Bone Healing In Rats Research Articles

The effects of an injury to the brain on bone healing and callus formation in young adults with fractures of the femoral shaft

In patients with traumatic brain injury and fractures of long bones, it is often clinically observed that the rate of bone healing and extent of callus formation are increased. However, the evidence has been unconvincing and an association between such an injury and enhanced fracture healing remains unclear. We performed a retrospective cohort study of 74 young adult patients with a mean age of 24.2 years (16 to 40) who sustained a femoral shaft fracture (AO/OTA type 32A or 32B) with or without a brain injury. All the fractures were treated with closed intramedullary nailing. The main outcome measures included the time required for bridging callus formation (BCF) and the mean callus thickness (MCT) at the final follow-up. Comparative analyses were made between the 20 patients with a brain injury and the 54 without brain injury. Subgroup comparisons were performed among the patients with a brain injury in terms of the severity of head injury, the types of intracranial haemorrhage and gender. Patients with a brain injury had an earlier appearance of BCF (p < 0.001) and a greater final MCT value (p < 0.001) than those without. There were no significant differences with respect to the time required for BCF and final MCT values in terms of the severity of head injury (p = 0.521 and p = 0.153, respectively), the types of intracranial haemorrhage (p = 0.308 and p = 0.189, respectively) and gender (p = 0.383 and p = 0.662, respectively). These results confirm that an injury to the brain may be associated with accelerated fracture healing and enhanced callus formation. However, the severity of the injury to the brain, the type of intracranial haemorrhage and gender were not statistically significant factors in predicting the rate of bone healing and extent of final callus formation.

Comparison of Surface Area across the Allograft-Host Junction Site Using Conventional and Navigated Osteotomy Technique

Bulk allograft reconstruction plays an important role in limb-salvage surgery; however, non-union has been reported in up to 27% of cases. The purpose of this study is to quantify average surface contact areas across simulated intraoperative osteotomies using both free-hand and computer-assisted navigation techniques. Pressure-sensitive paper was positioned between two cut ends of a validated composite sawbone and compression was applied using an eight-hole large fragment dynamic compression plate. Thirty-two samples were analyzed for surface area contact to determine osteotomy congruity. Mean contact area using the free-hand osteotomy technique was equal to 0.21 square inches. Compared with a control of 0.69 square inches, average contact area was found to be 30.5% of optimal surface contact. Mean contact area using computer-assisted navigation was equal to 0.33 square inches. Compared with a control of 0.76 square inches, average contact area was found to be 43.7% of optimal surface contact. Limited contact achieved using standard techniques may play a role in the high rate of observed non-union, and an increase in contact area using computer-assisted navigation may improve rates of bone healing. The development of an oncology software package and navigation hardware may serve an important role in decreasing non-union rates in limb salvage surgery.

Osteosintesi e artrodesi circonferenziale in un caso di “burst-split fracture” di L2

We present the case of a burst-split fracture of L2 presenting with paraplegia in a young woman. After surgical decompression and posterior L1–3 instrumentation the patient significantly improved and her consent to a second anterior approach was not given. Six months later, after a moderate lumbar trauma we documented a rupture of the pedicular screws with further L2 collapse and kyphosis. The patient was then submitted to revision of the posterior instrumentation and further anterior arthrodesis through an anterolateral retroperitoneal approach with implant of an expandable cage. The case confirms the low bone healing rate of this type of fractures in which a circumferential arthrodesis is mandatory.

Degenerate Wave and Capacitive Coupling Increase Human MSC Invasion and Proliferation While Reducing Cytotoxicity in an In Vitro Wound Healing Model

Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC), capacitive coupling (CC), pulsed electromagnetic field (PEMF) and degenerate wave (DW) on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G2/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p<0.05). We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site.

