Bone Growth Rate Research Articles

BONE HEALTH AND GROWTH IN SPINAL MUSCULAR ATROPHY TYPE 2 AND 3

Objective: Spinal muscular atrophy is a lower motor neuron disease, but other parts of the body could be affected. This study compared bone mineral density with bone metabolism and physical growth rates in patients diagnosed with spinal muscular atrophy type 2 and type 3. Material and Methods: Twenty-six patients with spinal muscular atrophy were included in the study (15 patients for type 2 and 11 for type 3). Weights and heights of patients were measured, standard deviation scores were determined, and the body-mass index was calculated. Motor function and pubertal assessment were performed. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin vitamin D levels were compared. Spine radiography for scoliosis and bone densitometry for bone mineral density were performed, and volumetric bone mineral density was calculated for age and sex. Results: Medians of height standard deviation scores were significantly lower in type 2 patients. There was no difference between the two groups in terms of serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin D levels. The ratio of scoliosis was higher in type 2 patients as was its severity, but Z-scores of volumetric bone mineral density was lower in the same group. Conclusion: This study showed that bone mineralization and growth rates were significantly lower in spinal muscular atrophy, mainly in type 2. Further studies are needed to evaluate bone health in spinal muscular atrophy patients.

BONE HEALTH AND GROWTH IN SPINAL MUSCULAR ATROPHY TYPE 2 AND 3

Objective: Spinal muscular atrophy is a lower motor neuron disease, but other parts of the body could be affected. This study compared bone mineral density with bone metabolism and physical growth rates in patients diagnosed with spinal muscular atrophy type 2 and type 3. Material and Methods: Twenty-six patients with spinal muscular atrophy were included in the study (15 patients for type 2 and 11 for type 3). Weights and heights of patients were measured, standard deviation scores were determined, and the body-mass index was calculated. Motor function and pubertal assessment were performed. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin vitamin D levels were compared. Spine radiography for scoliosis and bone densitometry for bone mineral density were performed, and volumetric bone mineral density was calculated for age and sex. Results: Medians of height standard deviation scores were significantly lower in type 2 patients. There was no difference between the two groups in terms of serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin D levels. The ratio of scoliosis was higher in type 2 patients as was its severity, but Z-scores of volumetric bone mineral density was lower in the same group. Conclusion: This study showed that bone mineralization and growth rates were significantly lower in spinal muscular atrophy, mainly in type 2. Further studies are needed to evaluate bone health in spinal muscular atrophy patients.

Embryonic requirements for Tcf12 in the development of the mouse coronal suture.

A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in either of the bHLH transcription factors TWIST1 and TCF12. Although compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 had remained unexplored. Here, we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in embryonic neural crest and mesoderm, but not in postnatal suture mesenchyme, disrupts the coronal suture. We also detected asymmetric distribution of mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry is associated with bones meeting end-on-end, possibly contributing to synostosis. Our results support embryonic requirements of Tcf12 in proper formation of the overlapping coronal suture.

Validation of an in vivo micro-CT-based method to quantify longitudinal bone growth of pubertal rats.

Bone growth is an essential part of skeletal development during childhood and puberty. Accurately characterizing longitudinal bone growth helps to better understand the determining factors of peak bone mass, which has impacts on bone quality later in life. Animal models were largely used to study longitudinal bone growth. However, the commonly used histology-based method is destructive and unable to follow up the growth curve of live animals in longitudinal experiments. In this study, we validated an in vivo micro-CT-based method against the histology-based method to quantify longitudinal bone growth rates of young rats non-destructively. CD (Sprague Dawley) IGS rats aged 35, 49 and 63days received the same treatments: two series of repeated in vivo micro-CT scans on their proximal hind limb at a five-day interval, and two calcein injections separated by three days. The longitudinal bone growth rate was quantified by registering time-lapse micro-CT images in 3D, calculating the growth distance on registered images, and dividing the distance by the five-day gap. The growth rate was also evaluated by measuring the 2D distance between consecutive calcein fluorescent bands on microscopic images, divided by the three-day gap. The two methods were both validated independently with reproducible repeated measurements, where the micro-CT-based method showed higher precision. They were also validated against each other with low relative errors and a strong Pearson sample correlation coefficient (0.998), showing a significant (p<0.0001) linear correlation between paired results. We conclude that the micro-CT-based method can serve as an alternative to the histology-based method for the quantification of longitudinal growth. Thanks to its non-invasive nature and true 3D capability, the micro-CT-based method helps to accommodate in vivo longitudinal animal studies with highly reproducible measurements.

