Mineral and Bone Consequences of High Dose Denosumab Therapy to Treat an Aneurysmal Bone Cyst, a Child Case Report.

Aneurysmal bone cysts (ABCs) are rare benign pseudotumoral bone lesions with potential aggressive behavior due to the extensive destruction of surrounding bone. Traditionally, these tumors were treated with open surgery, but there is more and more a shift to less invasive procedures. In particular, treatment for spinal ABCs is generally unsatisfactory due to the risk of morbidity, neurological impairment and recurrence, and there is a need for innovative therapies. Denosumab has been reported as a useful treatment in giant cell tumors of bone (GCTB), so its efficacy has been tested also in other fibro-osseus lesions affecting children and adolescents, such as spinal aneurysmal bone cysts. The pediatric literature is limited to case reports and small series, all of which highlight the efficacy of this treatment on lesions growth and associated bone pain. Some of these reports have already reported well known side effects associated with denosumab, such as hypocalcemia at the beginning of the treatment, and rebound hypercalcemia at the discontinuation. The latter seems to be more frequent in children and adolescents than in adults, probably due to the higher baseline bone turnover in children. In addition, the use of denosumab in young patients could affect both bone modeling and remodeling, even if the consequences on the growing skeleton have not been reported in detail. Here we describe the case of a spinal ABC diagnosed in an 8-year old young boy which was not accessible to surgery but responded favorably to denosumab. Our aim is to describe the rapid changes in mineral and bone homeostasis in this patient, that required advice from the experts of the European Reference Network (ERN) for rare bone and endocrine diseases.

How coronal alignment affects distal femoral anatomy: an MRI-based comparison of varus and valgus knees.

PURPOSE: In contemporary total knee arthroplasty (TKA), most often, the goal is to align the femoral component to the epicondylar axis (EA). The posterior condylar axis (PCA) is easier to define than the EA, and thus the relationship of PCA to the EA is then used instead to align the femoral component to the EA. However, the relationship of PCA to EA is not constant and has been reported to differ between varus and valgus knees and with increasing deformity. The aim of this large MRI-based study was to evaluate the relationship between PCA and EA with varying coronal deformity especially with increasing valgus deformity. METHODS: EA, PCA, AP (Whiteside's line) and the mechanical axis were obtained from 474 magnetic resonance imaging (MRI) scans used to create patient-specific instrumentation (PSI) for the Biomet Signature (Warsaw, NJ) system. RESULTS: The relationship of EA relative to the PCA showed considerable heterogeneity in both varus and valgus groups. In the valgus group, there was statistically greater external rotation (P < 0.05) of the EA from the PCA with a mean of 2.52° (range - 1.9° to 6°) compared to the varus group with a mean of 2.03° (range - 3.9° to 6.9°). This relationship did not significantly change with increasing severity of coronal malalignment. Externally rotating the femoral cutting guide by 3° from the PCA, 11% (42 of 382) of varus knees would lie outside of ± 3° from EA. In valgus knees, externally rotating the femoral cutting block by 3° or 5° from the PCA, 6.5% (6 of 92) and 33.7% (31 of 92) of knees, respectively, would lie outside of ± 3° from EA. CONCLUSION: The relationship of PCA to EA is heterogeneous and is not altered significantly with increasing valgus coronal deformity. External rotation beyond 3° from PCA in valgus knees may lead to significant femoral component malrotation in a large proportion cases.

Correlation of radiological and clinical measurement of genu valgum in children.

INTRODUCTION: Genu valgus is a condition characterised by a lateral shift of the knee's mechanical axis. The deformity can be characterised using clinical examinations and long hip-knee-ankle (HKA) angles, but it is unclear how these investigations correlate with each other. Our aim was to examine the correlation between clinical and radiographic measurements of the lower extremities in children. METHODS: A total of 49 children between 5.9 and 16.7 years of age who had been referred with genu valgum deformity were included. They all had their intermalleolar (IM) distance measured and a standardised anterior-posterior radiograph of the lower extremities taken. IM distance was adjusted for the mean tibial and femoral length to adjust for differences in leg length. We calculated the Spearman's rank correlation coefficient to study the reliability between radiographs and clinical examinations. RESULTS: We found no correlation between clinical IM distance and the HKA angles. Spearman's rho for comparison between adjusted clinical IM distance measurements and HKA angles on radiographs was found to be 0.36. CONCLUSIONS: We found a poor correlation between clinical examinations and HKA angles as data were corrected for leg length. More studies are needed to provide clear recommendations for following children with malalignment. FUNDING: none. TRIAL REGISTRATION: The study was registered with the Danish Data Protection Agency.

