A Mouse Femoral Ostectomy Model to Assess Bone Graft Substitutes.

The shortcomings of autografts and allografts in bone defect healing have prompted researchers to develop suitable alternatives. Numerous biomaterials have been developed as bone graft substitutes each with their own advantages and disadvantages. However, in order to test if these biomaterials provide an adequate replacement of the clinical standard, a clinically representative animal model is needed to test their efficacy. In this chapter, we describe a mouse model that establishes a critical sized defect in the mid-diaphysis of the femur to evaluate the performance of bone graft substitutes. This is achieved by performing a femoral ostectomy and stabilization utilizing a femoral plate and titanium screws. The resulting defect enables the bone regenerative potential of bone graft substitutes to be investigated. Lastly, we provide instruction on assessing the torsional strength of the healed femurs to quantitatively evaluate the degree of healing as a primary outcome measure.

The Transcription Factor HAND1 Is Involved in Cortical Bone Mass through the Regulation of Collagen Expression.

Temporal and/or spatial alteration of collagen family gene expression results in bone defects. However, how collagen expression controls bone size remains largely unknown. The basic helix-loop-helix transcription factor HAND1 is expressed in developing long bones and is involved in their morphogenesis. To understand the functional role of HAND1 and collagen in the postnatal development of long bones, we overexpressed Hand1 in the osteochondroprogenitors of model mice and found that the bone volumes of cortical bones decreased in Hand1Tg/+;Twist2-Cre mice. Continuous Hand1 expression downregulated the gene expression of type I, V, and XI collagen in the diaphyses of long bones and was associated with decreased expression of Runx2 and Sp7/Osterix, encoding transcription factors involved in the transactivation of fibril-forming collagen genes. Members of the microRNA-196 family, which target the 3' untranslated regions of COL1A1 and COL1A2, were significantly upregulated in Hand1Tg/+;Twist2-Cre mice. Mass spectrometry revealed that the expression ratios of alpha 1(XI), alpha 2(XI), and alpha 2(V) in the diaphysis increased during postnatal development in wild-type mice, which was delayed in Hand1Tg/+;Twist2-Cre mice. Our results demonstrate that HAND1 regulates bone size and morphology through osteochondroprogenitors, at least partially by suppressing postnatal expression of collagen fibrils in the cortical bones.

Finite element modelling of the developing infant femur using paired CT and MRI scans.

Bone finite element (FE) studies based on infant post-mortem computed tomography (CT) examinations are being developed to provide quantitative information to assist the differentiation between accidental and inflicted injury, and unsuspected underlying disease. As the growing skeleton contains non-ossified cartilaginous regions at the epiphyses, which are not well characterised on CT examinations, it is difficult to evaluate the mechanical behaviour of the developing whole bone. This study made use of paired paediatric post mortem femoral CT and magnetic resonance imaging (MRI) examinations at two different stages of development (4 and 7 months) to provide anatomical and constitutive information for both hard and soft tissues. The work aimed to evaluate the effect of epiphyseal ossification on the propensity to shaft fractures in infants. The outcomes suggest that the failure load of the femoral diaphysis in the models incorporating the non-ossified epiphysis is within the range of bone-only FE models. There may however be an effect on the metaphysis. Confirmation of these findings is required in a larger cohort of children.

A comparative evaluation of tibial metaphyseal-diaphyseal angle changes between physiologic bowing and Blount disease.

The purpose of this study was to estimate the rate of spontaneous improvement in tibial metaphyseal-diaphyseal angle (TMDA) in physiologic bowing in comparison to that in Blount disease and to provide reference values of TMDA for monitoring patients with highly suspected to have Blount disease.We retrospectively reviewed patients with physiologic bowing meeting the following criteria:(1) TMDA greater than 9° before 36 months of age at initial evaluation;(2) two or more standing long bone radiographs available; and(3) follow-up conducted up to resolution of deformity.Patients with Blount disease had(1) more than 2 standing long bone radiographs obtained before 36 months of age and(2) underwent no treatment during the period in which these images were obtained.TMDA measurements were obtained from 174 patients with physiologic bowing and 32 patients with Blount disease. Rates of TMDA improvement were adjusted by multiple factors using a linear mixed model, with sex and laterality as fixed effects and age and individual patients as the random effects.In the physiologic bowing group, TMDA improved significantly, by 3° per 6 months and by 6° per year. Changes in TMDA were not significant in the Blount disease group.Knowing the rate of TMDA change can be helpful for physicians seeking to monitor infants with suspected as having Blount disease with a high TMDA and to avoid unnecessary repeat radiographic evaluations.

