; Pesce, Carlo; Pugliese, Giuseppe; Menini, Stefano

2018-02-09

Galectin-3 is constitutively expressed in bone cells and was recently shown to modulate osteogenic transdifferentiation of vascular smooth muscle cells and atherosclerotic calcification. However, the role of galectin-3 in bone physiology is largely undefined. To address this issue, we analyzed (1) the skeletal features of 1-, 3- and 6-month-old galectin-3 null (Lgals3 -/- ) and wild type (WT) mice and (2) the differentiation and function of osteoblasts and osteoclasts derived from these animals. Long bone phenotype, gene expression profile, and remodeling were investigated by micro-computed tomography, real time-PCR, static and dynamic histomorphometry, and assessment of biochemical markers of bone resorption and formation. Bone competence was also evaluated by biomechanical testing at 3 months. In vitro, the effects of galectin-3 deficiency on bone cell differentiation and function were investigated by assessing (a) gene expression of osteoblast markers, alkaline phosphatase activity, mineralization assay, and WNT/β-catenin signaling (of which galectin-3 is a known regulator) in osteoblasts; and (b) tartrate-resistant acid phosphatase activity and bone resorption activity in osteoclasts. Lgals3 -/- mice revealed a wide range of age-dependent alterations including lower bone formation and higher bone resorption, accelerated age-dependent trabecular bone loss (p < 0.01 vs. WT at 3 months) and reduced bone strength (p < 0.01 vs. WT at 3 months). These abnormalities were accompanied by a steady inflammatory state, as revealed by higher bone expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-6 (p < 0.001 vs. WT at 3 months), increased content of osteal macrophages (p < 0.01 vs. WT at 3 months), and reduced expression of markers of alternative (M2) macrophage activation. Lgals3 -/- osteoblasts and osteoclasts showed impaired terminal differentiation, reduced mineralization capacity (p < 0.01 vs. WT cells) and

Bone regeneration with biomaterials and active molecules delivery.

PubMed

D' Este, Matteo; Eglin, David; Alini, Mauro; Kyllonen, Laura

2015-01-01

The combination of biomaterials and drug delivery strategies is a promising avenue towards improved synthetic bone substitutes. With the delivery of active species biomaterials can be provided with the bioactivity they still lack for improved bone regeneration. Recently, a lot of research efforts have been put towards this direction. Biomaterials for bone regeneration have been supplemented with small or biological molecules for improved osteoprogenitor cell recruitment, osteoinductivity, anabolic or angiogenic response, regulation of bone metabolism and others. The scope of this review is to summarize the most recent results in this field.

The regulation and regulatory role of collagenase in bone

NASA Technical Reports Server (NTRS)

Partridge, N. C.; Walling, H. W.; Bloch, S. R.; Omura, T. H.; Chan, P. T.; Pearman, A. T.; Chou, W. Y.

1996-01-01

Interstitial collagenase plays an important role in both the normal and pathological remodeling of collagenous extracellular matrices, including skeletal tissues. The enzyme is a member of the family of matrix metalloproteinases. Only one rodent interstitial collagenase has been found but there are two human enzymes, human collagenase-1 and -3, the latter being the homologue of the rat enzyme. In developing rat and mouse bone, collagenase is expressed by hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat calvariae show greater amounts of collagenase transcripts late in differentiation. These levels can be regulated by parathyroid hormone (PTH), retinoic acid, and insulin-like growth factors, as well as the degree of matrix mineralization. Much of the work on collagenase in bone has been derived from studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents stimulate these cells to produce collagenase mRNA and protein, with PTH being the most potent stimulator. Determination of secreted levels of collagenase has been difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess a scavenger receptor that removes the enzyme from the extracellular space, internalizes and degrades it, thus imposing another level of control. PTH can also regulate the abundance of the receptor as well as the expression and synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to involve the cAMP pathway as well as a primary response gene, possibly Fos, which then contributes to induction of the collagenase gene. The rat collagenase gene contains an activator protein-1 sequence that is necessary for basal expression, but other promoter regions may also participate in PTH regulation. Thus, there are many levels of regulation of collagenase in bone perhaps constraining what would otherwise be a rampant enzyme.

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice.

PubMed

Pereira, M; Jeyabalan, J; Jørgensen, C S; Hopkinson, M; Al-Jazzar, A; Roux, J P; Chavassieux, P; Orriss, I R; Cleasby, M E; Chenu, C

2015-12-01

Some anti-diabetic therapies can have adverse effects on bone health and increase fracture risk. In this study, we tested the skeletal effects of chronic administration of two Glucagon-like peptide-1 receptor agonists (GLP-1RA), increasingly used for type 2 diabetes treatment, in a model of osteoporosis associated bone loss and examined the expression and activation of GLP-1R in bone cells. Mice were ovariectomised (OVX) to induce bone loss and four weeks later they were treated with Liraglutide (LIR) 0.3mg/kg/day, Exenatide (Ex-4) 10 μg/kg/day or saline for four weeks. Mice were injected with calcein and alizarin red prior to euthanasia, to label bone-mineralising surfaces. Tibial micro-architecture was determined by micro-CT and bone formation and resorption parameters measured by histomorphometric analysis. Serum was collected to measure calcitonin and sclerostin levels, inhibitors of bone resorption and formation, respectively. GLP-1R mRNA and protein expression were evaluated in the bone, bone marrow and bone cells using RT-PCR and immunohistochemistry. Primary osteoclasts and osteoblasts were cultured to evaluate the effect of GLP-1RA on bone resorption and formation in vitro. GLP-1RA significantly increased trabecular bone mass, connectivity and structure parameters but had no effect on cortical bone. There was no effect of GLP-1RA on bone formation in vivo but an increase in osteoclast number and osteoclast surfaces was observed with Ex-4. GLP-1R was expressed in bone marrow cells, primary osteoclasts and osteoblasts and in late osteocytic cell line. Both Ex-4 and LIR stimulated osteoclastic differentiation in vitro but slightly reduced the area resorbed per osteoclast. They had no effect on bone nodule formation in vitro. Serum calcitonin levels were increased and sclerostin levels decreased by Ex-4 but not by LIR. Thus, GLP-1RA can have beneficial effects on bone and the expression of GLP-1R in bone cells may imply that these effects are exerted directly

Galectin-3 as a novel regulator of osteoblast-osteoclast interaction and bone homeostasis.

PubMed

Simon, Dominic; Derer, Anja; Andes, Fabian T; Lezuo, Patrick; Bozec, Aline; Schett, Georg; Herrmann, Martin; Harre, Ulrike

2017-12-01

Bone tissue undergoes permanent and lifelong remodeling with a concerted action of bone-building osteoblasts and bone-resorbing osteoclasts. A precise cooperation between those two cell types is critical in the complex process of bone renewal. Galectin-3 is a member of the β-galactoside-binding lectin family playing multiple roles in cell growth, differentiation and aggregation. As it has been described to be expressed in bone, galectin-3 might influence bone homeostasis by regulating the function and/or interplay of osteoblasts and osteoclasts. Here, we investigated the role of galectin-3 in osteoclastogenesis and osteoblast-osteoclast interactions. Bone histomorphometric analysis and μCT measurements revealed a decreased trabecular bone volume and an increased osteoclast number in 12weeks old male galectin-3 knockout mice compared to wildtype littermates. Galectin-3 deficient bone marrow cells displayed a higher osteoclastogenic capacity in ex vivo differentiation assays, associated with elevated TRAF6 mRNA levels, suggesting an intrinsic inhibition of osteoclastogenesis by galectin-3 interfering with RANKL-mediated signaling. Furthermore, the addition of extracellular galectin-3 to murine or human osteoclastogenesis assays inhibited osteoclast formation and osteoclast numbers were higher in co-culture assays with galectin-3 deficient osteoblasts. In conclusion, our data suggest the secretion of galectin-3 as a novel mechanism for osteoblasts to control osteoclastogenesis and to maintain trabecular bone homeostasis independently of the RANKL/OPG-axis. Copyright © 2017 Elsevier Inc. All rights reserved.

The protocol for the isolation and cryopreservation of osteoclast precursors from mouse bone marrow and spleen.

PubMed

Boraschi-Diaz, Iris; Komarova, Svetlana V

2016-01-01

Osteoclasts are responsible for physiological bone remodeling as well as pathological bone destruction in osteoporosis, periodontitis and rheumatoid arthritis, and thus represent a pharmacological target for drug development. We aimed to characterize and compare the cytokine-induced osteoclastogenesis of bone marrow and spleen precursors. Established protocols used to generate osteoclasts from bone marrow were modified to examine osteoclastogenesis of the spleen cells of healthy mice. Osteoclast formation was successfully induced from spleen precursors using receptor activator of nuclear factor κB ligand (50 ng/ml) and macrophage colony stimulating factor (50 ng/ml). Compared to bone marrow cultures, differentiation from spleen required a longer cultivation time (9 days for spleen, as compared to 5 days for marrow cultures) and a higher plating density of non-adherent cells (75,000/cm(2) for spleen, as compared to 50,000/cm(2) for bone marrow). Osteoclasts generated from spleen precursors expressed osteoclast marker genes calcitonin receptor, cathepsin K and matrix metalloproteinase 9 and were capable of resorbing hydroxyapatite. The differentiation capacity of spleen and bone marrow precursors was comparable for BALB/c, C57BL/6 and FVB mice. We also developed and tested a cryopreservation protocol for the osteoclast precursors. While 70-80 % of cells were lost during the first week of freezing, during the subsequent 5 weeks the losses were within 2-5 % per week. Osteoclastogenesis from the recovered bone marrow precursors was successful up to 5 weeks after freezing. Spleen precursors retained their osteoclastogenic capacity for 1 week after freezing, but not thereafter. The described protocol is useful for the studies of genetically modified animals as well as for screening new osteoclast-targeting therapeutics.

Purification processes of xenogeneic bone substitutes and their impact on tissue reactions and regeneration.

PubMed

Perić Kačarević, Zeljka; Kavehei, Faraz; Houshmand, Alireza; Franke, Jörg; Smeets, Ralf; Rimashevskiy, Denis; Wenisch, Sabine; Schnettler, Reinhard; Jung, Ole; Barbeck, Mike

2018-04-01

Xenogeneic bone substitute materials are widely used in oral implantology. Prior to their clinical use, purification of the former bone tissue has to be conducted to ensure the removal of immunogenic components and pathogens. Different physicochemical methods are applied for purification of the donor tissue, and temperature treatment is one of these methods. Differences in these methods and especially the application of different temperatures for purification may lead to different material characteristics, which may influence the tissue reactions to these materials and the related (bone) healing process. However, little is known about the different material characteristics and their influences on the healing process. Thus, the aim of this mini-review is to summarize the preparation processes and the related material characteristics, safety aspects, tissue reactions, resorbability and preclinical and clinical data of two widely used xenogeneic bone substitutes that mainly differ in the temperature treatment: sintered (cerabone ® ) and non-sintered (Bio-Oss ® ) bovine-bone materials. Based on the summarized data from the literature, a connection between the material-induced tissue reactions and the consequences for the healing processes are presented with the aim of translation into their clinical application.

Limb reconstruction with vascularized fibular grafts after bone tumor resection.

PubMed

Brown, K L

1991-01-01

Limb-salvage operations are being used with increasing frequency for patients with malignant bone tumors. For children, when a biologic reconstruction is desired, the choice is often between conventional and vascularized fibular grafts. An experimental study was performed in dogs to compare the two types of fibular grafts for bridging segmental defects in the radius and ulna. Twenty-six adult dogs were divided into two groups and studied at intervals of two, three, four, six, and 12 months after transplantation. The conventional grafts healed by creeping substitution i.e., they were first partially resorbed before new bone was laid down. In contrast, the vascularized fibulae maintained their normal structure and hypertrophied by subperiosteal new bone formation. The conventional fibulae eventually hypertrophied but much later than the vascularized grafts. The vascularized grafts were stronger at four and six months. Between six and 12 months, both grafts remodeled to resemble the size and shape of the forearm bones they were replacing. These experimental results have influenced the treatment of patients. Vascularized fibular grafts are ideal for diaphyseal defects greater than 10 cm long, especially in very young children, a poorly vascularized bed, or when bone healing is delayed by chemotherapeutic agents. To maximize hypertrophy, an external fixator is used to immobilize the graft rather than a plate, which acts as a stress shield.

[Effects of calcitonin on osteoclast].

PubMed

Suzuki, H; Takahashi, N

2001-09-01

Osteoclasts are cells that resorb bone, and calcitonin potently inhibits this bone resorptive activity. While calcitonin does not affect primary osteoclastic differentiation, it does manifest an inhibitory effect on the bone resorptive activity of osteoclasts. It is believed that calcitonin, acting upon calcitonin receptors and through PKA and PKC signal transduction pathways, destroys cytoskeleton components such as podosomes. The "escape phenomenon" seen with osteoclasts is a known issue occurring with the use of calcitonin, and is also believed to arise due to calcitonin receptors and the PKA and PKC signal transduction pathways.

Bone remodeling in onlay beta-tricalcium phosphate and coral grafts to rat calvaria: microcomputerized tomography analysis.

PubMed

Anavi, Yakir; Avishai, Gal; Calderon, Shlomo; Allon, Dror M

2011-08-01

This study was conducted to establish the efficiency of microcomputerized tomography (micro-CT) in detection of trabecular bone remodeling of onlay grafts in a rodent calvaria model, and to compare bone remodeling after onlay grafts with beta-tricalcium phosphate (TCP) or coral calcium carbonate. Ten rats received calvarial onlay blocks-5 with TCP and 5 with coral calcium carbonate. The grafts were fixed with a titanium miniplate screw and were covered with a collagen resorbable membrane. Three months after surgery, the calvaria were segmented, and a serial 3-dimensional micro-CT scan of the calvarium and grafted bone block at 16-micrometer resolution was performed. Image analysis software was used to calculate the percentage of newly formed bone from the total block size. Newly formed bone was present adjacent to the calvarium and screw in all specimens. The mean area of newly formed bone of the total block size ranged from 34.67%-38.34% in the TCP blocks, and from 32.41%-34.72% in the coral blocks. In the TCP blocks, bone remodeling was found to be slightly higher than in the coral blocks. Micro-CT appears to be a precise, reproducible, specimen-nondestructive method of analysis of bone formation in onlay block grafts to rat calvaria.