Multi-stage controllable degradation of strontium-doped calcium sulfate hemihydrate-tricalcium phosphate microsphere composite as a substitute for osteoporotic bone defect repairing: degradation behavior and bone response

Various requirements for the repair of complex bone defects have motivated to development of scaffolds with adjustable degradation rates and biological functions. Tricalcium phosphate (TCP) and calcium sulfate are the most commonly used bone repair materials in the clinic, how to better combine TCP and calcium sulfate and play their greatest advantages in the repair of osteoporotic bone defect is the focus of our research. In this study, a series of scaffolds with multistage-controlled degradation properties composed of strontium-doped calcium sulfate (SrCSH) and strontium-doped tricalcium phosphate (Sr-TCP) microspheres scaffolds were prepared, and their osteogenic activity, in vivo degradation and bone regeneration ability in tibia of osteoporotic rats were evaluated. In vitro studies revealed that different components of SrCSH/Sr-TCP scaffolds significantly promoted the proliferation and differentiation of MC3T3-E1 cells, which showed a good osteogenic induction activity. In vivo degradation results showed that the degradation time of composite scaffolds could be controlled in a large range (6–12 months) by controlling the porosity and phase composition of Sr-TCP microspheres. The results of osteoporotic femoral defect repair showed that when the degradation rate of scaffold matched with the growth rate of new bone, the parameters such as bone mineral density, bone volume/total volume ratio, trabecular thickness, angiogenesis marker platelet endothelial cell adhesion molecule-1 and new bone formation marker osteocalcin expression were higher, which promoted the rapid repair of osteoporotic bone defects. On the contrary, the slow degradation rate of scaffolds hindered the growth of new bone to a certain extent. This study elucidates the importance of the degradation rate of scaffolds for the repair of osteoporotic bone defects, and the design considerations can be extended to other bone repair materials, which is expected to provide new ideas for the development of tissue engineering materials in the future.

Effects of Soft Tissue Closure on Medication-Related Osteonecrosis of the Jaw in a Rabbit Model with Tooth Extraction: A Pilot Study

Objectives The study investigated the effect of soft tissue closure after tooth extraction on the prevention of medication-related osteonecrosis of the jaw in a rabbit model. Materials and Methods Twenty female New Zealand white rabbits were randomly assigned into the experimental group administrated with zoledronic acid (ZA) and control groups treated with saline. Bilateral lower premolar extraction was performed 4 weeks after ZA/saline administration. Immediately after extraction, the wound on the right mandible was closed by suture while the other side was left open. Animals were sacrificed 4 weeks and 8 weeks after tooth extraction. Fluorochrome labeling solutions were injected subcutaneously to evaluate the bone growth rates. The mandibles were harvested and subjected for microcomputed tomography, confocal microscope, and histomorphological examinations. Results All extraction sites healed well without any signs of infection. Trabecular thickness (Tb.Th) was significantly higher in the ZA-treated group than in the control group at both week 4 and week 8, while no significant difference was detected in the rest of the assessed parameters. The bone growth rate in mandibles showed gradual reduction in the ZA-treated group. Histological analysis showed that at week 8, the animals in the ZA-treated group had significantly higher incidence of osteonecrosis than that in the control group, while no significance was revealed between the sutured and nonsutured side. Conclusions ZA treatment significantly reduces bone growth rates but does not reveal a significant effect on bone mineral density and bone microarchitecture. Soft tissue closure of the extraction socket does not reduce the incidence of ONJ in the ZA-treated rabbit model.

