Bone Growth Rate Research Articles

The influence of plane of section on the identification of bone tissue types in amniotes with implications for paleophysiological inferences.

The proportion of woven bone (WB) to parallel-fibered bone has been extensively used to infer bone growth rates and resting metabolic rates of extinct organisms. The aim of this study is to test in a variety of amniotes how reliably WB content can be measured using transverse sections. For this, we analyzed femoral transverse mid-diaphyseal thin sections of 14 extant and extinct taxa and the corresponding longitudinal sections for comparative purposes. We used the following characters to identify WB in transverse sections because they are known to be distinct from those observed in parallel-fibered bone: an isotropic bone matrix at tissue scale; an anisotropic microlamellar arrangement in former osteoblast secretory territories at cellular scale; no alignment between osteocytes; and canaliculi running radially from large irregular osteocyte lacunae. Our null hypothesis predicts no differences between the amount of WB quantified in the transverse and longitudinal sections of a given long bone. Qualitatively, when a stripe or a patch of WB was identified in a transverse section, the corresponding stripe or patch of WB was always found at the same location in the corresponding longitudinal section. Quantitatively, a Wilcoxon signed-rank nonparametric paired test did not detect a significant difference in the WB content of the two section planes. Thus, the null hypothesis is not rejected. Considering that paleohistology is a destructive method, we recommend a workflow to efficiently establishing the proportion of WB: quantifying it in transverse sections; preparing and analyzing longitudinal sections only in cases where an ambiguity remains; reanalyzing the corresponding transverse sections.

TGF-β prevents the denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway.

Background: Transforming growth factor beta (TGF-β) can stimulate osteogenesis as a multifunctional protein. The present study was to explore if TGF-β can prevent denervation-induced reduction of bone formation.Materials & methods: The 6-week-old male mice were treated with recombinant human TGF-β1 (rhTGF-β1). Bone formation, endochondral bone growth rates, and gene expression of osteoblast markers were measured in the skeletal tissue by real-time PCR.Results: RhTGF-β1 treatment prevented the denervation-induced decrease in bone formation rates, endochondral growth, and expression of Cbfa1/Runx2 (runt-related transcription factor 2), Ostecalcin (OC), and ColIA1. TGF-β1 partially inhibited the denervation-induced ubiquitination of Cbfa1/Runx2 in mouse cancellous bones via ubiquitin-proteasome pathway.Conclusion: TGF-β prevents denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway at least partially.

Antarctic krill oil promotes longitudinal bone growth in adolescent male mice

The effects of dietary supplementation with Antarctic krill oil (AKO) on longitudinal bone growth in adolescent male Institute for Cancer Research (ICR) mice for 21 days were investigated. Histological results showed that AKO promoted longitudinal bone growth, increased skeletal mineral content and strength, enhanced entochondrostosis supported by higher longitudinal bone growth rate and growth plate height. Then, the potential mechanisms responsible for these observations were measured, results showed that AKO increased the secretion of the GH-IGF-1 pathway and entochondrostosis-related factors in serum increased the expression of IGF-1 in the liver and bone, which promoted proliferation and differentiation of chondrocytes, vascular invasion and bone formation related gene expression. AKO promoted longitudinal bone growth, using the GH-IGF-1 pathway, suggesting that AKO might be a potential functional food to improve growth potential of adolescents.

Combination Use of BMP2 and VEGF165 Promotes Osseointegration and Stability of Titanium Implants in Irradiated Bone.

Background Clinical data demonstrated that failure rate of titanium implant in irradiated bone was 2-3 times higher than that in nonirradiated bone and it is difficult to get the ideal results in irradiated bone. Purpose The aim of the study was to investigate the effects of HBO, BMP2, VEGF165, and combined use of BMP2/VEGF165 on osseointegration and stability of titanium implant in irradiated bone. Materials and Methods Sixty rabbits were randomly assigned to 5 groups (control group, HBO group, VEGF165 group, BMP2 group, and BMP2/VEGF165 group) after receiving 15 Gy radiation. Implant surgery was performed on tibias eight weeks later. They were sacrificed at two or eight weeks after operation. Implant stability, calcium, and ALP activity in serum, the ratio of bone volume to total volume, the rate of bone growth, and gene expression were assessed. Result There was no mortality and no implants failed during the experiment. Implant stability was significantly compromised in the control group compared to the other four experimental groups, and the BMP2/VEGF165 group had the highest implant stability. HBO, BMP2, and VEGF165 significantly increased BV/TV and the rate of bone growth, while the BMP2/VEGF165 showed the best effect among groups. The expression of RUNX2 in HBO, BMP2, and VEGF165/BMP2 group was higher than that in the VEGF165 and control groups at two weeks. The expression of OCN in HBO, BMP2, VEGF165, and VEGF165/BMP2 groups was higher than that in the control group, and the gene expression of CD31 was higher in HBO, VEGF165, and BMP2/VEGF165 groups than that in control and BMP2 groups. Conclusion HBO, BMP2, and VEGF165 could increase bone formation around the implant and improved the implant stability in irradiated bone. The combination use of BMP2 and VEGF165 may be promising in the treatment of implant patients with radiotherapy.