From Milk to Bones, Moving Calcium Through the Body: Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

2002-01-01

Did you know that when astronauts are in space, their height increases about two inches? This happens because the weightlessness of space allows the spine, usually compressed in Earth's gravity, to expand. While this change is relatively harmless, other more serious things can happen with extended stays in weightlessness, notably bone loss. From previous experiments, scientists have observed that astronauts lose bone mass at a rate of about one percent per month during flight. Scientists know that bone is a dynamic tissue - continually being made and repaired by specialized bone cells throughout life. Certain cells produce new bone, while other cells are responsible for removing and replacing old bone. Research on the mechanisms of bone metabolism and the effects of space flight on its formation and repair are part of the exciting studies that will be performed during STS-107. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. Ninety-nine percent of calcium in the body is stored in the skeleton. However, calcium may be released, or resorbed, from bone to provide for other tissues when you are not eating. To better understand how and why weightlessness induces bone loss, astronauts will participate in a study of calcium kinetics - that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Intra-oral soft tissue expansion and volume stability of onlay bone grafts.

PubMed

Abrahamsson, Peter

2011-01-01

Insufficient regeneration of missing bone and soft-tissue may present aesthetic or functional problems in patients indicated for dental implant surgery. Several techniques such as bone grafts, bone substitutes and guided tissue regeneration (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft-tissue coverage of grafted bone and titanium-mesh is important to avoid exposure which may result in loss of the bone graft. The general aim of this thesis was to evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue--creating a surplus of soft tissue-- in preparation for onlay bone grafting. An experimental rabbit model was used in studies (I), (II) and (III). In (I) an osmotic soft-tissue expander was placed bilaterally on the lateral wall of the mandible via an extra-oral approach. After two weeks of expansion the rabbits were killed and specimens were collected for histology. No inflammatory reaction and no resorbtion of the cortical bone occured. The periosteum was expanded and new bone formation was seen in the edges of the expander. In (II) and (III) the expander was placed under the periosteum in the same way as in (I): bilaterally in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of expansion the expander was identified and removed. In (II) particulated bone was placed at the recipient site protected by a titanium mesh in one site and a bio-resorbable mesh on the other site. In (III), DBBM particles and bone particles collected from the lateral border of the mandible separated by a collagen membrane was placed at the recipient site. The graft was protected by a pre-bent titanium mesh covered by a collagen membrane. After a healing period of 3 months specimens were collected for histological and SEM examination. New bone was growing in direct contact with the titanium mesh and bio resorbable mesh. The newly formed bone had the same calcium content as the mature bone in the base of the

Optimization of implant/bone attachment: The effects of implant surface porosity, bioactive ceramic coatings, and delivery of adsorbed growth factors

NASA Astrophysics Data System (ADS)

Melican, Mora Carolynne

Various surface treatments and coating materials have been tested for use on metal alloy orthopaedic implants. Their purpose has been to enhance the bioactivity of the implant surfaces, and thus to increase the rate and degree of bony attachment in vivo in an attempt to hasten recovery time, increase implant service lifetime, and lessen pain associated with loosened orthopaedic implants. A series of in vivo and in vitro studies were performed to determine the influence of different implant surfaces including porous metal surfaces with varied porosity with depth, resorbable and non-resorbable plasma-sprayed hydroxyapatite (HA) coatings, and finally HA coatings with an adsorbed layer of human recombinant bone morphogenetic protein (rhBMP-2), an osteoinductive protein. Textured as-cast metal surfaces produced by investment casting in three dimensionally printed ceramic molds have exhibited superior bony ingrowth and attachment. Plasma-sprayed HA coatings have been shown to be appropriate substrates for osteoblast proliferation (particularly on highly crystalline HA) and stem cell proliferation (particularly on less crystalline HA). Less crystalline HA coatings have shown promise as delivery systems for different levels of rhBMP-2. The osteoinductive protein has been shown to remain active after delivery to the system, and was most effective when delivered in concentrations ranging from 30 to 50 ng/ml. Combinations of these surface treatments for metal implant surfaces warrant further investigation.

Stimulation of Bone Formation in Cortical Bone of Mice Treated with a Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-binding Peptide That Possesses Osteoclastogenesis Inhibitory Activity

PubMed Central

Furuya, Yuriko; Inagaki, Atsushi; Khan, Masud; Mori, Kaoru; Penninger, Josef M.; Nakamura, Midori; Udagawa, Nobuyuki; Aoki, Kazuhiro; Ohya, Keiichi; Uchida, Kohji; Yasuda, Hisataka

2013-01-01

To date, parathyroid hormone is the only clinically available bone anabolic drug. The major difficulty in the development of such drugs is the lack of clarification of the mechanisms regulating osteoblast differentiation and bone formation. Here, we report a peptide (W9) known to abrogate osteoclast differentiation in vivo via blocking receptor activator of nuclear factor-κB ligand (RANKL)-RANK signaling that we surprisingly found exhibits a bone anabolic effect in vivo. Subcutaneous administration of W9 three times/day for 5 days significantly augmented bone mineral density in mouse cortical bone. Histomorphometric analysis showed a decrease in osteoclastogenesis in the distal femoral metaphysis and a significant increase in bone formation in the femoral diaphysis. Our findings suggest that W9 exerts bone anabolic activity. To clarify the mechanisms involved in this activity, we investigated the effects of W9 on osteoblast differentiation/mineralization in MC3T3-E1 (E1) cells. W9 markedly increased alkaline phosphatase (a marker enzyme of osteoblasts) activity and mineralization as shown by alizarin red staining. Gene expression of several osteogenesis-related factors was increased in W9-treated E1 cells. Addition of W9 activated p38 MAPK and Smad1/5/8 in E1 cells, and W9 showed osteogenesis stimulatory activity synergistically with BMP-2 in vitro and ectopic bone formation. Knockdown of RANKL expression in E1 cells reduced the effect of W9. Furthermore, W9 showed a weak effect on RANKL-deficient osteoblasts in alkaline phosphatase assay. Taken together, our findings suggest that this peptide may be useful for the treatment of bone diseases, and W9 achieves its bone anabolic activity through RANKL on osteoblasts accompanied by production of several autocrine factors. PMID:23319583

Effects of Gymnastics Activities on Bone Accrual during Growth: A Systematic Review

PubMed Central

Jürimäe, Jaak; Gruodyte-Raciene, Rita; Baxter-Jones, Adam D. G.

2018-01-01

The amount of bone gained during childhood and adolescence impacts greatly on lifetime skeletal health. The purpose of this review is to summarize current evidence of the effects of gymnastics activities on bone mineral accrual during growth and to describe possible factors that influence bone mineral gains. The PubMed and SportDiscus databases were searched, and a total of 24 articles met the selection criteria and were included in this review. Artistic and rhythmic gymnasts presented higher bone mineral density and content values compared to untrained controls, despite possible negative effects associated with hormonal levels, dietary restrictions and body fat. The results suggest that gymnasts had similar bone turnover values compared to untrained controls. High-intensity mechanical loading of gymnastics activity appears to increase bone development and counterbalance negative effects, such as later pubertal development, lower body fat mass and lower hormone levels. In conclusion, gymnasts present higher bone mineral values in comparison with untrained controls. The osteogenic effect of gymnastics athletic activity has a positive influence on bone mineral accrual and overcomes the possible negative influence of high athletic activity that may cause negative energy balance and low body fat mass which are associated with lower bone accrual. Key points Children and adolescent gymnasts present higher bone mineral density and content values compared to untrained controls, despite a variety of possible negative factors. Gymnastics activity with high-impact mechanical loading appears to be especially osteogenic to achieve maximum possible peak bone accrual during growth and maturation. Skeletal benefits of gymnastics activity in childhood are maintained for several years after retirement from gymnastics trainings in young adulthood. PMID:29769826

The Expression of Fn14 via Mechanical Stress-activated JNK Contributes to Apoptosis Induction in Osteoblasts*

PubMed Central

Matsui, Hiroyuki; Fukuno, Naoto; Kanda, Yoshiaki; Kantoh, Yusuke; Chida, Toko; Nagaura, Yuko; Suzuki, Osamu; Nishitoh, Hideki; Takeda, Kohsuke; Ichijo, Hidenori; Sawada, Yasuhiro; Sasaki, Keiichi; Kobayashi, Takayasu; Tamura, Shinri

2014-01-01

Bone mass is maintained by the balance between the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. It is well known that adequate mechanical stress is essential for the maintenance of bone mass, whereas excess mechanical stress induces bone resorption. However, it has not been clarified how osteoblasts respond to different magnitudes of mechanical stress. Here we report that large-magnitude (12%) cyclic stretch induced Ca2+ influx, which activated reactive oxygen species generation in MC3T3-E1 osteoblasts. Reactive oxygen species then activated the ASK1-JNK/p38 pathways. The activated JNK led to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, the ASK1-p38 pathway induced expression of the monocyte chemoattractant protein 3 (MCP-3) gene, which promoted chemotaxis of preosteoclasts. In contrast, the ERK pathway was activated by small-magnitude stretching (1%) and induced expression of two osteogenic genes, collagen Ia (Col1a) and osteopontin (OPN). Moreover, activated JNK suppressed Col1a and OPN induction in large-magnitude mechanical stretch-loaded cells. The enhanced expression of Fn14 and MCP-3 by 12% stretch and the enhanced expression of Col1a and OPN by 1% stretch were also observed in mouse primary osteoblasts. These results suggest that differences in the response of osteoblasts to varying magnitudes of mechanical stress play a key role in switching the mode of bone metabolism between formation and resorption. PMID:24446436

Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells

NASA Technical Reports Server (NTRS)

McAllister, T. N.; Du, T.; Frangos, J. A.

2000-01-01

Bone is a porous tissue that is continuously perfused by interstitial fluid. Fluid flow, driven by both vascular pressure and mechanical loading, may generate significant shear stresses through the canaliculi as well as along the bone lining at the endosteal surface. Both osteoblasts and osteocytes produce signaling factors such as prostaglandins and nitric in response to fluid shear stress (FSS); however, these humoral agents appear to have more profound affects on osteoclast activity at the endosteal surface. We hypothesized that osteoclasts and preosteoclasts may also be mechanosensitive and that osteoclast-mediated autocrine signaling may be important in bone remodeling. In this study, we investigated the effect of FSS on nitric oxide (NO), prostaglandin E(2) (PGE(2)), and prostacyclin (PGI(2)) release by neonatal rat bone marrow-derived preosteoclast-like cells. These cells were tartrate-resistant acid phosphatase (TRAP) positive, weakly nonspecific esterase (NSE) positive, and capable of fusing into calcitonin-responsive, bone-resorbing, multinucleated cells. Bone marrow-derived preosteoclast-like cells exposed for 6 h to a well-defined FSS of 16 dynes/cm(2) produced NO at a rate of 7.5 nmol/mg protein/h, which was 10-fold that of static controls. This response was completely abolished by 100 microM N(G)-amino-L-arginine (L-NAA). Flow also stimulated PGE(2) production (3.9 microg/mg protein/h) and PGI(2) production (220 pg/mg protein/h). L-NAA attenuated flow-induced PGE(2) production by 30%, suggesting that NO may partially modulate PGE(2) production. This is the first report demonstrating that marrow derived cells are sensitive to FSS and that autocrine signaling in these cells may play an important role in load-induced remodeling and signal transduction in bone. Copyright 2000 Academic Press.

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

PubMed Central

2013-01-01

Background Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting. PMID:23286366

Effects of Gymnastics Activities on Bone Accrual during Growth: A Systematic Review.

PubMed

Jürimäe, Jaak; Gruodyte-Raciene, Rita; Baxter-Jones, Adam D G

2018-06-01

The amount of bone gained during childhood and adolescence impacts greatly on lifetime skeletal health. The purpose of this review is to summarize current evidence of the effects of gymnastics activities on bone mineral accrual during growth and to describe possible factors that influence bone mineral gains. The PubMed and SportDiscus databases were searched, and a total of 24 articles met the selection criteria and were included in this review. Artistic and rhythmic gymnasts presented higher bone mineral density and content values compared to untrained controls, despite possible negative effects associated with hormonal levels, dietary restrictions and body fat. The results suggest that gymnasts had similar bone turnover values compared to untrained controls. High-intensity mechanical loading of gymnastics activity appears to increase bone development and counterbalance negative effects, such as later pubertal development, lower body fat mass and lower hormone levels. In conclusion, gymnasts present higher bone mineral values in comparison with untrained controls. The osteogenic effect of gymnastics athletic activity has a positive influence on bone mineral accrual and overcomes the possible negative influence of high athletic activity that may cause negative energy balance and low body fat mass which are associated with lower bone accrual.

3D Powder Printed Bioglass and β-Tricalcium Phosphate Bone Scaffolds.

PubMed

Seidenstuecker, Michael; Kerr, Laura; Bernstein, Anke; Mayr, Hermann O; Suedkamp, Norbert P; Gadow, Rainer; Krieg, Peter; Hernandez Latorre, Sergio; Thomann, Ralf; Syrowatka, Frank; Esslinger, Steffen

2017-12-22

The use of both bioglass (BG) and β tricalcium phosphate (β-TCP) for bone replacement applications has been studied extensively due to the materials' high biocompatibility and ability to resorb when implanted in the body. 3D printing has been explored as a fast and versatile technique for the fabrication of porous bone scaffolds. This project investigates the effects of using different combinations of a composite BG and β-TCP powder for 3D printing of porous bone scaffolds. Porous 3D powder printed bone scaffolds of BG, β-TCP, 50/50 BG/β-TCP and 70/30 BG/β-TCP compositions were subject to a variety of characterization and biocompatibility tests. The porosity characteristics, surface roughness, mechanical strength, viability for cell proliferation, material cytotoxicity and in vitro bioactivity were assessed. The results show that the scaffolds can support osteoblast-like MG-63 cells growth both on the surface of and within the scaffold material and do not show alarming cytotoxicity; the porosity and surface characteristics of the scaffolds are appropriate. Of the two tested composite materials, the 70/30 BG/β-TCP scaffold proved to be superior in terms of biocompatibility and mechanical strength. The mechanical strength of the scaffolds makes them unsuitable for load bearing applications. However, they can be useful for other applications such as bone fillers.

Monocytes Induce STAT3 Activation in Human Mesenchymal Stem Cells to Promote Osteoblast Formation

PubMed Central

Nicolaidou, Vicky; Wong, Mei Mei; Redpath, Andia N.; Ersek, Adel; Baban, Dilair F.; Williams, Lynn M.; Cope, Andrew P.; Horwood, Nicole J.