Pediatric Cranioplasty Using Hydroxyapatite Cement: A Retrospective Review and Preliminary Computational Model

Introduction: Cranioplasty is a standard technique for skull defect repair. Restoration of cranial defects is imperative for brain protection and allowing for homeostasis of cerebral spinal fluid within the cranial vault. Calcium phosphate hydroxyapatite (HA) is a synthetic-organic material that is commonly used in cranioplasty. We evaluate a patient series undergoing HA cement cranioplasty with underlying bioresorbable mesh for various cranial defects and propose a preliminary computational model for understanding skull osteointegration. Methods: A retrospective review was performed at the institution for all pediatric patients who underwent HA cement cranioplasty. Seventeen patients were identified, and success of cranioplasty was determined based on clinical and radiographic follow-up. A preliminary computational model was developed using bone growth and scaffold decay equations from previously published literature. The model was dependent on defect size and shape. Patient data were used to optimize the computational model. Results: Seventeen patients were identified with an average age of 6 ± 5.6 years. Average defect size was 11.7 ± 16.8 cm². Average time to last follow-up computer tomography scan was 10 ± 6 months. Three patients had failure of cranioplasty, all with a defect size above 15 cm². The computational model developed shows a constant decay rate of the scaffold, regardless of size or shape. The bone growth rate was dependent on the shape and number of edges within the defect. Thus, a star-shaped defect obtained a higher rate of growth than a circular defect because of faster growth rates at the edges. The computational simulations suggest that shape and size of defects may alter success of osteointegration. Conclusion: Pediatric cranioplasty is a necessary procedure for cranial defects with a relatively higher rate of failure than adults. Here, we use HA cement to perform the procedure while creating a preliminary computational model to understand osteointegration. Based on the findings, cranioplasty shape may alter the rate of integration and lead to higher success rates.

Vitamin D Status in Children With Short Stature: Accurate Determination of Serum Vitamin D Components Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

ObjectiveVitamin D is critical for calcium and bone metabolism. Vitamin D insufficiency impairs skeletal mineralization and bone growth rate during childhood, thus affecting height and health. Vitamin D status in children with short stature is sparsely reported. The purpose of the current study was to investigate various vitamin D components by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) to better explore vitamin D storage of short-stature children in vivo.MethodsSerum circulating levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], and 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3, C3-epi] were accurately computed using the LC-MS/MS method. Total 25(OH)D [t-25(OH)D] and ratios of 25(OH)D2/25(OH)D3 and C3-epi/25(OH)D3 were then respectively calculated. Free 25(OH)D [f-25(OH)D] was also measured.Results25(OH)D3 and f-25(OH)D levels in short-stature subgroups 2 (school age: 7~12 years old) and 3 (adolescence: 13~18 years old) were significantly lower compared with those of healthy controls. By contrast, C3-epi levels and C3-epi/25(OH)D3 ratios in all the three short-stature subgroups were markedly higher than the corresponding healthy cases. Based on cutoff values developed by Endocrine Society Recommendation (but not suitable for methods 2 and 3), sufficient storage capacities of vitamin D in short-stature subgroups 1, 2, and 3 were 42.8%, 23.8%, and 9.0% as determined by Method 3 [25(OH)D2/3+25(OH)D3], which were lower than those of 57.1%, 28.6%, and 18.2% as determined by Method 1 [25(OH)D2+25(OH)D3+C3-epi] and 45.7%, 28.5%, and 13.6% as determined by Method 2 [25(OH)D2/3+25(OH)D3+C3-epi]. Levels of 25(OH)D2 were found to be weakly negatively correlated with those of 25(OH)D3, and higher 25(OH)D3 levels were positively correlated with higher levels of C3-epi in both short-stature and healthy control cohorts. Furthermore, f-25(OH)D levels were positively associated with 25(OH)D3 and C3-epi levels in children.ConclusionsThe current LC-MS/MS technique can not only separate 25(OH)D2 from 25(OH)D3 but also distinguish C3-epi from 25(OH)D3. Measurement of t-25(OH)D [25(OH)D2+25(OH)D3] alone may overestimate vitamin D storage in children, and short-stature children had lower vitamin D levels compared with healthy subjects. Ratios of C3-epi/25(OH)D3 and 25(OH)D2/25(OH)D3 might be alternative markers for vitamin D catabolism/storage in short-stature children. Further studies are needed to explore the relationships and physiological roles of various vitamin D metabolites.