Bone Repair and Regeneration: Editorial Comment

Regenerative therapies for bone and muscle reconstitution require understanding of both biologic and mechanical conditions. Even though this is well known, its implications for clinical therapies are only to a limited degree recognized. The goal of this symposium was to initiate discussion on the cellular, tissue, and organ levels, formulate current concepts in musculoskeletal regeneration, and promote the translation of their techniques into the clinic. Recent advances in both musculoskeletal biomechanics and molecular and cell biologic approaches in tissue engineering have led to high expectations among scientists, clinicians, and patients, especially in joint and bone reconstruction. Mechanobiology plays here a central role in linking mechanotransduction and tissue engineering with macroscopic tissue behavior and characteristics of native and artificial biomaterials. Successful translation to clinical practice additionally requires extensive interaction with physicians. By initiating discussion and interaction between the basic disciplines involved in investigating the regeneration of musculoskeletal tissues, together with clinical partners, we aim to identify strategic areas within and interactions between the disciplines that are essential for bringing new therapies to the clinic (Fig. 1). Fig. 1 Dr. Georg N. Duda is shown. The work from Ball et al. [1] reflects recent developments in bio-inspired nanomaterials and tissue regeneration of bone. Engineering of large volumes of bone in vivo seems applicable; however, a thorough materials analysis of tissue-engineered bone still remains mandatory to come to an understanding of native tissue formation. Willie et al. [7] present an approach to vary fixation stiffness and describe how stiffness affects bone healing in rat osteotomies. Mehta et al. [4] describe delayed bone healing in female aged rats compared to male rats and how mechanical stimulation affects tissue formation and maturation between the genders. Johnson et al. [2] explain the highly metabolic and vascularized bone tissue essential for normal growth and repair. A logical strategy to promote healing is therefore to deliver factors that stimulate increased or accelerated vascular growth. Effective sustained delivery of small-molecule activators of specific pathways open new and exciting therapeutic approaches. Kolar et al. [3] analyzed hematoma in patients with autoimmune diseases or otherwise restricted immune functions. They compared these hematoma samples with ones from otherwise healthy controls and found an upregulation of specific immune cells. Other work [5] has also recently illustrated specific subsets of immune cells apparently relevant for prompt healing. These studies raise the question to what degree the early immune response in healing should be differentiated in a more and in a less beneficial phase to bone healing. If so, treatment modalities should specifically address the distinct aspects of the immune responses after injury. Finally and from a completely different perspective, von Domarus et al. [6] describe the relevance of vitamin D for skeletal health and cancer prevention. Such a link is important to understand since a substantial portion of the global population suffers from a vitamin D deficit. It will be of importance for the future care of patients with fractures to better understand bone regeneration and healing from the standpoint of influencing factors, such as the immune status, bone metabolism, and gender-specific aspects of healing. The comprehensive view of the patient itself and the modalities of treatment currently available present a great chance to come to a realistic understanding of deficits in healing and—in a true sense—a personalized medical approach in musculoskeletal surgery.

Undifferentiated Human Adipose Tissue–Derived Stromal Cells Induce Mandibular Bone Healing in Rats

To test the osteo-regenerative potential of adipose tissue-derived stromal cells (ATSCs), an attractive human source for tissue engineering, in a rat model of mandibular defect. Human dermal fibroblasts (HDFs) were used as a differentiated cellular control in the study. The ATSCs and HDFs were isolated from human lipoaspirate and skin biopsy specimens, respectively. Cells were characterized in vitro and then adsorbed on an osteo-conductive scaffold to be transplanted in a mandibular defect of immunosuppressed rats. Naked unseeded scaffold was used as a negative control. Bone healing was studied by computerized tomography and histologic analysis after 4, 8, and 12 weeks. Computed tomography showed that undifferentiated ATSCs induced successful bone healing of the mandible defect when transplanted in animals, compared with HDFs and negative controls. Histologic analysis demonstrated that the newly formed tissue in the surgical defect retained the features of compact bone. Undifferentiated human ATSCs are suitable for cell-based treatment of mandibular defects, even in the absence of previous osteogenic induction in vitro.