2012-01-01

A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair. PMID:22802946

Two dimensional alveolar ridge augmentation using particulate hydroxyapatite and collagen membrane: A case report

PubMed Central

Singh, Aparna; Daing, Anika; Anand, Vishal; Dixit, Jaya

2014-01-01

Background Ridge augmentation procedures require bone regeneration outside of the existing bony walls or housing and are therefore often considered to be the most challenging surgical procedures. The bony deficiencies can be managed with GBR techniques involving bone grafting material and membrane while vertical augmentation may require the use of space-creating support mechanisms. Non-degradable membranes have been used for ridge augmentation with encouraging results however; requirement of second surgery for its removal and associated infection on exposure may compromise the desired results. These problems can be overcome by employing resorbable collagen membranes. Different bone graft materials are also used in combination with resorbable membranes, for prevention of membrane collapse and maintenance of space, as they lack sufficient rigidity. Particulate hydroxyapatite bone graft may be better alternative, because it treats the underlying bone defect to restore the natural support of the tissue architecture. Moreover, its use avoids potential donor site complications associated with autogenous block grafts. Method Patient described in this report presented with missing right maxillary incisor with ridge deficiency. A treatment approach involving localised ridge augmentation with particulate hydroxyapatite and collagen membrane was used. Result Six month post-operative periapical radiograph demonstrated a significant vertical bone fill. Conclusion The clinical and radiographic findings of the present case suggests that HA in conjunction with a resorbable collagen membrane may be an acceptable alternative to the autogenous block graft and non-resorbable membrane in the treatment of compromised alveolar ridge deficiencies. PMID:25737935

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

PubMed Central

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

PubMed

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

Lower Eyelid Retraction Repair with Resorbable Polydioxanone Implants.

PubMed

Alsuhaibani, Adel H; Al-Faky, Yasser H

2016-01-01

To report a unique technique to repair lower eyelid retraction using resorbable polydioxanone implants. This was a retrospective, consecutive, nonrandomized interventional case series. Patients with lower eyelid retraction after trauma repaired facial fracture, thyroid eye disease, lower eyelid blepharoplasty, and long-standing facial palsy were treated with middle lamellar spacer using absorbable polydioxanone implant. All patients were recruited from the King Abdulaziz University Hospital, Riyadh, Saudi Arabia. Only patients with minimum follow-up of 12 months were included in the study. Eight patients (4 males and 4 females) underwent lower eyelid retraction repair using absorbable polydioxanone implant. The mean age was 43 years (range, 23-63 years). All patients noted improved ocular surface symptoms. The improvement in eyelid retraction ranged from 1.5 to 4 mm with an average of 2.7 mm postoperatively. The implant was well tolerated with no major complications. Several options for spacer materials are available. Absorbable polydioxanone implants seem to be an effective middle lamellar spacer that is a good alternative for repairing middle lamella related lower eyelid retraction and lower eyelid support.

Physical activity alters limb bone structure but not entheseal morphology.

PubMed

Wallace, Ian J; Winchester, Julia M; Su, Anne; Boyer, Doug M; Konow, Nicolai

2017-06-01

Studies of ancient human skeletal remains frequently proceed from the assumption that individuals with robust limb bones and/or rugose, hypertrophic entheses can be inferred to have been highly physically active during life. Here, we experimentally test this assumption by measuring the effects of exercise on limb bone structure and entheseal morphology in turkeys. Growing females were either treated with a treadmill-running regimen for 10 weeks or served as controls. After the experiment, femoral cortical and trabecular bone structure were quantified with μCT in the mid-diaphysis and distal epiphysis, respectively, and entheseal morphology was quantified in the lateral epicondyle. The results indicate that elevated levels of physical activity affect limb bone structure but not entheseal morphology. Specifically, animals subjected to exercise displayed enhanced diaphyseal and trabecular bone architecture relative to controls, but no significant difference was detected between experimental groups in entheseal surface topography. These findings suggest that diaphyseal and trabecular structure are more reliable proxies than entheseal morphology for inferring ancient human physical activity levels from skeletal remains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bone cutting capacity and osseointegration of surface-treated orthodontic mini-implants.

PubMed

Kim, Ho-Young; Kim, Sang-Cheol

2016-11-01

The objective of the study was to evaluate the practicality and the validity of different surface treatments of self-drilling orthodontic mini-implants (OMIs) by comparing bone cutting capacity and osseointegration. Self-drilling OMIs were surface-treated in three ways: Acid etched (Etched), resorbable blasting media (RBM), partially resorbabla balsting media (Hybrid). We compared the bone cutting capacity by measuring insertion depths into artificial bone (polyurethane foam). To compare osseointegration, OMIs were placed in the tibia of 25 rabbits and the removal torque value was measured at 1, 2, 4, and 8 weeks after placement. The specimens were analyzed by optical microscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The bone cutting capacity of the etched and hybrid group was lower than the machined (control) group, and was most inhibited in the RBM group ( p < 0.05). At 4 weeks, the removal torque in the machined group was significantly decreased ( p < 0.05), but was increased in the etched group ( p < 0.05). In the hybrid group, the removal torque significantly increased at 2 weeks, and was the highest among all measured values at 8 weeks ( p < 0.05). The infiltration of bone-like tissue surface was evaluated by SEM, and calcium and phosphorus were detected via EDS only in the hybrid group. Partial RBM surface treatment (hybrid type in this study) produced the most stable self-drilling OMIs, without a corresponding reduction in bone cutting capacity.

Bone cutting capacity and osseointegration of surface-treated orthodontic mini-implants

PubMed Central

Kim, Ho-Young

2016-01-01

Objective The objective of the study was to evaluate the practicality and the validity of different surface treatments of self-drilling orthodontic mini-implants (OMIs) by comparing bone cutting capacity and osseointegration. Methods Self-drilling OMIs were surface-treated in three ways: Acid etched (Etched), resorbable blasting media (RBM), partially resorbabla balsting media (Hybrid). We compared the bone cutting capacity by measuring insertion depths into artificial bone (polyurethane foam). To compare osseointegration, OMIs were placed in the tibia of 25 rabbits and the removal torque value was measured at 1, 2, 4, and 8 weeks after placement. The specimens were analyzed by optical microscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). Results The bone cutting capacity of the etched and hybrid group was lower than the machined (control) group, and was most inhibited in the RBM group (p < 0.05). At 4 weeks, the removal torque in the machined group was significantly decreased (p < 0.05), but was increased in the etched group (p < 0.05). In the hybrid group, the removal torque significantly increased at 2 weeks, and was the highest among all measured values at 8 weeks (p < 0.05). The infiltration of bone-like tissue surface was evaluated by SEM, and calcium and phosphorus were detected via EDS only in the hybrid group. Conclusions Partial RBM surface treatment (hybrid type in this study) produced the most stable self-drilling OMIs, without a corresponding reduction in bone cutting capacity. PMID:27896213

MiR-142-5p promotes bone repair by maintaining osteoblast activity.

PubMed

Tu, Manli; Tang, Juanjuan; He, Hongbo; Cheng, Peng; Chen, Chao

2017-05-01

MicroRNAs play important roles in regulating bone regeneration and remodeling. However, the pathophysiological roles of microRNAs in bone repair remain unclear. Here we identify a significant upregulation of miR-142-5p correlated with active osteoblastogenesis during the bone healing process. In vitro, miR-142-5p promoted osteoblast activity and matrix mineralization by targeting the gene encoding WW-domain-containing E3 ubiquitin protein ligase 1. We also found that the expression of miR-142-5p in the callus of aged mice was lower than that in the callus of young mice and directly correlated with the age-related delay in bone healing. Furthermore, treatment with agomir-142-5p in the fracture areas stimulated osteoblast activity which repaired the bone fractures in aged mice. Thus, our study revealed that miR-142-5p plays a crucial role in healing fractures by maintaining osteoblast activity, and provided a new molecular target therapeutic strategy for bone healing.

TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

PubMed Central

Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and confirmed by western blot and quantitative RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank-shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank expression was downregulated by 90% by Tank-shRNA, which is confirmed by western blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts was increased by 176% compared with WT cells, as shown by wheat germ agglutinin (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of Tank-silenced mature osteoclast is also increased. However, acid production of Tank-knockdown cells was not changed compared with control cells. IκBα phosphorylation is increased in tank-silenced cells, indicating that TANK may negatively regulate NF-κB activity in osteoclast. In conclusion, Tank, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NF-κB activity and c-FLIP expression. Tank enrolls itself in a negative feedback loop in bone resorption. These results may provide means for therapeutic intervention in diseases of excessive bone resorption. PMID:23139637

TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function.

PubMed

Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and confirmed by western blot and quantitative RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank-shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank expression was downregulated by 90% by Tank-shRNA, which is confirmed by western blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts was increased by 176% compared with WT cells, as shown by wheat germ agglutinin (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of Tank-silenced mature osteoclast is also increased. However, acid production of Tank-knockdown cells was not changed compared with control cells. IκBα phosphorylation is increased in tank-silenced cells, indicating that TANK may negatively regulate NF-κB activity in osteoclast. In conclusion, Tank, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NF-κB activity and c-FLIP expression. Tank enrolls itself in a negative feedback loop in bone resorption. These results may provide means for therapeutic intervention in diseases of excessive bone resorption.

Quantifying leisure physical activity and its relation to bone density and strength.

PubMed

Shedd, Kristine M; Hanson, Kathy B; Alekel, D Lee; Schiferl, Daniel J; Hanson, Laura N; Van Loan, Marta D

2007-12-01

Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength-strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss.

Fixation of fractures of the condylar head of the mandible with a new magnesium-alloy biodegradable cannulated headless bone screw.

PubMed

Leonhardt, H; Franke, A; McLeod, N M H; Lauer, G; Nowak, A

2017-07-01

It is difficult to fix fractures of the condylar head of the mandible. Several techniques have been described which show satisfactory outcomes, but stability can be questionable, and some can cause irritation of the soft tissues. We describe a technique and first results of treating such fractures with resorbable magnesium-based headless bone screws (Magnezix ® 2.7mm CS; Syntellix AG, Hanover, Germany). Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Transosseous fixation of pediatric displaced mandibular fractures with polyglactin resorbable suture--a simplified technique.

PubMed

Chandan, Sanjay; Halli, Rajshekhar; Joshi, Samir; Chhabaria, Gaurav; Setiya, Sneha

2013-11-01

Management of pediatric mandibular fractures presents a unique challenge to surgeons in terms of its numerous variations compared to adults. Both conservative and open methods have been advocated with their obvious limitations and complications. However, conservative modalities may not be possible in grossly displaced fractures, which necessitate the open method of fixation. We present a novel and simplified technique of transosseous fixation of displaced pediatric mandibular fractures with polyglactin resorbable suture, which provides adequate stability without any interference with tooth buds and which is easy to master.

Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head.

PubMed

Shen, Yun; Zhang, Zi-Ming; Jiang, Sheng-Dan; Jiang, Lei-Sheng; Dai, Li-Yang

2009-04-09

Osteoporosis (OP) and osteoarthritis (OA) are public health diseases affecting the quality of life of the elderly, and bring about a heavy burden to the society and family of patients. It has been debated whether or not there is an inverse relationship between these two disorders. To compare the exact difference in bone tissue structure between osteoporosis and osteoarthritis, we observed the ultrastructure of trabecular bone from the femoral heads using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A total of 15 femoral head specimens from postmenopausal women were collected during the procedures of total or hemi hip replacement (OP, n = 8; OA, n = 7). The morphologic structure of the trabecular bone, collagen fibers, resorption lacuna and osteoblasts were observed. Under SEM, osteoporotic trabeculae appeared to be thinning, tapering, breaking and perforating. A number of resorption lacunae of various shapes were seen on the surface of the trabeculum. The collagen fibers of lacuna were resorbed. On occasion, naked granular bone crystals could be found. In the OA group, the trabecular bone looked thick with integrated structure. Reticular and granular new bone could be found. The trabeculum was covered by well-arranged collagen fibers around the resorption lacuna. In the OP group, under TEM, marginal collagen fibers were observed to be aligned loosely with enlarged spaces. A few inactive osteoblasts and no inflammatory cells were seen. In the OA group, the collagen fibers inside the trabeculum were arranged in a dense manner with many active osteoblasts and inflammatory cells infiltrating the matrix. We found significant differences in the trabecular bone, collagen fibers, lacunae and osteoblasts between postmenopausal women with OP and OA. These findings support the hypothesis that there is an inverse relationship between OP and OA.

Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head

PubMed Central

Shen, Yun; Zhang, Zi-Ming; Jiang, Sheng-Dan; Jiang, Lei-Sheng; Dai, Li-Yang

2009-01-01

Background Osteoporosis (OP) and osteoarthritis (OA) are public health diseases affecting the quality of life of the elderly, and bring about a heavy burden to the society and family of patients. It has been debated whether or not there is an inverse relationship between these two disorders. Methods To compare the exact difference in bone tissue structure between osteoporosis and osteoarthritis, we observed the ultrastructure of trabecular bone from the femoral heads using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A total of 15 femoral head specimens from postmenopausal women were collected during the procedures of total or hemi hip replacement (OP, n = 8; OA, n = 7). The morphologic structure of the trabecular bone, collagen fibers, resorption lacuna and osteoblasts were observed. Results Under SEM, osteoporotic trabeculae appeared to be thinning, tapering, breaking and perforating. A number of resorption lacunae of various shapes were seen on the surface of the trabeculum. The collagen fibers of lacuna were resorbed. On occasion, naked granular bone crystals could be found. In the OA group, the trabecular bone looked thick with integrated structure. Reticular and granular new bone could be found. The trabeculum was covered by well-arranged collagen fibers around the resorption lacuna. In the OP group, under TEM, marginal collagen fibers were observed to be aligned loosely with enlarged spaces. A few inactive osteoblasts and no inflammatory cells were seen. In the OA group, the collagen fibers inside the trabeculum were arranged in a dense manner with many active osteoblasts and inflammatory cells infiltrating the matrix. Conclusion We found significant differences in the trabecular bone, collagen fibers, lacunae and osteoblasts between postmenopausal women with OP and OA. These findings support the hypothesis that there is an inverse relationship between OP and OA. PMID:19356253

A Resorbable Antibiotic-Eluting Polymer Composite Bone Void Filler for Perioperative Infection Prevention in a Rabbit Radial Defect Model

PubMed Central

Brooks, Benjamin D.; Sinclair, Kristofer D.; Grainger, David W.; Brooks, Amanda E.

2015-01-01

Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 107 CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results. PMID:25815727

miR-218 is involved in the negative regulation of osteoclastogenesis and bone resorption by partial suppression of p38MAPK-c-Fos-NFATc1 signaling: Potential role for osteopenic diseases.

