Skeletal Maturity Research Articles

Compensatory thoracic curve correction in lumbar anterior vertebral body tether (VBT) versus lumbar posterior spinal fusion (PSF).

Anterior vertebral body tethering (VBT) is a non-fusion surgical option for skeletally immature patients with idiopathic scoliosis. Prior studies demonstrated compensatory correction of the thoracic curve after lumbar posterior spinal fusion (PSF); however, no studies have examined thoracic curve correction after lumbar VBT. Patients with Lenke 5 + 6 lumbar scoliosis who underwent VBT and at least 2years' follow-up were compared to matched lumbar PSF patients. Groups were compared for major lumbar (L) and compensatory thoracic (T) curve correction, coronal/sagittal balance, and complications. 24 AVBT and 24 PSF patients were matched 1:1 for skeletal maturity and curve flexibility. There were no significant differences between VBT and PSF for average pre-operative or 2year post-operative major L or compensatory T curves. Average final L curve correction was 50% VBT and 60% PSF (p = 0.08); average T curve correction was 17% VBT and 20% PSF (p = 0.18). Compared to pre-operative flexibility radiographs, the final post-op thoracic curves were 6° (VBT) and 5° (PSF) larger. PSF had better coronal balance by average of 17mm (p < 0.0001). There were seven (24%) reoperations in the VBT group: two overcorrections relaxed, two T adding-on (extended to T by PSF-1, VBT-1), one broken tether converted to PSF. There was one (4%) reoperation in the PSF group (10-year post-op extension). Compensatory thoracic correction was achieved to a similar degree for lumbar VBT and PSF patients. There was little change in thoracic curve magnitude over time, and, on average, the correction did not reach the pre-operative flexibility curve measurement. There was better coronal balance by PSF, and a higher rate of re-operation in VBT patients. III.

Radiographic Outcome Following Treatment of Residual Hip Dysplasia with Pemberton Versus Salter Osteotomy: Comparison of Results in Patients Followed to Skeletal Maturity.

Salter osteotomy (SO) and Pemberton acetabuloplasty (PA) are procedures to treat skeletally immature patients with developmental dysplasia of the hip (DDH). The purpose of this study was to compare the radiographic results and rate of residual dysplasia (RD) after treatment with SO and with PA. This was a retrospective analysis of pediatric patients treated with either SO or PA for DDH between 1980 and 2013 who were skeletally mature at the time of follow-up. The preoperative and postoperative acetabular index (AI) and postoperative lateral center-edge angle (LCEA) and anterior center-edge angle (ACEA) were collected. RD was defined as an LCEA or ACEA of <20° or an acetabular inclination (AIn) of >15° at skeletal maturity. Continuous variables were compared between treatment groups with 2-sample t tests, and categorical variables were compared using chi-square tests. Multivariable analysis was used to identify risk factors for RD with p < 0.05. The study included 113 hips in 102 patients with a mean follow-up of 10.5 years. The SO group had 73 hips treated at a mean patient age of 5.4 years, and the PA group had 40 hips treated at a mean age of 5.3 years. The preoperative AI did not differ between the treatment groups (32.2° versus 31.3°, p = 0.658), nor did the immediate postoperative AI (20.0° versus 20.2°, p = 0.459). At the time of final follow-up, the SO group had a significantly smaller AIn (8.6° versus 13.2°, p = 0.001), a trend toward a greater LCEA (26.2° versus 21.6°, p = 0.056), and a similar ACEA (24.1° versus 26.1°, p = 0.808). By the abovementioned definition, 36 hips (31.9%) had evidence of RD, with a lower rate in the SO group (26.0% versus 42.5%, p = 0.07). Patients who had a positive family history of hip dysplasia were more likely to have RD (odds ratio = 4.311, 95% confidence interval = 1.125 to 16.528). Patients with RD could be effectively treated with either SO or PA, with overall good radiographic outcomes. However, SO achieved a better AI and may thus yield better long-term health of the affected hip. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Analysis of Serial Foot Radiographs to Determine Foot Height Multipliers.