Repair of rat cranial bone defects with nHAC/PLLA and BMP‐2‐related peptide or rhBMP‐2

An ideal artificial substitute has good biocompatibility properties and is able to provide for rapid bone formation. Bone morphogenetic protein-2 (BMP-2) is considered as one of the most important growth factors for bone regeneration. In this study, a synthetic BMP-2-related peptide (designated P24) corresponding to residues of the knuckle epitope of BMP-2 was introduced into a bioactive scaffold based on nano-hydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLLA); its in vitro release kinetics was then measured. A 5 mm diameter cranial bone defect was created in the calvariae of 30 rats and randomly implanted with three groups of biomaterials: Group A (nHAC/PLLA alone); Group B (P24/nHAC/PLLA composite); and Group C (recombinant human BMP-2 (rhBMP-2)/nHAC/PLLA composite). The P24/nHAC/PLLA implants significantly stimulated bone growth similarly to the rhBMP-2/nHAC/PLLA implants based on the radiographic and three-dimensional CT evaluation and histological examination, thereby confirming the enhanced bone healing rate of these compounds compared with the stand-alone nHAC/PLLA scaffold material. The osteoinductive ability of 3 mg P24 was similar to that of 1 µg rhBMP-2. P24/nHAC/PLLA is a promising scaffold biomaterial for bone tissue regeneration.

Histometric Study of Alveolar Bone Healing in Rats Treated With the Nonsteroidal Anti-Inflammatory Drug Nimesulide

There is extensive experimental and clinical evidence in the orthopedic area that prolonged use of nonselective (inhibitor of both cyclooxygenases 1 and 2) nonsteroidal anti-inflammatory drugs can hinder long bone fracture healing, spinal fusion rate, and new bone formation around implants. The purpose of the present study was to investigate whether nimesulide (Nimesulida, Medley S.A., Campinas, SP, Brazil), a preferential cyclooxygenase-2 inhibitor, can hinder alveolar bone healing, in rats. Treated rats received oral doses (5 mg/kg/rat/day) of nimesulide from the day of tooth extraction until euthanasia 2 weeks later and control rats received tap water (n = 5 per group). The volume of neoformed bone inside the alveolar socket was estimated in semiserial longitudinal histological sections by a differential point-counting method, and the significance of the difference between groups was analyzed by Student t test (P < 0.05 for statistical significance). Histometric data confirmed histological observation that the volume fraction of new bone trabeculae in treated rats was not significantly different from that in control rats. Short-term treatment with nimesulide, although its capacity to inhibit preferentially the enzyme cyclooxygenase-2, does not interfere with alveolar bone healing in rats.

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP) family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF)-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue. Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

The Effect of Silver Ions Improved Oxydic Glass upon Bone Healing in Rats

The Effect of Silver Ions Improved Oxydic Glass upon Bone Healing in Rats

Low-Intensity Pulsed Ultrasound Produced an Increase of Osteogenic Genes Expression During the Process of Bone Healing in Rats

The aim of this study was to measure the temporal expression of osteogenic genes during the process of bone healing in low-intensity pulsed ultrasound (LIPUS) treated bone defects by means of histopathologic and real-time polymerase chain reaction (PCR) analysis. Animals were randomly distributed into two groups ( n = 30): control group (bone defect without treatment) and LIPUS treated (bone defect treated with LIPUS). On days 7, 13 and 25 postinjury, 10 rats per group were sacrificed. Rats were treated with a 30 mW/cm 2 LIPUS. The results pointed out intense new bone formation surrounded by highly vascularized connective tissue presenting a slight osteogenic activity, with primary bone deposition was observed in the group exposed to LIPUS in the intermediary (13 days) and late stages of repair (25 days) in the treated animals. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) showed an upregulation of bone morphogenetic protein 4 (BMP4), osteocalcin and Runx2 genes 7 days after the surgery. In the intermediary period, there was no increase in the expression. The expression of alkaline phosphatase, BMP4 and Runx2 was significantly increased at the last period. Our results indicate that LIPUS therapy improves bone repair in rats and upregulated osteogenic genes, mainly at the late stages of recovery. (E-mail: a.renno@unifesp.br)

