Management of Juvenile Hallux Valgus Deformity: the role of combined Hemiepiphysiodesis.

BACKGROUND: This study aimed to investigate the efficacy of percutaneous hemiepiphysiodesis for gradual correction of symptomatic juvenile hallux valgus (HV) deformity. METHODS: Between 2012 to 2014, 24 patients with symptomatic juvenile HV were treated by combined percutaneous medial drilling hemiepiphysiodesis of the first proximal phalanx and lateral transphyseal screw hemiepiphysiodesis of the first metatarsal at our institution. Twenty-one of 24 patients fulfilled inclusion criteria had a complete radiological and clinical follow-up of at least 2 years. Preoperative and postoperative radiographs of the feet were reviewed for measurements of hallux valgus angle (HVA), intermetatarsal angle (IMA), proximal metatarsal articular angle (PMAA), proximal phalangeal articular angle (PPAA), and metatarsal length ratio (MTLR). Clinical outcomes were assessed using the AOFAS hallux metatarsophalangeal-interphalangeal score. RESULTS: The study included 21 consecutive patients (37 ft) for analysis. The mean age at surgery was 12.0 years (SD = 1.3) and mean follow-up after surgery was 35.1 months (SD = 6.0). With the data available, the HV deformity improved in terms of the reduction of HVA by a mean of 4.7 degrees (P < .001) and the reduction of IMA by 2.2 degrees (P < .001). The PMAA and PPAA also improved significantly in the anteroposterior plane; however, the PMAA difference was insignificant in lateral plane as expected. The mean difference in the MTLR was 0.00 (P = .216) which was indicative of no length discrepancy between first and second metatarsals. The AOFAS score increased from 68.7 to 85.2 (P < .001). In correlation analysis, time to physeal closure was significantly correlated with the final HVA change (r = -.611, P = .003). CONCLUSION: Although combined hemiepiphysiodesis does not create a large degree of correction as osteotomy, yet it did improve HV deformity with adequate growth remaining in our series. It is a procedure that can be of benefit to patients with symptomatic juvenile HV from this minimal operative approach before skeletal maturity. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Excision of Physeal Bars of the Distal Femur, Proximal and Distal Tibia Followed to Maturity.

OBJECTIVE: In the 50 years since a premature partial physeal arrest (a physeal bar) was first excised from an epiphysis there have been no large in-depth studies reporting the results in patients followed to skeletal maturity. This paper reports the results of physeal bar resection surgery in a group of patients followed to skeletal maturity, documenting the restored growth of the affected physis, the affected bone, and the final limb-length discrepancy. METHODS: Forty-eight patients underwent physeal bar resection of the distal femur (21), proximal tibia (9), and distal tibia (18) by 1 surgeon (H.A.P.) from 1968 through 1996, and were followed prospectively to skeletal maturity with clinical and radiologic examinations. Factors such as sex, age at time of injury, etiology of the bar, physeal bar location and size, age at time of bar excision, interposition material, and additional surgical procedures were analyzed with respect to physis, bone, and limb growth following bar resection. RESULTS: The mean growth for the entire bone following physeal bar excision was 7.6 cm for the distal femur, 4.7 cm for the proximal tibia, and 7.5 cm for the distal tibia, compared with growth in the contralateral control bone of 6.8 cm in the femur, 5.0 cm in the proximal tibia, and 7.8 cm in the distal tibia. The maximum bone growth following bar excision in a single patient was 21.3 cm for the distal femur, 10.3 cm for the proximal tibia, and 18.6 cm for the distal tibia. The mean limb-length discrepancy at maturity was -1.7 cm for the distal femur, -1.3 cm for the proximal tibia, and -1.1 cm for the distal tibia (all sites combined -1.4 cm). Fourteen patients (29%) had only the 1 bar excision with no other accompanying or subsequent surgery. Thirty-four patients (71%) had 1 to 4 accompanying or subsequent leg length or angular correcting procedures. CONCLUSIONS: Physeal bar excision to restore growth when applied to the appropriate patient is a useful, rewarding procedure, reducing the number of surgical limb length equalizing procedures. It is a demanding surgical procedure and requires diligent and careful follow-up until maturity. Additional limb length equalizing surgery is frequently needed. LEVEL OF EVIDENCE: Case series, level IV.