PubMed

Qu, Bo; Xia, Xun; Yan, Ming; Gong, Kai; Deng, Shaolin; Huang, Gang; Ma, Zehui; Pan, Xianming

2015-10-15

The increased osteoclastic activity accounts for pathological bone loss in diseases including osteoporosis. MicroRNAs are widely accepted to be involved in the regulation of osteopenic diseases. Recently, the low expression of miR-218 was demonstrated in CD14(+) peripheral blood mononuclear cells (PBMCs) from patients with postmenopausal osteoporosis. However, its role and the underlying mechanism in osteoporosis are still undefined. Here, an obvious decrease in miR-218 expression was observed during osteoclastogenesis under receptor activator of nuclear factor κB ligand (RANKL) stimulation, in both osteoclast precursors of bone marrow macrophages (BMMs) and RAW 264.7. Further analysis confirmed that overexpression of miR-218 obviously attenuated the formation of multinuclear mature osteoclasts, concomitant with the decrease in Trap and Cathepsin K levels, both the master regulators of osteoclastogenesis. Moreover, miR-218 up-regulation dramatically inhibited osteoclast precursor migration, actin ring formation and bone resorption. Mechanism assay demonstrated that miR-218 overexpression attenuated the expression of p38MAPK, c-Fos and NFATc1 signaling molecules. Following preconditioning with P79350, an agonist of p38MAPK, the inhibitor effect of miR-218 on osteoclastogenesis and bone-resorbing activity was strikingly ameliorated. Together, this study revealed a crucial role of miR-218 as a negative regulator for osteoclastogenesis and bone resorption by suppressing the p38MAPK-c-Fos-NFATc1 pathway. Accordingly, this research will provide a promising therapeutic agent against osteopenic diseases including osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantifying Leisure Physical Activity and Its Relation to Bone Density and Strength

PubMed Central

SHEDD, KRISTINE M.; HANSON, KATHY B.; ALEKEL, D. LEE; SCHIFERL, DANIEL J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2010-01-01

Purpose Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Methods Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. Results UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength–strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Conclusion Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss. PMID:18046190

Chitin-fibroin-hydroxyapatite membrane for guided bone regeneration: micro-computed tomography evaluation in a rat model.

PubMed

Baek, Young-Jae; Kim, Jung-Han; Song, Jae-Min; Yoon, Sang-Yong; Kim, Hong-Sung; Shin, Sang-Hun

2016-12-01

In guided bone regeneration (GBR) technique, many materials have been used for improving biological effectiveness by adding on membranes. The new membrane which was constructed with chitin-fibroin-hydroxyapatite (CNF/HAP) was compared with a collagen membrane (Bio-Gide®) by means of micro-computed tomography. Fifty-four rats were used in this study. A critical-sized (8 mm) bony defect was created in the calvaria with a trephine bur. The CNF/HAP membrane was prepared by thermally induced phase separation. In the experimental group ( n  = 18), the CNF/HAP membrane was used to cover the bony defect, and in the control group ( n  = 18), a resorbable collagen membrane (Bio-Gide®) was used. In the negative control group ( n  = 18), no membrane was used. In each group, six animals were euthanized at 2, 4, and 8 weeks after surgery. The specimens were analyzed using micro-CT. Bone volume (BV) and bone mineral density (BMD) of the new bone showed significant difference between the negative control group and membrane groups ( P  < 0.05). However, between two membranes, the difference was not significant. The CNF/HAP membrane has significant effect on the new bone formation and has the potential to be applied for guided bone regeneration.

Bone Talk: Activated Osteoblasts Promote Lung Cancer Growth.

PubMed

Bružas, Emilis; Egeblad, Mikala

2018-03-01

Cancer cells can directly stimulate the generation and recruitment of tumor-supportive bone marrow-derived cells (BMDCs), including neutrophils, via secreted factors. A new study demonstrates that lung tumors also remotely activate bone-residing osteoblasts, which in turn promote neutrophil production. This is a multistep mechanism of establishing a supportive tumor microenvironment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity.

PubMed

Swamy, N; Ghosh, S; Schneider, G B; Ray, R

2001-01-01

Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal

Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cells.

PubMed

Andersen, Thomas L; Søe, Kent; Sondergaard, Teis E; Plesner, Torben; Delaisse, Jean-Marie

2010-02-01

Osteolytic lesions are a hallmark of multiple myeloma. They are due to the hyperactivity of bone resorbing osteoclasts and hypoactivity of bone forming osteoblasts, in response to neighbouring myeloma cells. This study identified a structure that deeply affects this response, because of its impact on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy over bone remodelling compartment (BRC). These canopies are frequently disrupted in myeloma, and this disruption correlates with increased proximity and density of myeloma cells. In vitro evidence indicates that this disruption may be due to direct contact between myeloma and BRC canopy cells. Importantly, this disruption and increased proximity and density of myeloma cells coincides with key myeloma-induced bone events, such as osteolytic lesions, impaired bone formation despite increased bone resorption, and fusion of myeloma cells with osteoclasts thereby forming myeloma-osteoclast hybrid cells. These findings strongly support a critical role of BRC canopies in myeloma-induced bone disease. BRC canopies could therefore be considered as a new therapeutic target.

A visco-poroelastic model of functional adaptation in bones reconstructed with bio-resorbable materials.

PubMed

Giorgio, Ivan; Andreaus, Ugo; Scerrato, Daria; dell'Isola, Francesco

2016-10-01

In this paper, the phenomena of resorption and growth of bone tissue and resorption of the biomaterial inside a bicomponent system are studied by means of a numerical method based on finite elements. The material behavior is described by a poro-viscoelastic model with infiltrated voids. The mechanical stimulus that drives these processes is a linear combination of density of strain energy and viscous dissipation. The external excitation is represented by a bending load slowly variable with sinusoidal law characterized by different frequencies. Investigated aspects are the influence of the load frequency, of type of the stimulus and of the effective porosity on the time evolution of the mass densities of considered system.

Assessing bone banking activities at University of Malaya medical centre.

PubMed

Mohd, Suhaili; Samsuddin, Sharifah Mazni; Ramalingam, Saravana; Min, Ng Wuey; Yusof, Norimah; Zaman, T Kamarul; Mansor, Azura

2015-12-01

The main advantage of establishing in-house bone banks is its ability to readily provide allograft bones for local surgeries. Bone procurement activities of our university bone bank during the 10 years of operation were reviewed. Socio-demographic data of donors, types of bone procured, cases of rejected bones and types of allograft bones transplanted are presented. From 179 potential donors, 73 % were accepted with 213 procured bones. Femoral head was the common bone transplanted (45 %), as it was also the most common procured (82 %). Bones were rejected mainly due to non-technical reasons (83 %) rather than positive results of microbiological (13 %) and serological (4 %) tests. Comprehensive data could not be obtained for further analysis due to difficulties in retrieving information. Therefore, quality assurance system was improved to establish more systematic documentations, as the basis of good banking practice with process control hence allowing traceability.

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

PubMed Central

Charles, Julia F.; Hsu, Lih-Yun; Niemi, Erene C.; Weiss, Arthur; Aliprantis, Antonios O.; Nakamura, Mary C.

2012-01-01

Increased osteoclastic bone resorption leads to periarticular erosions and systemic osteoporosis in RA patients. Although a great deal is known about how osteoclasts differentiate from precursors and resorb bone, the identity of an osteoclast precursor (OCP) population in vivo and its regulatory role in RA remains elusive. Here, we report the identification of a CD11b–/loLy6Chi BM population with OCP activity in vitro and in vivo. These cells, which can be distinguished from previously characterized precursors in the myeloid lineage, display features of both M1 and M2 monocytes and expand in inflammatory arthritis models. Surprisingly, in one mouse model of RA (adoptive transfer of SKG arthritis), cotransfer of OCP with SKG CD4+ T cells diminished inflammatory arthritis. Similar to monocytic myeloid-derived suppressor cells (M-MDSCs), OCPs suppressed CD4+ and CD8+ T cell proliferation in vitro through the production of NO. This study identifies a BM myeloid precursor population with osteoclastic and T cell–suppressive activity that is expanded in inflammatory arthritis. Therapeutic strategies that prevent the development of OCPs into mature bone-resorbing cells could simultaneously prevent bone resorption and generate an antiinflammatory milieu in the RA joint. PMID:23114597

The interactions of the cells in the development of osteoporotic changes in bones under space flight conditions

NASA Astrophysics Data System (ADS)

Rodionova, Natalia; Kabitskaya, Olga

2016-07-01

Using the methods of electron microscopy and autoradiography with ³N-glycine and ³N-thymidine on biosatellites "Bion-11" (Macaca mulatta, the duration of the experiments -10 days), "Bion-M1" (mouse C57 Black, duration of the flight - 30 days) in the experiments with modeled hypokinesia (white rats, hind limbs unloading, the duration of the experiments 28 days) new data about the morpho-functional peculiarities of cellular interactions in adaptive remodeling zones of bone structures under normal conditions and after exposure of animals to microgravity. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and paving endost one as well as to the bone-marrow stromal cells and perivascular cells. As a response to the mechanical stimulus (microgravity) the system of perivascular cell-stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, the number of apoptotic osteoblasts increases. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts, bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn't occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in remodeling loci. These cell reactions

Correlating the nanoscale mechanical and chemical properties of knockout mice bones

NASA Astrophysics Data System (ADS)

Kavukcuoglu, Nadire Beril

Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2

Comparison of resorbable poly-L-lactic acid-polyglycolic acid and internal Palmaz stents for the surgical correction of severe tracheomalacia.

PubMed

Sewall, Gregory K; Warner, Thomas; Connor, Nadine P; Hartig, Gregory K

2003-06-01

Tracheomalacia (TM) is associated with expiratory airway collapse and potentially fatal respiratory distress. Internal and external tracheal stents and, recently, resorbable biopolymers have been used to treat this condition. In this study, the efficacy and biocompatibility of internal Palmaz stents and external poly-L-lactic acid-polyglycolic acid (PLPG) stents were compared in a model of severe TM induced in piglets. The tracheas were repaired with one of two stenting methods, and the animals survived for up to 16 weeks. Weight gain, adverse respiratory signs and symptoms, tracheal or lung histopathologic changes, and internal and external tracheal diameters were measured. The animals in the PLPG group uniformly were free of respiratory distress and tracheal stenosis or inflammation, whereas all animals in the Palmaz group developed respiratory distress as a result of pneumonia or tracheal stenosis caused by intraluminal granulation tissue. In conclusion, superior efficacy of external, resorbable PLPG stents was found relative to internal Palmaz stents for the surgical repair of severe TM.

Physical activity, but not sedentary time, influences bone strength in late adolescence.

PubMed

Tan, Vina Ps; Macdonald, Heather M; Gabel, Leigh; McKay, Heather A

2018-03-20

Physical activity is essential for optimal bone strength accrual, but we know little about interactions between physical activity, sedentary time, and bone outcomes in older adolescents. Physical activity (by accelerometer and self-report) positively predicted bone strength and the distal and midshaft tibia in 15-year-old boys and girls. Lean body mass mediated the relationship between physical activity and bone strength in adolescents. To examine the influence of physical activity (PA) and sedentary time on bone strength, structure, and density in older adolescents. We used peripheral quantitative computed tomography to estimate bone strength at the distal tibia (8% site; bone strength index, BSI) and tibial midshaft (50% site; polar strength strain index, SSI p ) in adolescent boys (n = 86; 15.3 ± 0.4 years) and girls (n = 106; 15.3 ± 0.4 years). Using accelerometers (GT1M, Actigraph), we measured moderate-to-vigorous PA (MVPA Accel ), vigorous PA (VPA Accel ), and sedentary time in addition to self-reported MVPA (MVPA PAQ-A ) and impact PA (ImpactPA PAQ-A ). We examined relations between PA and sedentary time and bone outcomes, adjusting for ethnicity, maturity, tibial length, and total body lean mass. At the distal tibia, MVPA Accel and VPA Accel positively predicted BSI (explained 6-7% of the variance, p < 0.05). After adjusting for lean mass, only VPA Accel explained residual variance in BSI. At the tibial midshaft, MVPA Accel , but not VPA Accel , positively predicted SSI p (explained 3% of the variance, p = 0.01). Lean mass attenuated this association. MVPA PAQ-A and ImpactPA PAQ-A also positively predicted BSI and SSI p (explained 2-4% of the variance, p < 0.05), but only ImpactPA PAQ-A explained residual variance in BSI after accounting for lean mass. Sedentary time did not independently predict bone strength at either site. Greater tibial bone strength in active adolescents is mediated, in part, by lean mass. Despite

Metals for bone implants. Part 1. Powder metallurgy and implant rendering.

PubMed

Andani, Mohsen Taheri; Shayesteh Moghaddam, Narges; Haberland, Christoph; Dean, David; Miller, Michael J; Elahinia, Mohammad

2014-10-01

New metal alloys and metal fabrication strategies are likely to benefit future skeletal implant strategies. These metals and fabrication strategies were looked at from the point of view of standard-of-care implants for the mandible. These implants are used as part of the treatment for segmental resection due to oropharyngeal cancer, injury or correction of deformity due to pathology or congenital defect. The focus of this two-part review is the issues associated with the failure of existing mandibular implants that are due to mismatched material properties. Potential directions for future research are also studied. To mitigate these issues, the use of low-stiffness metallic alloys has been highlighted. To this end, the development, processing and biocompatibility of superelastic NiTi as well as resorbable magnesium-based alloys are discussed. Additionally, engineered porosity is reviewed as it can be an effective way of matching the stiffness of an implant with the surrounding tissue. These porosities and the overall geometry of the implant can be optimized for strain transduction and with a tailored stiffness profile. Rendering patient-specific, site-specific, morphology-specific and function-specific implants can now be achieved using these and other metals with bone-like material properties by additive manufacturing. The biocompatibility of implants prepared from superelastic and resorbable alloys is also reviewed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Alendronate promotes bone formation by inhibiting protein prenylation in osteoblasts in rat tooth replantation model.

PubMed

Komatsu, Koichiro; Shimada, Akemi; Shibata, Tatsuya; Wada, Satoshi; Ideno, Hisashi; Nakashima, Kazuhisa; Amizuka, Norio; Noda, Masaki; Nifuji, Akira

2013-11-01

Bisphosphonates (BPs) are a major class of antiresorptive drug, and their molecular mechanisms of antiresorptive action have been extensively studied. Recent studies have suggested that BPs target bone-forming cells as well as bone-resorbing cells. We previously demonstrated that local application of a nitrogen-containing BP (N-BP), alendronate (ALN), for a short period of time increased bone tissue in a rat tooth replantation model. Here, we investigated cellular mechanisms of bone formation by ALN. Bone histomorphometry confirmed that bone formation was increased by local application of ALN. ALN increased proliferation of bone-forming cells residing on the bone surface, whereas it suppressed the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Moreover, ALN treatment induced more alkaline phosphatase-positive and osteocalcin-positive cells on the bone surface than PBS treatment. In vitro studies revealed that pulse treatment with ALN promoted osteocalcin expression. To track the target cells of N-BPs, we applied fluorescence-labeled ALN (F-ALN) in vivo and in vitro. F-ALN was taken into bone-forming cells both in vivo and in vitro. This intracellular uptake was inhibited by endocytosis inhibitors. Furthermore, the endocytosis inhibitor dansylcadaverine (DC) suppressed ALN-stimulated osteoblastic differentiation in vitro and it suppressed the increase in alkaline phosphatase-positive bone-forming cells and subsequent bone formation in vivo. DC also blocked the inhibition of Rap1A prenylation by ALN in the osteoblastic cells. These data suggest that local application of ALN promotes bone formation by stimulating proliferation and differentiation of bone-forming cells as well as inhibiting osteoclast function. These effects may occur through endocytic incorporation of ALN and subsequent inhibition of protein prenylation.