The multiplier method is an arithmetic calculation that estimates the amount of growth remaining until skeletal maturity. When predicting lower limb length discrepancy, differences in foot height are added to femur and tibia discrepancies. Foot height multipliers have not been calculated using radiographic measurements, so it is unclear whether foot height develops at the same pace as the femur and tibia. This study used serial images to calculate foot height multipliers and compared them to published lower limb and foot length multipliers. The Bolton Brush radiograph collection was used to measure foot height on the lateral foot view. Multipliers were calculated for ages with at least 10 serial study visits. 212 patients (2195 radiographs) were included in the study (102 female, 110 male patients). Foot height multipliers were calculated for ages 0 to 17 years (females) and 0 to 18 years (males). Multipliers decreased with age, but qualitatively plateau at age 13 (females) and age 15 (males). Lower extremity multipliers have a more dramatic growth curve, indicating comparatively greater lower extremity growth after birth. However, when comparing the limb length discrepancy calculation using the lower extremity multiplier versus the foot height multiplier for the foot portion, the difference was negligible. This paper provides a database of foot height multipliers. Foot height seems to grow on a different trajectory than other lower limb components, confirming that one should consider separate multiplier values. The difference created by the foot height multiplier versus the lower extremity multiplier appears to be modest. Separate use of the foot height multiplier may only be necessary for young children with large foot height discrepancies, but further study to confirm the lack of impact of the foot height multiplier on limb length discrepancy calculations is needed. Our data were derived from normal children, so it is unknown if the presence of a talo-calcaneal coalition would affect foot height on the involved side. Level III-retrospective comparative study.

SMN depletion impairs skeletal muscle formation and maturation in a mouse model of SMA.

Spinal muscular atrophy (SMA) is characterized by low levels of the ubiquitously expressed Survival Motor Neuron (SMN) protein, leading to progressive muscle weakness and atrophy. Skeletal muscle satellite cells play a crucial role in muscle fiber maintenance, repair, and remodelling. While the effects of SMN depletion in muscle are well documented, its precise role in satellite cell function remains largely unclear. Using the Smn2B/- mouse model, we investigated SMN-depleted satellite cell biology through single fiber culture studies. Myofibers from Smn2B/- mice were smaller in size, shorter in length, had reduced myonuclear domain size, and reduced sub-synaptic myonuclear clusters-all suggesting impaired muscle function and integrity. These changes were accompanied by a reduction in the number of myonuclei in myofibers from Smn2B/- mice across all disease stages examined. Although the number of satellite cells in myofibers was significantly reduced, those remaining retained their capacity for myogenic activation and proliferation. These findings support the idea that a dysregulated myogenic process could be occurring as early in muscle stem cells during muscle formation and maturation in SMA. Targeting those pathways could offer additional options for combinatorial therapies for SMA.

What imaging does my AIS patient need? A multi-group survey of provider preferences.

Adolescent idiopathic scoliosis (AIS) is a common diagnosis managed by pediatric orthopedic surgeons with nonoperative radiographic monitoring representing a cornerstone of treatment. Differences in practices and techniques for obtaining radiographic studies contribute to variation, cost of care, and hamper data aggregation. We surveyed several large organizations dedicated to children's orthopedics or scoliosis care to obtain a consensus for radiographic evaluation of AIS. A REDCap-based survey was developed across four institutions and beta-tested by staff and fellows from a single institution. The finalized survey was distributed to members of POSNA, PSSG, and SOSORT, and shared on social media. Participants were asked to rank the importance of various datapoints in radiographic assessment of the spinal deformity, skeletal maturity, and study indications during initial, subsequent, preoperative, and final office visits for AIS. Response rate for the overall group was 26%. Cobb angle was considered the most important (> 94%) radiographic index across all time points. For positioning, 46% of respondents favored arms bent touching clavicles as the ideal positioning for X-rays, and another 24% favored arms down with palms forward (Table2). The majority of respondents obtain lateral X-rays at the first visit (99%) and at the preoperative visit (70%). At the preoperative visit, sagittal contour (86%), apex location (85%), and Lenke classification (73%) were considered important factors to record. Flexibility studies are primarily obtained at the preoperative visit (89%) and 81% of respondents prefer bending films as the flexibility technique of choice. Regarding measures of skeletal maturity, Sanders bone age was considered to be the most important by over 70% of respondents across initial, subsequent, preoperative and brace wean visits (Fig.2). MRIs were obtained routinely by 34% of respondents and only when the patient had a concerning symptom or finding for 67% of respondents. Despite large variations in radiographic examination of AIS, large areas of agreement were found. It is important to establish standards for positioning patients, evaluating skeletal maturity, and obtaining assessments including lateral views, flexibility studies, and advanced imaging. Establishing common practices for radiographic evaluation of AIS will allow for less variation in care and for critical questions to be answered through registry formation and large multicenter data collection. This study establishes current practitioner opinion on the radiographic evaluation of the AIS patient. Minimum data sets are useful for data aggregation and answering research questions in the face of data variability. Level V.

Convolutional Neural Network-Based Deep Learning Methods for Skeletal Growth Prediction in Dental Patients

This study aimed to predict the skeletal growth maturation using convolutional neural network-based deep learning methods using cervical vertebral maturation and the lower 2nd molar calcification level so that skeletal maturation can be detected from orthopantomography using multiclass classification. About 1200 cephalometric radiographs and 1200 OPGs were selected from patients seeking treatment in dental centers. The level of skeletal maturation was detected by CNN using the multiclass classification method, and each image was identified as a cervical vertebral maturation index (CVMI); meanwhile, the chronological age was estimated from the level of the 2nd molar calcification. The model’s final result demonstrates a high degree of accuracy with which each stage and gender can be predicted. Cervical vertebral maturation reported high accuracy in males (98%), while females showed high accuracy of 2nd molar calcification. CNN multiclass classification is an accurate method to detect the level of maturation, whether from cervical maturation or the calcification of the lower 2nd molar, and the calcification level of the lower 2nd molar is a reliable method to trust in the growth level, so the traditional OPG is enough for this purpose.

Evaluation of the effects of cementless total hip replacement on femoral length in skeletally immature dogs.

To describe percentage length changes in the femur after total hip replacement (THR) performed before skeletal maturity. Retrospective study. Twenty-four dogs younger than 8.5 months which underwent unilateral THR and had radiographic follow up. Preoperative and follow-up radiographs were reviewed. Radiographic measurements included the length of the greater trochanter, femoral diaphysis and distal epiphysis, width of the femur 10 mm distal to the distal aspect of the greater trochanter, width of the femur at 50%, and femoral condylar offset. Percentage changes in length over time were compared among operated and contralateral femurs used as controls. Measurements were collected in triplicate in 10 dogs to evaluate consistency. All repeated measurements had excellent consistency. The percentage increase in length of the greater trochanter was smaller in operated femurs than controls (mean difference: -11.5%, p = .017), but no differences were observed for the femoral diaphysis and distal epiphysis (-1.0%, p = .595), or the femur overall (-2.3%, p = .232). The percentage increase in femoral cortical width was greater in operated femurs than controls, both 10 mm distal to the greater trochanter (4.6% difference, p = .037) and at 50% length (8.5% difference, p = .030). In growing dogs, cementless THR decreased trochanteric growth by approximately 10% but did not change diaphyseal growth and femoral growth. Cementless THR performed in skeletally immature dogs with severe hip problems did not impact femoral length in a clinically relevant fashion.

Charting the growth through intelligence: A SWOC analysis on AI-assisted radiologic bone age estimation.

Bone age estimation (BAE) is based on skeletal maturity and degenerative process of the skeleton. The clinical importance of BAE is in understanding the pediatric and growth-related disorders; whereas medicolegally it is important in determining criminal responsibility and establishing identification. Artificial Intelligence (AI) has been used in the field of the field of medicine and specifically in diagnostics using medical images. AI can greatly benefit the BAE techniques by decreasing the intra observer and inter observer variability as well as by reducing the analytical time. The AI techniques rely on object identification, feature extraction and segregation. Bone age assessment is the classical example where the concepts of AI such as object recognition and segregation can be used effectively. The paper describes various AI based algorithms developed for the purpose of radiologic BAE and the performances of the models. In the current paper we have also carried out qualitative analysis using Strength, Weakness, Opportunities and Challenges (SWOC) to examine critical factors that contribute to the application of AI in BAE. To best of our knowledge, the SWOC analysis is being carried out for the first time to assess the applicability of AI in BAE. Based on the SWOC analysis we have provided strategies for successful implementation of AI in BAE in forensic and medicolegal context.

Comparison of Standing Side Bending Using Biplanar Stereography and Fulcrum Bending for Flexibility Assessment of Adolescent Idiopathic Scoliosis.

Background: The surgical treatment of adolescent idiopathic scoliosis (AIS) is influenced by factors such as skeletal maturity, curve magnitude, progression, and spinal flexibility. The assessment of spinal flexibility is crucial for surgical planning; supine bending radiographs are commonly used but there is no consensus on the optimal technique. Fulcrum bending radiographs (FBRs) have shown better prediction of post-surgery correction compared to supine bending radiographs. New radiological techniques allow a significant reduction in radiation exposure. This study aims to compare spinal flexibility assessment and radiation exposure between FBRs and standing side-bending radiographs (SSRs) using biplanar stereoradiography. Materials and Methods: Twenty-five consecutive AIS patients scheduled for surgery were included in this prospective cohort study. Exclusion criteria were non-idiopathic etiology, age younger than 12 years, and older than 18 years. Pre-surgery FBRs and SSRs were performed, and the Cobb angles were measured. Flexibility and correction rates were calculated. Dose-area products (DAPs) were recorded. Statistical analysis was conducted using the Wilcoxon signed-rank test and Spearman correlation. Results: The mean pre-surgery Cobb angle of the thoracic curve was 66.3°. The FBR was superior to SSR for assessing flexibility for thoracic curves and provided a better prediction for post-surgery correction. There was no significant difference in lumbar curves between FBR and SSR. The mean DAP for SSRs was 0.81 Gy*cm2 compared to 3.42 Gy*cm2 for FBR, indicating a lower radiation exposure using SSRs. Conclusions: FBRs are superior for flexibility assessment of thoracic curves in AIS and offers a better prediction of post-surgery correction compared to SSRs. However, FBR is associated with a higher radiation exposure.

Forearm Fractures in Older Children and Adolescents: ORIF is Safer Than IMN With Equivalent Outcomes.

Greater understanding of the impact of skeletal maturity on outcomes is needed to guide operative treatment of diaphyseal forearm fractures in children and adolescents. The purpose of this study was to compare the complications and outcomes of pediatric diaphyseal forearm fractures treated with intramedullary nailing (IMN) or open reduction internal fixation (ORIF) and to identify a radiographic marker of skeletal maturity that will aid in selecting between treatment options. A retrospective review of patients aged 10 to 16 years treated operatively for diaphyseal forearm fractures was performed. Markers of skeletal maturity including the olecranon apophysis score, the presence of the thumb adductor sesamoid, and radial epiphyseal capping. Complications were graded with the modified Clavien-Dindo system. Outcomes were scored based on final postoperative range of motion combined with complication grade. A total of 260 patients were included: 163 treated with IMN, 97 treated with ORIF, mean age 12.7 years, 72% male. Among closed forearm fractures treated with IMN, open reduction was required in 45% (53/118). Patients treated with IMN had a higher complication rate than ORIF (27.0% vs. 9.3%, P<0.05), including when stratified by age. Complication rates were not impacted by greater skeletal maturity as indicated by the presence of thumb sesamoid or radial epiphyseal capping. There was no significant difference in outcomes between the ORIF and IMN groups. More skeletally immature patients, as identified by a lack of either the thumb adductor sesamoid or radial epiphyseal capping, had significantly better outcomes with ORIF than patients with greater maturity. Across all age groups and levels of skeletal maturity, ORIF had a significantly lower rates of complications compared with IMN with equivalent outcomes. More skeletally immature patients had significantly better outcomes with ORIF treatment when compared with older patients. The thumb adductor sesamoid, radial epiphyseal capping, and the olecranon apophysis score did not provide useful information to select between ORIF over IMN in this population. Level III-retrospective comparative study.

Early Sagittal Shape of the Spine Predicts Scoliosis Development in a Syndromic (22q11.2DS) Population: A Prospective Longitudinal Study.