The effect of triptorelin and leuprolide on the level of sex hormones in girls with central precocious puberty and its clinical efficacy analysis.

BackgroundThis study aimed to explore the effects of triptorelin and leuprolide on serum hormone levels and the clinical efficacy of girls with idiopathic central precocious puberty (ICPP).MethodsRetrospective analysis was performed on 128 girls with ICPP who were diagnosed and treated in our hospital from January 2017 to January 2020, including 71 girls in the leuprolide group and 57 girls in the triptorelin group. The differences of serum sex hormone level, ovarian volume, uterine volume, follicle diameter, bone age, growth rate (height change within half a year), maturity (bone age/living age), and other aspects between the two groups of girls were compared.ResultsBefore treatment, there was no significant difference in the baseline levels of sex hormones [estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH)] between the triptorelin group and the leuprorelin group (P>0.05). After 1 year of treatment, serum levels of E2 and FSH in the triptorelin group were lower than those in the leuprolide group (P<0.05). There was no significant difference in LH levels between the two groups after 1 year of treatment (P>0.05). At baseline, there was no significant difference in the ovarian volume, follicle diameter, and uterine volume between the triptorelin group and the leuprolide group (P>0.05). After 1 year of treatment, the ovarian volume, follicle diameter, and uterine volume of the girls in the triptorelin group were all lower than those in the leuprolide group (P<0.05). Before treatment, there was no statistical difference in bone age, growth rate, and maturity between the triptorelin group and the leuprolide group (P>0.05). After 1 year of treatment, the growth rate and maturity of participants in the triptorelin group were lower than those in the leuprolide group (P<0.05). There was no significant difference in bone age between the two groups after 1 year of treatment (P>0.05).ConclusionsFor girls with ICPP, triptorelin is superior to leuprolide in reducing sex hormone level, reducing uterine volume, follicle diameter, ovarian volume, slowing down the growth rate, and decreasing maturity. Triptorelin should be selected as a priority for the treatment of girls with ICPP.

Mineralized-tissue histology reveals protracted life history in the Pliocene three-toed horse from Langebaanweg (South Africa)

Abstract We studied the bone and dental histology of the tri-dactyl equid Eurygnathohippus hooijeri, one of the most iconic mammals found at the world-renowned Pliocene site of Langebaanweg, South Africa, to reconstruct important features of its life history. Our results show that key life-history events, such as weaning, skeletal maturity and reproductive maturity, occurred later in this African hipparionine compared with European three-toed equids and several extant Equus. Its late life-history schedule agrees with an ecological context of low adult extrinsic mortality and low juvenile survival rates. We also observed high rates of bone growth in Eu. hooijeri that were probably achieved through a high-quality diet and plentiful available water. Our research highlights the significance of combining bone and dental histology in the same taxon to obtain refined palaeobiological information about extinct vertebrates.

Possibilidade de ossificação intracondral dirigida a partir de uma matriz óssea com titânio

In the present study, the relation between bone, cartilage and titanium was analyzed. According to the established methodology, homogeneous cartilage grafts conserved in alcohol 100 GL for 7 days were used, after the fixation of a homologous cartilage graft above the bone cortical of a rat femur (Rattus novergicus var. Albinus rodentia mammalia cepa Wistar), using a titanium screw implant. The animals were sacrificed at 10, 20, 30 and 60 days after surgery. To the histological examination, in hematoxillin and eosin sections, intrachondral bone neoformation could be observed since cortical surface, with possibility of complete substitution of the cartilage graft by bone, with similar volume and shape. In this experimental study we concluded that the homogeneous cartilage conserved can be used as graft not only for tissue substitution but also as an inductor of bone growth in rats.