Distal Femoral Varus Osteotomy for the Management of Valgus Deformity of the Knee.

Distal femoral varus osteotomy is a well-described treatment option for patients with valgus malalignment associated with a variety of underlying conditions. This procedure may be the definitive treatment option in active patients with isolated lateral compartment osteoarthritis or posttraumatic arthritis. It may be a useful concomitant procedure in young patients with lateral meniscus deficiency, focal chondral defects, chronic medial collateral ligament insufficiency, and/or patellofemoral instability. Distal femoral varus osteotomy can be performed with medial closing wedge or lateral opening wedge techniques. Variable outcomes and complication rates have been reported. A framework for the use of distal femoral varus osteotomy can aid the orthopaedic surgeon in the evaluation and treatment of patients with symptomatic valgus malalignment.

Pseudohypoparathyroidism type 1B in a patient conceived by in vitro fertilization: another imprinting disorder reported with assisted reproductive technology.

Pseudohypoparathyroidism type 1B (PHP1B) is characterized by renal tubular resistance to parathyroid hormone (PTH) leading to hyperphosphatemia, hypocalcemia, elevated PTH, and hyperparathyroid bone changes. PHP1B is an imprinting disorder that results from loss of methylation at the maternal GNAS gene, which suppresses transcription of the alpha subunit of the stimulatory G protein of the PTH receptor. Emerging evidence supports an association between assisted reproductive technologies (ART) and imprinting disorders; however, there is currently little evidence linking PHP1B and ART. We present a twin boy conceived by ART to parents with no history of subfertility who presented at age 12 with bilateral slipped capital femoral epiphysis and bilateral genu valgum deformity. Clinical and laboratory investigation revealed markedly elevated PTH, low ionized calcium, elevated phosphorus, TSH resistance, and skeletal evidence of hyperparathyroidism, leading to the diagnosis of PHP1B. A partial loss of methylation at the GNAS exon A/B locus was observed. The patient's dizygotic twin sibling was asymptomatic and had normal laboratory evaluation. This is the second reported case of a child with PHP1B conceived by ART, further supporting the possibility that ART may lead to an increased risk for imprinting defects.

Geometry of the Valgus Knee: Contradicting the Dogma of a Femoral-Based Deformity.

BACKGROUND: Realignment osteotomies of valgus knee deformities are usually performed at the distal femur, as valgus alignment is considered to be a femoral-based deformity. This dogma, however, has not been proven in a large patient population. Valgus malalignment may also be caused by a tibial deformity or a combined tibial and femoral deformity. PURPOSE: The purposes of this study were (1) to analyze the coronal geometry of patients with valgus malalignment and identify the location of the underlying deformity and (2) to investigate the proportion of cases that require realignment osteotomy at the tibia, the femur, or both locations to avoid an oblique joint line. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The analysis included 420 standing full-leg radiographs of patients with valgus malalignment (mechanical femorotibial angle [mFTA], ≥4°). A systematic analysis of the coronal leg geometry was performed including the mFTA, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and joint-line convergence angle (JLCA). The localization of the deformity was determined according to the malalignment test described by Paley, and patients were assigned to 1 of 4 groups: femoral-based valgus deformity, tibial-based valgus deformity, femoral- and tibial-based valgus deformity, or intra-articular/ligamentary-based valgus deformity. Subsequently, the ideal osteotomy site was identified with the goal of a postoperative change of the joint line of two different maximum values, ±2° and ±4°, from its physiological varus position of 3°. RESULTS: Measurements of the coronal alignment revealed a mean (±SD) mFTA of 7.4° ± 4.3° (range, 4°-28.2°). The mean mLDFA and mean mMPTA were 84.8° ± 2.4° and 90.9° ± 2.6°, respectively. The mean JLCA was 1.2° ± 3.1°. The majority (41.0%) of valgus deformities were tibial based, 23.6% were femoral based, 26.9% were femoral and tibial based, and 8.6% were intra-articular/ligamentary based. To achieve a straight-leg axis and an anatomic postoperative joint line with a tolerance of ±4°, the ideal site of a corrective osteotomy was tibial in 55.2% of cases and femoral in 19.5% of cases. A double-level osteotomy would be necessary in 25.2% of cases. With a tolerance of ±2°, the ideal osteotomy site was the proximal tibia in 41.0% of cases and the distal femur in 13.6% of cases; a double-level osteotomy would be necessary in 45.5% of cases. CONCLUSION: In contrast to the widespread belief that valgus malalignment is usually caused by a femoral deformity, this study found that valgus malalignment was attributable to tibial deformity in the majority of patients. In addition, a combined femoral- and tibial-based deformity was more common than an isolated femoral-based deformity. As a clinical consequence, varus osteotomies to treat lateral compartment osteoarthritis must be performed at the tibial site or as a double-level osteotomy in a relevant number of patients to avoid an oblique joint line.

