Patterns Of Bone Growth Research Articles

Bone labeling experiments and intraskeletal growth patterns in captive leopard geckos (Eublepharis macularius).

An understanding of the dynamics of bone growth is key to interpreting life-history parameters of vertebrates. In this study, we used fluorochrome labels in captive leopard geckos (Eublepharis macularius) to track bone growth and intraskeletal variability from embryonic to adult growth stages. Thirteen individuals were administered fluorochromes from pre-hatching to 4 years of age. The left tibia, fibula, femur, humerus, radius, and ulna were examined histologically and compared for differences in the number of labels within and between individuals at each sampled growth stage, and the amount of bone growth between labels was calculated. Results suggest that limb elements had differing growth rates; the fibula grew the fastest per day on average and the femur grew the slowest per day on average. All labels administered in ovo were still present in all limb elements in adults except for the tibia, suggesting growth marks are not lost in most elements and accurate calculations of growth rates could be performed in individuals up to 3 years old. All ex ovo labels were accounted for; however, when two fluorochromes were administered 3 weeks apart, the labels could not be differentiated from each other due to the new bone not being deposited at a quantifiable level. Overall, the tibia in leopard geckos is the least reliable limb bone to use for skeletochronology and the humerus, radius, and fibula preserve the longest growth record. This research highlights that, as in other extinct and extant animals, patterns of bone growth are not consistent across reptiles. This study adds to the growing body of knowledge on growth variability in reptiles.

Advanced multi-scale mechanobiological simulations enable the distinction between healthy and pathological bone growth patterns

Advanced multi-scale mechanobiological simulations enable the distinction between healthy and pathological bone growth patterns

Dissolving magnesium hydroxide implants enhance mainly cancellous bone formation whereas degrading RS66 implants lead to prominent periosteal bone formation in rabbits

Bone fractures often require internal fixation using plates or screws. Normally, these devices are made of permanent metals like titanium providing necessary strength and biocompatibility. However, they can also cause long-term complications and may require removal. An interesting alternative are biocompatible degradable devices, which provide sufficient initial strength and then degrade gradually. Among other materials, biodegradable magnesium alloys have been developed for craniofacial and orthopaedic applications. Previously, we tested implants made of magnesium hydroxide and RS66, a strong and ductile ZK60-based alloy, with respect to biocompatibility and degradation behaviour. Here, we compare the effects of dissolving magnesium hydroxide and RS66 cylinders on bone regeneration and bone growth in rabbit condyles using microtomographical and histological analysis. Both magnesium hydroxide and RS66 induced a considerable osteoblastic activity leading to distinct but different spatio-temporal patterns of cancellous and periosteal bone growth. Dissolving RS66 implants induced a prominent periosteal bone formation on the medial surface of the original condyle whereas dissolving magnesium hydroxide implants enhance mainly cancellous bone formation. Especially periosteal bone formation was completed after 6 and 8 weeks, respectively. The observed bone promoting functions are in line with previous reports of magnesium stimulating cancellous and periosteal bone growth and possible underlying signalling mechanisms are discussed. Statement of significanceBiodegradable magnesium based implants are promising candidates for use in orthopedic and traumatic surgery. Although these implants are in the scientific focus for a long time, comparatively little is known about the interactions between degrading magnesium and the biological environment. In this work, we investigated the effects of two degrading cylindrical magnesium implants (MgOH2 and RS66) both on bone regeneration and on bone growth. Both MgOH2 and RS66 induce remarkable osteoblastic activities, however with different spatio-temporal patterns regarding cancellous and periosteal bone growth. We hypothesize that degradation products do not diffuse directionless away, but are transported by the restored blood flow in specific spatial patterns which is also dependent on the used surgical technique.