Endochondral growth disruption during vitamin D deficiency rickets in a mid-19th century series from Bethnal Green, London, UK.

OBJECTIVES: Vitamin D affects many aspects of cartilage and skeletal development. Inconsistent findings currently exist regarding the impact of vitamin D deficiency on childhood growth. This study aims to evaluate the impact of vitamin D deficiency on childhood skeletal development by exploring long bone growth in children with healed and active rickets. MATERIALS AND METHODS: Forty-four known-age children (2 months to 12 years) with rickets and 99 without rickets were compared with modern reference data from North America. Diaphyseal lengths of children with active rickets (34.1%, 15/44), healed rickets (65.9%, 29/44), and without rickets (99/143, 69.2%) were expressed as a percentage of expected length and an average percentage value was calculated across all available long bones. RESULTS: Combined data for all six long bones revealed that children with active rickets had achieved only 75.3% of their expected size whereas, on average, children with healed rickets had achieved 81.6% of their expected size. On average, children without skeletal evidence of rickets had achieved 83.7% of their expected size. Children with severe skeletal manifestations of active rickets had a lower average percentage of expected size (70.4%) than the remainder of children affected by the condition. DISCUSSION: Pronounced growth faltering existed in children with active rickets and affected the upper and lower limb, indicating systemic growth failures during the deficiency. Poor maternal health, early weaning and inadequate infant feeding, and lack of sunlight exposure likely contributed to the development of rickets. Complex interactions between pathological conditions, nutritional deficiencies and vitamin D deficiency may have exacerbated growth impacts.

Growth of the New Thumb Metacarpal After Pollicization for Thumb Hypoplasia.

PURPOSE: To investigate the radiographic length and width of the new thumb metacarpal in relation to the middle finger proximal phalanx; to assess the incidence of premature physeal closure of the new metacarpal; and to consider whether there is a relationship between growth characteristics and the presence of union or nonunion of the new trapezium to the retained index finger metacarpal base. METHODS: Forty pollicizations were assessed with preoperative or immediate postoperative radiographs and follow-up radiographs to establish the growth characteristics of the new thumb metacarpal. Functional outcomes comprising grip strength, pinch strength, and range of motion were correlated with radiological findings of presence or absence of open physes and presence or absence of union of the new trapezium to the metacarpal base. RESULTS: The new thumb metacarpal physis was open in 28 pollicizations and closed in 12. In the latter group, all physes of the hand had closed indicating skeletal maturity. The length and width indices of the new thumb metacarpal in relation to the middle finger proximal phalanx were equivalent to or greater than the perioperative growth indices. There was a reduced postoperative length ratio in those patients with nonunion of the new trapezium to the base of the metacarpal. There was no change in strength and range of motion parameters with growth other than that related to normal improvement with age. CONCLUSIONS: We are unable to demonstrate premature physeal closure following routine pollicization. The growth of the metacarpal continues in a normal manner to skeletal maturity. A failure of union of the new trapezium to the metacarpal base may compromise growth. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Torsional Growth Modulation of Long Bones by Oblique Plating in a Rabbit Model.

BACKGROUND: There is evidence that oblique tension band plating can affect torsional growth in long bones. This study sought to determine if the torsional growth could be modulated based on the angles of the tension band plating and whether or not oblique plating affected overall longitudinal growth. METHODS: New Zealand White rabbits (10.5 wk old) had one screw placed on the metaphyseal side and one on the epiphyseal side of both medial and lateral sides of the right knee distal femoral physis. The sham group (n=5) included screw placement only. For the plate group (n=13), unlocked plates, angled from 0 to 76 degrees, connected the screws and spanned the physis. Radiographs were taken at biweekly intervals. After 6 weeks of growth, hindlimbs were harvested and microCT scans performed. Femoral length, distances between screw heads and angle between the plates were measured on radiographs. Femoral length differences were compared between groups. Femoral version was measured from 3D microCT. Plate angle changes were correlated to the difference in femoral version between limbs using Pearson correlation (significance was set to P<0.05 for all comparisons). RESULTS: Femur length difference between the contralateral and the operative side was significantly greater in the plate group compared with the sham group over time (P=0.049). Medial and lateral screw distances changed significantly more in the sham group than the plate group on both sides (P<0.001). A greater initial angle between plates resulted in a greater change in the angle between plates (P<0.001). Significant correlations were found between right-left side femoral version differences and initial plate angle (P=0.003) and plate angle change (P=0.014). CONCLUSIONS: The torsional effect of oblique plating seems to correlate with the amount of initial plate angle, with an additional, not negligible, longitudinal growth effect. CLINICAL SIGNIFICANCE: Placing plates at given angles across open physes may result in predictable changes in bone torsion allowing for a safer and less invasive option when treating childhood torsional deformities, but the resulting shortening of the ipsilateral femur must be considered.