Scoliosis is a deformation of the spine and trunk that, in its more severe forms, creates a life-long burden of disease and requires intensive treatment. For its most prevalent form, adolescent idiopathic scoliosis, no underlying condition can be defined, and the pathomechanism appears to be multifactorial; however, it has been suggested that the biomechanics of the spine play a role. For nonidiopathic scoliosis, underlying conditions can be recognized, but what drives the deformity remains unclear. In this study, we examined the early sagittal shape of the spine before the onset of scoliosis in a population with 22q11.2 deletion syndrome (22q11.2DS). This cohort was chosen since children with this syndrome have an approximately 50% chance of developing scoliosis that shares certain characteristics with idiopathic scoliosis, namely, age of onset, curve morphology, and rate of progression. This prospective cohort study included patients with 22q11.2DS who were followed with the use of spinal radiographs during adolescent growth. All of the children, who initially had no scoliosis while still skeletally immature (Risser stages 0 and 1), were followed at 2-year intervals until they reached skeletal maturity (Risser stages 3 to 5). We assessed the segment of the spine that has previously been shown to be rotationally unstable, the posteriorly inclined segment, to determine if it was predictive of later scoliosis development. For quantification, the area of the "posteriorly inclined triangle" (PIT), a previously described parameter that integrates both the inclination and length of the at-risk segment, was measured. Of the 50 children who initially had no scoliosis (mean age at inclusion, 10.7 ± 1.7 years; mean follow-up, 4.8 ± 1.6 years), 24 (48%) developed scoliosis. Patients with an above-average PIT area (>60 cm2) at inclusion showed a relative risk of 2.55 for scoliosis development (95% confidence interval [CI]:1.22 to 5.34). PIT inclination was correlated with curve type: a taller and steeper hypotenuse predicted later thoracic scoliosis, while a shorter and less steep inclination predicted the development of (thoraco)lumbar scoliosis. This prospective study identified the pre-scoliotic sagittal shape of the spine as a risk factor for the later development of scoliosis in the population of children with 22q11.2DS. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

The reliability of a modified three-stage cervical vertebrae maturation method for estimating skeletal growth in males and females.

Reliability of the six-stage cervical vertebrae maturation method to evaluate skeletal growth was evaluated on the combined male and female samples and revealed diverse results. The current study aimed to determine the reliability of the modified three-stage cervical vertebrae maturation method for estimating the skeletal growth of males and females. Pretreatment lateral cephalometric radiographs of 137 orthodontic patients were utilized to evaluate the intra- and inter-observer reliability of a modified cervical vertebrae maturation method. Four independent examiners categorized each radiograph into one of the three skeletal growth stages according to the cervical vertebrae morphology: (1) a pre-peak group (combining the CS1 and CS2 stages), (2) a peak group (combining the CS3 and CS4 stages), and (3) a post-peak group (combining the CS5 and CS6 stages). The Kappa index and the Fleiss multirater Kappa test were carried out to determine the reproducibility of this method. The studied sample included cephalometric radiographs of 68 males (49.6%) and 69 females (50.4%) aged between 7 and 58 years; no significant age difference was found between the sexes (p = 0.189). The overall inter-observer reliability was 0.689 (p < 0.001), and the inter-observer reliability for the post-peak stage showed only Kappa = 0.896 (p < 0.001). The Kappa values were significantly greater in males than in females during the peak stage (0.626 and 0.488, respectively). A modified three-stage cervical vertebrae maturation method showed substantial overall inter-examiner agreement; however, differential reliability for diverse skeletal maturation stages and sexes was found.

Outcomes of operative fixation of loose trochlear osteochondral defects: A case series with subgroup analysis

Objectives To evaluate results of open reduction and internal fixation (ORIF) of loose osteochondritis dissecans (OCD) fragments of the trochlea including identification of any cases of fixation failure and assessment of post-operative patient-reported outcomes and activity level. Methods A retrospective chart review of OCD fixation surgeries performed between 2010 and 2021 identified 12 patients who underwent ORIF of loose OCD trochlear fragments. Patient demographics, history, imaging findings, surgical factors, and skeletal maturity were all collected. Primary outcome measures included reoperation for fixation failure, Knee Osteoarthritis Outcome Scores (KOOS), and Marx scores. Results The 12 patients (12 knees) with a mean age of 17.7 ± 6.4 years (range, 13-37 years) were included in the case series. Mean trochlear OCD size was 3.20 cm2 (range, 1.69-5.06 cm2) with mean follow-up of 78.9 months (range, 8 – 145). Failure of fixation occurred in. Failure of fixation occurred in 2 patients (17%). Of the 10 patients (83%) who completed PROs, the mean KOOS global score for all patients was 86.8 ± 16.3, symptoms/stiffness sub score 90.0 ± 11.0, pain 91.2 ± 12.1, Functions of daily living 95.5 ± 8.3, Sports/recreation 82.0 ± 23.9, quality of life 75.7 ± 28.6, and a mean Marx activity score of 10.5 ± 4.9. Conclusion ORIF of loose OCD lesions of the trochlea is associated with a low risk of failure of fixation and acceptable patient-reported outcomes.

Windswept deformity of the knee: prevalence and predictive factors in osteoarthritic and healthy populations.

This study examined windswept deformity (WSD) of the knee, comparing prevalence and contributing factors in healthy and osteoarthritic (OA) cohorts. A case-control radiological study was undertaken comparing 500 healthy knees (250 adults) with a consecutive sample of 710 OA knees (355 adults) undergoing bilateral total knee arthroplasty. The mechanical hip-knee-ankle angle (mHKA), medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were determined for each knee, and the arithmetic hip-knee-ankle angle (aHKA), joint line obliquity, and Coronal Plane Alignment of the Knee (CPAK) types were calculated. WSD was defined as a varus mHKA of < -2° in one limb and a valgus mHKA of > 2° in the contralateral limb. The primary outcome was the proportional difference in WSD prevalence between healthy and OA groups. Secondary outcomes were the proportional difference in WSD prevalence between constitutional varus and valgus CPAK types, and to explore associations between predefined variables and WSD within the OA group. WSD was more prevalent in the OA group compared to the healthy group (7.9% vs 0.4%; p < 0.001, relative risk (RR) 19.8). There was a significant difference in means and variance between the mHKA of the healthy and OA groups (mean -1.3° (SD 2.3°) vs mean -3.8°(SD 6.6°) respectively; p < 0.001). No significant differences existed in MPTA and LDFA between the groups, with a minimal difference in aHKA (mean -0.9° healthy vs -0.5° OA; p < 0.001). Backwards logistic regression identified meniscectomy, rheumatoid arthritis, and osteotomy as predictors of WSD (odds ratio (OR) 4.1 (95% CI 1.7 to 10.0), p = 0.002; OR 11.9 (95% CI 1.3 to 89.3); p = 0.016; OR 41.6 (95% CI 5.4 to 432.9), p ≤ 0.001, respectively). This study found a 20-fold greater prevalence of WSD in OA populations. The development of WSD is associated with meniscectomy, rheumatoid arthritis, and osteotomy. These findings support WSD being mostly an acquired condition following skeletal maturity.

Evaluating the Feasibility of Cervical Vertebral Maturation Stages as an Alternative to Risser Sign in Assessing Skeletal Maturity in Adolescent Idiopathic Scoliosis Patients

Radiographic methods for evaluating skeletal maturity traditionally include the Risser sign and the hand-wrist maturation method. While the cervical vertebral maturation (CVM) stage is widely recognized in orthodontics, its application in assessing spinal growth, particularly in adolescent idiopathic scoliosis (AIS), has been less explored. This study explores the correlation between CVM, chronological age, and the Risser sign to evaluate the feasibility of CVM in assessing skeletal development in adolescents. This prospective study included adolescent idiopathic scoliosis (AIS) patients and asymptomatic adolescents, aged 7-15 years, who underwent full-spine imaging with clear visibility of the cervical and pelvic regions. The correlation between CVM and the Risser sign was analyzed. The height of the cervical C3-7 vertebral body was measured, and its growth trend with age was examined. Differences between AIS patients and asymptomatic adolescents were compared. A total of 85 AIS patients (mean age 11.44±2.36 years) and 47 asymptomatic adolescents (mean age 11.48±3.14 years) were included. No statistically significant differences were observed in age, Risser sign grading, CVM staging, or C3-7 vertebral body height between the two groups. Chronological age showed a stronger correlation with CVM stages than with the Risser sign in both the AIS group (r=0.93 vs. r=0.82, P<0.01) and the asymptomatic group (r=0.81 vs. r=0.72, P<0.01). The CVM stage, which shows a strong correlation with Risser sign grading, could serve as a reliable alternative for assessing skeletal maturity in adolescent subjects, particularly in clinical scenarios where minimizing radiation exposure is a priority.

A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis

Iroquois homeobox gene 3 (Irx3) and Irx5 encode transcription factors that play crucial roles in limb development and bone formation. Previous studies using knockout mice have revealed a role of Irx3 and Irx5 in osteogenesis in young adult mice. However, whether these genes are also essential for bone homeostasis in adulthood and contribute to bone diseases remain poorly understood. Osteoporosis is a disease characterized by lower bone mineral density and disrupted bone microarchitecture, typically occurs in postmenopausal women. Here, we demonstrate that Irx3/5dHet mice with a half-reduction of Irx3 and Irx5 dosage serve as a novel model of osteoporosis. By micro-computed tomography, we found that Irx3/5dHet mice exhibited sex-dependent bone loss patterns. While male Irx3/5dHet mice progressively lost trabecular microstructures with aging, female mutants exhibited lower bone mineral density (BMD) and bone volume fraction (BV/TV) at early adulthood (9–15 weeks old) but without further loss later at 1 year of age. Bone marrow adipocytes are known to be elevated at the expenses of lower osteogenesis in osteoporotic bone marrow. Surprisingly, we found sex-dependent changes in adipogenesis at the age of skeletal maturity that bone marrow adipocytes were reduced in female Irx3/5dHet mice along with deteriorated osteogenesis, while male mice exhibited elevated adipogenesis. In summary, we reported a novel genetic model for osteoporosis-like phenotypes, highlighting sex-dependent bone mineral density and bone marrow adipocyte characteristics.

T2-weighted spoiled gradient echo MRI for forensic age estimation: a study on knee growth plates.

The timing of growth plate fusion is a key indicator for age estimation and is primarily used in forensic investigations. On the other hand, non-ionizing techniques such as MRI are being developed to provide safer and more ethical evaluations in forensic casework. This study aims to evaluate the closure process of growth plates in the distal femoral and proximal tibial epiphyses using Multiple Echo Recombined Gradient Echo (MERGE) MRI sequences and provide age estimation data based on staging methods for forensic purposes. We retrospectively analyzed 559 patients (294 males, 265 females, aged 8-25 years) diagnosed with trauma and knee pain at Tepecik Training and Research Hospital from 2016 to 2019. MRI scans were performed using a 1.5-T system with MERGE sequences and evaluated by two observers using a new staging system. Observer agreement was assessed using Cohen's κ test, yielding high agreement values (κ > 0.8). Positive correlations were found between age and ossification stages (p < 0.001). Minimum age thresholds for stages 5a and 5b of the distal femoral epiphysis were 16 and 18 years for females and 17 and 19 years for males, respectively. For the proximal tibial epiphysis, the minimum ages for stages 5a and 5b were 15 years for females and 17 years for males. The MERGE sequence provides a viable method for assessing skeletal maturity in living individuals with significant ethical advantages due to non-ionizing radiation. This study supports the potential application of the MERGE sequence in forensic age estimation, demonstrating high observer agreement and consistency. Future research should focus on comparing different sequences and populations to enhance the methodology's applicability.

Orthodontic treatment of patients with cleft lip and palate from birth through maturity

Cleft lip and palate (CLP) is one of the most common congenital anomalies, requiring lifelong care by a team of craniofacial specialists. A key member of that team is the craniofacial orthodontist, who provides treatment for these patients throughout the lifetime. This care actually begins prenatally, when families first meet with a craniofacial team. The family is provided with resources to prepare for their child's arrival and counseled about future treatment. Presurgical infant orthopedics (PSIO) will usually begin within a week of birth and continues for 3–5 months. PSIO helps approximate the lip and alveolar segments and reshapes the nostrils to facilitate primary surgical repairs. This is followed by a phase of monitoring growth and dental development throughout childhood, as patients with CLP are at increased risk for dental anomalies. Once the maxillary canine roots are one-third developed, the patient will be prepared for secondary alveolar bone grafting. This may include expansion, alignment, and/or maxillary protraction via facemask therapy. A short phase of maxillary dental alignment might follow if functional or esthetic concerns arise. Comprehensive orthodontic treatment is then performed at skeletal maturity, and coordinated with orthognathic surgery when indicated. The orthodontist and surgeon will collaborate closely in planning and managing the surgical correction. It is crucial that each stage of orthodontics is followed by an appropriate retention protocol. Finally, surgical and esthetic finishing procedures take place after surgical orthodontics is complete. This may include surgery to address lip, nose, speech, and breathing concerns, as well as definitive dental restorations.

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p&amp;lt;0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

6903 The Treatment May Be Worse Than The Disease: The Real-World Clinical Burden Of Disease And Treatment In Congenital Adrenal Hyperplasia

Abstract Disclosure: W. Huang: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. R. Charlton: Employee; Self; Spruce Biosciences. S. Sile: Employee; Self; Spruce Biosciences. C. Dieyi: Employee; Self; STATinMED. S. Adams: Employee; Self; STATinMED. J. Maynard: Employee; Self; STATinMED. C.N. Barnes: Employee; Self; Spruce Biosciences. A.H. Hamrahian: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. Background and Aims: Classic congenital adrenal hyperplasia (CAH) is a group of autosomal recessive conditions that affects the production of adrenal hormones, leading to deficiencies in cortisol and aldosterone, and excess in adrenal androgens. Current treatment includes mineralocorticoids and oral glucocorticoids (GCs) for physiologic cortisol replacement and hypothalamic-pituitary-adrenal (HPA) axis suppression to control androgen levels. The health impacts of hyperandrogenemia include accelerated skeletal maturation leading to adult short stature, precocious puberty, acne, hirsutism, male pattern baldness, adrenal rest tumors, and infertility. There are also serious adverse events due to the long-term use of supraphysiologic doses of GCs. The aim of this study was to explore the risks associated with CAH diagnosis and treatment. Methods: This cross-sectional study used medical administrative claims data within 2014-2021 from RWD Insights®, an all-payer claims database in the US. Adult patients were required to have a diagnosis of CAH (ICD-9/10-CM: 255.9, E25.0, E25.9) and continuous use of oral GCs (defined as a proportion of days covered of 75% or more in any given calendar year). Patients were further required to receive an average daily GC dose of ≥10mg/day hydrocortisone equivalent and be free of pituitary disorders. Non-CAH controls were also selected if they did not have a CAH diagnosis or any GC use. Demographic characteristics and comorbidity rates were compared between patients with and without CAH during the study period. For comorbidity rate comparisons, rate ratios (RR) and 95% confidence intervals (CI) were computed. Results: A total of 1,532,141 (CAH: 2,033; Non-CAH: 1,530,108) were eligible for the study. A lower proportion of the CAH cohort was elderly (i.e., 65+ years; 11% vs. 26%), and there were more females (67% vs. 57%), as compared to the non-CAH cohort. After propensity score matching (PSM) on demographic characteristics, there were 2,019 and 8,076 patients in the CAH and non-CAH cohort, respectively, and patient characteristics were balanced. There were higher rates of comorbidities in the CAH cohort. Some notable differences, RR (95%CI), include GC related comorbidities such as osteoporosis/necrosis, 3.48 (3.36, 3.60) and fractures, 2.14 (1.90, 2.39); metabolic disorders, 2.20 (2.08, 2.33), obesity, 1.35 (1.26-1.44), type 2 diabetes, 1.27 (1.18,1.36), and cardiovascular disorders, 1.24 (1.16, 1.33); and CAH related comorbidities, hirsutism, 11.70 (11.34, 12.06) and testicular hypofunction, 5.48 (5.24, 5.71). Conclusions: This study suggests the association of several comorbidities with CAH, highlighting the burden of both the disease and treatment. Novel, non-steroidal treatments that improve hormonal balance in CAH could ameliorate the systemic risks associated with hyperandrogenemia and chronic overexposure to GCs. Presentation: 6/1/2024