Modulation of bone remodeling via mechanically activated ion channels

NASA Technical Reports Server (NTRS)

Duncan, Randall L. (Principal Investigator)

1996-01-01

A critical factor in the maintenance of bone mass is the physical forces imposed upon the skeleton. Removal of these forces, such as in a weightless environment, results in a rapid loss of bone, whereas application of exogenous mechanical strain has been shown to increase bone formation. Numerous flight and ground-based experiments indicate that the osteoblast is the key bone cell influenced by mechanical stimulation. Aside from early transient fluctuations in response to unloading, osteoclast number and activity seem unaffected by removal of strain. However, bone formation is drastically reduced in weightlessness and osteoblasts respond to mechanical strain with an increase in the activity of a number of second messenger pathways resulting in increased anabolic activity. Unfortunately, the mechanism by which the osteoblast converts physical stimuli into a biochemical message, a process we have termed biochemical coupling, remains elusive. Prior to the application of this grant, we had characterized a mechanosensitive, cation nonselective channel (SA-cat) in osteoblast-like osteosarcoma cells that we proposed is the initial signalling mechanism for mechanotransduction. During the execution of this grant, we have made considerable progress to further characterize this channel as well as to determine its role in the osteoblastic response to mechanical strain. To achieve these goals, we combined electrophysiologic techniques with cellular and molecular biology methods to examine the role of these channels in the normal function of the osteoblast in vitro.

Effects of Physical Activity and Muscle Quality on Bone Development in Girls

PubMed Central

Farr, Joshua N.; Laddu, Deepika R.; Blew, Robert M.; Lee, Vinson R.; Going, Scott B.

2013-01-01

Poor muscle quality and sedentary behavior are risk factors for metabolic dysfunction in children and adolescents. However, because longitudinal data are scarce, relatively little is known about how changes in muscle quality and physical activity influence bone development. Purpose In a 2-year longitudinal study, we examined the effects of physical activity and changes in muscle quality on bone parameters in young girls. Methods The sample included 248 healthy girls aged 9–12 years at baseline. Peripheral quantitative computed tomography was used to measure calf and thigh muscle density, an indicator of skeletal muscle fat content or muscle quality, as well as bone parameters at diaphyseal and metaphyseal sites of the femur and tibia. Physical activity was assessed using a validated questionnaire specific for youth. Results After controlling for covariates in multiple regression models, increased calf muscle density was independently associated with greater gains in cortical (β = 0.13, P < 0.01) and trabecular (β = 0.25, P < 0.001) volumetric bone mineral density (vBMD) and the bone strength index (BSI; β = 0.25, P < 0.001) of the tibia. Importantly, these relationships were generalized, as similar changes were present at the femur. Associations between physical activity and changes in bone parameters were weaker than those observed for muscle density. Nevertheless, physical activity was significantly (all P < 0.05) associated with greater gains in trabecular vBMD and the BSI of the distal femur. Conclusions These findings suggest that poor muscle quality may put girls at risk for suboptimal bone development. Physical activity is associated with more optimal gains in weight-bearing bone density and strength in girls, but to a lesser extent than changes in muscle quality. PMID:23698240

Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

PubMed

Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

2018-05-01

GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Magnolol on the Function of Osteoblastic MC3T3-E1 Cells

PubMed Central

Kwak, Eun Jung; Lee, Young Soon; Choi, Eun Mi

2012-01-01

Objectives. In the present study, the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to stimulate osteoblast function and inhibit the release of bone-resorbing mediators was investigated in osteoblastic MC3T3-E1 cells. Methods. Osteoblast function was measured by cell growth, alkaline phosphatase activity, collagen synthesis, and mineralization. Glutathione content was also measured in the cells. Bone-resorbing cytokines, receptor activator of nuclear factor-κB ligand (RANKL), TNF-α, and IL-6 were measured with an enzyme immunoassay system. Results. Magnolol caused a significant elevation of cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, and glutathione content in the cells (P < 0.05). Skeletal turnover is orchestrated by a complex network of regulatory factors. Among cytokines, RANKL, TNF-α, and IL-6 were found to be key osteoclastogenetic molecules produced by osteoblasts. Magnolol significantly (P < 0.05) decreased the production of osteoclast differentiation inducing factors such as RANKL, TNF-α, and IL-6 in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as an ROS generator. Conclusion. Magnolol might be a candidate as an agent for the prevention of bone disorders such as osteoporosis. PMID:22474400

Complex effect of hydroxyapatite nanoparticles on the differentiation and functional activity of human pre-osteoclastic cells.

PubMed

Costa-Rodrigues, João; Silva, Ana; Santos, Catarina; Almeida, Maria Margarida; Costa, Maria Elisabete; Fernandes, Maria Helena

2014-12-01

Nanosized hydroxyapatite (HA) is a promising material in clinical applications targeting the bone tissue. NanoHA is able to modulate bone cellular events, which accounts for its potential utility, but also raises safety concerns regarding the maintenance of the bone homeostasis. This work analyses the effects of HA nanoparticles (HAnp) on osteoclastic differentiation and activity, an issue that has been barely addressed. Rod-like HAnp, produced by a hydrothermal precipitation method, were tested on peripheral blood mononuclear cells (PBMC), which contains the CD14+ osteoclastic precursors, in unstimulated or osteoclastogenic-induced conditions. HAnp were added at three time-points during the osteoclastic differentiation pathway, and cell response was evaluated for osteoclastic related parameters. Results showed that HAnp modulated the differentiation and function of osteoclastic cells in a dose- and time-dependent manner. In addition, the effects were dependent on the stage of osteoclastic differentiation. In unstimulated PBMC, HAnp significantly increased osteoclastogenesis, leading to the formation of mature osteoclasts, as evident by the significant increase of TRAP activity, number of TRAP-positive multinucleated cells, osteoclastic gene expression and resorbing ability. However, in a population of mature osteoclasts (formed in osteoclastogenic-induced PBMC cultures), HAnp caused a dose-dependent decrease on the osteoclastic-related parameters. These results highlight the complex effects of HAnp in osteoclastic differentiation and activity, and suggest the possibility of HAnp to modulate/disrupt osteoclastic behavior, with eventual imbalances in the bone metabolism. This should be carefully considered in bone-related and other established and prospective biomedical applications of HAnp.

Radiographic evaluation of bone adaptation adjacent to percutaneous osseointegrated prostheses in a sheep model.

PubMed

Jeyapalina, Sujee; Beck, James Peter; Bachus, Kent N; Chalayon, Ornusa; Bloebaum, Roy D

2014-10-01

Percutaneous osseointegrated prostheses (POPs) are being investigated as an alternative to conventional socket suspension and require a radiographic followup in translational studies to confirm that design objectives are being met. In this 12-month animal study, we determined (1) radiographic signs of osseointegration and (2) radiographic signs of periprosthetic bone hypertrophy and resorption (adaptation) and (3) confirmed them with the histologic evidence of host bone osseointegration and adaptation around a novel, distally porous-coated titanium POP with a collar. A POP device was designed to fit the right metacarpal bone of sheep. Amputation and implantation surgeries (n = 14) were performed, and plane-film radiographs were collected quarterly for 12 months. Radiographs were assessed for osseointegration (fixation) and bone adaptation (resorption and hypertrophy). The cortical wall and medullary canal widths were used to compute the cortical index and expressed as a percentage. Based on the cortical index changes and histologic evaluations, bone adaptation was quantified. Radiographic data showed signs of osseointegration including those with incomplete seating against the collar attachment. Cortical index data indicated distal cortical wall thinning if the collar was not seated distally. When implants were bound proximally, bone resorbed distally and the diaphyseal cortex hypertrophied. Histopathologic evidence and cortical index measurements confirmed the radiographic indications of adaptation and osseointegration. Distal bone loading, through collar attachment and porous coating, limited the distal bone resorption. Serial radiographic studies, in either animal models or preclinical trials for new POP devices, will help to determine which designs are likely to be safe over time and avoid implant failures.

Quantifying Bone–relevant Activity and its Relation to Bone Strength in Girls

PubMed Central

Farr, Joshua N.; Lee, Vinson R.; Blew, Robert M.; Lohman, Timothy G.; Going, Scott B.

2011-01-01

Physical activity (PA) is critical for maximizing bone development during growth. However, there is no consensus on how well existing PA measurement tools predict bone strength. PURPOSE Compare four methods of quantifying physical activity (PA) (pedometer, 3-day physical activity recall (3DPAR), bone-specific physical activity questionnaire (BPAQ), and past year physical activity questionnaire (PYPAQ)), in young girls and evaluate their ability to predict indices of bone strength. METHODS 329 girls aged 8–13 years completed a pedometer assessment, the 3DPAR, the BPAQ, and a modified PYPAQ. Peripheral quantitative computed tomography (pQCT) was used to assess bone strength index (BSI) at metaphyseal (4% distal femur and tibia) sites and strength-strain index (SSI) at diaphyseal (femur = 20%, tibia = 66%) sites of the non-dominant leg. Correlations and hierarchical multiple regression were used to assess relationships among PA measures and indices of bone strength. RESULTS After adjustment for maturity, correlations between PA measures and indices of bone strength were positive, although low (r = 0.01–0.20). Regression models that included covariates (maturity, body mass, leg length, and ethnicity) and PA variables showed that PYPAQ score was significantly (P < 0.05) associated with BSI and SSI at all sites and explained more variance in BSI and SSI than any other PA measure. Pedometer steps were significantly (P < 0.05) associated with metaphyseal femur and tibia BSI and 3DPAR score was significantly (P < 0.05) associated with metaphyseal femur BSI. BPAQ score was not significantly (P > 0.05) associated with BSI or SSI at any sites. CONCLUSION A modified PYPAQ that accounts for the duration, frequency, and load of PA predicted indices of bone strength better than other PA measures. PMID:20631644

Gingival crevicular fluid bone turnover biomarkers: How postmenopausal women respond to orthodontic activation.

PubMed

Smuthkochorn, Sorapan; Palomo, J Martin; Hans, Mark G; Jones, Corey S; Palomo, Leena

2017-07-01

Bone turnover associated with orthodontic tooth movement is evidenced by increased bone turnover markers in gingival crevicular fluid (GCF). Postmenopausal women have an increased concentration of serum bone turnover markers. The filtrate of this serum makes up GCF, but little is known of the bone turnover around teeth in this cohort. The objective of this investigation was to compare the GCF bone turnover markers in premenopausal vs postmenopausal women receiving orthodontic treatment at baseline and at orthodontic activation. Twenty-eight women were enrolled in the study and separated into 2 groups: premenopausal (16) and postmenopausal (12). Bone turnover was evaluated by GCF at baseline and 24 hours after orthodontic appliance activation. GCF concentrations of RANKL and OPN were measured using ELISA. Baseline and change in concentrations were compared between groups. Baseline RANKL and OPN were significantly different between the premenopausal and postmenopausal groups (P <0.05). Both markers increased significantly from baseline to 24 hours after orthodontic appliance activation in both groups (P <0.05). However, the response to orthodontic activation was not significantly different between groups. Although postmenopausal women have a different bone turnover profile at baseline than do their premenopausal counterparts, there is no difference in their response to orthodontic activation. This confers a level of security associated with orthodontic activation. Future studies are warranted to construct biomarker curves throughout orthodontic therapy. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Response Of Mineralizing And Non-Mineralizing Bone Cells To Fluid Flow: An In Vitro Model For Mechanotransruction

NASA Technical Reports Server (NTRS)

Makuch, Lauren A.

2004-01-01

Humans reach peak bone mass at age 30. After this point, we lose 1 to 2 percent of bone mass each decade. In the microgravity environment of space, astronauts lose bone mass at an accelerated rate of 1 to 2 percent each month. When astronauts travel to Mars, they may be in space for as long as 3 years. During this time, they may lose about half of their bone mass from weight-bearing bones. This loss may be irreversible. The drastic loss in bone that astronauts experience in space makes them much more vulnerable to fractures. In addition, the corresponding removal of calcium from bone results in higher levels of calcium in the blood, which increases the risk of developing kidney stones. Currently, studies are being conducted which investigate factors governing bone adaptation and mechanotransduction. Bone is constantly adapting in response to mechanical stimuli. Increased mechanical loading stimulates bone formation and suppresses bone resorption. Reduction in mechanical loading caused by bedrest, disuse, or microgravity results in decreased bone formation and possibly increased bone resorption. Osteoblasts and osteoclasts are the two main cell types that participate in bone remodeling. Osteoblasts are anabolic (bone-forming) cells and osteoclasts are catabolic (bone-resorbing) cells. In microgravity, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a loss of bone density. Mechanotransduction, the molecular mechanism by which mechanical stimuli are converted to biochemical signals, is not yet understood. Exposure of cells to fluid flow imposes a shear stress on the cells. Several studies have shown that the shear stress that results from fluid flow induces a cellular response similar to that induced by mechanical loading. Thus, fluid flow can be used as an in vitro model to simulate the mechanical stress that bone cells experience in vivo. Previous in vitro studies have shown that fluid flow induces several responses in

Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

PubMed

Hambli, Ridha

2014-01-01

Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

PubMed

Havill, Lorena M; Mahaney, Michael C; L Binkley, Teresa; Specker, Bonny L

2007-05-01

Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p bone; high activity was associated with higher aBMD at all sites, but the magnitude of this effect varied. Activity among men was associated with higher FN BMC and cross-sectional area (CSA) at the 4% radius, but this was not observed among women (sex-by-activity interaction, both p activity levels. Influence of activity was greater in older women: older women with low activity had lower Cort-vBMD than older men, but older women with high activity had higher

Association between bacteria occurring in the apical canal system and expression of bone-resorbing mediators and matrix metalloproteinases in apical periodontitis.