Fractional fetal thigh volume in the prediction of normal and abnormal fetal growth during the third trimester of pregnancy.

BACKGROUND: Currently, 2-dimensional ultrasound estimation of fetal size rather than fetal growth is used to define fetal growth restriction, but single estimates in late pregnancy lack sensitivity and may identify small for gestational age rather than growth restriction. Single or longitudinal measures of 3-dimensional fractional thigh volume may address this problem. OBJECTIVE: We sought to derive normal values for 3-dimensional fractional thigh volume in the third trimester, determine if fractional thigh volume is superior to 2-dimensional ultrasound biometry alone for detecting fetal growth restriction, and determine whether individualized growth assessment parameters have the potential to identify fetal growth restriction remote from term delivery. STUDY DESIGN: This was a longitudinal prospective cohort study of 115 unselected pregnancies in a tertiary referral unit (St Mary's Hospital, Manchester, United Kingdom). Standard 2-dimensional ultrasound biometry measurements were obtained, along with fractional thigh volume measurements (based on 50% of the femoral diaphysis length). Measurements were used to calculate estimated fetal weight (Hadlock). Individualized growth assessment parameters and percentage deviations in longitudinally measured biometrics were determined using a Web-based system (iGAP; http://iGAP. RESEARCH: bcm.edu). Small for gestational age was defined <10th and fetal growth restriction <3rd customized birthweight centile. Logistic regression was used to compare estimated fetal weight (Hadlock), estimated fetal weight (biparietal diameter-abdominal circumference-fractional thigh volume), fractional thigh volume, and abdominal circumference for the prediction of small for gestational age or fetal growth restriction at birth. Screening performance was assessed using area under the receiver operating characteristic curve. RESULTS: There was a better correlation between fractional thigh volume and estimated fetal weight ((biparietal diameter-abdominal circumference-fractional thigh volume) obtained at 34-36 weeks with birthweight than between 2-dimensional biometry measures such as abdominal circumference and estimated fetal weight (Hadlock). There was also a modest improvement in the detection of both small for gestational age and fetal growth restriction using fractional thigh volume-derived measures compared to standard 2-dimensional measurements (area under receiver operating characteristic curve, 0.86; 95% confidence interval, 0.79-0.94, and area under receiver operating characteristic curve, 0.92; 95% confidence interval, 0.85-0.99, respectively). CONCLUSION: Fractional thigh volume measurements offer some improvement over 2-dimensional biometry for the detection of late-onset fetal growth restriction at 34-36 weeks.

A method for estimating gestational age of fetal remains based on long bone lengths.

The estimation of gestational age (GA) in fetal human remains is important in forensic settings, particularly to assess fetal viability, in addition to often being the only biological profile parameter that can be assessed with some accuracy for non-adults. The length of long bone diaphysis is one of the most frequently used methods for fetal age estimation. The main objective of this study was to present a simple and objective method for estimating GA based on the measurements of the diaphysis of the femur, tibia, fibula, humerus, ulna, and radius. Conventional least squares regression equations (classical and inverse calibration approaches) and quick reference tables were generated. A supplementary objective was to compare the performance of the new formulae against previously published models. The sample comprised 257 fetuses (136 females and 121 males) with known GA (between 12 and 40 weeks) and was selected based on clinical and pathological information. All measurements were performed on radiographic images acquired in anonymous clinical autopsy records from spontaneous and therapeutic abortions in two Portuguese hospitals. The proposed technique is straightforward and reproducible. The models for the GA estimation are exceedingly accurate and unbiased. Comparisons between inverse and classical calibration show that both perform exceptionally well, with high accuracy and low bias. Also, the newly developed equations generally outperform earlier methods of GA estimation in forensic contexts. Quick reference tables for each long bone are now available. The obtained models for the estimation of gestational age are of great applicability in forensic contexts.

Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations.