Prognosis recovery score of apical surgery Guided Bone Regeneration using cone beam computed tomography and digital bioinformatics

ObjectiveGuided Bone Regeneration (GBR) is a dental surgical procedure that uses barrier membranes to prevent soft tissue invasion and conduct new bone growth. This study aimed to define a Prognosis Recovery score (PR score) to objectively classify post-surgery responders from non-responder patients who underwent GBR using Cone Beam Computed Tomography (CBCT). MethodsThis prospective-observational-longitudinal-cohort study recruited 250 individuals who were assigned to: Conventional-Apical-Surgery (CAS, n = 39), Apical-Surgery using human fascia lata Membrane placement (ASM, n = 42), and Apical-Surgery using human fascia lata Membrane placement and lyophilized allograft Bone powder (ASMB, n = 39); and Apical-Surgery using collagen membrane Porcine origin and Bovine Bone-matrix (ASPBB, n = 130), an independent external validation cohort. Surgery was performed, and evolution was monitored by CBCTs at 0, 6-, 12-, 18-, and 24 months post-surgery. ResultsNormalized lesion volumes were calculated, and non-linear time evolution morphology curves were characterized. The three-time evolution bone growth patterns were: a linear tendency (PR0), “S'' shaped log-logistic (PR1), and “C" cellular growth (PR2). The treatment success rates were PR2-46 %, PR2-88 %, and PR2-95 %/PR1-5% for CAS, ASM, and ASMB groups. The xenograft ASPBB counterpart achieved PR2-92 % and PR1-8%. The score PR had a sensitivity, specificity, and accuracy of 100 %. ConclusionsPatients' treatment success can be quantitatively, objectively, and precisely predicted with the Prognosis Recovery score (using only two CBCTs), according to their biological response to allograft or xenograft materials (time-evolution bone growth curves), reducing cost and radiation exposure. Clinical significanceThrough digital imaging and bioinformatic analysis of bone regeneration observed in CBCTs, we defined a Prognosis Recovery (PR) score using only two CBCT volume assessments (0 and 6 months). The PR score allowed us to define three time-evolution curves depending on the biomaterials used and to classify patients in a quantitative, objective, and accurate way.

Radiographic and histologic assessment of osseointegration for surface-treated titanium dental implants: An experimental study in dogs.

Modifying the dental implant's surface texture enhances its biological response to the bone and implant‒tissue interface, resulting in the successful support of forces. This study assessed the impact of sandblasting, sandblasting plus acid etching, Er,Cr:YSGG laser, and propolis implant surface treatments and occlusal load on the osseointegration of titanium dental implants in dogs. Seventy-two titanium dental implants with a diameter of 4 mm and a length of 10 mm were divided into four groups according to implant surface modifications (n=18 for each group): group A: sandblasting plus acid etching, group B: sandblasting with Al2 O3, group C: Er,Cr:YSGG laser, group D: propolis coating. Twenty-four local breed male dogs were used. Premolar teeth (P1, P2, and P3) were extracted on the left side of the mandible, and after 12 weeks of bone healing, implants were unilaterally installed. The osseointegration at three study times from implant installation (14, 90, and 180 days) was evaluated. The dog jaws were scanned using an intraoral scanner for the virtual design of screw-retained three-unit crowns after 90 days of osseointegration. Final radiographs were taken before the animals were sacrificed at 14, 90, and 180 days, and the histological analysis was performed. Radiographic analysis showed new bone formation (NBF) along and in contact with the implant surface of the treated groups. The histological analysis after 14 days in groups A and B revealed a uniform and ongoing pattern of bone growth and many osteoblasts with few osteocytes within lacunae in new bone trabeculae. Group C showed an increase in the number of osteoblasts lining thin bone trabeculae. Group D showed a generative power concerning bone. At 90 days, there was increased bone ingrowth, and the new bone matured in all the treated implant groups. At 180 days, dense mature bone apposition was in direct contact with delayed-loaded implant surfaces. A radiographic examination revealed that surface modification significantly impacted osseointegration, with a strong bond between the implant surface and the surrounding bone. The histological sections at the 14-day interval revealed obvious bone remodeling activity, especially in sandblasting plus acid etching and sandblasting-modified implant surface groups. At the 90-day interval, bone ingrowth had increased, and the new bone became mature, especially in sandblasting and propolis surface modification groups. After 180 days of the delayed-loaded implant osseointegration, differences were observed between different implant-treated groups with a remarkable remodeling of the bone, especially in the propolis coating group.