The effect of whole-body vibration on peri-implant bone healing in rats

The aim of this study was to evaluate the effect of low-magnitude, high-frequency (LMHF) loading, applied by means of whole-body vibration (WBV), on peri-implant bone healing and implant osseointegration in rat tibiae. A custom-made titanium implant was inserted into the proximal metaphysis of the tibiae of 42 rats and left to heal for 3, 7, 14 or 25 days. Half of the animals received LMHF mechanical vibration for 5 days per week (test), whereas the others served as unloaded controls. The WBV consisted of 15 consecutive frequency steps (12, 20, 30, … to 150 Hz). Each of the 15 frequencies was applied for 2000 cycles, at an acceleration of 0.3 g. In the group with a 25-day healing period, PET images were taken at -1 (day before surgery), 3, 5, 7, 10, 14 and 21 days of loading, after an injection of [(18)F]sodium fluoride, a positron-emitting tracer. The ratio of the metabolic activity around the implants to that of a reference site (uptake ratio) was calculated as a measure of bone metabolism. Bone-to-implant contact (BIC) and peri-implant bone fraction (BF) were analysed for histomorphometrical measurement. The mean BIC and BF were significantly influenced by both the loading and the healing time (ANOVA, P<0.01). The PET images did not reveal any significant difference in uptake ratio between the test and the control implants. LMHF loading increased BIC and BF significantly. The results confirm the bone-stimulating potential of LMHF loading, through WBV, on peri-implant bone healing and osseointegration.

Bone‐Like Elastomer‐Toughened Scaffolds with Degradability Kinetics Matching Healing Rates of Injured Bone

AbstractBiomaterial scaffolds provide a potentially powerful means of creating precisely engineered bone tissue substitutes with appropriate architecture and mechanical properties. Despite many efforts, there are few satisfactory products available for clinical use, and significant challenges remain in the design of smart constructs, especially for mechanically functional scaffolds. For successful long‐term repair of bone, a scaffold must be strong yet have degradation kinetics matching the healing rate of remodeling bone. Here we report a new family of elastomer‐toughened composite scaffolds fabricated from poly(glycerol sebacate) and Bioglass®. These synthetic scaffolds have very similar mechanical properties to that of cancellous bone of the same porosity, and exhibit a mechanically steady state over an extended period in a physiologic environment. The second feature is of great importance to bone tissue engineering, where a lag phase of degradation following implantation is highly desirable in order to provide support to the damaged or fragmented bone tissue. This work shows that a mechanically smart construct with the three‐stage profile (lag, log, and plateau phases) of ideal degradation kinetics in mechanical function is achievable with synthetic biomaterials.

Triple arthrodesis with osteotomy for the treatment of stage IIB and stage III adult-acquired flatfoot deformity

To analyze the clinical outcomes of triple arthrodesis with osteotomy in the treatment of Stage IIB and Stage III adult-acquired flatfoot. The authors reviewed 10 cases of adult-acquired flatfoot, including 3 cases of stage IIB adult-acquired flatfoot and 7 cases of stage III adult-acquired flatfoot. They were treated by triple arthrodesis with osteotomy of subtalar joint (STJ), talonavicular joint (TNJ) and calcaneocuboid joint (CCJ). The combined medial and lateral incisions were used to obtain adequate exposure for CCJ, STJ and TNJ. Then the cartilages of CCJ, STJ and TNJ were completely denuded and osteotomies to restore their proper alignments. The optimal positioning of hindfoot could be achieved and fixed by Kirschner wires. Two cannulated screws of 7.3 mm were delivered through the plantar aspect of heel to fix STJ. And then two 4.5 mm cannulated screws individually fixed TNJ and CCJ distal to proximal. Clinical evaluations were based on the AOFAS ankle-hindfoot scale and subjective assessments of pains, function, cosmesis and overall satisfaction. Radiographic evaluations included measurements of anterior-posterior talo-first metatarsal angle, lateral talocalcaneal angle, lateral talo-first metatarsal angle and an assessment of time to union for all arthrodeses. All patients were followed-up with a mean time of 13.2 (6 - 21) months. The average AOFAS ankle-hindfoot scale improved from 39.4 ± 4.4 preoperatively to 83.7 ± 2.6 postoperatively (P < 0.01). And the patients experienced subjective improvements in pain, function and cosmesis. Overall, all patients were satisfied. Radiographically, the rate of bone healing was 100%. The anterior-posterior talo-first metatarsal angle, lateral talocalcaneal angle and lateral talo-first metatarsal angle statistically improved. No complication, such as infection and un-union, was reported. Triple arthrodesis with osteotomy is an effective procedure for the treatment of stage IIB and III adult-acquired flatfoot deformity. It may relieve pains, correct structural deformities and obtain excellent clinical outcomes.