Drifting Diaphyses: Asymmetry in Diametric Growth and Adaptation Along the Humeral and Femoral Length.

This study quantifies regional histomorphological variation along the human humeral and femoral diaphysis in order to gain information on diaphyseal growth and modeling drift patterns. Three thin sections at 40, 50, and 60% bone length were prepared from a modern Mexican skeletal sample with known age and sex to give a longitudinal perspective on the drifting cortex (12 adults and juveniles total, 7 male and 5 female). Point-count techniques were applied across eight cross-sectional regions of interest using the starburst sampling pattern to quantify percent periosteal and endosteal primary lamellar bone at each diaphyseal level. The results of this study show a posterio-medial drift pattern in the humerus with a posterior rotational trend along the diaphysis. In the femur, we observed a consistent lateral to anteriolateral drift and an increase in primary lamellar bone area of both, periosteal and endosteal origin, towards the distal part of the diaphysis. These observations characterize drifting diaphyses in greater detail, raising important questions about how to resolve microscopic and macroscopic cross-sectional analysis towards a more complete understanding of bone growth and mechanical adaptation. Accounting for modeling drift has the potential to positively impact age and physical activity estimation, and explain some of the significant regional variation in bone histomorphology seen within (and between) bone cross-sections due to differing ages of tissue formation. More study is necessary, however, to discern between possible drift scenarios and characterize populational variation.

Form follows function: a computational simulation exercise on bone shape forming and conservation.

The present paper explores whether the shape of long bone shafts can be explained as a mere result of mechano-adapation. A computer simulation study was conducted in order to investigate adaptation processes of bone-like structures under load patterns comparable to those acting on the diaphysis of long bones. The aim of the study was to have a deeper look into the relationship between typical loading patterns and resulting bone shape and structure. The simulations are based on a mechanistic model approach for mechano-transduction and bone transformation. Results of the simulations are that axial torsion around the long axis is important for the evolvement and maintenance of tube-like structures. Of note such structures can form from a variety of starting geometries, provided that axial torsion is present. The selection of the set-point parameter for the regulation of load adapted bone transformation has an impact on the final structure as well. In conclusion, the present study confirms the mechanical environment's potential to generate shaft-like structures and demonstrates the respective boundary conditions.

Ontogeny of the female femur: geometric morphometric analysis applied on current living individuals of a Spanish population.

In this study we describe the development of the female femur based on the analysis of high-resolution radiographic images by means of geometric morphometrics, while assessing the usefulness of this method in these kinds of studies. The material analysed consisted of digital images in DICOM format (telemetries), corresponding to 184 left femora in anterior view, obtained from the database of the Hospital Sant Joan de Déu of Barcelona (Spain). Bones analysed corresponded to individuals from 9 to 14 years old. Size and shape variation of the entire femur was quantified by 22 two-dimensional landmarks. Landmark digitisation errors were assessed using Procrustes anova test. Centroid size (CS) variation with age was evaluated by an anova test. Shape variation was assessed by principal component analysis. A mancova test between the first five principal components and age, using the CS as covariable, was applied. Results indicated that both size and shape vary significantly with age. Several age-related shape changes remained significant after removing the allometric effect. In general, an increase in the robustness of the bone and noticeable phenotypic changes in certain areas of the femur were observed. During growth in the proximal region of the femur, the collo-diaphyseal angle decreases, the neck of the femur widens and the fovea moves to a lower position, standing more in line with the plane of the neck. Likewise, the size of the greater and lesser trochanters increase. In the distal region, a significant increase of epiphyseal dimensions was recorded, mainly in the medial condyle. The angular remodelling of the neck and the bicondylar region of the femur in females continues until 13 years old. The information provided in the present study increases our knowledge on the timing and morphology of the femur during development, and in particular the morphology of the different femoral ossification centres during development.

Forensic age estimation in living subjects based on ultrasound examination of the ossification of the olecranon.

Radiation-free imaging procedures for the purposes of forensic age diagnosis are highly desirable, especially for children. With this in mind, the stage of ossification of the olecranon was prospectively determined in 309 male and 307 female healthy volunteers aged between 10 and 25 years, based on ultrasound. A four-stage classification system was used for this purpose. This stage classification system takes into account whether an isolated secondary ossification centre, an epiphyseal cartilage or an epiphysis which is completely fused with the diaphysis can be detected. The earliest observation of stage 2 was at 10.0 years in males and 10.1 years in females. Both findings are determined by the lower age limit of the sample and are thus not representative of the minimum age for ossification stage 2. Stage 3 was first noticed at age 13.5 years in males and 10.6 years in females. Stage 4 was first reached at age 13.7 years in males and 12.3 years in females. Hence, in our sample, ossification stage 3 can be seen as evidence that females have reached the age of 10 years and males the age of 13 years. In our sample, stage 4 provides evidence that a female individual has reached the age of 12 years. It was concluded that the results of our study should be validated using other samples.