Ceramic composite with gentamicin decreases persistent infection and increases bone formation in a rat model of debrided osteomyelitis.

Introduction: Current methods of managing osteomyelitic voids after debridement are inadequate and result in significant morbidity to patients. Synthetic ceramic void fillers are appropriate for non-infected bone defects but serve as a nidus of re-infection in osteomyelitis after debridement. CERAMENT G (CG) is an injectable ceramic bone void filler which contains gentamicin and is currently being evaluated for use in osteomyelitic environments after debridement due to its theoretical ability to serve as a scaffold for healing while eliminating residual bacteria after debridement through the elution of antibiotics. The goal of this study was to evaluate (1) the rate of persistent infection and (2) new bone growth of a debrided osteomyelitic defect in a rat model which has been treated with either gentamicin-impregnated ceramic cement (CERAMENT G) or the same void filler without antibiotics (CERAMENT, CBVF). Methods: Osteomyelitis was generated in the proximal tibia of Sprague Dawley rats, subsequently debrided, and the defect filled with either (1) CG (), (2) CBVF (), or (3) nothing (). Each group was euthanized after 6 weeks. Infection was detected through bacterial culture and histology. Bone growth was quantified using microCT. Results: Infection was not detected in defects treated with CG as compared with 35 % of defects () treated with CBVF and 50 % () of empty defects (). Bone volume in the defect of CG-treated rats was greater than the CBVF (0.21 vs. 0.17, ) and empty groups (0.21 vs. 0.11, ) at 6 weeks after implantation. Conclusions: Ceramic void filler with gentamicin (CERAMENT G) decreased the rate of persistent infection and increased new bone growth as compared to the same void filler without antibiotics (CERAMENT) and an empty defect in a rat model of debrided osteomyelitis.

Tooth development in the Early Devonian sarcopterygian Powichthys and the evolution of the crown osteichthyan dentition

AbstractIn osteichthyans (bony fishes) the dentition is characterized by marginal tooth rows replaced by basal resorption. Basal resorption was present in the stem osteichthyan Andreolepis, which also possessed overgrowing tooth‐shaped odontodes, a possible intermediate state between external odontodes and teeth. Andreolepis, however, lacked the enlarged marginal tooth rows found in more advanced osteichthyans, and how these evolved from the stem osteichthyan condition is unknown. Here we present computed tomography and synchrotron‐based x‐ray phase‐contrast imaging of the jaws and teeth of the Early Devonian sarcopterygian Powichthys. We reveal the presence of fields of overgrowing tooth‐like odontodes, resembling the dentitions of stem‐group osteichthyans, alongside the marginal tooth row. In the inner dental arcade, we show a continuous variation between regions of tooth‐like and external odontode‐like replacement, apparently driven by variations in the relative rates of bone growth, odontode addition and odontode size. These results suggest that there is a degree of plasticity in oral odontode development. We propose that the tooth rows of crown osteichthyans develop in an essentially similar manner to the teeth of stem osteichthyans, with differences explained by increased resorption activity linked to the larger size of the teeth. Therefore, the external odontodes and teeth of both stem and crown osteichthyan lie on the same developmental continuum.

