Objective: Lower limb malalignment accelerates the progression of knee osteoarthritis (KOA). Knee realignment osteotomy is a well-established treatment for unicompartmental KOA with malalignment. Traditional planning in KOA patients corrects deformities with an osteotomy at the metaphysis but overlooks Paley’s approach, which targets the center of rotation angulation (CORA). Osteotomy at the metaphysis may induce secondary translational deformities, which remain unstudied in KOA patients. This study aims to identify the CORA in KOA patients with tibial malalignment. Methods: Thirty tibiae (10 varus, 10 neutral, 10 valgus) from the IMI-APPROACH cohort were analyzed using computed tomography (CT) scans. The CORA, defined as the intersection of the proximal and distal mechanical axes, was identified. Translational deformity was calculated by multiplying the CORA-to-osteotomy distance by the tangent of the correction angle. Results: Among the varus tibiae, 9 out of 10 CORAs were located in the diaphysis, while 8 out of 10 valgus tibiae had their CORA in the diaphysis. When osteotomies were performed in the proximal metaphysis instead of the CORA location, secondary translational deformities of up to 3 cm were induced. Conclusion: In KOA patients with tibial malalignment, the CORA is predominantly located in the diaphysis rather than in the proximal metaphysis, where osteotomies are typically performed. This discrepancy leads to iatrogenic translational deformities. Future research should investigate the clinical impact of these deformities to optimize osteotomy planning and potentially improve long-term surgical outcomes.

Background and purpose — Hip dysplasia can present challenges for total hip arthroplasty (THA) due to anatomic abnormalities. We aimed to assess the association of age, sex, osteotomies prior to THA, and fixation method on 5-and 10-year revision-free implant survival and patient-reported outcome measures (PROMs) of THAs in patients with hip dysplasia. Methods — Using Dutch Arthroplasty Register data, we studied hip dysplasia patients receiving primary THAs in 2007–2021 (n = 7,465). THAs were categorized by age, pelvic osteotomy prior to THA (yes/no), and fixation (cemented, uncemented, hybrid, reverse hybrid). Kaplan–Meier and multivariable Cox models were used to determine 5-and 10-year revision-free implant survival and adjusted hazard ratios including 95% confidence intervals (CIs). Reasons for revision and PROMs were compared within the categories. Results — We found a 10-year revision-free implant survival of 94.9% (CI 94.3–95.5). Patients younger than 50 years had a 10-year implant survival of 93.3% (CI 91.9– 94.7), Patients with prior pelvic osteotomy had a 10-year implant survival of 92.0% (CI 89.8–94.2). Fixation method and sex were not associated with implant survival. Patients with a prior pelvic osteotomy had more revisions due to cup loosening and reported lower PROM scores than patients without earlier osteotomy. Conclusion — 5-and 10-year revision-free implant survival rates of THA for hip dysplasia are 96.4% and 94.9%. Age and prior osteotomies were associated with decreased implant survival rates in patients with hip dysplasia, while fixation method was not. Prior osteotomies were also associated with reduced PROM scores.

A solution for challenging hip dysplasia surgery could be a patient-specific 3D-printed shelf implant that is positioned extra-articular and restores the dysplastic acetabular rim to normal anatomical dimensions. The anatomical correction and biomechanical stability of this concept were tested in a canine model that, like humans, also suffers from hip dysplasia. Using 3D reconstructed computed tomography images the 3D shelf implant was designed to restore the radiological dysplastic hip parameters to healthy parameters. It was tested ex vivo on three dog cadavers (six hips) with hip dysplasia. Each hip was subjected to a biomechanical subluxation test, first without and then with the 3D shelf implant in place. Subsequently, an implant failure test was performed to test the primary implant fixation. At baseline, the dysplastic hips had an average Norberg angle of 88 ± 3° and acetabular coverage of 47 ± 2% and subluxated at an average of 83 ± 2° of femoral adduction. After adding the patient-specific shelf implants the dysplastic hips had an average Norberg angle of 122 ± 2° and acetabular coverage of 67 ± 3% and subluxated at an average of 117 ± 2° of femoral adduction. Implant failure after primary implant fixation occurred at an average of 1330 ± 320 Newton. This showed that the patient-specific shelf implants significantly improved the coverage and stability of dysplastic hips in a canine model with naturally occurring hip dysplasia. The 3D shelf is a promising concept for treating residual hip dysplasia with a straightforward technology-driven approach; however, the clinical safety needs to be further investigated in an experimental proof-of-concept animal study.

Bone is a complex natural material with a complex hierarchical multiscale organization, crucial to perform its functions. Ultrastructural analysis of bone is crucial for our understanding of cell to cell communication, the healthy or pathological composition of bone tissue, and its three-dimensional (3D) organization. A variety of techniques has been used to analyze bone tissue. This article describes a combined approach of optical, scanning electron, and transmission electron microscopy for the ultrastructural analysis of bone from the nanoscale to the macroscale, as illustrated by two pathological bone tissues. By following a top-down approach to investigate the multiscale organization of pathological bones, quantitative estimates were made in terms of calcium content, nearest neighbor distances of osteocytes, canaliculi diameter, ordering, and D-spacing of the collagen fibrils, and the orientation of intrafibrillar minerals which enable us to observe the fine structural details. We identify and discuss a series of two-dimensional (2D) and 3D imaging techniques that can be used to characterize bone tissue. By doing so we demonstrate that, while 2D imaging techniques provide comparable information from pathological bone tissues, significantly different structural details are observed upon analyzing the pathological bone tissues in 3D. Finally, particular attention is paid to sample preparation for and quantitative processing of data from electron microscopic analysis.

Fractures in patients with osteogenesis imperfecta (OI) are caused by a decreased strength of bone due to a decreased quality and quantity of bone matrix and architecture. Mutations in the collagen type 1 encoding genes cause the altered formation of collagen type I, one of the principal building blocks of bone tissue. Due to the complexity of the disease and the high variation of the clinical problems between patients, treatment for these patients should be individually tailored. In general, short immobilization periods with flexible casting material, use of intramedullary implants, and simultaneous deformity correction are preferred. Multidisciplinary care with a broad view of the support needed for the patient and his/her living environment is necessary for the optimal rehabilitation of these patients. Increasing bone strength with exercise, medication, and sometimes alignment surgery is generally indicated to prevent fractures.

BACKGROUND AND PURPOSE:   The Chiari osteotomy was a regular treatment for developmental hip dysplasia before it became mostly reserved as a salvage therapy. However, the long-term survival of the Chiari osteotomy has not been systematically investigated. We investigated the survival time of the Chiari osteotomy until conversion to total hip arthroplasty (THA) in patients with primary hip dysplasia, and factors which correlated with survival, complications, and the improvement measured in radiographic parameters. PATIENTS AND METHODS: Studies were included when describing patients (> 16 years) with primary hip dysplasia treated with a Chiari osteotomy procedure with 8 years' follow-up. Data on patient characteristics, indications, complications, radiographic parameters, and survival time (endpoint: conversion to THA) were extracted. RESULTS:   8 studies were included. The average postoperative center-edge angle, acetabular head index, and Sharp angle were generally restored within the target range. 3 studies reported Kaplan-Meier survival rates varying from 96% at 10 years to 72% at 20 years' follow-up. Negative survival factors were high age at intervention and pre-existing advanced preoperative osteoarthritis. Moreover, reported complications ranged between 0% and 28.3 %. INTERPRETATION:   The Chiari osteotomy has high reported survival rates and is capable of restoring radiographic hip parameters to healthy values. When carefully selected by young age, and a low osteoarthritis score, patients benefit from the Chiari osteotomy with satisfactory survival rates. The position of the Chiari osteotomy in relation to the periacetabular osteotomies should be further (re-)explored.

The concept of a novel patient-specific 3D-printed shelf implant should be evaluated in a relevant large animal model with hip dysplasia. Therefore, three dogs with radiographic bilateral hip dysplasia and a positive subluxation test underwent unilateral acetabular augmentation with a 3D-printed dog-specific titanium implant. The contralateral side served as control. The implants were designed on CT-based pelvic bone segmentations and extended the dysplastic acetabular rim to increase the weight bearing surface without impairing the range of motion. Outcome was assessed by clinical observation, manual subluxation testing, radiography, CT, and gait analysis from 6 weeks preoperatively until termination at 26 weeks postoperatively. Thereafter, all hip joints underwent histopathological examination. The implantation and recovery from surgery was uneventful. Clinical subluxation tests at the intervention side became negative. Imaging showed medialization of the femoral head at the intervention side and the mean (range) CE-angle increased from 94° (84°-99°) preoperative to 119° (117°-120°) postoperative. Gait analysis parameters returned to pre-operative levels after an average follow-up of 6 weeks. Histology showed a thickened synovial capsule between the implant and the femoral head without any evidence of additional damage to the articular cartilage compared to the control side. The surgical implantation of the 3D shelf was safe and feasible. The patient-specific 3D-printed shelf implants restored the femoral head coverage and stability of dysplastic hips without complications. The presented approach holds promise to treat residual hip dysplasia justifying future veterinary clinical trials to establish clinical effectiveness in a larger cohort to prepare for translation to human clinic.

BACKGROUND: The introduction of stem cell transplantation has improved life expectancy and cognitive outcome in patients with mucopolysaccharidosis I, but this condition remains associated with substantial residual disease in several parts of the body. Many patients have hip dysplasia with progressive medial flattening of the femoral head. Quantitative evidence on the effect of surgery on remodeling to sphericity of flattened femoral heads is lacking. In the present study, we used statistical shape modeling to quantify the effect of hip surgery on the sphericity of the femoral head in patients with mucopolysaccharidosis I. METHODS: We performed a retrospective case control study involving a series of 23 patients with hip dysplasia due to mucopolysaccharidosis I. Surgery was not offered to the first 11 children (control group). Following a change in treatment protocol, the next 12 children underwent bilateral proximal femoral varus derotation osteotomy and Pemberton osteotomy for the treatment of acetabular dysplasia with progressive femoral head flattening (surgery group). The surgery and control groups were compared with a reference group of patients with normal hips. Statistical shape modeling was used to quantify the shape of the femoral head (i.e., flattening and/or roundness of the epiphysis). RESULTS: The mean age at the time of stem cell transplantation in the surgery and control groups was comparable (1.2 years). The mean age at the time of surgical intervention was 5.5 years, and mean duration of postoperative follow-up was 3.3 years. Statistical shape modeling showed variations within the total group in terms of medial indentation, width, height, and sphericity of the femoral heads. In contrast to the progressive femoral head flattening in the control group, the surgery group showed improvement of the sphericity of the femoral head after surgery. The overall shape characteristics of the femoral head in the surgery group were similar to those of the reference group of patients with normal hips. CONCLUSIONS: To our knowledge, this is the first study in patients with mucopolysaccharidosis I that has shown quantitative remodeling of the dysplastic, flattened femoral head to normal sphericity after increasing containment of the femoral head. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background and purpose — The shelf arthroplasty was the regular treatment for residual hip dysplasia before it was substituted by the peri-acetabular osteotomy. Yet, evidence regarding the survival of shelf arthroplasty surgery has never been systematically documented. Hence, we investigated the survival time of the shelf procedure until revision to THA in patients with primary hip dysplasia. Factors that influenced survival and complications were also examined, along with the accuracy of correcting radiographic parameters to characterize dysplasia. Material and methods — The inclusion criteria were studies of human adolescents and adults (> 16 years) with primary or congenital hip dysplasia who were treated with a shelf arthroplasty procedure. Data were extracted concerning patient characteristics, survival time, complications, operative techniques, and accuracy of correcting radiographic parameters. Results — Our inclusion criteria were applicable to 9 studies. The average postoperative Center-Edge Angle and Acetabular Head Index were mostly within target range, but large variations were common. Kaplan–Meier curves (endpoint: conversion to THA) varied between 37% at 20 years’ follow-up and 72% at 35 years’ follow-up. Clinical failures were commonly associated with pain and radiographic osteoarthritis. Only minor complications were reported with incidences between 17% and 32%. Interpretation — The shelf arthroplasty is capable of restoring normal radiographic hip parameters and is not associated with major complications. When carefully selected on minimal osteoarthritic changes, hip dysplasia patients with a closed triradiate cartilage may benefit from the shelf procedure with satisfactory survival rates. The importance of the shelf arthroplasty in relation to peri-acetabular osteotomies needs to be further (re)explored.

The majority of patients with osteogenesis imperfecta (OI) have mutations in the COL1A1 or COL1A2 gene, which has consequences for the composition of the bone matrix and bone architecture. The mutations result in overmodified collagen molecules, thinner collagen fibres and hypermineralization of bone tissue at a bone matrix level. Trabecular bone in OI is characterized by a lower trabecular number and connectivity as well as a lower trabecular thickness and volumetric bone mass. Cortical bone shows a decreased cortical thickness with less mechanical anisotropy and an increased pore percentage as a result of increased osteocyte lacunae and vascular porosity. Most OI patients have mutations at different locations in the COL1 gene. Disease severity in OI is probably partly determined by the nature of the primary collagen defect and its location with respect to the C-terminus of the collagen protein. The overall bone biomechanics result in a relatively weak and brittle structure. Since this is a result of all of the above-mentioned factors as well as their interactions, there is considerable variation between patients, and accurate prediction on bone strength in the individual patient with OI is difficult. Current treatment of OI focuses on adequate vitamin-D levels and interventions in the bone turnover cycle with bisphosphonates. Bisphosphonates increase bone mineral density, but the evidence on improvement of clinical status remains limited. Effects of newer drugs such as antibodies against RANKL and sclerostin are currently under investigation. This paper was written under the guidance of the Study Group Genetics and Metabolic Diseases of the European Paediatric Orthopaedic Society. Cite this article: Nijhuis WH, Eastwood DM, Allgrove J, Hvid I, Weinans HH, Bank RA, Sakkers RJ. Current concepts in osteogenesis imperfecta: bone structure, biomechanics and medical management.