[The effect of tibial transphyseal reinforcement on the growth and response of leg tissues].

Transphyseal reinforcement of right intact tibia performed with thin steel rods in six mongrel dogs at the age of six months. Contralateral segment served as control. The leg growth and blood supply studied under the created conditions for the next six months. Radiographic, physiologic (surface thermometry, photoplethysmography), and statistical methods used for studying. The significant effect of transphyseally inserted rods on the leg longitudinal growth and blood supply has not been revealed. The changes in natural shape-formation oftibial proximal and distal meta-epiphyses observed influenced by the transphyseal rods in the experiment. In order to evaluate the tissue response and the degree of the functional activity of leg bone meta-epiphyseal zones the most informative areas considered to be the following: the area of medial malleolus in the early period of physiological growth completion, and the area of the tibial lateral condyle--at the late stage.

Ontogenetic changes in limb bone structural proportions in mountain gorillas (Gorilla beringei beringei).

Behavioral studies indicate that adult mountain gorillas (Gorilla beringei) are the most terrestrial of all nonhuman hominoids, but that infant mountain gorillas are much more arboreal. Here we examine ontogenetic changes in diaphyseal strength and length of the femur, tibia, humerus, radius, and ulna in 30 Virunga mountain gorillas, including 18 immature specimens and 12 adults. Comparisons are also made with 14 adult western lowland gorillas (Gorilla gorilla gorilla), which are known to be more arboreal than adult mountain gorillas. Infant mountain gorillas have significantly stronger forelimbs relative to hind limbs than older juveniles and adults, but are nonsignificantly different from western lowland gorilla adults. The change in inter-limb strength proportions is abrupt at about two years of age, corresponding to the documented transition to committed terrestrial quadrupedalism in mountain gorillas. The one exception is the ulna, which shows a gradual increase in strength relative to the radius and other long bones during development, possibly corresponding to the gradual adoption of stereotypical fully pronated knuckle-walking in older juvenile gorillas. Inter-limb bone length proportions show a contrasting developmental pattern, with hind limb/forelimb length declining rapidly from birth to five months of age, and then showing no consistent change through adulthood. The very early change in length proportions, prior to significant independent locomotion, may be related to the need for relatively long forelimbs for climbing in a large-bodied hominoid. Virunga mountain gorilla older juveniles and adults have equal or longer forelimb relative to hind limb bones than western lowland adults. These findings indicate that both ontogenetically and among closely related species of Gorilla, long bone strength proportions better reflect actual locomotor behavior than bone length proportions.

Differential effects of exercise on tibial shaft marrow density in young female athletes.

CONTEXT: Increased mechanical loading can promote the preferential differentiation of bone marrow mesenchymal stem cells to osteoblastogenesis, but it is not known whether long-term bone strength-enhancing exercise in humans can reduce marrow adiposity. OBJECTIVE: Our objective was to examine whether bone marrow density (MaD), as an estimate of marrow adiposity 1) differs between young female athletes with contrasting loading histories and bone strengths and 2) is an independent predictor of bone strength at the weight-bearing tibia. DESIGN: Mid-tibial MaD, cortical area (CoA), total area, medullary area, strength strain index (SSI), and cortical volumetric bone mineral density (vBMD) (total, endocortical, midcortical, and pericortical) was assessed using peripheral quantitative computed tomography in 179 female athletes involved in both impact and nonimpact loading sports and 41 controls aged 17-40 years. RESULTS: As we have previously reported CoA, total area, and SSI were 16% to 24% greater in the impact group compared with the controls (all P < .001) and 12% to 18% greater than in the nonimpact group (all P < .001). The impact group also had 0.5% higher MaD than the nonimpact and control groups (both P < .05). Regression analysis further showed that midtibial MaD was significantly associated with SSI, CoA, endocortical vBMD, and pericortical vBMD (P < .05) in all women combined, after adjusting for age, bone length, loading groups, medullary area, muscle cross-sectional area, and percent fat. CONCLUSION: In young female athletes, tibial bone MaD was associated with loading history and was an independent predictor of tibial bone strength. These findings suggest that an exercise-induced increase in bone strength may be mediated via reduced bone marrow adiposity and consequently increased osteoblastogenesis.