The role of interfragmentary strain on the rate of bone healing—A new interpretation and mathematical model

It is postulated that there is a causal relationship between mechanical stimulus and the rate of bone healing post fracture. However, despite numerous experimental studies in the literature, no quantifiable relationship has been proposed. It is hypothesized in the present study that the temporal rate of bone fracture healing, measured in terms of callus stiffening per week, can be described mathematically based on the relative motions between bone fragments at the initial stage of the healing process. To test this, a comparative reanalysis of experimental data found in the literature was conducted. These individual data sets described a relationship between an initial intermittently applied peak interfragmentary strain and the change in interfragmentary motion or the increase in callus stiffness over time. The data were converted into a relative increase in stiffness, which normalised the results and reduced inter-study variability. The rates of healing for the various initial strains were compared, and based on this a mathematical phenomenological model was derived. Error analyses were then performed, which showed a high level of congruence between the in-vivo and simulated rates of healing. The results of the comparative analysis revealed that there is a positive correlation between the rate of callus stiffening and interfragmentary strain. Finally, the proposed model has shown for the first time that a quantifiable cause–and–effect relationship exists between the rate of bone healing and mechanical stimulus.

Repair of rabbit radial bone defects using true bone ceramics combined with BMP-2-related peptide and type I collagen

An ideal bone graft material is the one characterized with good biocompatibility, biodegradation, osteoconductivity and osteoinductivity. In this study, a novel synthetic BMP-2-related peptide (designated P24) corresponding to residues of the knuckle epitope of BMP-2 was introduced into a biomimetic scaffold based on sintered bovine bone or true bone ceramics (TBC) and type I collagen (TBC/collagen I) using a simulated body fluid (SBF). Hydroxylapatite crystal mineralization with a Ca/P molar ratio of 1.63 was observed on the surface of P24/TBC/collagen I composite by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) techniques. Cell adhesion rate evaluation of bone marrow stromal cells (BMSCs) seeded on materials in vitro showed that the percentage of cells attached to P24/TBC/collagen I composite was significantly higher than that of the TBC/collagen I composite. A 10 mm unilateral segmental bone defect was created in the radius of New Zealand white rabbits and randomly implanted with three groups of biomaterials (Group A: P24/TBC/collagen I composite; Group B: TBC/collagen I composite and Group C: TBC alone). Based on radiographic evaluation and histological examination, the implants of P24/TBC/collagen I composite significantly stimulated bone growth, thereby confirming the enhanced rate of bone healing compared with that of TBC/collagen I composite and TBC alone. It was concluded that BMP-2-related peptide P24 could induce nucleation of calcium phosphate crystals on the surface of TBC/collagen I composite. The TBC/collagen I composite loaded with the synthetic BMP-2-related peptide is a promising scaffold biomaterial for bone tissue engineering.

Comparison between Platelet-Rich Plasma and Autologous Iliac Grafts for Tibial Osteotomy.

Objective:Platelet-rich plasma (PRP) has the capacity to improve the bone-healing process. The aim of this pilot study was to investigate the occurrence of bone healing and the time taken to achieve this in patients submitted to medial opening wedge high tibial osteotomy (MOWHTO), comparing platelet-rich plasma with bone marrow aspirate to autologous iliac graft.Design:Twenty-five patients who underwent tibial osteotomy were randomly divided into 2 groups: a control group, which received autologous iliac grafts (14 patients), and a study group, which received a compound of PRP and bone marrow aspirate (11 patients).Results:The bone-healing rates achieved were 100% in the control group and 91% in the study group. There was no difference in the time taken to achieve bone healing between the groups.Conclusions:The use of a combination of PRP and bone marrow aspirate, as a bone substitute, did not demonstrate any advantage over the use of an autologous iliac graft in MOWHTO.

The influence of local administration of simvastatin in calvarial bone healing in rats

Some authors have associated the use of statins, hypolipidemic drugs, and new bone formation. The aim of this work was to evaluate the effect of locally administered simvastatin on bone healing. Bone calvarial defects 5 mm in diameter were made in 64 rats. The animals were divided into four groups according to the graft material: the control group, in which the defects were not treated, the SIM-1 group, which received a sponge of collagen soaked with simvastatin (2.2 mg/50 μl), the SIM-2 group, which received a sponge of collagen soaked with simvastatin (0.5 mg/50 μl), and the carrier (CAR) group, which received a sponge of collagen and water. The animals were sacrificed after 30 or 60 days. The skulls were removed, and radiographic densitometry and histometric analyses of the bone defect area were performed. Local crust formation was clinically verified in SIM-1 and SIM-2 animals. After statistical analysis ( p < 0.05) of bone area data, we observed no significant differences among the groups after 30 days. After 60 days, however, there was less bone formation in the CAR and SIM-2 groups. The SIM-2 group also presented with lower radiographic densities after 60 days. According to the methodology used, we conclude that locally administered simvastatin was detrimental to the repair of defects in the calvaria of rats.

Histochemical changes in bone healing after treatment with parecoxib

Event Abstract Back to Event Histochemical changes in bone healing after treatment with parecoxib Panagiotis Akritopoulos1, 2*, Paraskevi Papaioannidou1, Maria Dermentzopoulou3, Hippokrates Hatzokos2, Eirini Iosifidou2, Maria Kotoula1 and Vasiliki Mirtsou1 1 Aristotle University of Thessaloniki, Department of Pharmacology, Greece 2 Aristotle University of Thessaloniki, 1st Department of Orthopaedics, Greece 3 Aristotle University of Thessaloniki, Laboratory of Histology-Embryology, Greece Cyclo-oxygenase inhibitors (COX inhibitors) impair bone healing by inhibiting prostaglandin synthesis, angiogenesis and bone formation1-4. The purpose of this work was to study histochemically the effect of parecoxib, a selective COX inhibitor, on bone healing in rats. Closed non-displaced mid-diaphyseal fractures of the left femoral shaft were generated in each animal. In the study group, parecoxib was administered intra-peritoneally every day for seven days, immediately after fracture. In the control group, normal saline was administered intraperitoneally every day for seven days, immediately after fracture. The dose of parecoxib was selected to be sufficient enough to produce inhibition of COX, while it was quite close to doses used in clinical practice: similar to the average recommended therapeutic dose in humans. In both groups bone healing was evaluated histologically 42 days after fracture. In both groups calsified cartilage and transition to bone was observed, as well as shaped osteocytes, osteoblasts, remaining islets of osteoclasts and Haversian canals. One of the animals in the control group appeared with remaining chondrocytes, a picture corresponding to late porosis.

Micronutrients in Parenteral Nutrition: Boron, Silicon, and Fluoride

Boron may be beneficial for bone growth and maintenance, central nervous system function, and the inflammatory response, and silicon may be beneficial for bone maintenance and wound healing. Fluoride is not an essential element but amounts provided by contamination may be beneficial for bone strength. Fluoride toxicity may be a concern in parenteral nutrition. Further studies are warranted to determine whether there are optimal amounts of boron and silicon that should be delivered to typical and special population patients receiving parenteral nutrition. In addition, further studies are needed to determine whether providing the dietary guideline of adequate intake amounts of fluoride parenterally would prevent or treat parenteral nutrition osteopenia.