Intermittent Imatinib Mesylate in Children with Chronic Myeloid Leukemia: Results and Outcome

Intermittent Imatinib Mesylate in Children with Chronic Myeloid Leukemia: Results and Outcome

Can repeated in vivo micro-CT irradiation during adolescence alter bone microstructure, histomorphometry and longitudinal growth in a rodent model?

In vivo micro-computed tomography (micro-CT) can monitor longitudinal changes in bone mass and microstructure in small rodents but imposing high doses of radiation can damage the bone tissue. However, the effect of weekly micro-CT scanning during the adolescence on bone growth and architecture is still unknown. The right proximal tibia of male Sprague-Dawley rats randomized into three dose groups of 0.83, 1.65 and 2.47 Gy (n = 11/group) were CT scanned at weekly intervals from 4th to 12th week of age. The left tibia was used as a control and scanned only at the last time point. Bone marrow cells were investigated, bone growth rates and histomorphometric analyses were performed, and bone structural parameters were determined for both left and right tibiae. Radiation doses of 1.65 and 2.47 Gy affected bone marrow cells, heights of the proliferative and hypertrophic zones, and bone growth rates in the irradiated tibiae. For the 1.65 Gy group, irradiated tibiae resulted in lower BMD, Tb.Th, Tb.N and a higher Tb.Sp compared with the control tibiae. A decrease in BMD, BV/TV, Tb.Th, Tb.N and an increase in Tb.Sp were observed between the irradiated and control tibiae for the 2.47 Gy group. For cortical bone parameters, no effects were noticed for 1.65 and 0.83 Gy groups, but a lower Ct.Th was observed for 2.47 Gy group. Tibial bone development was adversely impacted and trabecular bone, together with bone marrow cells, were negatively affected by the 1.65 and 2.47 Gy radiation doses. Cortical bone microstructure was affected for 2.47 Gy group. However, bone development and morphometry were not affected for 0.83 Gy group. These findings can be used as a proof of concept for using the reasonable high-quality image acquisition under 0.83 Gy radiation doses during the adolescent period of rats without interfering with the bone development process.

Eggshell spotting pattern is related to hatching asynchrony, hematocrit value and growth of nestling great titsParus major

Eggshell pigmentation may signal the quality of the egg, that of the female and the environment, and thus nestling development may be related to this egg trait. However, so far, few studies have investigated the relationship between eggshell pigmentation and nestling development. Our aim was to study in a partial cross‐fostering experiment whether the protoporphyrin‐based eggshell pigmentation (spot intensity and spot distribution) showed any significant associations with several traits related to the development of nestling great titsParus major. We found that nestlings from clutches with darker spotted eggshells hatched more synchronously, had higher hematocrit value and shorter wings. Females under adverse environmental circumstances were previously shown to lay darker‐spotted eggs, and these females probably delayed the start of incubation due to energetic constraints, resulting in a more synchronous hatching. The shorter wings of fledglings originating from clutches with darker‐spotted eggs may be caused by the lower general quality of their mothers, mediated through either genetic factors or early maternal effects. Darker spotted eggs may contain different levels of some biomolecules than paler spotted eggs, which could have an effect on nestling metabolism and activity, resulting in an elevated hematocrit value. More aggregated eggshell spotting was related to faster bone growth and slightly longer fledging tarsus length. Eggs with aggregated spotting may have thinner eggshells that could lead to hatchlings with smaller bones due to the lower availability of calcium during development. Nestlings may increase bone growth rate to compensate for their smaller initial size. Overall, our results indirectly suggest lower fitness for nestlings hatched from darker spotted eggs and for nestlings hatched from eggs with more aggregated spotting distribution due to the possible long‐term costs of synchronous hatching, shorter wings, and accelerated tarsus growth rate.