Predictors of recurrent instability after acute patellofemoral dislocation in pediatric and adolescent patients.

BACKGROUND: Patellofemoral instability is common in the pediatric and adolescent population, yet prognosis after the first dislocation has been difficult to determine. PURPOSE: To describe the demographics of pediatric and adolescent patients with a first-time patellofemoral dislocation and to determine predictors of recurrent instability. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A search of the Mayo Medical Index database between 1998 to 2010 was performed, and 2039 patients were identified. Inclusion criteria were (1) age 18 years or younger, (2) no history of patellofemoral subluxation/dislocation of the affected knee, (3) radiographs within 4 weeks of the initial instability episode, and (4) a dislocated patella requiring reduction or convincing history/findings suggestive of acute patellar dislocation (effusion/hemarthrosis, tenderness along medial parapatellar structures, and apprehension with lateral patellar translation). Radiographs were evaluated for trochlear dysplasia (Dejour classification) and patella alta (Caton-Deschamps and Insall-Salvati indices). Skeletal maturity was graded based on the distal femoral and proximal tibial physes (open, closing, or closed). RESULTS: A total of 222 knees (120 male [54.1%] and 102 female [45.9%]) in 210 patients with an average age of 14.9 years (range, 9-18 years), met the inclusion criteria. Twenty-four patients (10.8%) underwent early surgery. All others were initially treated nonoperatively. Of the 198 patients in this group, 76 (38.4%) had recurrent instability, and 39 (51.3%) of these required surgical treatment. Recurrent instability was associated with trochlear dysplasia (P < .01). Patients with both immature physes and trochlear dysplasia had a recurrence rate of 69% (33/48), with a hazard ratio of 3.3. Age, sex, body mass index, and patella alta were not statistically associated with recurrent instability. CONCLUSION: Nonoperative treatment for first-time patellofemoral dislocation resulted in a 62% success rate. However, skeletally immature patients with trochlear dysplasia had only a 31% success rate with nonoperative management. Nearly half of patients with recurrent instability required surgical intervention to gain stability.

Increasing participation of sclerostin in postnatal bone development, revealed by three-dimensional immunofluorescence morphometry.

Confocal immunofluorescence tiling imaging revealed the spatio-temporal distributions of osterix and sclerostin in femurs from 3-day-old, 2-week-old and 4-week-old rats to be reciprocally exclusive at the tissue level. Further quantitative three-dimensional immuno fluorescence morphometry demonstrated the increasing distribution of sclerostin in the osteocytic lacuno-canalicular system specifically in diaphysis, which paralleled the cooperative participation and depletion of osterix and ß-catenin in adjacent periosteum cells. Treating MC3T3-E1 cells with BIO (a GSK3 inhibitor) induced the stabilization of ß-catenin and nuclear translocation of osterix, and negatively regulated osteocalcin/BGLAP and Dmp1. These results collectively demonstrate that the increasing distribution of sclerostin in diaphyseal cortical bone appears to be involved in the attenuation of osterix and ß-catenin in adjacent periosteum cells, thus possibly contributing to osteoblast maturation and reducing the osteoblast formation at this bone site. Our confocal microscopy-based imaging analyses provide a comprehensive and detailed view of the spatio-temporal distribution of sclerostin, ß-catenin and osterix at the tissue to subcellular level in a coherent manner, and uncovered their spatio-temporal cooperation in postnatal bone development, thus providing evidence that they link skeletogenic growth and functional bone development.

Postmortem CT investigation of skeletal and dental maturation of the fetuses and newborn infants: a serial case study.

Physical maturation involving bones and teeth is a classic indication of fetal maturity in forensic practice, for which radiological examination is effective. The present study preliminarily investigated the efficacy of postmortem computed tomography (PM-CT) in estimating the gestational age of fetuses (n = 3) and newborn infants (n = 4), compared with plain radiography. Body length and weight estimated in reconstructed CT images approximated the measured values, providing additional data of body mass volume and fat development. The diaphyses of humerus and femur, and the epiphyseal ossification centers of femur and calcaneus were more easily identified and accurately measured in CT images than in plain radiographs. The developmental stage of deciduous teeth was also clearly identified. PM-CT was useful to evaluate the physical maturity of infants.