PubMed

Takahama, A; Rôças, I N; Faustino, I S P; Alves, F R F; Azevedo, R S; Gomes, C C; Araújo-Filho, W R; Siqueira, J F

2018-07-01

To evaluate the association between the presence of selected bacterial species/groups in the apical root canal and expression of mediators of soft and bone tissue destruction in apical periodontitis lesions. Relationships between bacteria and some other features of apical periodontitis were also investigated. Seventeen freshly extracted teeth with pulp necrosis and apical periodontitis were included. The apical root segment was sectioned and cryopulverized; DNA was extracted and evaluated for the presence of 9 bacterial species/groups using real-time polymerase chain reaction. Lesions were processed for histopathological and immunohistochemical analyses, which targeted matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Associations of the target bacteria with expression of these mediators, presence of symptoms, lesion size and histopathological diagnosis were evaluated. Data were analysed using the chi-square, Fisher's exact, Mann-Whitney and Pearson tests. P values lower than 0.05 were considered significant. All pulverized apical root samples were positive for bacteria. The most prevalent taxa were Actinobacteria (53%), Streptococcus species (35%), Fusobacterium species and Parvimonas micra (18%). The target mediators exhibited a high mean expression in the lesions (MMP-2: 82%; MMP-9: 73%; RANK: 78%; RANKL; 81%; OPG; 83%). Mean RANKL:OPG ratio was significantly higher in granulomas than cysts (P < 0.05, Mann-Whitney test). Actinobacteria were associated with granulomas, higher MMP-2 expression, lower OPG expression, and higher RANKL:OPG ratio (P < 0.05 for all, Fisher's exact test or Mann-Whitney test). No other significant associations were found. Actinobacteria may play an important role in the active phase of soft and bone tissue destruction in apical periodontitis. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Genetic Ablation of CD68 Results in Mice with Increased Bone and Dysfunctional Osteoclasts

PubMed Central

Ashley, Jason W.; Shi, Zhenqi; Zhao, Haibo; Li, Xingsheng; Kesterson, Robert A.; Feng, Xu

2011-01-01

CD68 is a member of the lysosome associated membrane protein (LAMP) family that is restricted in its expression to cells of the monocyte/macrophage lineage. This lineage restriction includes osteoclasts, and, while previous studies of CD68 in macrophages and dendritic cells have proposed roles in lipid metabolism, phagocytosis, and antigen presentation, the expression and function of CD68 in osteoclasts have not been explored. In this study, we investigated the expression and localization of CD68 in macrophages and osteoclasts in response to the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL). We found that M-CSF stimulates CD68 expression and RANKL alters the apparent molecular weight of CD68 as measured by Western immunoblotting. In addition, we explored the significance of CD68 expression in osteoclasts by generating mice that lack expression of CD68. These mice have increased trabecular bone, and in vitro assessment of CD68−/− osteoclasts revealed that, in the absence of CD68, osteoclasts demonstrate an accumulation of intracellular vesicle-like structures, and do not efficiently resorb bone. These findings demonstrate a role for CD68 in the function of osteoclasts, and future studies will determine the mechanistic nature of the defects seen in CD68−/− osteoclasts. PMID:21991369

Wound Healing Complications Following Guided Bone Regeneration for Ridge Augmentation: A Systematic Review and Meta-Analysis.

PubMed

Lim, Glendale; Lin, Guo-Hao; Monje, Alberto; Chan, Hsun-Liang; Wang, Hom-Lay

The rate of developing soft tissue complications that accompany guided bone regeneration (GBR) procedures varies widely, from 0% to 45%. The present review was conducted to investigate the rate for resorbable versus nonresorbable membranes and the timing of soft tissue complications. Electronic and manual literature searches were conducted by two independent reviewers using several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, for articles published through July 2015, with no language restriction. Articles were included if they were clinical trials aimed at demonstrating the incidence of soft tissue complications following GBR procedures. Overall, 21 and 15 articles were included in the qualitative and quantitative synthesis, respectively. The weighted complication rate of the overall soft tissue complications, including membrane exposure, soft tissue dehiscence, and acute infection/abscess, into the calculation was 16.8% (95% CI = 10.6% to 25.4%). When considering the complication rate based on membrane type used, resorbable membrane was associated with a weighted complication rate of 18.3% (95% CI: 10.4% to 30.4%) and nonresorbable membrane with a rate of 17.6% (95% CI: 10.0% to 29.3%). Moreover, soft tissue lesions were reported as early as 1 week and as late as 6 months based on the included studies. Soft tissue complications after GBR are common (16.8%). Membrane type did not appear to significantly affect the complication rate, based on the limited number of data retrieved in this study. Technique sensitivity (ie, soft tissue management) may still be regarded as the main component to avoid soft tissue complications and, hence, to influence the success of bone regenerative therapy.

Reduction of retrosternal and pericardial adhesions with rapidly resorbable polymer films.

PubMed

Okuyama, N; Wang, C Y; Rose, E A; Rodgers, K E; Pines, E; diZerega, G S; Oz, M C

1999-09-01

The formation of postoperative cardiac adhesions makes a repeat sternotomy time consuming and dangerous. Many attempts have been made to solve this problem by using either drugs to inhibit fibrinolytic activity or different types of pericardial substitutes. The results have not been satisfactory. The efficacy of bioresorbable film prototypes made of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesions after cardiac operations in canine models was tested. After desiccation and abrasion of the epicardium, a transparent bioresorbable film was placed over the heart. The pericardium was closed to allow intrapericardial adhesions (n = 32) or left open and attached to the chest wall to induce retrosternal adhesions (n = 17). Postoperative recovery was similar among the groups. Retrosternal and pericardial adhesions were evaluated at necropsy 3 weeks later by assessing area, tenacity, and density of the adhesions. In the control dogs, tenacious, dense adhesions were observed. In contrast, adhesion formation was reduced at all sites covered by the films. The bioresorbable films were efficacious in the reduction of adhesion formation between epicardium and pericardium or between epicardium and sternum after cardiac operation. The EO/LA 1.5 film most effectively prevented the early adhesions. The bioresorbable films (EO/LA = 1.5, 2.5, and 3.0) significantly reduced adhesion formation, with EO/LA = 1.5 (Repel CV) being optimal. As the barrier was rapidly resorbed, the capsule formation induced by permanent barriers was avoided.

Increased physical activity ameliorates high fat diet-induced bone resorption in mice

USDA-ARS?s Scientific Manuscript database

It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality. On the other hand, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased excretion of pro-...

Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.

PubMed

Jung, Ronald E; Kokovic, Vladimir; Jurisic, Milan; Yaman, Duygu; Subramani, Karthikeyan; Weber, Franz E

2011-08-01

The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. In four out of five PLGA/NMP membrane-treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone-to-implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. © 2010 John Wiley & Sons A/S.

Resorbable fixation in facial plastic and head and neck reconstructive surgery: an initial report on polylactic acid implants.

PubMed

Moe, K S; Weisman, R A

2001-10-01

The purpose of this study was to evaluate and report our initial experience with a resorbable fixation system in facial cosmetic and head and neck reconstructive surgery. The specific goals were to determine in which settings the absorbable system could be used, to evaluate the outcome of its use, to detail complications that occurred, and to report our observations on advantages and disadvantages of the system compared with traditional methods of osteosynthesis and fixation. A retrospective review of the initial 30 consecutive patients at the University of California, San Diego Division of Head and Neck Surgery who received polylactic acid (PLA) implants. Academic tertiary referral/level I trauma center. Criteria for inclusion into the study were any patient over age 18 who underwent a procedure involving the use of a PLA implant between March 1999 and October 2000. In addition to the typical indications for metal plate or mesh implantation, PLA was used for "protected bone regeneration." Detailed records were kept of all patients in whom PLA implants were used, including the exact procedure and type of implant. All patients were operated by the authors. Operative reports, hospital charts, and office records were analyzed for any perioperative or postoperative complications. The attending surgeon noted advantages and disadvantages of the system. Patients have been followed from 2 to 18 months at the time of this report and are part of an ongoing long-term follow-up study. PLA implants were used in 35 procedures on 30 consecutive patients (multiple unilateral fracture repairs were counted as a single procedure). Uses included fixation of craniofacial fractures (zygomaticomaxillary, orbit floor, frontal bone [N = 9]; fixation of craniofacial osteotomy [N = 8]; protected bone regeneration [N = 3]; mandible, cranial bone donor site [N = 2]; bone grafting [N = 2]; craniectomy reconstruction [N = 2], and soft tissue suspension [endoscopic browlifting, N = 6, static

Single crowns in the resorbed posterior maxilla supported by either 6-mm implants or by 11-mm implants combined with sinus floor elevation surgery: a 1-year randomised controlled trial.

PubMed

Guljé, Felix L; Raghoebar, Gerry M; Vissink, Arjan; Meijer, Henny J A

2014-01-01

The aim of this randomised controlled trial was to assess the clinical performance of single crowns in the posterior maxilla supported by either 6-mm or 11-mm implants combined with maxillary sinus floor elevation. 41 consecutive patients with one missing premolar or molar in the posterior maxilla and with an estimated bone height of 6 to 8 mm in that area were included. Each patient was randomly allocated to one of the two treatment groups, namely to receive an 11-mm implant (Osseo Speed 4.0 S, Dentsply Implants, Mölndal, Sweden) in combination with maxillary sinus floor elevation surgery or to receive a 6-mm implant (Osseo Speed 4.0 S) without any grafting. After a 3-month osseointegration period, all implants were restored with custom-made titanium abutments and cemented zirconia-based porcelain crowns. Outcome measures were: implant survival; radiographic bone changes; plaque accumulation; bleeding tendency; peri-implant inflammation; presence of dental calculus; biological and technical complications; and patients' satisfaction. Clinical and radiographic examinations were performed at placement of the crown and 12 months thereafter. Patients' satisfaction was scored before treatment and after 12 months of functioning of the crown. One patient of the 11 mm implant group died during the follow-up. No implant failed and no biological or technical complications occurred. From loading to the 12 months follow-up, no difference was found in mean marginal bone changes between the groups (bone resorption in both groups 0.1 ± 0.3 mm). Clinical items revealed very healthy peri-implant soft tissues in both groups. Patients' satisfaction scores were high in both groups. 6-mm implants and 11-mm implants combined with sinus floor elevation surgery are equally successful to support a single crown in the resorbed posterior maxilla after 1-year follow-up.

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

PubMed

Langlois, M R; Delanghe, J R; Kaufman, J M; De Buyzere, M L; Van Hoecke, M J; Leroux-Roels, G G

1994-09-01

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

Annulus Fibrosus Can Strip Hyaline Cartilage End Plate from Subchondral Bone: A Study of the Intervertebral Disk in Tension.

PubMed

Balkovec, Christian; Adams, Michael A; Dolan, Patricia; McGill, Stuart M

2015-10-01

Study Design Biomechanical study on cadaveric spines. Objective Spinal bending causes the annulus to pull vertically (axially) on the end plate, but failure mechanisms in response to this type of loading are poorly understood. Therefore, the objective of this study was to identify the weak point of the intervertebral disk in tension. Methods Cadaveric motion segments (aged 79 to 88 years) were dissected to create midsagittal blocks of tissue, with ∼10 mm of bone superior and inferior to the disk. From these blocks, 14 bone-disk-bone slices (average 4.8 mm thick) were cut in the frontal plane. Each slice was gripped by its bony ends and stretched to failure at 1 mm/s. Mode of failure was recorded using a digital camera. Results Of the 14 slices, 10 failed by the hyaline cartilage being peeled off the subchondral bone, with the failure starting opposite the lateral annulus and proceeding medially. Two slices failed by rupturing of the trabecular bone, and a further two failed in the annulus. Conclusions The hyaline cartilage-bone junction is the disk's weak link in tension. These findings provide a plausible mechanism for the appearance of bone and cartilage fragments in herniated material. Stripping cartilage from the bony end plate would result in the herniated mass containing relatively stiff cartilage that does not easily resorb.

Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices. Clinical outcome at a minimum of 2-year follow-up.

PubMed

Jiya, Timothy U; Smit, T; van Royen, B J; Mullender, M

2011-04-01

Previous papers on resorbable poly-L-lactide-co-D,L-lactide (PLDLLA) cages in spinal fusion have failed to report adequately on patient-centred clinical outcome measures. Also comparison of PLDLLA cage with a traditionally applicable counterpart has not been previously reported. This is the first randomized prospective study that assesses clinical outcome of PLDLLA cage compared with a poly-ether-ether-ketone (PEEK) implant. Twenty-six patients were randomly assigned to undergo instrumented posterior lumbar interbody fusion (PLIF) whereby either a PEEK cage or a PLDLLA cage was implanted. Clinical outcome based on visual analogue scale scores for leg pain and back pain, as well as Oswestry Disability Index (ODI) and SF-36 questionnaires were documented and analysed. When compared with preoperative values, all clinical parameters have significantly improved in the PEEK group at 2 years after surgery with the exception of SF-36 general health, SF-36 mental health and SF-36 role emotional scores. No clinical parameter showed significant improvement at 2 years after surgery compared with preoperative values in the PLDLLA patient group. Only six patients (50%) in the PLDLLA group showed improvement in the VAS scores for leg and back pain as well as the ODI, as opposed to 10 patients (71%) in the PEEK group. One-third of the patients in the PLDLLA group actually reported worsening of their pain scores and ODI. Three cases of mild to moderate osteolysis were seen in the PLDLLA group. Following up on our preliminary report, these 2-year results confirm the superiority of the PEEK implant to the resorbable PLDLLA implant in aiding spinal fusion and alleviating symptoms following PLIF in patients with degenerative spondylolisthesis associated with either canal stenosis or foramen stenosis or both and emanating from a single lumbar segment.

Holding fast.

PubMed

Gourville, John T

2005-06-01

CEO Peter Walsh faces a classic innovator's dilemma. His company, Crescordia, produces high-quality metal plates, pins, and screws that orthopedic surgeons use to repair broken bones. In fact, because the company has for decades refused to compromise on quality, there are orthopedic surgeons who use nothing but Crescordia hardware. And now these customers have begun to clamor for the next generation technology: resorbable hardware. Resorbables offer clear advantages over the traditional hardware. Like dissolving sutures, resorbable plates and screws are made of biodegradable polymers. They hold up long enough to support a healing bone, then gradually and harmlessly disintegrate in the patient's body. Surgeons are especially looking forward to using resorbables on children, so kids won't have to undergo a second operation to remove the old hardware after their bones heal, a common procedure in pediatrics. The new products, however, are not yet reliable; they fail about 8% of the time, sometimes disintegrating before the bone completely heals and sometimes not ever fully disintegrating. That's why Crescordia, mindful of its hard-earned reputation, has delayed launching a line using the new technology. But time is running out. A few competitors have begun to sell resorbables despite their imperfections, and these companies are picking up market share. Should Crescordia join the fray and risk tarnishing its brand? Or should the company sit tight until it can offer a perfect product? Commenting on this fictional case study are Robert A. Lutz, vice chairman of product development at General Motors; Clayton M. Christensen, the Robert and Jane Cizik Professor of Business Administration at Harvard Business School; Jason Wittes, a senior equity analyst covering medical supplies and devices at Leerink Swann; and Nick Galakatos, a general partner of MPM Capital.

Evaluation of carbonate apatite blocks fabricated from dicalcium phosphate dihydrate blocks for reconstruction of rabbit femoral and tibial defects.

PubMed

Kanazawa, Masayuki; Tsuru, Kanji; Fukuda, Naoyuki; Sakemi, Yuta; Nakashima, Yasuharu; Ishikawa, Kunio

2017-06-01

This study aimed to evaluate in vivo behavior of a carbonate apatite (CO 3 Ap) block fabricated by compositional transformation via a dissolution-precipitation reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO 4 ·2H 2 O] block as a precursor. These blocks were used to reconstruct defects in the femur and tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the control. Both the CO 3 Ap and HAp blocks showed excellent tissue response and good osteoconductivity. HAp block maintained its structure even after 24 weeks of implantation, so no bone replacement of the implant was observed throughout the post-implantation period in either femoral or tibial bone defects. In contrast, CO 3 Ap was resorbed with increasing time after implantation and replaced with new bone. The CO 3 Ap block was resorbed approximately twice as fast at the metaphysis of the proximal tibia than at the epiphysis of the distal femur. The CO 3 Ap block was resorbed at an approximately linear change over time, with complete resorption was estimated by extrapolation of data at approximately 1-1.5 years. Hence, the CO 3 Ap block fabricated in this study has potential value as an ideal artificial bone substitute because of its resorption and subsequent replacement by bone.

Fcγ receptor-mediated influx of S100A8/A9-producing neutrophils as inducer of bone erosion during antigen-induced arthritis.

PubMed

Di Ceglie, Irene; Ascone, Giuliana; Cremers, Niels A J; Sloetjes, Annet W; Walgreen, Birgitte; Vogl, Thomas; Roth, Johannes; Verbeek, J Sjef; van de Loo, Fons A J; Koenders, Marije I; van der Kraan, Peter M; Blom, Arjen B; van den Bosch, Martijn H J; van Lent, Peter L E M

2018-05-02

correlations were found between bone erosion and the number of neutrophils present in the joint as well as between bone erosion and the number of S100A8-positive cells, with S100A8 being an alarmin strongly produced by neutrophils that stimulates osteoclast resorbing activity. FcγRs play a crucial role in the development of bone erosion during AIA by inducing inflammation. In particular, FcγRIV mediates bone erosion in AIA by inducing the influx of S100A8/A9-producing neutrophils into the arthritic joint.

Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

PubMed Central

Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

2012-01-01

Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

Preparation of Emulsifying Wax/GMO Nanoparticles and Evaluation as a Delivery System for Repurposing Simvastatin in Bone Regeneration.

PubMed

Eskinazi-Budge, Aaron; Manickavasagam, Dharani; Czech, Tori; Novak, Kimberly; Kunzler, James; Oyewumi, Moses O

2018-05-30

Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia that has attracted so much attention in bone regeneration based on its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 µg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy simvastatin-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.

The calculation of annual limits of intake for plutonium-239 in man using a bone model which allows for plutonium burial and recycling.

PubMed

Priest, N D; Hunt, B W

1979-05-01

Values of the annual limit of intake (ALI) for plutonium-239 in man have been calculated using committed dose equivalent limits as recommended by ICRP in Publication 26. The calculations were made using a multicompartment bone model which allows for plutonium burial and recycling in the skeleton. In one skeletal compartment, the growing surfaces of cortical bone, it is assumed that plutonium deposits are retained and are not subject to resorption or recycling. In the trabecular bone compartment plutonium is taken to be resorbed with either subsequent redeposition onto bone surfaces or retention in the bone marrow. ALIs for plutonium-239 have been calculated assuming a range of rates of bone accretion (0-32 micron yr-1), different amounts of plutonium retained in the marrow (0-60%) and a 20%, 45% or 70% deposition of plutonium in the skeleton from the blood. The calculations made using this bone model suggest that 750 Bq (20 nCi) is an appropriate ALI for the inhalation of class W and class Y plutonium compounds and that 830 kBq and 5 MBq (23 muCi and 136 muCi) are the appropriate ALIs for the ingestion of soluble and insoluble forms of plutonium respectively.

Osteoclastogenesis and Osteoclastic Resorption of Tricalcium Phosphate: Effect of Strontium and Magnesium Doping

PubMed Central

Roy, Mangal; Bose, Susmita

2012-01-01

Bone substitute materials are required to support the remodeling process, which consists of osteoclastic resorption and osteoblastic synthesis. Osteoclasts, the bone resorbing cells, generate from differentiation of hemopoietic mononuclear cells. In the present study we have evaluated the effects of 1.0 wt% strontium (Sr) and 1.0 wt% magnesium (Mg) doping in beta-tricalcium phosphate (β-TCP) on the differentiation of mononuclear cells into osteoclast-like cells and its resorptive activity. In vitro osteoclast-like cell formation, adhesion, and resorption were studied using osteoclast precursor RAW 264.7 cell, supplemented with receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast-like cell formation was noticed on pure and Sr doped β-TCP samples at day 8 which was absent on Mg doped β-TCP samples indicating decrease in initial osteoclast differentiation due to Mg doping. After 21 days of culture, osteoclast-like cell formation was evident on all samples with osteoclastic markers such as actin ring, multiple nuclei, and presence of vitronectin receptor αvβ3 integrin. After osteoclast differentiation, all substrates showed osteoclast-like cell mediated degradation, however; significantly restricted for Mg doped β-TCP samples. Our present results indicated substrate chemistry controlled osteoclast differentiation and resorptive activity which can be used in designing TCP based resorbable bone substitutes with controlled degradation properties. PMID:22566212

Osteoclastogenesis and osteoclastic resorption of tricalcium phosphate: effect of strontium and magnesium doping.

PubMed

Roy, Mangal; Bose, Susmita

2012-09-01

Bone substitute materials are required to support the remodeling process, which consists of osteoclastic resorption and osteoblastic synthesis. Osteoclasts, the bone-resorbing cells, generate from differentiation of hemopoietic mononuclear cells. In the present study, we have evaluated the effects of 1.0 wt % strontium (Sr) and 1.0 wt % magnesium (Mg) doping in beta-tricalcium phosphate (β-TCP) on the differentiation of mononuclear cells into osteoclast-like cells and its resorptive activity. In vitro osteoclast-like cell formation, adhesion, and resorption were studied using osteoclast precursor RAW 264.7 cell, supplemented with receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast-like cell formation was noticed on pure and Sr-doped β-TCP samples at day 8, which was absent on Mg-doped β-TCP samples indicating decrease in initial osteoclast differentiation due to Mg doping. After 21 days of culture, osteoclast-like cell formation was evident on all samples with osteoclastic markers such as actin ring, multiple nuclei, and presence of vitronectin receptor α(v)β(3) integrin. After osteoclast differentiation, all substrates showed osteoclast-like cell-mediated degradation, however, significantly restricted for Mg-doped β-TCP samples. Our present results indicated that substrate chemistry controlled osteoclast differentiation and resorptive activity, which can be used in designing TCP-based resorbable bone substitutes with controlled degradation properties. Copyright © 2012 Wiley Periodicals, Inc.

Long-term leisure time physical activity and properties of bone: a twin study.

PubMed

Ma, Hongqiang; Leskinen, Tuija; Alen, Markku; Cheng, Sulin; Sipilä, Sarianna; Heinonen, Ari; Kaprio, Jaakko; Suominen, Harri; Kujala, Urho M

2009-08-01

Effects of physical activity on bone properties, when controlled for genetic effects, are not fully understood. We aimed to study the association between long-term leisure time physical activity (LTPA) and bone properties using twin pairs known to be discordant for leisure time physical activity for at least 30 yr. Volumetric BMD and geometric properties were measured at the tibia shaft and distal end using pQCT in 16 middle-aged (50-74 yr) same-sex twin pairs (seven monozygotic [MZ] and nine dizygotic [DZ] pairs) selected from a population-based cohort. Paired differences between active and inactive co-twins were studied. Active members of MZ twin pairs had larger cortical bone cross-sectional area (intrapair difference: 8%, p = 0.006), thicker cortex (12%, p = 0.003), and greater moment of inertia (I(max), 20%, p = 0.024) at the tibia shaft than their inactive co-twins. At the distal tibia, trabecular BMD (12%, p = 0.050) and compressive strength index (18%, p = 0.038) were also higher in physically active MZ pair members than their inactive co-twins. The trends were similar, but less consistently so, in DZ pairs as in MZ pairs. Our genetically controlled study design shows that LTPA during adulthood strengthens bones in a site-specific manner, that is, the long bone shaft has a thicker cortex, and thus higher bending strength, whereas the distal bone has higher trabecular density and compressive strength. These results suggest that LTPA has a potential causal role in decreasing the long-term risk of osteoporosis and thus preventing osteoporotic fractures.

[Neuro-skeletal biology and its importance for clinical osteology].

PubMed

Zofková, I

2012-01-01

Bone remodeling is determined by function of two basic cell forms--bone resorbing osteoclasts and bone formation activating osteoblasts. Both cells are under control of a variety of endogenic and environmental factors, which ensure balance between bone resorption and bone formation. This article reviews the neuro-hormonal factors with osteoanabolic (central isoform of serotonin, melatonin, cannabinoids, beta 1 adrenergic system, oxytocin, ACTH and TSH) or osteocatabolic effects (neuropeptide Y, neuromedin U, beta2 adrenergic system). The dual effects of the beta-adrenergic system, serotonin and leptin are also discussed. The goal of studies focused on neuro-skeletal interaction is to synthesize new molecules, which can modify osteo-anabolic or osteo-catabolic pathways.

TSG-6 Regulates Bone Remodeling through Inhibition of Osteoblastogenesis and Osteoclast Activation*S⃞

PubMed Central

Mahoney, David J.; Mikecz, Katalin; Ali, Tariq; Mabilleau, Guillaume; Benayahu, Dafna; Plaas, Anna; Milner, Caroline M.; Day, Anthony J.; Sabokbar, Afsaneh

2008-01-01

TSG-6 is an inflammation-induced protein that is produced at pathological sites, including arthritic joints. In animal models of arthritis, TSG-6 protects against joint damage; this has been attributed to its inhibitory effects on neutrophil migration and plasmin activity. Here we investigated whether TSG-6 can directly influence bone erosion. Our data reveal that TSG-6 inhibits RANKL-induced osteoclast differentiation/activation from human and murine precursor cells, where elevated dentine erosion by osteoclasts derived from TSG-6-/- mice is consistent with the very severe arthritis seen in these animals. However, the long bones from unchallenged TSG-6-/- mice were found to have higher trabecular mass than controls, suggesting that in the absence of inflammation TSG-6 has a role in bone homeostasis; we have detected expression of the TSG-6 protein in the bone marrow of unchallenged wild type mice. Furthermore, we have observed that TSG-6 can inhibit bone morphogenetic protein-2 (BMP-2)-mediated osteoblast differentiation. Interaction analysis revealed that TSG-6 binds directly to RANKL and to BMP-2 (as well as other osteogenic BMPs but not BMP-3) via composite surfaces involving its Link and CUB modules. Consistent with this, the full-length protein is required for maximal inhibition of osteoblast differentiation and osteoclast activation, although the isolated Link module retains significant activity in the latter case. We hypothesize that TSG-6 has dual roles in bone remodeling; one protective, where it inhibits RANKL-induced bone erosion in inflammatory diseases such as arthritis, and the other homeostatic, where its interactions with BMP-2 and RANKL help to balance mineralization by osteoblasts and bone resorption by osteoclasts. PMID:18586671

Fixation Release and the Bone Bandaid: A New Bone Fixation Device Paradigm

PubMed Central

Shayesteh Moghaddam, Narges; Jahadakbar, Ahmadreza; Amerinatanzi, Amirhesam; Skoracki, Roman; Miller, Michael; Dean, David; Elahinia, Mohammad

2017-01-01

The current gold standard of care for mandibular segmental defeat reconstruction is the use of Ti-6Al-4V immobilization hardware and fibular double barrel graft. This method is often successful immediately at restoring mandible function, however the highly stiff fixation hardware causes stress shielding of the grafted bone and stress concentration in the fixation device over time which can lead to fixation device failure and revision surgery. The purpose of reconstructive surgery could be to create normal stress trajectories in the mandible following engraftment. We investigate the use of a two stage mechanism which separates the immobilization/healing and regenerative phases of mandibular segmental defect treatment. The device includes the use of a very stiff, Ti-6Al-4V, releasable mechanism which assures bone healing. Therefore it could be released once the reconstructed boney tissue and any of its ligamentous attachments have completely healed. Underneath the released Ti-6Al-4V plate would be a pre-loaded nitinol (NiTi) wire-frame apparatus that facilitates the normal stress-strain trajectory through the engrafted bone after the graft is healed in place and the Ti-6Al-4V fixation device has been released. Due to the use of NiTi wires forming a netting that connects vascularized bone and possibly bone chips, bone grafts are also more likely to be incorporate rather than to resorb. We first evaluated a healthy adult mandible during normal mastication to obtain the normal stress-strain distribution. Then, we developed the finite element (FE) model of the mandibular reconstruction (in the M1-3 region) with the proposed fixation device during the healing (locked state) and post-healing (released state) periods. To recreate normal stress trajectory in the reconstructed mandible, we applied the Response Surface Methodology (RMS) to optimize the Bone Bandaid geometry (i.e., wire diameters and location). The results demonstrate that the proposed mechanism immobilizes the

An Evaluation of Select Physical Activity Exercise Classes on Bone Metabolism.

PubMed

Stone, Tori M; Wingo, Jonathan E; Young, John C; Navalta, James W

2018-01-01

Weight-bearing physical activity can optimize bone mass early in life and prevent the development of osteoporosis. However, less is known about the potential benefits of non-weight-bearing activities. The purpose of this study was to assess the efficacy of structured physical activity classes on bone metabolism. Twenty-eight premenopausal women, aged 18-35 years who were either enrolled in a yoga class (n=14) or cardio-kickboxing class (n=14) voluntarily consented to participate. Both classes were introductory classes meeting twice per week for 50 min per session for 12 weeks. Anteroposterior spine (L1-L4), hip (dual femur), and total body bone mineral density (BMD) was measured in both groups pre and post intervention using dual-energy X-ray absorptiometry (DXA). Pre and post blood samples were drawn for measurement of serum osteocalcin (OC) by enzyme-linked immunosorbent assay (ELISA) in each group. Baseline subject characteristics including age, height, weight, body fat percentage, and lean body mass did not differ between groups. BMD levels did not increase but were held stable over the course of the intervention. Yoga increased OC by 68% (P < 0.001) and cardio-kickboxing increased OC by 67% (P < 0.001) over the course of the 12-week classes. While 12 weeks of yoga and cardio-kickboxing were insufficient to induce BMD changes, OC levels reflect the bone formation process was initiated, but not yet complete. Increased OC levels suggest the selected physical activity classes provided enough of a stimulus to precipitate a future response of bone growth, assuming exercise training remains constant.

Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty.

PubMed

Tian, Xiao-bin; Sun, Li; Yang, Shu-hua; Zhang, Yu-kun; Hu, Ru-yin; Fu, De-hao

2008-04-20

Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone

Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley.

PubMed

Sharma, Chetan; Dixit, Manisha; Singh, Rohit; Agrawal, Manali; Mansoori, Mohd Nizam; Kureel, Jyoti; Singh, Divya; Narender, Tadigoppula; Arya, Kamal Ram

2015-07-21

Pholidota articulata Lindley (PA) locally known as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India. Bone is a dynamic organ and is constantly being remodeled in order to facilitate growth and repair. This process requires the involvement of bone forming osteoblast and bone resorbing osteoclast cells, which function in generating and mineralizing bone, giving strength and rigidity to the skeletal system. Present study was aimed to determine the therapeutic potential of ethanolic extract of PA and its isolated compound oxoflavidin, by characterizing their fracture healing properties. Ovariectomized (Ovx) estrogen deficient adult female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing potential of ethanolic extract of PA. Further, its isolated compounds were tested for their osteogenic efficacy using alkaline phosphatase assay and mineralization assay in vitro in mice calvarial osteoblasts. The ethanolic extract of PA exhibited significant restoration of trabecular micro-architecture in both femoral and tibial bones. Additionally, treatment with PA extract led to better bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin. These results warrant that ethanolic extract of PA and it's pure compound oxoflavidin have fracture healing properties. The extract and oxoflavidin exhibit a strong threapeutical potential for the treatment and management of postmenopausal osteoporosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sinus Floor Elevation and Augmentation Using Synthetic Nanocrystalline and Nanoporous Hydroxyapatite Bone Substitute Materials: Preliminary Histologic Results.

PubMed

Belouka, Sofia-Maria; Strietzel, Frank Peter

To compare the tissue composition of augmented sites after using two different synthetic bone substitute materials, nanocrystalline and nanoporous hydroxyapatite (HA), for sinus floor elevation and augmentation. Forty-four patients received 88 titanium screw implants (Camlog Promote plus) of 4.3-mm diameter and 11- or 13-mm length, placed simultaneously during sinus floor elevation and augmentation. Nanocrystalline (Ostim) or nanoporous (NanoBone) HA were used exclusively. Bone substitute materials and implant lengths were allocated by randomization. Bone biopsy specimens were obtained from the former area of the lateral access window at implant exposure during healing abutment placement after 6 months. Biopsy specimens were prepared and examined histologically and histomorphometrically. All implants were osseointegrated at the time of exposure. Clinically and histologically, no signs of inflammation in the augmented sites were present. The histomorphometric analysis of 44 biopsy specimens revealed 31.8% ± 11.6% newly formed bone for sites augmented with nanocrystalline HA and 34.6% ± 9.2% for nanoporous HA (P = .467). The proportion of remaining bone substitute material was 28.4% ± 18.6% and 30% ± 13%, respectively (P = .453). The proportion of soft tissue within the biopsy specimens was 39.9% ± 11.1% and 35.4% ± 6.8%, respectively (P = .064). No significant differences were found between the area fractions of bone, bone substitute material, and soft tissue concerning the bone substitute material utilized. Within the present study, both synthetic bone substitute materials, nanocrystalline and nanoporous HA, were found to support bone formation in sinus floor elevation and augmentation procedures by osteoconductivity. They were not completely resorbed after 6 months. The amounts of newly formed bone, soft tissue, and bone substitute material remnants were found to be similar, indicating that both materials are likewise suitable for sinus floor elevation and

Evaluating adhesion reduction efficacy of type I/III collagen membrane and collagen-GAG resorbable matrix in primary flexor tendon repair in a chicken model.

PubMed

Turner, John B; Corazzini, Rubina L; Butler, Timothy J; Garlick, David S; Rinker, Brian D

2015-09-01

Reduction of peritendinous adhesions after injury and repair has been the subject of extensive prior investigation. The application of a circumferential barrier at the repair site may limit the quantity of peritendinous adhesions while preserving the tendon's innate ability to heal. The authors compare the effectiveness of a type I/III collagen membrane and a collagen-glycosaminoglycan (GAG) resorbable matrix in reducing tendon adhesions in an experimental chicken model of a "zone II" tendon laceration and repair. In Leghorn chickens, flexor tendons were sharply divided using a scalpel and underwent repair in a standard fashion (54 total repairs). The sites were treated with a type I/III collagen membrane, collagen-GAG resorbable matrix, or saline in a randomized fashion. After 3 weeks, qualitative and semiquantitative histological analysis was performed to evaluate the "extent of peritendinous adhesions" and "nature of tendon healing." The data was evaluated with chi-square analysis and unpaired Student's t test. For both collagen materials, there was a statistically significant improvement in the degree of both extent of peritendinous adhesions and nature of tendon healing relative to the control group. There was no significant difference seen between the two materials. There was one tendon rupture observed in each treatment group. Surgical handling characteristics were subjectively favored for type I/III collagen membrane over the collagen-GAG resorbable matrix. The ideal method of reducing clinically significant tendon adhesions after injury remains elusive. Both materials in this study demonstrate promise in reducing tendon adhesions after flexor tendon repair without impeding tendon healing in this model.

A modified cementing technique using BoneSource to augment fixation of the acetabulum in a sheep model.

PubMed

Timperley, A John; Nusem, Iulian; Wilson, Kathy; Whitehouse, Sarah L; Buma, Pieter; Crawford, Ross W

2010-08-01

Our aim was to assess in an animal model whether the use of HA paste at the cement-bone interface in the acetabulum improves fixation. We examined, in sheep, the effect of interposing a layer of hydroxyapatite cement around the periphery of a polyethylene socket prior to fixing it using polymethylmethacrylate (PMMA). We performed a randomized study involving 22 sheep that had BoneSource hydroxyapatite material applied to the surface of the acetabulum before cementing a polyethylene cup at arthroplasty. We studied the gross radiographic appearance of the implant-bone interface and the histological appearance at the interface. There were more radiolucencies evident in the control group. Histologically, only sheep randomized into the BoneSource group exhibited a fully osseointegrated interface. Use of the hydroxyapatite material did not give any detrimental effects. In some cases, the material appeared to have been fully resorbed. When the material was evident in histological sections, it was incorporated into an osseointegrated interface. There was no giant cell reaction present. There was no evidence of migration of BoneSource to the articulation. The application of HA material prior to cementation of a socket produced an improved interface. The technique may be useful in humans, to extend the longevity of the cemented implant by protecting the socket interface from the effect of hydrodynamic fluid flow and particulate debris.

Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

PubMed

van der Pol, U; Mathieu, L; Zeiter, S; Bourban, P-E; Zambelli, P-Y; Pearce, S G; Bouré, L P; Pioletti, D P

2010-09-01

Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

PubMed

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Top 10 Research Questions Related to Physical Activity and Bone Health in Children and Adolescents

ERIC Educational Resources Information Center

Janz, Kathleen F.; Thomas, David Q.; Ford, M. Allison; Williams, Skip M.

2015-01-01

Evidence strongly supports a positive, causal effect of physical activity on bone strength and suggests long-term benefits of childhood physical activity to the prevention of osteoporosis. The contribution of healthy bone development in youth is likely to be as important to fracture prevention as the amount of late adulthood bone loss. Families,…

Polycythemia is associated with bone loss and reduced osteoblast activity in mice.

PubMed

Oikonomidou, P R; Casu, C; Yang, Z; Crielaard, B; Shim, J H; Rivella, S; Vogiatzi, M G

2016-04-01

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO). PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO. Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2(V617F) knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO. Compared to wt, both JAK2(V617F) and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P < 0.01) suggesting a more severe bone phenotype than JAK2(V617F). Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice. This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

Polymer-ceramic nanocomposites for applications in the bone surgery

NASA Astrophysics Data System (ADS)

Stodolak, E.; Gadomska, K.; Lacz, A.; Bogun, M.

2009-01-01

The subject of this work was preparation and investigation of properties of a nanocomposite material based on polymer matrix modified with nanometric silica particles (SiO2). The composite matrix consisted of resorbable P(L/DL)LA polymer with certified biocompatibility. Nanometric silica was introduced into the matrix by means of ultrasonic homogenisation and/or mechanical stirring. The silica was introduced directly e.g. as nanoparticles or inside calcium alginate fibres which contained 3 wt.% of amorphous SiO2. Proper dispersion of nano-filliers was confirmed by means of thermal analysis (TG/DTA, DSC). It was observed, that the presence of inorganic nanoparticles influenced several surface parameters of the nanocomposites i.e. hydrophility (a decrease of surface energy) and topography (both in micro- and nano-scale). Additionally, the nanocomposites exhibited enhanced mechanical properties (Young's modulus, tensile strength) compared to the pure polymer. The nanocomposites were bioactive materials (SBF/3 days/37oC). Biological tests (MTT test) showed a good viability of human osteoblasts (hFOB 1.19) in contact with the nanocomposites surface. Results of preliminary biological tests carried out with the use of mother cells extracted from human bone marrow showed that the nanocomposites may provide differenation of bone cells.

Physical activity programs for promoting bone mineralization and growth in preterm infants.

PubMed

Schulzke, Sven M; Kaempfen, Siree; Trachsel, Daniel; Patole, Sanjay K

2014-04-22

Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth. The primary objective was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fracture.The secondary objectives included other potential benefits in terms of length of hospital stay, skeletal deformities and neurodevelopmental outcomes, and adverse events.Subgroup analysis:• Given that the smallest infants are most vulnerable for developing osteopenia (Bishop 1999), a subgroup analysis was planned for infants with birth weight < 1000 g.• Calcium and phosphorus intake may affect an infant's ability to increase bone mineral content (Kuschel 2004). Therefore, an additional subgroup analysis was planned for infants receiving different amounts of calcium and phosphorus, along with full enteral feeds as follows. ∘ Below 100 mg/60 mg calcium/phosphorus or equal to/above 100 mg/60 mg calcium/phosphorus per 100 mL milk. ∘ Supplementation of calcium without phosphorus. ∘ Supplementation of phosphorus without calcium. The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9), MEDLINE, EMBASE, CINAHL (1966 to March 2013), and cross-references, as well as handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) versus no organized physical activity programs in preterm infants. Data collection, study selection, and data analysis were performed according to the methods of the CNRG. Eleven trials enrolling 324 preterm infants

Osteopenia of Prematurity: Does Physical Activity Improve Bone Mineralization in Preterm Infants?

PubMed

Stalnaker, Kelsey A; Poskey, Gail A

2016-01-01

Bone mineralization of preterm infants is significantly less than full-term infants at birth, placing preterm infants at risk for osteopenia of prematurity and other metabolic bone diseases. Advances in nutritional supplementation and standard nursing care alone have been unsuccessful in improving bone mineralization postnatally. Research supports a daily physical activity protocol of passive range of motion and gentle joint compression when combined with adequate nutritional supplementation reduces osteopenia of prematurity. This article provides a systematic review of the current evidence surrounding early physical activity and neonatal massage for the treatment of osteopenia and indicates the need for universal handling protocols in caring for this unique population.

Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittal, Monika; Pal, Subhashis; China, Shyamsundar

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuatedmore » the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda

Composition of bone and apatitic biomaterials as revealed by intravital Raman microspectroscopy.

PubMed

Penel, G; Delfosse, C; Descamps, M; Leroy, G

2005-05-01

Microcharacterization of biominerals allows a better understanding of the pathophysiological events that occur in calcified tissues and synthetic biomaterials. Different methods have been extensively used to conduct such investigations. A new model for the intravital study of the composition and structure of membranous bone by Raman microspectroscopy is described. Titanium bone chambers equipped with a fused-silica optical window were implanted transcutaneously in the calvaria of New Zealand rabbits. The implanted optical windows were well tolerated, and spectral acquisitions were performed without any additional invasive procedure. Bone and implanted apatitic biomaterials were analyzed at different times after surgery. All Raman bands were unambiguously identified in the bone and biomaterial spectra. The main PO4 and CO3 Raman bands in bone spectra were consistent with those found in the carbonated apatite spectrum. The major collagen bands were always observed around 1200-1300 (amide III) and 1600-1700 (amide I) delta cm(-1) and, 1400-1470 and 2800-3100 delta cm(-1) (bending and stretching modes of CH groups, respectively). The phenylalanine (Phe) band was identified in all spectra at 1003 delta cm(-1) and overlapped that of the weak HPO4(2-) ion. The CH bands frequently overlapped the lipid bands. However a distinct protein and lipid bands were detected at 2950 and 2852 delta cm(-1), respectively. In bone areas close to blood vessels, the Raman signature of hemoglobin was detected with a characteristic band at 754 delta cm(-1). The changes observed in bone varied as a function of time and location. The composition and structure of all of the biomaterials studied--including those that were resorbable--seemed to remain stable over time and location. We report for the first time the complete intravital study of Raman spectra of bone and calcium phosphate biomaterials over a period of 8 months. This new approach does not require specimen preparation and allows

Osteoclast size heterogeneity in rat long bones is associated with differences in adhesive ligand specificity.

PubMed

Hu, Yingwei; Ek-Rylander, Barbro; Karlström, Erik; Wendel, Mikael; Andersson, Göran

2008-02-01

Prothrombin (PT) is an RGD-containing bone-residing precursor to the serine protease thrombin (TH), which acts as an agonist for a variety of cellular responses in osteoblasts and osteoclasts. We show here that PT, TH, osteopontin (OPN) and fibronectin (FN) promoted adhesion of isolated neonatal rat long bone osteoclasts. However, the cells that adhered to PT and TH were smaller in size, rounded and contained 3-4 nuclei, in comparison to the cells adhering to OPN and FN, which were larger with extended cytoplasmic processes and 6-7 nuclei. Attachment of the larger osteoclasts to OPN and FN was inhibited by antibodies towards beta 3 and beta 1 integrin subunits, respectively. Whereas an RGD-containing peptide inhibited adhesion of the smaller osteoclasts to PT and TH, this was not seen with the beta 3 or beta 1 antibodies. In contrast, the beta 1 antibody augmented osteoclast adhesion to PT and TH in an RGD-dependent manner. Small osteoclasts were less efficient in resorbing mineralized bovine bone slices, as well as expressed lower mRNA levels of MMP-9 and the cathepsins K and L compared to large osteoclasts. The small osteoclast adhering to PT and TH may represent either an immature, less functional precursor to the large osteoclast or alternatively constitute a distinct osteoclast population with a specific role in bone.