How tibiofemoral alignment and contact locations affect predictions of medial and lateral tibiofemoral contact forces.

Understanding degeneration of biological and prosthetic knee joints requires knowledge of the in-vivo loading environment during activities of daily living. Musculoskeletal models can estimate medial/lateral tibiofemoral compartment contact forces, yet anthropometric differences between individuals make accurate predictions challenging. We developed a full-body OpenSim musculoskeletal model with a knee joint that incorporates subject-specific tibiofemoral alignment (i.e. knee varus-valgus) and geometry (i.e. contact locations). We tested the accuracy of our model and determined the importance of these subject-specific parameters by comparing estimated to measured medial and lateral contact forces during walking in an individual with an instrumented knee replacement and post-operative genu valgum (6°). The errors in the predictions of the first peak medial and lateral contact force were 12.4% and 11.9%, respectively, for a model with subject-specific tibiofemoral alignment and contact locations determined through radiographic analysis, vs. 63.1% and 42.0%, respectively, for a model with generic parameters. We found that each degree of tibiofemoral alignment deviation altered the first peak medial compartment contact force by 51N (r(2)=0.99), while each millimeter of medial-lateral translation of the compartment contact point locations altered the first peak medial compartment contact force by 41N (r(2)=0.99). The model, available at www.simtk.org/home/med-lat-knee/, enables the specification of subject-specific joint alignment and compartment contact locations to more accurately estimate medial and lateral tibiofemoral contact forces in individuals with non-neutral alignment.

Severe valgus deformity of the knee with permanent patellar dislocation associated with melorheostosis: a case report and review of the literature.

We present a case of an 8-year-old boy diagnosed with melorheostosis who was suffering from severe genu valgum, permanent dislocation of the patella, knee flexion contracture and leg length shortening. Soft tissue contracture of the limb and subsequent joint deformities were reported to represent clinical manifestations of pediatric melorheostosis. As the epiphyseal plate had not closed, patellar reduction was achieved by soft tissue surgical stabilization, including lateral retinacular release, medial retinaculum plication, and transfer of the lateral half of the patellar tendon. At 4 years postoperatively, as a result of improved limb alignment and knee flexion contracture, the leg length shortening has improved, and the patient does not limp and participates in sports activities. Surgical intervention should be performed as early as possible, because genu valgum and external rotation of the tibia may deteriorate with age, rendering the patellar dislocation irreversible in patients with melorheostosis before epiphyseal closure.

Range of variation of genu valgum and association with anthropometric characteristics and physical activity: comparison between children aged 3-9 years.

The lower limbs of children aged 3-9 years present varying knock-knee deformities that have a direct impact on the diversification of the load-bearing axis of the valgus limb and on the modification of gait kinematics. The purpose of our study was to establish the reference values of knee alignment in a Greek population and whether this is linked to a change in the physical activity of children depending on the severity of the genu valgum. Using a clinical method, we measured both the tibiofemoral (TF) angle and the intermalleolar (IM) distance of the lower extremities of normal children. Subsequently, forms of the Netherlands Physical Activity Questionnaire (NPAQ) for young children and the Baecke questionnaire on habitual physical activity, modified especially for children, were completed by the parents. We examined both the development of the TF angle and the IM distance in relation to age and the degree of restriction of physical activity in relation to the severity of the genu valgum. We analysed 316 unaffected lower extremities in children aged 3-9 years. The average value of the TF angle starts around 7° at the age of 3 years and gradually decreases to 4° at the age of 7-8 years. The average value of the IM distance ranges over 3.5 cm at the age of 3 years and progressively decreases to 2 cm at the age of 7-8 years. Physical activity appears to be influenced by sex and the severity of the genu valgum. We provide age-specific values for limb alignment and joint orientation of the lower extremity in children aged 3-9 years. A statistical correlation between all indexes (sport, leisure time and total) of the Baecke and the NPAQs and measurements of genu valgum was noted depending on the severity of the valgus deformity.

Lamellar ichthyosis with genu valgum: unfolding the link.

We describe a case of lamellar ichthyosis with bilateral genu valgum. The association of genu valgum with congenital ichthyosis is rare. Our patient, a 22-year-old girl, had lamellar ichthyosis and was born with a collodion membrane. She developed progressive valgus deformity of the knees of 5 years duration associated with difficulty in walking. On evaluation, she had generalised scaly skin lesions along with bilateral genu valgum and biochemical evidence of vitamin D deficiency. Skin serves as an important site for vitamin D synthesis and thus skeletal deformities secondary to vitamin D deficiency may occur in cases of congenital ichthyosis, causing a diagnostic dilemma due to the unusual association. This case serves as a reminder that clinicians need to be aware of such an association in order to prevent, appropriately diagnose and adequately treat the rare case of congenital ichthyosis with rickets and osteomalacia.

Retrograde dynamic locked nailing for valgus knee correction: a revised technique.

PURPOSE: Traditionally, valgus knee deformity is predominately corrected by stabilisation with a plate inserted via the medial approach to the supracondylar region of the femur. However, this technique is unfavourable from both a biomechanical and a biological point of view. A revised retrograde dynamic locked nailing was developed to improve correction of this defect. METHOD: Forty-one knees with valgus deformity (average tibiofemoral angle, 22°; range, 16-29°) in 25 adult patients were treated by oblique femoral supracondylar varus osteotomy and stabilised with retrograde dynamic locked nails. Postoperatively, early ambulation with protected weight bearing and range of motion knee exercises were encouraged. RESULT: Thirty-five knees of 21 patients were followed-up for an average of 2.6 years (range, 1.1-4.5 years). All osteotomy sites healed with an average union period of 3.4 months (range, 2.5-5.0 months). There were no significant complications. At the latest follow-up, the average tibiofemoral angle was 7.1° valgus (range, 4-10° valgus). For all of the knees, the outcomes were satisfactory (p < 0.001). CONCLUSION: The technique described here may be a feasible alternative for correction of valgus knee deformity. The advantages of this technique include the use of a biomechanically more appropriate method, a minimal complication rate and a high rate of satisfactory outcomes.

Recurrent knee valgus deformity in Ellis-van Creveld syndrome.

We report a case of recurrent knee valgus deformity in a patient with Ellis-van Creveld syndrome. Varus osteotomy, distraction osteogenesis, or epiphyseal stapling is one treatment option for valgus malalignment to improve appearance, gait, and function. However, surgical correction of valgus knee deformity by varus osteotomies of the proximal tibia was not maintained postoperatively, necessitating additional varus osteotomies of the distal femur in this case. The main cause of recurrence was attributed to large bony defect of the anterior segment of the proximal tibia, in addition to depression of the lateral tibial plateau.

Ángulo de Inclinación del Fémur en el Hombre y su Relación con la Coxa Vara y la Coxa Valga / Angle of Inclination of Femur in Man and its Relationship with Coxa Vara and Coxa Valga

Los autores realizan mediciones en fémures aislados, realizando comparación de los datos obtenidos con los resultados encontrados en la literatura investigada, con el objeto de determinar de forma porcentual los valores limítrofes para clasificar la coxa como vara o valga. Fueron analizados 56 fémures de cadáveres adultos, siendo determinado el ángulo de inclinación del fémur, que fue medido a través de un Goniómetro. Utilizamos el patrón poblacional normal de 66 por ciento (o test Z) para determinar cuál es el intervalo donde se encuentra el alineamiento ideal. En las mediciones de los ángulos de inclinación de los 56 fémures, los valores se encontraban entre 117,67 grados y 136,67 grados. Utilizando el patrón poblacional normal de 66 por ciento (o test Z), verificamos que el intervalo ideal (o normal) se encuentra entre 117 grados y 136 grados, siendo éste el intervalo donde se encuentra el alineamiento ideal. En este intervalo encontramos 47 fémures (84 por ciento). La determinación normal del ángulo entre 117 grados y 136 grados, posibilita clasificar de coxa valga cuando el ángulo de inclinación está debajo de 177 grados y coxa vara encima de 136 grados.

The authors carried out isolated mensuration in femurs to compare data with the results found in literature. The objective was to determine in percentile form, bordering values to classify the thigh as pole or valgum. Fifty six femurs of adult corpses were analyzed, determining the angle of inclination in the femur, which was measured through a Goniometry. We used the normal population standard of 66 percent (or tested Z): to determine in which interval the ideal alignment is found. In the mensuration of inclination angles in 56 femurs., the values were between 117.67 and 136.67 degrees. Using the normal population standard of 66 percent (or tested Z), we verified the ideal interval (or normal) with findings between 117 and 136 degrees, the ideal alignment. In this interval we found 47 femurs (84 percent). The normal determination of the angle between 117 and 135 degrees allows classifying thigh valgum, when the angle of inclination is below 117 degrees and coxa vara is above 136 degrees.