Manipulation of the degradation behavior of calcium phosphate and calcium sulfate bone cement system by the addition of micro-nano calcium phosphate

The mismatch between the degradation performance of bioactive bone cement (calcium phosphate-CPC and calcium sulfate-CSC) and the growth rate of new bone has always restricted its clinical application. In view of the weak mechanical strength and poor degradation performance of CPC and CSC, this study first prepared micro-nano calcium phosphate (MNC) with different Ca/P ratio and explored the influence of MNC on the hydration and mechanical properties of cement by adding MNC to the CPC and CSC. The results show that MNC can promote the hydration reaction of CPC and CSC and affect the growth of cement crystals. Among all groups, MNC with Ca/P ratio of 1.2 can greatly improve the mechanical properties and setting time of CPC, increase the compressive strength of CPC from 10.18 ± 1.51 to 19.23 ± 0.55 MPa, and shorten the setting time from 38.33 ± 2.89 to 18.33 ± 2.89 min. In addition, the addition of low content of MNC promoted the degradation of CPC, and also promoted the self-reinforcing effect of CPC during the degradation process, and further improved the mechanical properties of cement. MNC not only affects the morphology of CSC crystals but also produces calcium phosphate particles with smaller diameters to fill between the CSC crystals, which reduces porosity, improves mechanical properties, and delays the degradation of CSC. The as-prepared cements were supposed to match the new bone ingrowth in vivo and have the potential application in orthopedic surgery for filling non-load-bearing bone defects.

Labelling experiments in red deer provide a general model for early bone growth dynamics in ruminants

Growth rates importantly determine developmental time and are, therefore, a key variable of a species' life history. A widely used method to reconstruct growth rates and to estimate age at death in extant and particularly in fossil vertebrates is the analysis of bone tissue apposition rates. Lines of arrested growth (LAGs) are of special interest here, as they indicate a halt in bone growth. However, although of great importance, the time intervals between, and particularly the reason of growth arrests remains unknown. Therefore, experiments are increasingly called for to calibrate growth rates with tissue types and life history events, and to provide reliable measurements of the time involved in the formation of LAGs. Based on in vivo bone labelling, we calibrated periods of bone tissue apposition, growth arrest, drift and resorption over the period from birth to post-weaning in a large mammal, the red deer. We found that bone growth rates tightly matched the daily weight gain curve, i.e. decreased with age, with two discrete periods of growth rate disruption that coincided with the life history events birth and weaning, that were visually recognisable in bone tissue as either partial LAGs or annuli. Our study identified for the first time in a large mammal a general pattern for juvenile bone growth rates, including periods of growth arrest. The tight correlation between daily weight gain and bone tissue apposition suggests that the red deer bone growth model is valid for ruminants in general where the daily weight gain curve is comparable.

Architected implant designs for long bones: Advantages of minimal surface-based topologies

Large bone fractures often require porous implants for complete healing. In this work, we numerically investigate the suitability of three topologically very different architected materials for long bone implants: the octet truss-based lattice, the Schwartz P minimal surface-based lattice and the spinodal stochastic surface-based lattice. Each implant topology (reinforcement) and its surrounding tissue (soft matrix) are modeled as a composite system via finite element analysis. Performance metrics are defined based on the Young’s modulus, the peak stress under service conditions, the interfacial surface area per unit volume and the relative bone growth rate (estimated based on the strain transferred to the soft matrix). We show that surface-based topologies are less prone to fatigue failure and may promote superior bone growth than conventional truss-based designs. Spinodal surface-based architected materials have the best performance, and can be fabricated via self-assembly approaches followed by material conversion, potentially allowing scalable fabrication of implants with unit cell sizes at the micro-scale, thus dramatically amplifying surface area per unit volume and bone growth efficiency.

Effects of a Mixture of Humulus japonicus on Longitudinal Bone Growth in Hypophysectomized Rats.

Previously, we reported that the administration of a mixture of Humulus japonicus (MH) increased the longitudinal bone growth rate in Sprague Dawley rats. In this study, we investigated the effects of the dietary administration of MH on longitudinal bone growth in growth hormone (GH)-deficient hypophysectomized male and female rats to determine whether the effect of MH was similar to that of GH. We measured the nose-to-anus and nose-to-tail length gain, femur and tibia lengths, growth plate zones, and expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) after the dietary administration of MH or the injection of GH into hypophysectomized rats for 4 weeks. Results demonstrated that the dietary administration of MH had no effect on longitudinal bone growth, whereas the injection of GH increased the nose-to-tail length gain and femur and tibia lengths in hypophysectomized rats. In addition, MH did not affect the growth plate, bone mineralization, and expression of IGF-1 and IGFBP-3. These findings indicate that MH does not exert a GH-like effect and that the effects of MH and GH on longitudinal bone growth involve different pathways.