Concomitant Anterior Cruciate Ligament Reconstruction and Temporary Hemiepiphysiodesis in the Skeletally Immature: A Combined Technique.

BACKGROUND: Young athletes with an anterior cruciate ligament (ACL) disruption and limb malalignment pose a treatment dilemma. Little has been published regarding limb malalignment in this population. Our aim is to review the results of combined treatment of an ACL deficient knee and genu valgum in skeletally immature patients. METHODS: A retrospective review of skeletally immature patients who underwent transphyseal ACL reconstruction and concomitant hemiepiphysiodesis between 2004 and 2015 by 1 surgeon at a single institution was performed. Included patients had at least a year of growth remaining and were followed to skeletal maturity. Patients with a diagnosis of a connective tissue disorder were excluded. Knee stability, rate of retear, the rate of mechanical axis correction, and time to full correction were determined. RESULTS: Ninety skeletally immature patients underwent transphyseal ACL reconstruction, 8 of which met inclusion criteria. Mean time to correction of the valgus deformity was 13 months (0.4 degree/mo). No patient required additional surgeries for malalignment. All patients had improvement in knee stability. One patient had a retear of their ACL reconstruction, for a failure rate of 13%. Preoperative mechanical lateral distal femoral angle and mechanical axis deviation corrected to near-neutral alignment for all treated limbs and were significantly different (P=0.001) than those measured preoperatively. CONCLUSIONS: Promising results were seen for simultaneous correction of genu valgum and transphyseal ACL reconstruction. Treatment of both pathologies in a concomitant surgery can be considered in the appropriate population, with expected results comparable to each procedure in isolation. LEVEL OF EVIDENCE: Level IV-case series.

Growth of epiphysis after epiphyseal-preservation surgery for childhood osteosarcoma around the knee joint.

BACKGROUND: Epiphyseal-preservation surgery for osteosarcoma is an alternative method which has been indicated carefully to selected patients. The tumor-devitalised autograft treated with liquid nitrogen procedure is one of the biological reconstruction method to reconstruct the defect after tumor excision. The limb length discrepancy is usually appeared in children with their growth after limb-sparing surgery. This study was aimed to investigated the growth of residual epiphysis following epiphyseal-preservation surgery for childhood osteosarcoma around the knee joint. METHODS: We retrospectively reviewed 12 patients with osteosarcoma who underwent epiphysis preserving tumor excision (8 in distal femur and 4 in proximal tibia) and reconstructed by using tumor-devitalized autograft treated with liquid nitrogen. The mean patient age was 11 (range, 6 to 14) years. The mean follow-up period were 63 (range, 41 to 90) months. Epiphysis transverse growth rate, epiphysis-width discrepancy (EWD) and collapse of epiphysis were evaluated by using pre- and post-operative whole standing leg radiographs. A retrospective chart review was performed to investigate functional outcome, complications and oncological status. RESULTS: The mean growth of epiphysis rate was 12.6% (range, 3.3 to 28.0%) of affected side and 12.7% (range, 3.8 to 28.9%) of contralateral side, mean EWD was 0.1 mm (range, - 1.0 to 1.7 mm), mean LLD was + 26.1 mm (range, + 1 to + 48 mm) and two patients with distal femoral reconstruction underwent limb lengthening of tibia. There was no collapse of the residual epiphysis. The mean MSTS score was 27.7 (range, 18 to 30). CONCLUSIONS: Epiphysis transverse growth was not diminished, and there was absence of epiphyseal collapse even after epiphyseal-preservation surgery in this small series of childhood osteosarcoma around the knee. With careful assessment for epiphyseal tumor involvement, epiphyseal-preservation surgery shall be possible, and could be an alternative method worth considering.

Epiphyseal growth plate architecture is unaffected by early postnatal activation of the expression of R992C collagen II mutant.

Spondyloepiphyseal dysplasia (SED) exemplifies a group of heritable diseases caused by mutations in collagenous proteins of the skeletal system. Its main feature is altered skeletal growth. Pathomechanisms of SED include: changes in the stability of collagen II molecules, inability to form proper collagen fibrils, excessive intracellular retention of mutant molecules, and endoplasmic reticulum stress. The complexity of this pathomechanism presents a challenge for designing therapies for SED. Our earlier research tested whether such therapies only succeed when applied during a limited window of development. Here, employing an inducible mouse model of SED caused by the R992C mutation in collagen II, we corroborate our earlier observations that a therapy must be applied at the prenatal or early postnatal stages of skeletal growth in order to be successful. Moreover, we demonstrate that blocking the expression of the R992C collagen II mutant at the early prenatal stages leads to long-term positive effects. Although, we could not precisely mark the start of the expression of the mutant, these effects are not significantly changed by switching on the mutant production at the early postnatal stages. By demonstrating the need for early therapeutic interventions, our study provides, for the first time, empirically-based directions for designing effective therapies for SED and, quite likely, for other skeletal dysplasias caused by mutations in key macromolecules of the skeletal system.

2018 International Olympic Committee consensus statement on prevention, diagnosis and management of paediatric anterior cruciate ligament (ACL) injuries.

In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric anterior cruciate ligament (ACL) injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery and Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America, and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis, and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.

Orthopaedic Management of Leg-length Discrepancy in Proteus Syndrome: A Case Series.

INTRODUCTION: Proteus syndrome (PS) is a rare mosaic disorder comprising asymmetric bony and soft tissue overgrowth leading to significant morbidity. Placement of growth inhibition hardware with subsequent epiphyseal arrest improves leg-length and angular deformities in pediatric patients without PS. The purpose of this study was to review the surgical approach and present outcomes, complications, and recommendations in 8 patients with PS and leg-length discrepancy (LLD). METHODS: We conducted a retrospective chart review of 8 patients with PS whose primary reason for surgery was LLD. Patients were eligible if they met clinical diagnostic criteria for PS and if the National Institutes of Health team performed at least 1 of their surgical interventions between 2005 and 2015. Surgical techniques included growth inhibition, with tension band plates, applied ≥1 times, and epiphyseal arrest. RESULTS: Eight patients, followed for an average of 4.6 years (range, 1.0 to 7.1 y) after the index procedure, were included in this analysis. Average age at first LLD surgery was 9.4 years (range, 6.1 to 13.6 y); the average LLD was 3.4 cm (range, 0.4 to 7.0 cm) at presentation, and 5.0 cm (range, 1.8 to 10.0 cm) at the time of the first LLD surgery. Participants underwent 23 total surgeries (range, 1 to 5 per patient) and 7 patients have completed surgical intervention. For the 7 patients who did not require overcorrection the average LLD at the last clinical encounter was 2.6 cm (range, 0.6 to 7.2 cm). We encountered 2 complications: 2 patients developed mild knee valgus, which responded to standard guided growth techniques. CONCLUSIONS: This case series suggests that growth inhibition and epiphyseal arrest in children with PS can reduce LLD with few complications. Careful monitoring, rapid mobilization, deep venous thrombosis prophylaxis, and sequential compression devices were also integral elements of our surgical protocol. LEVEL OF EVIDENCE: Level IV.

Long-term follow-up after bilateral percutaneous epiphysiodesis around the knee to reduce excessive predicted final height.

CONTEXT: Percutaneous epiphysiodesis (PE) around the knee to reduce predicted excessive final height. Studies until now included small numbers of patients and short follow-up periods. OBJECTIVE AND DESIGN: This Dutch multicentre, long-term, retrospective, follow-up study aimed to assess adult height (AH), complications, knee function and patient satisfaction after PE. The primary hypothesis was that PE around the knee in constitutionally tall boys and girls is an effective treatment for reducing final height with low complication rates and a high level of patient satisfaction. PARTICIPANTS: 77 treated adolescents and 60 comparisons. INTERVENTION: Percutaneous epiphysiodesis. OUTCOME: AH, complications, knee function, satisfaction. RESULTS: In the PE-treated group, final height was 7.0 cm (±6.3 cm) lower than predicted in boys and 5.9 cm (±3.7 cm) lower than predicted in girls. Short-term complications in file search were seen in 5.1% (three infections, one temporary nerve injury), one requiring reoperation. Long-term complications in file search were seen in 2.6% (axis deformity 1.3%, prominent head of fibula 1.3%). No significant difference in knee function was found between treated cases and comparisons. Satisfaction was high in both the comparison and PE groups; most patients in the PE group recommended PE as the treatment for close relatives with tall stature. CONCLUSION: PE is safe and effective in children with predicted excessive AH. There was no difference in patient satisfaction between the PE and comparison group. Careful and detailed counselling is needed before embarking on treatment.

A new formula for assessing skeletal age in growing infants and children by measuring carpals and epiphyses of radio and ulna.

The aim of this study is to develop a specific formula for the purpose of assessing skeletal age in a sample of Italian growing infants and children by measuring carpals and epiphyses of radio and ulna. A sample of 332 X-rays of left hand-wrist bones (130 boys and 202 girls), aged between 1 and 16 years, was analyzed retrospectively. Analysis of covariance (ANCOVA) was applied to study how sex affects the growth of the ratio Bo/Ca in the boys and girls groups. The regression model, describing age as a linear function of sex and the Bo/Ca ratio for the new Italian sample, yielded the following formula: Age = -1.7702 + 1.0088 g + 14.8166 (Bo/Ca). This model explained 83.5% of total variance (R(2) = 0.835). The median of the absolute values of residuals (observed age minus predicted age) was -0.38, with a quartile deviation of 2.01 and a standard error of estimate of 1.54. A second sample test of 204 Italian children (108 girls and 96 boys), aged between 1 and 16 years, was used to evaluate the accuracy of the specific regression model. A sample paired t-test was used to analyze the mean differences between the skeletal and chronological age. The mean error for girls is 0.00 and the estimated age is slightly underestimated in boys with a mean error of -0.30 years. The standard deviations are 0.70 years for girls and 0.78 years for boys. The obtained results indicate that there is a high relationship between estimated and chronological ages.

Growth Arrest Following ACL Reconstruction With Hamstring Autograft in Skeletally Immature Patients: A Review of 4 Cases.

BACKGROUND: Anterior cruciate ligament (ACL) tears are becoming more common in the skeletally immature population as participation in high-risk sports continues to grow. This presents a challenge for the treating surgeon as ACL reconstruction in this patient set has the added aim of preservation of the growth plate anatomy. The purpose of this investigation is to report on 4 patients who developed growth arrest following ACL reconstruction and offer a review of the available literature. METHODS: Four skeletally immature patients (2 male and 2 female) were identified who underwent ACL reconstruction at mean age of 14.2 years (range, 13.5 to 14.8 y) and developed growth arrests. Bone ages at the time of reconstruction were 14 and 16 years for the boys and 13 years 6 months and 14 years for the girls. All patients had a transphyseal reconstruction with a hamstring autograft. Standard postoperative care was provided including clinical and radiographic follow-up at regular intervals. Clinically significant postoperative physeal arrest was confirmed on MRI or CT scan. Detailed chart review examined demographics, operative variables, and postoperative subjective and objective clinical measures. RESULTS: Two patients developed tibial recurvatum; 2 patients developed genu valgum. Three patients required further surgery. One patient underwent distal femoral-guided growth procedure, 2 underwent proximal tibial epiphysiodesis, and 1 patient was skeletally mature at presentation and did not require deformity correction. CONCLUSIONS: This report of 4 patients demonstrates that growth arrest following ACL reconstruction in skeletally immature patients is a real concern and highlights the importance of careful preoperative evaluation and discussion with patients and family members. We routinely obtain long-leg AP and lateral hip-to-ankle films on skeletally immature patients before performing an ACL reconstruction and then at 6 and 12 months postoperatively or every 6 months until the growth plates are closed to assess leg lengths and lower extremity alignment. LEVEL OF EVIDENCE: Level IV-therapeutic study, case series.

Developmental pattern of the hip in patients with hereditary multiple exostoses.

BACKGROUND: Coxa valga is a common clinical feature of hereditary multiple exostoses (HME). The current study aimed to determine the unique developmental pattern of the hip in patients with HME and evaluate the factors that influence its progression. METHODS: Thirty patients (57 hips) with HME were divided into two groups according to the Hilgenreiner epiphyseal angle (HEA). Twenty-two patients (44 hips) including 13 men and 9 women were assigned to group 1 (HEA <25°), and 8 patients (13 hips) including 3 men and 5 women were assigned to group 2 (HEA ≥25°). The mean age at the initial presentation was 6.0 (4-12) years with 6.8 (4-11) years of follow-up in group 1, and 10.4 (8-13) years with 5.4 (2-9) years of follow-up in group 2. We measured the HEA, neck-shaft angle (NSA), acetabular index (AI), center-edge angle (CEA), and migration percentage (MP) for radiographic evaluation. RESULTS: Among the hips, 50 (87.7%) hips had coxa valga and 27 (47.4%) hips had abnormal MP (42.1% were borderline and 5.3% were subluxated). There was a significant difference in the HEA and NSA between the groups (p < 0.001 and p < 0.05, respectively). The HEA significantly correlated with the development of the NSA and no correlation was found between the HEA and AI, CEA, and MP. CONCLUSIONS: There was a significant relationship between the HEA at the initial presentation and the NSA at skeletal maturity. We should consider guided growth for patients with lower HEA to prevent significant coxa valga deformity with close follow-up.

Clinical use of deslorelin implants for the long-term contraception in prepubertal bitches: effects on epiphyseal closure, body development, and time to puberty.

Long-acting GnRH agonists have been used both for canine estrus induction and prevention. The objective of the study was to investigate the use of a deslorelin implant as a long-term and reversible contraceptive in prepubertal bitches with special regard to the time of epiphyseal closure. Thirteen healthy, crossbreed, medium-sized prepubertal female dogs were used in this study. An implant containing 9.4 mg (G1, n = 5) and 4.7 mg (G2, n = 4) deslorelin acetate (Suprelorin) or a placebo (sodium chloride 0.9%; G3, n = 4) was inserted subcutaneously in the interscapular region. Estrus was monitored once daily by physical and sexual behavioral changes. Body development, vaginal cytology, and serum progesterone and estradiol 17ß concentration were monitored weekly for the first 5 weeks, and then every 3 weeks throughout the treatment period. Radiographic examinations were performed monthly to determine the epiphyseal closure. Half of the deslorelin-treated bitches (G1: n = 2 and G2: n = 2) came into estrus during the 83-week observation period. All animals in the control group showed estrus between the 39th and 64th weeks of observation. Time to puberty averaged 82.7 ± 8.9 and 61.9 ± 9.7 weeks in the deslorelin-treated (G1 and G2) and the control bitches, respectively (P < 0.02). Both deslorelin implants (9.4 and 4.7 mg) can be used efficiently for the long-term prevention of estrus in prepubertal bitches; however, epiphyseal closure is clearly delayed which was without any clinical effect in the present study.

Intra-articular Radial Head Fractures In the Skeletally Immature Patient: Complications and Management.

BACKGROUND: Intra-articular (IARH) and extra-articular (EARH) radial head fractures in skeletally immature patients are rare injuries that have not been well studied. The objective of this study was to investigate the rate of complications associated with IARH fractures relative to EARH fractures in pediatric patients treated at a tertiary referral children's hospital. METHODS: With IRB approval, Current-Procedural Terminology codes were used to identify all patients who underwent management of radial head and/or neck fractures between 2005 and 2012. A retrospective chart review was used to collect variables related to: demographics, fracture type, treatment method(s), complications, need for physical/occupational therapy, and the need for subsequent surgery. Mid-P exact tests and logistic regression analyses were used to compare differences in the incidence of complications, need for physical therapy (PT), and need for revision surgery between the IARH and EARH fracture groups. RESULTS: Among the 311 patients included in the cohort, 12 (3.86%) were affected by IARH fractures and 299 (96.14%) were affected by EARH fractures. The mean age at the time of injury was 11.46 (±3.09) years and 8.32 (±3.31) years in the IARH and EARH group, respectively. The estimated incidence of complications was significantly (P<0.0001) higher in the IARH group (50 per 100) compared with the EARH group (1.34 per 100). A significantly (P<0.0001) greater proportion of the subjects with IARH fractures also required revision surgery (25% IARH vs. 0% EARH) and PT (50% IARH vs. 19.59% EARH). CONCLUSIONS: Compared with EARH fractures, IARH fractures were associated with a significantly higher rate of complications, greater need for PT, and greater need for surgical intervention. The significant complication rate associated with pediatric IARH fractures necessitates an increased awareness of this fracture pattern and prompt, aggressive diagnostic and treatment modalities. LEVEL OF EVIDENCE: Therapeutic studies: Level III.

Hemiepiphysiodeses for guided growth in children.

Lower-extremity angular deformities are among the most common non-traumatic conditions in children being referred to pediatric orthopedists. Understanding of this abnormality and knowledge of current treatment is essential for pediatricians and primary caregivers. A development in the surgical management of these problems has improved the quality of care of affected children and adolescents. Traditionally, angular deformities are treated by means of osteotomy. In patients who are skeletally immature, this major intervention can be avoided by influencing or guiding the growth of the affected physis using hemiepiphysiodesis techniques. Recently, alternative surgical techniques and implants have been described for improved control of the guided growth.

Nonanatomic anterior cruciate ligament reconstruction with double-stranded semitendinosus grafts in children with open physes: minimum 15-year follow-up.

BACKGROUND: Nonanatomic anterior cruciate ligament (ACL) reconstruction (ACLR) with double-stranded semitendinosus grafts in children with open physes has been described as a successful surgical technique in short-term follow-up clinical reports. PURPOSE: To evaluate the clinical outcomes of nonanatomic ACLR in children with open physes and a minimum of 15 years' follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twelve patients with an average age of 10.7 years (range, 8.3-12.4 years) underwent ACLR between 1991 and 1998. All patients were classified as Tanner development stage 2 or lower. The surgical technique involved transphyseal tibial tunnel drilling and over-the-top (OTT) femoral fixation using a double-stranded graft for all patients. Clinical outcomes were evaluated in terms of the manual Lachman test, pivot-shift test, return to sports activity, and International Knee Documentation Committee (IKDC) score at the end of growth and at a minimum 15-year follow-up (range, 15-22 years). RESULTS: No clinically significant growth disturbance was observed. Ten patients had a grade A IKDC score, and 2 patients had a grade B IKDC score at the end of growth. There was no progression of laxity or modification of knee stability with growth. Three patients (25%) had ACL reruptures during sports activities after growth plate closure. All patients with reruptured ACLs underwent additional reconstructive surgery. CONCLUSION: Anterior cruciate ligament reconstruction using the OTT technique in the femur and the transphyseal technique in the tibia produces good results with regard to growth plate closure but a high failure rate in adulthood.

The multiple effects of thyroid disorders on bone and mineral metabolism / Os múltiplos efeitos das disfunções tireoidianas sobre o metabolismo osteomineral

Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.

Diferentemente da maioria dos hormônios, que usualmente são moléculas especializadas capazes de influenciar outras células, tecidos e sistemas, os hormônios da tireoide (HT) são peptídeos pleiotrópicos, cuja função primordial é difícil de identificar. A ação complexa dos HT na fisiologia humana pode ser facilmente reconhecida ao observar as diversas consequências do excesso e da deficiência de HT durante e após o pleno desenvolvimento. Em particular as diferentes manifestações na modelação e remodelação óssea refletem que as consequências esqueléticas das disfunções tireoidianas dependem das circunstâncias e variam com a idade. Enquanto o hipertireoidismo durante a infância aumenta a mineralização óssea e acelera a maturação epifisária, em adultos induz a perda óssea pela ativação predominante da ação osteoclástica. Além disso, a síndrome de resistência ao HT é uma condição multifacetada na qual diferentes tecidos apresentam sinais de excesso ou deficiência hormonal, dependendo da predominância da expressão das diversas isoformas do receptor de HT. O impacto da resistência ao HT sobre o esqueleto ainda é motivo de investigação. Apresentamos aqui uma revisão abrangente sobre as ações ósseas dos HT e o impacto no esqueleto dos distúrbios da tireoide, incluindo hipo e hipertireoidismo e síndrome de resistência ao HT.

MR imaging of normal epiphyseal development and common epiphyseal disorders.

During infancy and childhood, multiple developmental changes occur in the epiphysis. Initially the epiphysis is composed entirely of hyaline cartilage. As skeletal maturation progresses, one or several secondary ossification centers (SOCs) develop within the epiphyseal cartilage. The SOCs enlarge by endochondral ossification and undergo marrow transformation in a process analogous to that of the primary physis and metaphysis. Magnetic resonance (MR) imaging can be used to evaluate vascularity, marrow, and cartilage and plays a critical role in the assessment of epiphyseal disorders in children. In cases of shoulder and hip dysplasia, MR imaging demonstrates unossified structures and helps guide treatment. In cases of trauma, the intracartilaginous pathway of fractures, the degree of physeal involvement, and early bridge formation can be assessed. With the use of intravenous gadolinium-based contrast material, avascular necrosis and reperfusion can be characterized. This article reviews the normal structure of the epiphysis, its appearance at MR imaging, and age-related changes to the epiphysis. Common conditions that lead to epiphyseal damage in children are reviewed, with an emphasis on the role of MR imaging in diagnosis, prognosis, and treatment.