Genome-wide association study of growth curve parameters reveals novel genomic regions and candidate genes associated with metatarsal bone traits in chickens

The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433–176.318 Mb), GGA2 (96.791–103.543 Mb), GGA4 (65.003–83.104 Mb) and GGA6 (64.685–95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.

Jaw Fibro-Osseous Lesions: Use of a Predictive Index in Grading Probable Malignant Changes and a Review of Cases.

Fibro-osseous lesions (FLs), may rarely exhibit malignant features likewise undergo malignant transformation. Awareness of these features can assist in screening for potentially malignant cases and identifying low-grade central osteogenic sarcoma (LGCOS) that may mimic FLs. The objective of this study was to determine the usability of an index in predicting malignant changes in jaw FLs. This was a retrospective study where hematoxylin and eosin (H&E) slides and archival records of fibrous dysplasia (FD) and ossifying fibroma (OF) cases were reviewed. The sections were assessed for permeation of marrow spaces, stromal growth pattern, cytologic atypia, mitotic activity, and pattern of bone growth, which are parameters for diagnosing LGCOS. The predictive histologic index of malignancy (PHIM) was determined by a sum of the scores and graded as 0=nil, 1=low, 2 & 3=moderate, and 4 & 5=high. Data were presented using descriptive analysis. Ninety-three cases of FLs met the inclusion criteria, consisting of 40(43%) cases of FD and 53(57%) cases of OF. The peak age of presentation for FD and OF was 2nd and 3rd decade. There was a female preponderance of 1:1.6. The maxilla was the most common site affected by FD, while the mandible was most commonly affected by OF. For FD cases, the PHIM was moderate in 10(25%) cases and low in 21(52.5%) cases. Similarly, for OF cases, 30(56.6%) cases had low grade PHIM while 10(17%) cases had moderate grade PHIM. The PHIM depicted low to moderate malignancy grade in some of the cases studied. Follow up studies would be necessary to assess the PHIM.

New Bone Growth into Surgical Bone Defects Grafted with a Novel Cultivated Coral Graft: A Histomorphometric Study in Rabbit Calvarias.

To evaluate a new cultivated coral graft (CCG) in an in vivo experimental guided bone regeneration (GBR) procedure. The calvarias of eight rabbits were surgically exposed, and circular defects 8 mm in diameter were prepared. One defect was filled with CCG particles (experimental group); the contralateral defect (control group) was spontaneously filled by blood clot. All defects were covered with a collagen membrane. Subjects were euthanized after 8 weeks. Histologic observations of the defects showed similar bone growth patterns in both experimental and control osteotomies. In the experimental defects, no traces of coral particles were observed. Histometric analysis showed denser bone in the pristine zone (65%-66%) than in the peripheral zone for both the control (50%) and experimental defects (31%) (P = not significant). The new bone percentage was reduced from the peripheral zone toward the middle and the center of the defect (31%, 32%, and 27%, respectively) as the distance from the peripheral pristine bone borders increased. The existing data supports the complete degradation of CCG as a spacemaintaining scaffold for GBR procedures.

Developmental changes in tibia and humerus of goose: morphometric, densitometric, and mechanical analysis.

The skeletal system of young animals undergoes a series of intensive and rapid changes. In this study, we aimed to verify the hypothesis that geese exhibit a distinct pattern of bone growth compared to gallinaceous species. Specifically, we hypothesised that geese would experience an accelerated growth rate in the humerus bone, which can be attributed to the increased wing mobility facilitated by their rearing in free-range systems. This need for access to both ground and water environments contributes to the unique demands placed on their skeletal development. We focused on evaluating the mechanical properties and geometry of the humerus as the forelimb bone, and the tibia as the hindlimb bone. The 320 geese used in this study were divided into 12 groups according to sex (females and males) and age (0-,1-,3-,6-,8-,12-,14-week-old). To assess bone mechanical properties, a three-point bending test was performed, along with densitometry and morphological measurements. The tibiae of the geese showed the most intensive growth until 6weeks of age and then stabilised. The wing bones (humerus) showed only slight changes in the first weeks after hatching, and then a rapid growth between the third and sixth week, both in terms of mechanical and morphological properties. This is most likely due to a change in the geese's living environment during this period, i.e., allowing them to leave their enclosures and enter open space, which gives them the opportunity to use their wings, resulting in the rapid growth of the wing bones to support increasing muscle mass in this area. This study increases our understanding of bone growth and development in domesticated birds, specifically waterfowl species, and highlights the importance of rearing methods on the proper bone development and functionality of the entire skeletal system, and thus, on their welfare.

Osteoid osteomas of the hands and feet: a series of 71 cases.

Osteoid osteomas typically arise in the long bones of extremities. Patients often report pain relieved by NSAIDS, and radiographic findings are often sufficient for diagnosis. However, when involving the hands/feet, these lesions may go unrecognized or misdiagnosed radiographically due to their small size and prominent reactive changes. The clinicopathologic features of this entity involving the hands and feet are not well-described. Our institutional and consultation archives were searched for all cases of pathologically confirmed osteoid osteomas arising in the hands and feet. Clinical data was obtained and recorded. Seventy-one cases (45 males and 26 females, 7 to 64 years; median 23 years) arose in the hands and feet, representing 12% of institutional and 23% of consultation cases. The clinical impression often included neoplastic and inflammatory etiologies. Radiology studies demonstrated a small lytic lesion in all cases (33/33), the majority of which had a tiny focus of central calcification (26/33). Nearly, all cases demonstrated cortical thickening and/or sclerosis and perilesional edema which almost always had an extent two times greater than the size of the nidus. Histologic examination showed circumscribed osteoblastic lesions with formation of variably mineralized woven bone with single layer of osteoblastic rimming. The most common growth pattern of bone was trabecular (n = 34, 48%) followed by combined trabecular and sheet-like (n = 26, 37%) with only 11 (15%) cases presenting with pure sheet-like growth pattern. The majority (n = 57, 80%) showed intra-trabecular vascular stroma. No case showed significant cytology atypia. Follow up was available for 48 cases (1-432 months), and 4 cases recurred. Osteoid osteomas involving the hands and feet follow a similar age and sex distribution as their non-acral counterparts. These lesions often present with a broad differential diagnosis and may initially be confused with chronic osteomyelitis or a reactive process. While the majority of cases have classic morphologic features on histologic exam, a small subset consists solely of sheet-like sclerotic bone. Awareness that this entity may present in the hands and feet will help pathologists, radiologists, and clinicians accurately diagnose these tumors.

Bone growth and body weight patterns in juvenile raccoon dogs in Wakayama Prefecture, western Japan

Abstract Information on growth of the Japanese raccoon dog, Nyctereutes procyonoides is limited. We collected 237 juvenile raccoon dogs, road-killed and culled for pest control in Wakayama Prefecture, western Japan from 2002 to 2019. We measured the skull, mandible, femur lengths, and body weights of all specimens and used the body weights of healthy animals (n = 136). We found that these variables increased rapidly up to September and reached maximum values in October. Evidence of dorsal surface roughness of the neurocranium became obvious in October, and up to 35 % of individuals had rough dorsal surfaces of neurocranium in December. Epiphyseal fusion of femurs appeared in September, and 27 % of specimens having fused femurs was recorded in December. This study firstly described the growth patterns of the Japanese raccoon dogs based on a lot of samples.

Nonadult vertebral maturation in Late Holocene hunter‐gatherers from Patagonia (Salitroso Lake, Argentina)

AbstractBioarchaeological research of bone growth patterns provides information on the health status and disease of past populations. Recent studies have pointed out the potential of metric analysis of nonadult vertebrae as indicators of stress during different stages of ontogeny, highlighting that most vertebral measurements present low sexual dimorphism, a stable and known pattern of growth and give useful information even in incomplete spines. The aims of this paper are first, to construct a vertebral growth profile for nonadults of a skeletal series of Patagonian Late Holocene hunter‐gatherers from Salitroso Lake (SAC); second, to compare it to the ones obtained in other archaeological and modern populations with different stress experiences; and third, building on this, to assess whether individuals with evidence of stress experienced in early development demonstrate different patterns in vertebral growth than those without. Two spinal dimensions are used: vertebral body height (VBH) and transverse diameter of the neural canal (TDNC) in a sample of 23 nonadult skeletons with ages previously estimated from dental and bone indicators. The vertebral dimensions of 20 adults between 18 and 35 years of age were also measured as reference information. Results show that the growth of the VBH is steady over the years and reaches adulthood size by approximately 16 years of age whereas TDNC dimensions do not experience marked fluctuations in size throughout life and adult dimensions are reached at approximately 4 years of age as expected. The vertebral growth pattern observed in SAC is similar to that obtained in other archaeological samples from very different settings but experiencing relatively high nutritional or pathological stress in early stages of life. However, it is markedly different, and systematically smaller, to the 20th century sample pattern, probably responding to a secular trend in the modern population with a more stable access to resources and medical treatment. Finally, SAC individuals with systemic stress markers do not tend to exhibit smaller vertebral dimensions than those without them.

Rapid growth in Late Cretaceous sea turtles reveals life history strategies similar to extant leatherbacks.

Modern sea turtle long bone osteohistology has been surprisingly well-studied, as it is used to understand sea turtle growth and the timing of life history events, thus informing conservation decisions. Previous histologic studies reveal two distinct bone growth patterns in extant sea turtle taxa, with Dermochelys (leatherbacks) growing faster than the cheloniids (all other living sea turtles). Dermochelys also has a unique life history compared to other sea turtles (large size, elevated metabolism, broad biogeographic distribution, etc.) that is likely linked to bone growth strategies. Despite the abundance of data on modern sea turtle bone growth, extinct sea turtle osteohistology is virtually unstudied. Here, long bone microstructure of the large, Cretaceous sea turtle Protostega gigas is examined to better understand its life history. Humeral and femoral analysis reveals bone microstructure patterns similar to Dermochelys with variable but sustained rapid growth through early ontogeny. Similarities between Progostegea and Dermochelys osteohistology suggest similar life history strategies like elevated metabolic rates with rapid growth to large body size and sexual maturity. Comparison to the more basal protostegid Desmatochelys indicates elevated growth rates are not present throughout the entire Protostegidae, but evolved in larger and more derived taxa, possibly in response to Late Cretaceous ecological changes. Given the uncertainties in the phylogenetic placement of the Protostegidae, these results either support convergent evolution towards rapid growth and elevated metabolism in both derived protostegids and dermochelyids, or a close evolutionary relationship between the two taxa. Better understanding the evolution and diversity of sea turtle life history strategies during the Late Cretaceous greenhouse climate can also impact current sea turtle conservation decisions.

Complications in craniosynostosis surgery in patients with rickets: illustrative case and systematic review of literature.

Craniosynostosis (CSS) is the premature fusion of calvarial sutures associated with identified genetic mutations or secondary to alterations in intracranial pressure, brain, or bone growth patterns. Of the metabolic etiologies implicated in CSS, X-linked hypophosphatemic rickets (XLHR) is the most common, with dysfunctional bone mineralization leading to progressive hyperostosis and delayed synostosis. There is a paucity of literature discussing the unique surgical considerations for XLHR-related CSS. A 26-month-old male with XLHR-related sagittal CSS underwent cranial vault remodeling (CVR). Surgery was complicated by the presence of diploic hypertrophy with significant intraoperative estimated blood loss (EBL). EBL greatly exceeded reference ranges for CVR in all-cause CSS. As a result, the surgical goals were modified and the complete planned procedure aborted. Subsequent review of preoperative imaging revealed multiple fine vascular lacunae within the bone. A systematic literature review was conducted to identify reported complications relating to surgical intervention for rickets-associated CSS. Future considerations for patients with XLHR-related CSS should emphasize awareness of metabolic risk factors with associated complications, and the need for selection of approach and operative management techniques to avoid EBL. Further research is required to elucidate underlying mechanisms and determine whether the encountered phenomenon is characteristic across this patient population and potentially minimized by preoperative medical therapy.

The Impact of Genes and the Environment on Calvarial Bone Repair and Remodeling in a Murine Model of Craniosynostosis

INTRODUCTION: TWIST1 mutation leads to Seathre-Chotzen syndrome involving coronal craniosynostosis. Recent studies have shown that exposure to a selective serotonin reuptake inhibitor, citalopram, can cause craniosynostosis. The purpose of this study is to investigate the genetic and environmental mechanisms underlying aberrant bone repair in a murine model of craniosynostosis. METHODS: Thirteen Twist1+/– mutant mice and wild-type (WT) mice with or without in utero citalopram exposure were generated (n = 5 per group): WT, Twist1+/–, WT + citalopram (n = 5), and Twist1+/– + citalopram. Mice underwent calvarial defect surgery followed by microCT imaging at 1, 2, 3, and 4 weeks postoperatively, at which point they were sacrificed for histological analysis. RESULTS: All mice were fully ambulatory after surgery, with no perioperative complications. MicroCT analysis demonstrated that all Twist1+/– mice exposed to citalopram had craniosynostosis and exhibited excessive and disorganized bone growth after injury. Some Twist1+/– mice without citalopram treatment also developed craniosynostosis and exhibited a similar excessive bone growth pattern; Twist1+/– mice without suture fusion had bone repair similar to that of WT mice. WT defects remained incompletely healed at 4-weeks postoperatively. In contrast, the Twist1+/– mice with citalopram exposure demonstrated full bone fill of the defect at 4-weeks. Twist1+/– mice without citalopram demonstrated more bone fill than WT, but the defect was not entirely filled. CONCLUSION: These preliminary findings after calvarial defect surgeries improve our understanding of bone repair in craniosynostosis. By investigating the mechanisms of bone dynamics in craniosynostosis, we can better understand and prevent the factors implicated in resynostosis after surgery.

Parathyroid hormone-related protein and primary teeth eruption in stunting children

Stunting is a linear growth failure as an indicator of malnutrition status which is identified by comparing the height of children with normal height according to the same age and sex. Children are categorized as stunting if the child`s height is shorter than the average height of the same age and sex and has a standard deviation of below minus 2 according to the standard who. The cause of stunting is multifactorial, including disruption of hormone function, one of which is a parathyroid hormone. Parathyroid Hormone-related Protein (PTHrP) plays a role in the tooth-eruption process. This literature review aims to study the role of PTHrP on the eruption rate of primary teeth in stunting children. Malfunction of the parathyroid glands in stunted children can cause a deficiency of PTHrP levels. PTHrP and vitamin D play a role in the maintenance and affect calcium levels. Deficiency levels of PTHrP and vitamin d can lead to decreased absorption of calcium in the blood. Calcium deficiency in children can cause osteoclasts and osteoblasts to decrease, which can affect bone growth and tooth eruption patterns. In stunting children, the level of PTHrP will decrease so that tooth eruption will be inhibited.

Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies

BackgroundLongitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories.MethodsThis expository paper provides an illustrative guide to summarising nonlinear growth trajectories for repeatedly measured continuous outcomes using (i) linear spline and (ii) natural cubic spline linear mixed-effects (LME) models, (iii) Super Imposition by Translation and Rotation (SITAR) nonlinear mixed effects models, and (iv) latent trajectory models. The underlying model for each approach, their similarities and differences, and their advantages and disadvantages are described. Their application and correct interpretation of their results is illustrated by analysing repeated bone mass measures to characterise bone growth patterns and their sex differences in three cohort studies from the UK, USA, and Canada comprising 8500 individuals and 37,000 measurements from ages 5–40 years. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts.ResultsLinear and natural cubic spline LME models and SITAR provided similar summary of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Growth velocity (in grams/year) peaked during adolescence, and peaked earlier in females than males e.g., mean age at peak bone mineral content accrual from multicohort SITAR models was 12.2 years in females and 13.9 years in males. Latent trajectory models (with trajectory shapes estimated using a natural cubic spline) identified up to four subgroups of individuals with distinct trajectories throughout adolescence.ConclusionsLME models with linear and natural cubic splines, SITAR, and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data. Scripts and synthetic datasets are provided for readers to replicate trajectory modelling and visualisation using the R statistical computing software.

The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice.

The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman’s analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERβ antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.

Different Effects of Soy and Whey on Linear Bone Growth and Growth Pattern in Young Male Sprague-Dawley Rats.

The aim of this investigation was to determine the better protein for supporting optimal linear growth, as the exact composition and benefits of specific dietary proteins in supporting linear growth is unknown. In the current study, we compared the effect of soy and whey proteins, both proteins contain all essential amino acids and are considered the best proteins in their categories. Young male rats were subjected to multiple feeding protocols using iso-energetic diets containing soy or whey as the sole protein source. The rats were allowed to eat ad libitum for 11, 24, or 74 days in the first set of experiments, and the soy group was pair-fed to the whey group in the second set. The differences in weight gain, food consumption, and humeri length of the soy group that were greater at the beginning of the ad libitum experiments lessened over time. Pair-fed experiments revealed that the increased weight and humeri length resulted from the differences in food consumption. However, other parameters were protein specific. Bone quality, which was better in the soy group at 24 days, was matched by the whey group and even surpassed that of the soy group in the long-term experiment, with a significantly greater bone mineral density, cortical thickness, and growth plate. Although in the short term the levels of insulin like growth factor (IGF)-I were similar between the groups, IGF-I increased with age in the whey group, and the levels at the long-term experiment were significantly higher compared to the soy group. Furthermore, using the pair fed setup made it clear that when the difference in food consumption were no longer playing part, whey was more efficient in increasing IGF-I. There were no indications of metabolic sequelae. Although the use of soy is gaining in popularity as a sustainable protein, our findings indicate a better effect of whey on linear growth by leading to slower growth with better-organized epiphyseal growth plates and bone quality.

Bioactive chitosan biguanidine-based injectable hydrogels as a novel BMP-2 and VEGF carrier for osteogenesis of dental pulp stem cells

Nowadays, vascularization and mineralization of bone defects is the main bottleneck in the bone regeneration field that is needed to be overcome and developed. Here, we prepared novel in-situ formed injectable hydrogels based on chitosan biguanidine and carboxymethylcellulose loaded with vascular endothelial growth factor (VEGF) and recombinant Bone morphogenetic protein 2 (BMP-2) and studied its influence on osteoblastic differentiation of dental pulp stem cells (DPSCs). The sequential release behavior of the VEGF and BMP-2 from hydrogels adjusted with the pattern of normal human bone growth. MTT assay exhibited that these hydrogels were non-toxic and significantly increased DPSCs proliferation. The Real-time PCR and Western blot analysis on CG11/BMP2-VEGF showed significantly higher gene and protein expression of ALP, COL1α1, and OCN. These results were confirmed by mineralization assay by Alizarin Red staining and Alkaline phosphatase enzyme activity. Based on these evaluations, these hydrogel holds potential as an injectable bone tissue engineering platform.