Quantitative histological models suggest endothermy in plesiosaurs.

BackgroundPlesiosaurs are marine reptiles that arose in the Late Triassic and survived to the Late Cretaceous. They have a unique and uniform bauplan and are known for their very long neck and hydrofoil-like flippers. Plesiosaurs are among the most successful vertebrate clades in Earth’s history. Based on bone mass decrease and cosmopolitan distribution, both of which affect lifestyle, indications of parental care, and oxygen isotope analyses, evidence for endothermy in plesiosaurs has accumulated. Recent bone histological investigations also provide evidence of fast growth and elevated metabolic rates. However, quantitative estimations of metabolic rates and bone growth rates in plesiosaurs have not been attempted before.MethodsPhylogenetic eigenvector maps is a method for estimating trait values from a predictor variable while taking into account phylogenetic relationships. As predictor variable, this study employs vascular density, measured in bone histological sections of fossil eosauropterygians and extant comparative taxa. We quantified vascular density as primary osteon density, thus, the proportion of vascular area (including lamellar infillings of primary osteons) to total bone area. Our response variables are bone growth rate (expressed as local bone apposition rate) and resting metabolic rate (RMR).ResultsOur models reveal bone growth rates and RMRs for plesiosaurs that are in the range of birds, suggesting that plesiosaurs were endotherm. Even for basal eosauropterygians we estimate values in the range of mammals or higher.DiscussionOur models are influenced by the availability of comparative data, which are lacking for large marine amniotes, potentially skewing our results. However, our statistically robust inference of fast growth and fast metabolism is in accordance with other evidence for plesiosaurian endothermy. Endothermy may explain the success of plesiosaurs consisting in their survival of the end-Triassic extinction event and their global radiation and dispersal.

Effects of Combined Magnetic Fields Treatment and Nano-Hydroxyapatite Coating on Porous Biphasic Calcium Phosphate Bone Graft in Rabbit Spinal Fusion Model.

An animal experimental study was designed to investigate the efficacy of combined magnetic fields (CMF) treatment and nano-hydroxyapatite (HA) coating in the biphasic calcium phosphate (BCP) graft in posterolateral lumbar fusion. To evaluate the effects of CMF treatment and nano-HA/BCP and their combination effect in posterolateral lumbar fusion. Enhancement of artificial bone graft bioeffects could improve spinal fusion outcomes. The bone graft integration is vital in spinal fusion, nano-HA coating, and CMF treatment were reported as effective methods to improve bone graft integration. A bilateral transverse process fusion model was performed on 32 rabbits. The CMF treatment was performed for 30 minutes per day postoperation. The fusion rate, new bone formation, artificial bone graft-autologous bone fusion interface in x-ray and scanning electron microscopy, biomechanics property of fusion rate, histological fusion condition, artificial bone residual rate, and immunohistochemistry assessment of bone morphogenetic protein 2 (BMP-2) and Transforming growth factor beta 1 (TGF-β1) expression were observed at 9th week after surgery. CMF treatment and nano-HA coating increased the fusion rate, adjusted optical density index, intensity of binding of artificial and autologous bone, bone growth rate, and bending stiffness. CMF treatment also significantly increased BMP-2 and TGF-β1 expression in fusion region while nano-HA coating significantly decreased artificial bone residual rate. Our findings suggest that porous nano-HA/BCP graft could significantly improve spine fusion outcome with excellent bioactivity, biocompatibility and degradability and CMF treatment could significantly improve spine fusion outcome by improving bioactivity and biocompatibility of artificial bone graft in rabbit. Combination of CMF treatment with nano-HA/BCP graft could significantly increase posterolateral lumbar fusion rate in rabbit, which would be a potential strategy for spine fusion preclinical study. N/A.

Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate.

Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate. Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β-0.098 and -0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS. Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

Relationships of bone characteristics in MYO9B deficient femurs.

The objective of this study was to examine relationships among a variety of bone characteristics, including volumetric, mineral density, geometric, dynamic mechanical analysis, and static fracture mechanical properties. As MYO9B is an unconventional myosin in bone cells responsible for normal skeletal growth, bone characteristics of wild-type (WT), heterozygous (HET), and MYO9B knockout (KO) mice groups were compared as an animal model to express different bone quantity and quality. Forty-five sex-matched 12-week-old mice were used in this study. After euthanization, femurs were isolated and scanned using microcomputed tomography (micro-CT) to assess bone volumetric, tissue mineral density (TMD), and geometric parameters. Then, a non-destructive dynamic mechanical analysis (DMA) was performed by applying oscillatory bending displacement on the femur. Finally, the same femur was subject to static fracture testing. KO group had significantly lower length, bone mineral density (BMD), bone mass and volume, dynamic and static stiffness, and strength than WT and HET groups (p < 0.019). On the other hand, TMD parameters of KO group were comparable with those of WT group. HET group showed volumetric, geometric, and mechanical properties similar to WT group, but had lower TMD (p < 0.014). Non-destructive micro-CT and DMA parameters had significant positive correlations with strength (p < 0.015) without combined effect of groups and sex on the correlations (p > 0.077). This comprehensive characterization provides a better understanding of interactive behavior between the tissue- and organ-level of the same femur. The current findings elucidate that MYO9B is responsible for controlling bone volume to determine the growth rate and fracture risk of bone.

Positive feedback effects of Mg on the hydrolysis of poly-l-lactic acid (PLLA): Promoted degradation of PLLA scaffolds

The degradation rate of poly-l-lactic acid (PLLA) is too slow to match the growth rate of bone, which limits its application in bone transplantation. In this study, Mg was introduced into PLLA to increase the degradation rate. Three-dimensional porous PLLA/Mg scaffolds were fabricated via selective laser sintering. The results indicated that the introduction of Mg elevated the pH of the degradation medium and accelerated the weight loss of the scaffolds. These could be attributed to the alkaline product Mg(OH)2 from the degradation of Mg. It neutralized the acid degradation products of PLLA, which retarded the inhibition of the acid products on the degradation of PLLA. Meanwhile, the acid degradation products of PLLA could consume the alkaline product Mg(OH)2, promoting the degradation of Mg. The mutual neutralization between PLLA and Mg gave a positive feedback on the degradation of the scaffolds. Besides, the compressive strength, compressive modulus and Vickers hardness of the scaffolds were also increased due to the particle strengthening effect of Mg. In addition, the scaffolds showed good cytocompatibility. This study suggested the PLLA/Mg scaffolds may be a potential candidate of bone implants.

A 10-year-old Male with Osteogenesis Imperfecta; Zebra Lines.

Case presentation: A 10-year-old male who was a known case of osteogenesis imperfecta was referred to our clinic for follow up. He had osteogenesis imperfecta since birth with multiple fractures. He was treated with pamidronate every 3 months. He did not have a new fracture after treatment. Hand radiography showed multiple metaphyseal bands, called zebra lines, parallel to the growth plate. Learning points: Osteogenesis imperfecta is a congenital disorder due to a mutation in the CoL1A1 or CoL1A2 gene. It is often called brittle bone disease. The incidence of osteogenesis imperfecta is 1 in 10000–20000 birth. These patients are often characterized by multiple fractures with minimal or no trauma, skeletal deformity, and short stature. Radiological findings show generalized osteopenia, skeletal deformity, and bone fractures. The bisphosphonates are analogs of pyrophosphate that inhibit osteoclast activity. Pamidronate increased bone mineral density, decreased bone fracture rate, decreased pain, and improved the functional ability (3). Radiography findings after treatment with bisphosphonate showed dens metaphyseal lines in the long bones, so-called zebra lines. These lines were parallel to the growth plate. Each line corresponded to one intravenous treatment course. The bone growth rate and the time gap between two treatment courses were determined from the space between two zebra lines.

Effects of Huang Bai (Phellodendri Cortex) on bone growth and pubertal development in adolescent female rats

BackgroundTo evaluate the effects of Huang Bai (Phellodendron amurense) on growth and maturation in adolescent female rats.MethodsFemale Sprague–Dawley rats (28 days old; n = 72) were divided into six daily treatment groups: control (distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20 μg/kg), estradiol (1 μg/kg), and triptorelin (100 μg). Body weight, food intake, and vaginal opening were measured daily from postnatal day (PND) 28 to PND 43. Tetracycline (20 mg/kg) was injected on PND 41. After sacrifice on PND 43, the ovaries and uterus were weighed, and the tibias were fixed in 4% paraformaldehyde. Decalcified and dehydrated tibias were sectioned at a thickness of 40 μm, and sectioned tissues were examined with a fluorescence microscope. Insulin-like growth factor (IGF)-1 and bone morphogenetic protein (BMP)-2 were detected using immunohistochemistry.ResultsRelative to controls, body weight was higher in the triptorelin group. Bone growth rate increased in the Huang Bai 100 mg/kg (354.00 ± 31.1 μm/day), rhGH (367.10 ± 27.11 μm/day), and triptorelin (374.50 ± 25.37 μm/day) groups. Expression of IGF-1 and BMP-2 in the hypertrophic zone was higher in all experimental groups. Vaginal opening occurred earlier in the estradiol group (PND 33.58 ± 1.62) than in controls and later in the triptorelin group (PND > 43). Ovarian and uterine weights were lower in the oestradiol and triptorelin groups. However, Huang Bai had nonsignificant effects on vaginal opening and the weights of ovaries and the uterus.ConclusionsHuang Bai stimulated bone growth by upregulating IGF-1 and BMP-2 in the growth plate. However, it had no effect on pubertal development.

Indirectly extruded biodegradable Zn-0.05wt%Mg alloy with improved strength and ductility: In vitro and in vivo studies

As compared to permanent orthopedic implants for load-bearing applications, biodegradable orthopedic implants have the advantage of no need for removing after healing, but they suffer from the “trilemma” problem of compromising among sufficiently high mechanical properties, good biocompatibility and proper degradation rate conforming to the growth rate of new bones. In the present work, in vitro and in vivo studies of a Zn-0.05wt%Mg alloy (namely, Zn-0.05Mg alloy) were conducted with pure Zn as a control. The Zn-0.05Mg alloy is composed of a small amount of Mg2Zn11 phase embedded in the refined Zn matrix with an average grain size of ∼20 μm. The addition of 0.05 wt% Mg into Zn significantly increases the ultimate tensile strength up to 225 MPa and the elongation to fracture to 26%, but has little influence on the in vitro degradation rate. Both Zn and Zn-0.05Mg alloy exhibit homogeneous in vitro degradation with a rate of about 0.15 mm/year. Based on the cytotoxicity evaluation, Zn and Zn-0.05Mg alloy do not induce toxicity to L-929 cells, indicating that they have little toxicity to the general functions of the animal. An in vivo biocompatibility study of Zn and Zn-0.05Mg alloy samples by placing them in a rabbit model for 4, 12 and 24 weeks, respectively did not show any inflammatory cells, and demonstrated that new bone tissue formed at the bone/implant interface, suggesting that Zn and Zn-0.05Mg alloy promote the formation of new bone tissue. The in vivo degradation of Zn and Zn-0.05Mg alloy does not bring harm to the important organs and their cell structures. More interestingly, Zn and Zn-0.05Mg alloy exhibit strong antibacterial activity against Escherichia coli and Staphylococcus aureus. The above results clearly demonstrate that the Zn-0.05Mg alloy could be a potential biodegradable orthopedic implant material.

A degradation fragment of type X collagen is a real-time marker for bone growth velocity.

Despite its importance as a key parameter of child health and development, growth velocity is difficult to determine in real timebecause skeletal growth is slowand clinical tools to accurately detect very small increments of growth do not exist. We report discovery of a marker for skeletal growth in infants and children. The intact trimeric noncollagenous 1 (NC1) domain of type X collagen, the markerwe designated as CXMfor Collagen X Marker, is a degradation by-product of endochondral ossification that is released into the circulation in proportion to overall growth plate activity. Thismarker corresponds to the rate of linear bone growth at timeofmeasurement. Serumconcentrations of CXMplotted against age showa pattern similar to well-established height growth velocity curves and correlate with height growth velocity calculated from incremental height measurements in this study. The CXM marker is stable once collected and can be accurately assayed in serum, plasma, and dried blood spots. CXMtestingmay be useful for monitoring growth in the pediatric population, especially responses of infants and children with genetic and acquired growth disorders to interventions that target the underlying growth disturbances. The utility of CXM may potentially extend to managing other conditions such as fracture healing, scoliosis, arthritis, or cancer.

Calcium (Ti,Zr) hexaorthophosphate bioceramics for electrically stimulated biomedical implant devices: A position paper

Osseointegration of biomedical implants as well as healing of broken bones are supported by novel bioceramic materials that, owing to their engineered ionic conductivity, in the presence of an electric field provide accumulation of negative electrical charges close to the interface between an implant and living bone tissue, thus stimulating the rate of bone growth. In this position paper, the structure as well as the chemical, electrical, and biomedical properties of Ca (Ti,Zr) hexaorthophosphates are reviewed. In addition, based on evaluation of the material’s properties, a conceptual configuration of a capacity-coupled bone growth stimulator will be presented. The advantage of the proposed novel device over already existing bone-growth stimulators is its provision of the intimate contact of a capacity-coupled electric field with the growing bone tissue as opposed to an externally applied inductively coupled electromagnetic field, which suffers substantial attenuation when transmitted through soft tissue covering the locus of bone growth. To achieve higher ionic conductivity in Ca (Ti,Zr) hexaorthophosphates, aliovalent doping with highly mobile Na or Li ions intercalated into the only partially occupied M1 sites appears to be a suitable route.

Effect of different doses of zoledronate on bone growth in rats

Effect of different doses of zoledronate on bone growth in rats

Comparative postnatal histomorphogenesis of the mandible in wild and laboratory mice

The coordinated activity of bone cells (i.e., osteoblasts and osteoclasts) during ontogeny underlies observed changes in bone growth rates (recorded in bone histology and bone microstructure) and bone remodeling patterns explaining the ontogenetic variation in bone size and shape. Histological cross-sections of the mandible in the C57BL/6J inbred mouse strain were recently examined in order to analyze the bone microstructure, as well as the directions and rates of bone growth according to the patterns of fluorescent labeling, with the aim of description of the early postnatal histomorphogenesis of this skeletal structure. Here we use the same approach to characterize the histomorphogenesis of the mandible in wild specimens of Mus musculus domesticus, from the second to the eighth week of postnatal life, for the first time. In addition, we assess the degree of similarity in this biological process between the wild specimens examined and the C57BL/6J laboratory strain. Bone microstructure data show that M. musculus domesticus and the C57BL/6J strain differ in the temporospatial pattern of histological maturation of the mandible, which particularly precludes the support of mandibular organization into the alveolar region and the ascending ramus modules at the histological level in M. musculus domesticus. The patterns of fluorescent labeling reveal that the mandible of the wild mice exhibits temporospatial differences in the remodeling pattern, as well as higher growth rates particularly after weaning, compared to the laboratory mice. Since the two mouse groups were reared under the same conditions, the dissimilarities found suggest the existence of differences between the groups in the genetic regulation of bone remodeling, probably as a result of their different genetic backgrounds. Despite the usual suitability of inbred mouse strains as model organisms, inferences from them to natural populations regarding bone growth should be made with caution.

Sinus Floor Augmentation Comparing an In Situ Hardening Biphasic Calcium Phosphate (Hydroxyapatite/β-Tricalcium Phosphate) Bone Graft Substitute with a Particulate Biphasic Calcium Phosphate (Hydroxyapatite/β-Tricalcium Phosphate) Bone Graft Substitute: An Experimental Study in Sheep.

The aim of the present split-mouth study in sheep was to assess the influence of in situ hardening properties of a biphasic calcium phosphate (BCP) bone graft substitute (BGS) (ratio hydroxyapatite/β-tricalcium phosphate = 60/40) compared with a particulate BGS with the same biphasic core-granule composition without in situ hardening properties on sinus floor augmentation. Therefore, bilateral sinus floor augmentation was performed in eight sheep. Poly(lactide-co-glycolide) (PLGA)-coated, in situ hardening biphasic BGS (PLGA-NMP [N-Methyl-2-pyrrolidone]-BCP) was placed at the test site, and a particulate biphasic BGS without PLGA coating (BCP) was used for the contralateral site as a control. Animals were sacrificed after 21 weeks. Sinus augmentation sites were analyzed histologically. The volume was analyzed by computed tomography. Histomorphometric parameters were assessed for the 12 and 21 weeks' time points. Slopes of new bone formation over time were compared with a linear growth regression model. Bone formation after 12 and 21 weeks of healing was 8.94% (±3.74) and 19.82% (±6.29) for PLGA-NMP-BCP and 7.00% (±2.58) and 14.38% (±4.51) for BCP, respectively. The bone growth rate for PLGA-NMP-BCP was higher than the growth rate for BCP (probability 97.5%). The total fraction of calcified hard tissue (% bone fraction + % biomaterial) was around 46% for both tested biomaterials, 21 weeks after sinus floor augmentation. The in situ hardening BGS (PLGA-NMP-BCP) performed better than the particulate material (BCP) in terms of bone formation rate. The in situ hardening properties of the PLGA-NMP-BCP material mediated by the PLGA coating and NMP solution as plasticizer had no negative influence on the bone formation.