Palmitoyl acyltransferase, Zdhhc13, facilitates bone mass acquisition by regulating postnatal epiphyseal development and endochondral ossification: a mouse model.

ZDHHC13 is a member of DHHC-containing palmitoyl acyltransferases (PATs) family of enzymes. It functions by post-translationally adding 16-carbon palmitate to proteins through a thioester linkage. We have previously shown that mice carrying a recessive Zdhhc13 nonsense mutation causing a Zdhcc13 deficiency develop alopecia, amyloidosis and osteoporosis. Our goal was to investigate the pathogenic mechanism of osteoporosis in the context of this mutation in mice. Body size, skeletal structure and trabecular bone were similar in Zdhhc13 WT and mutant mice at birth. Growth retardation and delayed secondary ossification center formation were first observed at day 10 and at 4 weeks of age, disorganization in growth plate structure and osteoporosis became evident in mutant mice. Serial microCT from 4-20 week-olds revealed that Zdhhc13 mutant mice had reduced bone mineral density. Through co-immunoprecipitation and acyl-biotin exchange, MT1-MMP was identified as a direct substrate of ZDHHC13. In cells, reduction of MT1-MMP palmitoylation affected its subcellular distribution and was associated with decreased VEGF and osteocalcin expression in chondrocytes and osteoblasts. In Zdhhc13 mutant mice epiphysis where MT1-MMP was under palmitoylated, VEGF in hypertrophic chondrocytes and osteocalcin at the cartilage-bone interface were reduced based on immunohistochemical analyses. Our results suggest that Zdhhc13 is a novel regulator of postnatal skeletal development and bone mass acquisition. To our knowledge, these are the first data to suggest that ZDHHC13-mediated MT1-MMP palmitoylation is a key modulator of bone homeostasis. These data may provide novel insights into the role of palmitoylation in the pathogenesis of human osteoporosis.

Effect of neutering and breed on femoral and tibial physeal closure times in male and female domestic cats.

The timing of physeal closure is dependent upon many factors, including gonadal steroids, and previous studies have shown that early neutering delays physeal closure. Pelvic and femoral radiographs of 808 cats were analysed and physes at the greater trochanter, proximal femur, distal femur and proximal tibia were recorded as being open or closed. Date of birth, gender, neuter status and breed of cases were recorded. Each physis was analysed individually at a specific age. The number of male entire (ME), male neutered (MN), female entire (FE), female neutered (FN), pedigree and non-pedigree cases at each of these ages was recorded. The number of cases that were open or closed at each stated age were compared between the neutered and entire, the female and male, and the pedigree and non-pedigree groups using a Fischer's exact test, with P <0.05 being considered significant. Seven hundred and eighty-three radiographs were included: 359 MN, 95 ME, 237 FN and 92 FE. Ninety-six cats were pedigree and 687 were non-pedigree. A statistically significant effect was shown with physes closing later in MN than in ME cats for the greater trochanter (P = 0.0037), distal femur (P = 0.0205) and tibial tuberosity (P = 0.0003). No effect was shown for the proximal tibial or proximal femoral physes, nor for any physis when comparing FE with FN cats. No statistically significant effect of breed or sex was noted. Physeal closure will occur later in MN cats than in ME cats for the greater trochanteric, distal femoral and tibial tuberosity physes, and the potential clinical consequences of this should be evaluated further.

Bilateral epiphyseal migration following fixation for slipped capital femoral epiphyses in a hypothyroid child.

Progression of slipped capital femoral epiphysis following in situ screw fixation typically occurs through loosening of the screw in the metaphysis. Epiphyseal migration off the screw due to physeal growth is rare. We report epiphyseal migration off bilateral screws in a child undergoing thyroid replacement therapy. Patients with mild and moderate slipped capital femoral epiphysis and endocrine disease should be followed-up with radiographs taken at intervals which reflect the rate of growth. Fixation should be revised if the tip of the screw approaches the physis and initial fixation with two screws may be considered.