Effects of Bisphosphonates on Osseointegration of Dental Implants in Rabbit Model.

This study is to investigate the effect of bisphosphonates on the osseointegration of dental implants in a rabbit model. Twenty female New Zealand White rabbits were equally assigned into control and experiment groups which received saline or zoledronic acid treatment 4 weeks prior to surgery. Titanium dental implant was placed on the calvarial bone. Zoledronic acid or saline treatment continued after surgery for 4 weeks (short-term subgroup) or 8 weeks (long-term subgroup) until sacrifice. Three different fluorochrome labeling solutions were administrated for assessing bone growth rates. Samples of the calvarial bone and mandible were subjected to microcomputed tomography (micro-CT), confocal microscope, and histology analysis. Zoledronic acid treatment significantly reduced bone growth rates in the calvarial bone, but had no significant influence in bone mineral density and trabecular microarchitecture. Significantly lower bone-to-implant contact ratios were found in zoledronic acid-treated animals compared to controls at week 4 but not at week 8. Oncologic dose zoledronic acid suppresses the bone growth rates of the calvarial bone; ZA may have an adverse effect on osseointegration of dental implant in short term, but this effect tends to diminish in long term.

Phosphate bioglass thin-films: Cross-area uniformity, structure and biological performance tailored by the simple modification of magnetron sputtering gas pressure

Currently, there is a considerable time-lag in the industrialisation of innovative technological solutions for the functionalization of osseous implants, with ever-demanding healthcare requirements (e.g., controlled release of therapeutic ions, match of biomaterial degradation – bone growth rates, antimicrobial efficiency). As third-generation biomaterials, phosphate bio-glasses (PBGs) have demonstrated an ability to stimulate specific biological responses from tissue to molecular level, by successfully coupling bioactive and resorbable material properties. Here, radio-frequency magnetron sputtered (RF-MS) PBGs were explored as sacrificial resorbable layers for prospective biomedical implant designs. A PBG powder with a 50–P2O5, 35–CaO, 10–Na2O and 5–Fe2O3 composition (mol%) was used as source (target) material. The influence of the argon working pressure (0.2–1 Pa) – one of the most prominent RF-MS variables – on the morphology, structure, uniformity, composition, degradation rate and cytocompatibility of PBG films was investigated. The engineered modification of physical-chemical and biological features of the PBG sputtered films was multi-parametrically surveyed by AFM, EDXS, spectroscopic ellipsometry, GIXRD, FTIR spectroscopy measurements and in vitro assays. Results suggested that the film thickness, composition, density and structure were preserved over a uniformity region having a diameter of ~30 mm, irrespective of sputtering pressure. The network connectivity and the surface porosity of the films were found to have antagonistic roles with respect to the in vitro degradation performance. The possibility of fine tuning the composition, structure and thereby biological interaction of the PBG films by conveniently modifying the sputtering pressure was shown (i.e., permitting their complete controlled degradation, without cytotoxic effects). This work is the first to show in vitro cytocompatibility outcomes of sputtered PBG films and their cross-area uniformity, and thus, it could prove to be an important technological step in their future biomedical application and suggest implications for future industrial scale-up.

Oral Exposure to ZnO Nanoparticles Disrupt the Structure of Bone in Young Rats via the OPG/RANK/RANKL/IGF-1 Pathway.

PurposeTo evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action.Materials and MethodsThree-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally.ResultsThe high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P<0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P>0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P<0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P>0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P<0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P<0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P<0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P<0.05), whereas RANKL expression did not change significantly (P>0.05).ConclusionWe infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway.