The Ambiguity of Names and Landmarks in Radiographs of the Pediatric Pelvis: Variations and a Historical Perspective.

For over a century, the plain radiograph has been used to measure and predict the development of pediatric hip conditions. Classic measurements, such as the acetabular index, the center-edge angle, and the migration percentage, have stood the test of time and remain the default tools for any pediatric orthopaedic surgeons. However, in contemporary research, the terminology regarding these measurements has become markedly inconsistent. A substantial number of synonyms, acronyms, and similar, but not identical, terms are used to label measurements. This is perhaps unsurprising, considering decades of use and numerous suggested modifications. The results of treatment cannot be reliably compared if the measured parameters are not identical, and scientific analysis of disease requires consistent terminology. In this review, we aim both to provide historical definitions and identification of radiographic landmarks commonly used in three parameters of interest on pediatric AP radiographs and to examine the variability of landmarks and definitions in contemporary research.

Postoperative stability following a triple pelvic osteotomy is affected by implant configuration: a finite element analysis.

BACKGROUND: The triple pelvic osteotomy is an established surgical method with multiple modifications regarding surgical technique and choice of implant. The stability of the osteotomy is affected by numerous factors, and among these, the three-dimensional implant configuration is a scientifically less explored aspect. METHODS: We used a finite element model of a hemi-pelvis with a standardized triple osteotomy to calculate relative flexibility for loads in all translational degrees of freedom for five different implant configurations. Two of the configurations used entry points only feasible when implant removal was not necessary. RESULTS: The stability of the osteotomy improved with an increased distance between the implants in the plane of the osteotomy as well as for a more perpendicular angle relative to the osteotomy plane. The implant configurations with more entry points available made this easier to adhere to. CONCLUSION: The use of bioabsorbable implants may provide better opportunities for optimal implant constructs which can, to a certain degree, compensate for the lesser mechanical stiffness of bioabsorbable polymers as compared to metal implants.

Stability in Pelvic Triple Osteotomies in Children Using Resorbable PLGA Screws for Fixation.

BACKGROUND: The triple pelvic osteotomy (TPO) is a major redirectional osteotomy used to improve the acetabular coverage of the femoral head in selected pediatric patients with hip disorders. Traditionally the iliac osteotomy is stabilized by metal screws that require a second surgery for removal. Despite favorable results for both adults and children in related pelvic osteotomies, resorbable implants have not previously been used for TPOs.This study aims to suggest a novel modified TPO surgical method in children using resorbable poly lactic-co-glycolic acid (PLGA) screws for fixation and to radiographically evaluate the postoperative stability achieved by these implants in a case series. METHODS: All patients (n=11) with dysplasia of the hip (2), Perthe disease (5), or Down syndrome (4), who underwent primary TPO surgery during 2013 to 2019, using resorbable PLGA screws for fixation were included. The stability of the osteotomy was evaluated in the postoperative radiograph series using the acetabular index, migration percentage, Sharp's angle and the center-edge angle. The osteotomy angle was introduced as a parameter to confirm the postoperative integrity of the achieved correction. All cases were evaluated until radiographic healing of the iliac osteotomy. Hospital notes were analyzed for complications or local reactions in relation to the implants. RESULTS: In all studied hips, the overall achieved correction was well maintained. The mean (SD) correction achieved, from the preoperative images to the last measurable postoperative image, was a 16.7 degrees decrease for Sharp angle, a 20.9 degrees decrease in acetabular index and a 24.7 degrees increase for the center-edge angle, respectively. There were no complications related to the bioabsorption of the implants. CONCLUSION: The present findings suggest that the modified TPO method, using resorbable PLGA screws, provides sufficient stability and appears to be a promising alternative to traditional TPO. Avoiding implant removal is a major benefit in a pediatric population. Resorbable screws enable the surgeon to place implants with more degrees of freedom since later implant removal is not a limiting factor. LEVEL OF EVIDENCE: Level IV-case series.

MRI evaluation of resorbable poly lactic-co-glycolic acid (PLGA) screws used in pelvic osteotomies in children-a retrospective case series.

PURPOSE: The orthopaedic use of resorbable poly lactic-co-glycolic acid (PLGA) implants carries multiple potential benefits. To our knowledge, only one publication exists regarding the use of PLGA implants in pelvic osteotomies in children, and data regarding resorption and potential side effects are lacking for resorbable pelvic screws in children. The aim of this study is to present an MRI-based evaluation of the resorption pattern and local tissue reactions in a paediatric case series after pelvic osteotomies fixated with PLGA screws. METHODS: Twelve children who had undergone a Salter or triple pelvic osteotomy fixated with 4.5 mm PLGA screws were included. A total of 18 MRIs was performed 0.5-4.5 years after surgery and were retrospectively analysed. Eight parameters relating to screw resorption, local reactions and re-formation of bone were interpreted. RESULTS: The screw canals were > 90% replaced with solid bone after 2-4.5 years in all cases but one, where the canals were only partly replaced with bone. There were no major soft tissue reactions but small (< 12 mm) bone cysts were observed in 3 of the 18 MRIs and discrete fatty patches in the adjacent bone were common. CONCLUSION: PLGA screws in the paediatric pelvis appear to be resorbed and replaced with solid bone in most cases but this process takes at least 2 years. Minor reactions could be seen in the adjacent bone but were judged to be of no clinical significance.

Using a 3D Printed Model as a Preoperative Tool for Pelvic Triple Osteotomy in Children: Proof of Concept and Evaluation of Geometric Accuracy.

The feasibility of 3D printing in clinical practice depends not only on the usability but also on the reliability of the method. The aims of this study were to demonstrate the feasibility of a 3D printing method for pediatric patients planned for pelvic triple osteotomy and to present a reliable quality assessment strategy for these printed models. A 10-year-old boy with Legg-Calvé-Perthes disease underwent a triple pelvic osteotomy. Preoperative and postoperative CT scans were printed as 3D models. An image-based quality assessment strategy was proposed: The printed 3D models were imaged with CT. The model images were systematically compared with the corresponding ground truth images, ie, patient images, to determine the reliability using distance measurements in the model and ground truth images. The 3D printed models were found useful in both the preoperative and postoperative stages. The models were found reliable: Strong linear correlation between the model and ground truth images both preoperatively (R = 0.99; P < 0.001) and postoperatively (R = 1.00; P < 0.001) was found. The study demonstrates the usefulness of 3D printed models in clinical practice. We also present a robust and simple strategy, using common clinical tools, to assess the reliability of 3D printed models.

Osteocyte Protein Expression Is Altered in Low-Turnover Osteoporosis Caused by Mutations in WNT1 and PLS3.

Context: Osteocytes express proteins that regulate bone remodeling and mineralization. Objective: To evaluate the relationship between osteocyte-specific protein expression and bone histology in patients with monogenic osteoporosis due to wingless integration site 1 (WNT1) or plastin 3 (PLS3) mutations. Design and Setting: Cross-sectional cohort study at a university hospital. Participants: Six patients (four males; ages: 14 to 72 years) with a heterozygous WNT1 mutation and five patients (four males; ages: 9 to 70 years) with a heterozygous/hemizygous PLS3 mutation. Methods and Main Outcome Measures: Immunohistochemistry was performed for fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1), sclerostin, and phosphorylated (phospho-)ß-catenin in iliac crest samples and compared with bone histomorphometry. Results: FGF23 expression in WNT1 patients was 243% that observed in PLS3 patients (P < 0.01). DMP1, sclerostin, and phospho-ß-catenin expression did not differ between groups. Serum phosphate correlated inversely with FGF23 expression (r = -0.79, P = 0.01) and serum ionized calcium correlated inversely with sclerostin expression (r = -0.60, P = 0.05). Phospho-ß-catenin expression correlated inversely with DMP1 expression (r = -0.88, P < 0.001), osteoid volume/bone volume (r = -0.68, P = 0.02), and bone formation rate (r = -0.78, P < 0.01). FGF23 expression did not correlate with DMP1 expression, sclerostin expression, or bone histomorphometry. Marrow adiposity was higher in WNT1 than in PLS3 patients (P = 0.04). Conclusions: Mutations that disrupt WNT signaling and osteocytic mechanosensing affect osteocyte protein expression. Abnormal osteocyte function may play a role in the pathogenesis of monogenetic forms of osteoporosis.

A novel splice mutation in PLS3 causes X-linked early onset low-turnover osteoporosis.

Genetic factors play an important role in the development of osteoporosis. Several monogenic forms of osteoporosis have been recognized, most recently an X-chromosomal form resulting from mutations in the gene encoding plastin 3 (PLS3). PLS3 is a protein involved in actin bundle formation in the cytoskeleton. We present a large family with early onset osteoporosis and X-linked inheritance. Phenotyping was performed on 19 family members and whole-exome sequencing on 7 family members (5 with a diagnosis of early onset osteoporosis and 2 with normal bone parameters). Osteoporosis had its onset in childhood and was characterized by recurrent peripheral fractures, low bone mineral density (BMD), vertebral compression fractures, and significant height loss in adulthood. Males were in general more severely affected than females. Bone histomorphometry findings in 4 males and 1 female showed severe trabecular osteoporosis, low amount of osteoid, and decreased mineral apposition rate, indicating impaired bone formation; resorption parameters were increased in some. All affected subjects shared a single base substitution (c.73-24T > A) in intron 2 of PLS3 on Xq23. The mutation, confirmed by Sanger sequencing, segregated according to the skeletal phenotype. The mutation introduces a new acceptor splice site with a predicted splice score of 0.99 and, thereby, as confirmed by cDNA sequencing, induces the insertion of 22 bases between exons 2 and 3, causing a frameshift and premature termination of mRNA translation (p.Asp25Alafs*17). The mutation affects the first N-terminal calcium-binding EF-hand domain and abolishes all calcium- and actin-binding domains of the protein. Our results confirm the role of PLS3 mutations in early onset osteoporosis. The mechanism whereby PLS3 affects bone health is unclear, but it may be linked to osteocyte dendrite function and skeletal mechanosensing. Future studies are needed to elucidate the role of PLS3 in osteoporosis and to define optimal treatment.

WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.

This report identifies human skeletal diseases associated with mutations in WNT1. In 10 family members with dominantly inherited, early-onset osteoporosis, we identified a heterozygous missense mutation in WNT1, c.652T→G (p.Cys218Gly). In a separate family with 2 siblings affected by recessive osteogenesis imperfecta, we identified a homozygous nonsense mutation, c.884C→A, p.Ser295*. In vitro, aberrant forms of the WNT1 protein showed impaired capacity to induce canonical WNT signaling, their target genes, and mineralization. In mice, Wnt1 was clearly expressed in bone marrow, especially in B-cell lineage and hematopoietic progenitors; lineage tracing identified the expression of the gene in a subset of osteocytes, suggesting the presence of altered cross-talk in WNT signaling between the hematopoietic and osteoblastic lineage cells in these diseases.

Diagnosis of Osteoporosis in Children and Adolescents.

Osteoporosis is traditionally regarded as a disease of elderly women. However, this bone disorder occurs in patients of both sexes and of all ages and is also increasingly recognised in the paediatric setting. In particular, patients, including young children, with other chronic diseases are at risk of developing bone fragility. There are also several forms of hereditary osteoporosis, which should be identified at an early stage to ensure adequate treatment. The diagnosis of osteoporosis in children is challenging, since their bone mineral density (BMD) is affected by growth and pubertal development. In addition to low BMD, a child must also exhibit a significant proneness to fractures before the osteoporosis diagnosis can be made. Through early diagnosis and treatment for paediatric bone fragility, we can also ameliorate bone health in adulthood. In this article we review the aetiology, known risk factors and the diagnostic criteria of osteoporosis in the young.

Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.

Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G > A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets.