Gabriel Tilmann Mindler

Aims: This study aimed to quantify ontogenetic changes in femoral morphology – specifically femoral head and condyle sizes – and joint loads in children. Methods: MRI and 3D movement data were recorded from nine children without any known pathologies at two timepoints, two years apart. Femoral geometry was segmented from the MRI to quantify femoral head and medial and lateral condyle volumes. Personalized MRI-informed musculoskeletal models were created and used to estimate hip and knee joint contact forces (JCFs) based on the 3D movement data. Multiple linear regression models were used to assess whether changes in JCF and femoral morphology can be predicted from simple measures such as age, body weight, and height. Results: Both femoral joint contact geometry and absolute JCF significantly increase with age. However, when normalized to body weight, JCF remained stable – or even decreased in the case of medial condyle JCF – over time. Predicting changes in JCF based on the simple measures of age, weight, and height worked reasonably well for hip JCF (R ² = 0.67) and lateral condyle JCF (R ² = 0.78), but less well for medial condyle JCF (R ² = 0.41). Changes in femoral morphology could be predicted with moderate accuracy, with R ² values ranging from 0.40 for lateral condyle volume to 0.59 for femoral head volume. Conclusion: Our findings demonstrate ontogenetic increases in both absolute JCF and joint contact surface areas, which may help maintain relatively stable cartilage pressures during growth. These data provide valuable reference values for differentiating normal developmental patterns from pathological alterations in femoral morphology and joint loading. While simple regression models effectively captured population-level trends, they were not suitable for subject-specific predictions, underscoring the need for more advanced and individualized modelling approaches in paediatric biomechanics. Cite this article: Bone Joint Res 2026;15(6):726–738.

Background/Objectives: Rickets is a pediatric disorder caused by impaired mineralization of the growth plate, primarily due to deficiencies in vitamin D, calcium, or phosphate. Lower limb deformities are among the most clinically relevant skeletal manifestations, significantly affecting quality of life. This review aims to summarize and compare lower limb deformities associated with different etiologies of rickets, specifically hypophosphatemic (HPR) and calcipenic (CR) forms. Methods: A systematic PubMed search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Of 2056 screened records, 126 studies including 21,568 patients met the inclusion criteria. Data on study characteristics, deformity types, and diagnostic methods were extracted and analyzed descriptively, with subgroup comparison between HPR and CR. Results: Among 2924 patients with reported with deformities (1537 CR, 1387 HPR), genu varum and genu valgum predominated, while windswept deformities were less frequent. Sagittal and torsional deformities, particularly femoral and tibial maltorsion or procurvatum, were mainly described in HPR but rarely reported in CR. Only a minority of studies met predefined quality standards regarding radiological assessment and deformity definition. Conclusions: Lower limb deformities are prevalent in both HPR and CR but differ significantly in type and documentation quality. While coronal plane deformities are common across both types, axial and sagittal deformities appear under-reported in rickets, particularly in CR. The results highlight the need for standardized diagnostic criteria and improved reporting in order to enhance comparability and clinical management of rickets-related deformities.

Objectives: X-linked hypophosphatemia (XLH, OMIM 307800) is a rare genetic disorder that affects phosphate metabolism. While lower limb deformity represents a hallmark symptom of patients with XLH, the effect on the foot has not been investigated. This study aimed to characterise foot pathologies and assess related outcome scores in adolescents and adults with XLH. Methods: Patients aged ≥ 16 years with genetically verified XLH were included in this study. Physical examination was performed, and foot scores as well as foot X-rays were assessed. Radiographic analysis included the assessment of osteoarthritis, enthesopathies, and alignment abnormalities. Results: Twenty-six participants (51 limbs) with a mean age of 33.9 ± 15.4 years were eligible for the study. Patients with XLH presented with flatfoot deformity (reduced Meary angles > −4° in 84.3%), elevated first and fifth metatarsal angles > 30° (IM 1–5, 53.5%) and hallux valgus angles > 15° (36.0%). Moderate-to-severe joint space narrowing was observed in the talonavicular (49%) and cuneonavicular joints (41.2%). The American Orthopedic Foot and Ankle Society (AOFAS) score was associated with mildly reduced midfoot function. Conclusions: A high rate of bony deformity, joint degeneration, and decreased foot scores indicated the impact of forefoot and midfoot disorders in patients with XLH.

Introduction & Purpose Bones adapt its shape and strength in response to mechanical loading. Tissue-level mechanical stresses, i.e., hydrostatic compressive stress and octahedral shear stress, regulate biological events on the cellular and molecular level, and thereby impact tissue histomorphology and changes in bony geometry (Carter & Beaupré, 2007). Mechanobiological multi-scale simulations based on gait analysis data, musculoskeletal (MSK) modelling and finite element (FE) analysis enable to estimate tissue-level bone loads and predict growth patterns (Shefelbine & Carter, 2004). Such simulations have the potential to inform clinical decision-making in patients with pathological bone deformations, e.g. increased femoral anteversion angle (AVA), which are common in children with cerebral palsy (CP). However, the time-consuming process of creating subject-specific models has previously restricted studies to small sample sizes (n = 1-4 participants), thereby limiting the generalizability of findings (Carriero et al., 2011; Yadav et al., 2021). Moreover, the simulations have not been validated directly due to a lack of longitudinal experimental data, which hinders the widespread use and implementation in clinical settings. Over the last years, we focused our research efforts to overcome these hurdles. We developed a workflow to streamline the process to create subject-specific FE model (Koller et al., 2023). In this study we aimed to use this workflow and 1) analyze growth patterns in a comparable large sample of typically developing (TD) children and children with CP and 2) validate the growth predictions, i.e. compare predicted with measured bone growth. Methods Magnetic resonance images (MRI) and three-dimensional motion capture data including marker trajectories and ground reaction forces of 13 TD children (10 ± 2.2 years old, mass: 36.8 ± 9.5 kg) and 12 children with CP (10.4 ± 3.8 years old, mass: 30.1 ± 10.8 kg) were analyzed for this study. All participants walked without walking aids and with a self-selected speed. Details of the data collection are described in previous publications (Kainz et al., 2017; Koller et al., 2023). From 10 TD children we collected the MRI and motion capture data twice with approximately two years between occasions. MRI images were used to create subject-specific MSK models (Veerkamp et al., 2021) based on an OpenSim model (Kaneda et al., 2023), which allows to estimate medial and lateral knee joint contact forces (JCF) as well as the patellofemoral JCF. Each participant’s model and the corresponding gait analysis data were used to calculate joint angles, muscle forces and JCFs using inverse kinematics, static optimization and joint reaction load analyses with OpenSim 4.2, respectively. For each participant, muscle forces and JCF of two representative steps (left and right) were chosen as loading condition for the FE simulations and each side was analyzed separately. Each femur was segmented using 3D Slicer and the geometry was used to calculate the bending of the femoral shaft. Our previously developed tool was used to create subject-specific hexahedral meshes with several layers of elements aligned with the growth plates (Koller et al., 2023). Nine load instances were selected based on the JCF peaks and the valley in-between during the stance phase. JCFs and muscle forces (n = 26) acting on the femur at these timepoints were used as loading conditions for FE analysis. Linear elastic material properties were assigned to the different parts of the femur and FEBio3 was used to calculate principal stresses within the growth plates. The growth rate due to mechanical loading was estimated as the osteogenic index (OI), which was calculated based on the hydrostatic compressive stress and octahedral shear stress for each element within the growth plates (Stevens et al., 1999; Yadav et al., 2021). Positive and negative OI values indicate regions where growth is likely to be promoted or inhibited, respectively. Image comparison methods were employed to identify variability between OIs (Bradski, 2000). The knee flexion angle alters the orientation of knee JCFs in respect to the distal growth plate resulting in different induced stress regimes. Hence, we divided the children with CP in two groups: one with normal knee flexion angles (n = 15 femurs, CPnormal) and one with increased knee flexion (n = 8 femurs, CPhigh_knee_flexion) during the stance phase. For aim 1, we compared the femoral geometry and OI between CP groups and the TD children. For aim 2 (validation), growth predictions were performed for all femurs where data of two occasions was available (n = 20 femurs). Monte-Carlo-analysis (n = 1,320 for each femur) were performed to estimate which mechanobiological model parameters lead to the most realistic simulations. Linear regression analyses were used to identify whether measured development of AVA can be predicted by the mechanobiological multi-scale simulations. Results The bending of the femoral shaft was significantly different between all groups (Figure 1B). The representative reference OI distribution from the TD femurs showed a ring-shape at the proximal growth plate. Within the CP cohort, image comparison revealed higher inter-subject variability (p < 0.001) whereas some participants show ring-shape distribution similar to the TD cohort and others linear-gradient shapes with high values on the lateral side of the growth plate. At the distal growth plate, OI distribution for TD femurs showed highest values in the posterior notch region and on the medial-anterior edge. The OI distribution of the CPnormal group had its peak values in similar areas as the TD group but with additional peaks at the anterior-lateral edge. The OI distribution generated from the CPhigh_knee_flexion group showed a linear gradient from high to low values from anterior to posterior side (Figure 1D). Between data collection sessions, TD...

Background: X-linked hypophosphatemia (XLH) is a rare monogenetic skeletal disorder. Lower limb deformities contribute substantially to impaired gait quality and burden of disease in patients with XLH. Standardized data regarding onset and severity of lower limb maltorsion are unavailable. This study aimed to evaluate lower limb maltorsion using rotational magnetic resonance imaging (MRI) and computed tomography (CT).Methods: Rotational MRI and CT of children and adolescents with verified XLH were evaluated retrospectively. Femoral and tibial torsion, acetabular anteversion, and axial acetabular coverage were measured and compared with published age-adapted radiographic, clinical measurements and MRI data, respectively.Results: Fifteen patients (mean age, 10.7 years) were included in the study. Decreased femoral torsion was observed in 47% (14/30 femora) and femoral retrotorsion in 17% (5/30 femora). Ten of 13 hips with coxa vara deformity presented with decreased femoral antetorsion. Reduced external tibial torsion manifested in 64% (18/28 tibiae). Abnormal axial femoral head coverage was present in 67% (20/30 hips), whereas 53% (16/30 hips) showed increased acetabular anteversion.Conclusion: Femoral and tibial torsional pathologies were found in children and adolescents with XLH. The occurrence of severe femoral retrotorsion in a 2-year-old child prior to ambulation raises questions regarding the biomechanical impact of gait on the development of torsional deformities in XLH.

Introduction: Osteogenesis imperfecta (OI) is a hereditary disorder primarily caused by mutations in type I collagen genes, resulting in bone fragility, deformities, and functional limitations. Studies on upper extremity deformities and associated functional impairments in OI are limited. This cross-sectional study aimed to evaluate upper extremity deformities and functional outcomes in OI. Methods: We included patients regardless of their OI subtypes with a minimum age of 7 years. Radiographic analysis of radial head dislocation, ossification of the interosseous membrane, and/or radioulnar synostosis of the forearm were performed, and deformity was categorized as mild, moderate, or severe. Clinical evaluation was performed using the Quick Disabilities of Arm, Shoulder, and Hand (qDASH) questionnaire and shoulder-elbow-wrist range of motion (ROM). Three-dimensional motion analysis of the upper limb was conducted using the Southampton Hand Assessment Procedure (SHAP). The SHAP quantifies execution time through the Linear Index of Function (LIF) and assesses the underlying joint kinematics using the Arm Profile Score (APS). Additionally, the maximum active Range of Motion (aRoM) was measured. Results: Fourteen patients aged 8 to 73 were included. Radiographic findings revealed diverse deformities, including radial head dislocation, interosseous membrane ossification, and radioulnar synostosis. Six patients had mild, six moderate, and two severe deformities of the upper extremity. Severe deformities and radial head dislocation correlated with compromised ROM and worse qDASH scores. The qDASH score ranged from 0 to 37.5 (mean 11.7). APS was increased, and LIF was reduced in OI-affected persons compared with non-affected peers. APS and LIF also varied depending on the severity of bony deformities. aRoM was remarkably reduced for pro-supination. Conclusion: Patients with OI showed variable functional impairment from almost none to severe during daily life activities, mainly depending on the magnitude of deformity in the upper extremity. Larger multicenter studies are needed to confirm the results of this heterogeneous cohort. Level of evidence: Retrospective clinical study; Level IV.

Achondroplasia, the most common form of inherited disproportionate short stature, is caused by mutations in the fibroblast growth factor receptor 3 gene. The typical clinical features of achondroplasia include short stature, rhizomelic disproportion, joint hyperlaxity, spinal deformity and deformity of the upper and lower limbs. The latter are among the challenges of state-of-the-art orthopaedic treatment plans and significantly contribute to the burden of the disease in individuals with achondroplasia. Multidisciplinary preoperative individual decision-making concerning surgical interventions should be considered. New medical treatments for achondroplasia have been developed and (some) have been approved for clinical use in several countries. While the number of research articles on achondroplasia is increasing rapidly, many unknown or controversial orthopaedic topics remain. Furthermore, in view of new medical developments with improvements in growth and potentially other effects, the timing and algorithms of orthopaedic treatments (e.g. guided growth, limb lengthening and deformity correction) need to be re-evaluated. While standing height is the primary research focus in medical therapy, it is crucial to comprehensively assess orthopaedic parameters in this multifactorial disease. The current treatment of patients with achondroplasia requires specialised multidisciplinary centres with transitional care and individual orthopaedic counselling.

Background: X-linked hypophosphatemia (OMIM 307800) is a rare bone disease caused by a phosphate-wasting condition with lifelong clinical consequences. Those affected suffer from bone pain, complex skeletal deformities, impaired mobility and a reduced quality of life. Early osteoarthritis and reduced range of motion of the lower limbs are known pathologies in XLH patients. However, XLH-specific data on the affected compartments such as the ankle joint through the evaluation of radiographic and gait analysis data is still lacking.Patients and methods: In this cross-sectional study, patients with genetically verified XLH, age ≥ 16 - 50 years and a complete record of gait analysis and or radiographic analysis data were included. Clinical examination, radiological and gait analysis data were compared to norms using the dataset of our gait laboratory registry. Radiographic analysis included tibial deformity analysis and assessment of osteoarthritis and enthesopathies. Western Ontario and McMaster Universities Arthritis Index (WOMAC), SF36v2, American Orthopedic Foot and Ankle Society score (AOFAS) and the Foot and Ankle Outcome Score (FAOS) were used. Twentythree participants with 46 limbs were eligible for the study.Results: A total of 23 patients (n=46 feet) met the inclusion criteria. Patients with XLH had significantly reduced gait quality, ankle power and plantar flexion (p < 0.001) compared to a historic gait laboratory control group. Ankle valgus deformity was detected in 22 % and ankle varus deformity in 30 % of the patients. The subtalar joint (59.1%) as well as the anterior tibiotalar joint (31.1%) were the main localizations of moderate to severe joint space narrowing. Ankle power was decreased in moderate and severe subtalar joint space narrowing (p < 0.05) compared to normal subtalar joint space narrowing. No lateral or medial ligament instability of the ankle joint was found in clinical examination. Tibial procurvatum deformity led to lower ankle power (p < 0.05).Conclusions: This study showed structural and functional changes of the ankle in patients with XLH. Subtalar ankle osteoarthritis, patient reported outcome scores and clinical ankle restriction resulted in lower gait quality and ankle power.