Early radiographic risk factors for rigid relapse in idiopathic clubfoot treated with the Ponseti method.

BACKGROUND: This study aimed at identifying early risk factors for rigid relapse in idiopathic clubfoot using foot radiographs. METHODS: Thirty-four patients with 43 idiopathic clubfeet treated with the Ponseti method were retrospectively reviewed. RESULTS: There were seven rigid relapse recalcitrant to manipulation and requiring extensive soft-tissue release. Three radiograabphic measurements on the maximum dorsiflexion lateral (MD-Lat) radiograph, talocalcaneal (TaloCalc-Lat), tibiocalcaneal (TibCalc-Lat), and calcaneus-first metatarsal (CalcMT1-Lat) angles, showed significant differences between patients with and without rigid relapse. The TaloCalc-Lat and CalcMT1-Lat angles showed significant hazard ratio for rigid relapse by multivariate survival analysis. Clubfeet demonstrating TibCalc-Lat>90° and CalcMT1-Lat<5° have a 24.9-fold odds ratio to develop rigid relapse compared to those demonstrating TibCalc-Lat≤90° or CalcMT1-Lat≥5°. CONCLUSIONS: The TaloCalc-Lat, TibCalc-Lat, and CalcMT1-Lat angles on the MD-Lat radiograph immediately before the tenotomy, probably representing intrinsic tightness of the midfoot and/or hindfoot, are significant risk factors for rigid relapse in patients treated with the Ponseti method.

Chronic lateral epiphyseal separation of the proximal tibia causes late-onset tibia vara.

An adolescent obese boy showed late-onset unilateral tibia vara associated with physeal separation (slipped epiphysis) of the lateral proximal tibia and physeal widening of the lateral distal femur. These affected physes showed normal signal intensities by MRI. He was treated with lateral hemiepiphysiodesis of the left proximal tibia and the distal femur using two parallel eight-Plates, and varus deformity rapidly improved postoperatively without recurrence. This is the first case of late-onset tibia vara caused by lateral physeal separation of the proximal tibia. Normal growth of the medial physes around the knee would contribute toward significant correction after surgery.

Activated FGFR3 promotes bone formation via accelerating endochondral ossification in mouse model of distraction osteogenesis.

Achondroplasia (ACH) is one of the most common short-limbed skeletal dysplasias caused by gain-of-function mutations in the fibroblast growth factor receptors 3 (FGFR3) gene. Distraction osteogenesis (DO) is a treatment option for short stature in ACH in some countries. Although the patients with ACH usually show faster healing in DO, details of the newly formed bone have not been examined. We have developed a mouse model of DO and analyzed new bone regenerates of the transgenic mice with ACH (Fgfr3ach mice) histologically and morphologically. We established two kinds of DO protocols, the short-DO consisted of 5days of latency period followed by 5days of distraction with a rate of 0.4mm per 24h, and the long-DO consisted of the same latency period followed by 7days of distraction with a rate of 0.3mm per 12h. The callus formation was evaluated radiologically by bone fill score and quantified by micro-CT scan in both protocols. The histomorphometric analysis was performed in the short-DO protocol by various stainings, including Villanueva Goldner, Safranin-O/Fast green, tartrate-resistant acid phosphatase, and type X collagen. Bone fill scores were significantly higher in Fgfr3ach mice than in wild-type mice in both protocols. The individual bone parameters, including bone volume and bone volume/tissue volume, were also significantly higher in Fgfr3ach mice than in wild-type mice in both protocols. The numbers of osteoblasts, as well as osteoclasts, around the trabecular bone were increased in Fgfr3ach mice. Cartilaginous tissues of the distraction region rapidly disappeared in Fgfr3ach mice compared to wild-type mice during the consolidation phase. Similarly, type X collagen-positive cells were markedly decreased in Fgfr3ach mice during the same period. Fgfr3ach mice exhibited accelerated bone regeneration after DO. Accelerated endochondral ossification could contribute to faster healing in Fgfr3ach mice.

Characteristic calcaneal ossification: an additional early radiographic finding in infants with fibrodysplasia ossificans progressiva.

BACKGROUND: We have clinically encountered children with fibrodysplasia ossificans progressiva who had abnormal calcaneal ossification. OBJECTIVE: To evaluate whether calcaneal ossification variants are significant radiographic findings in children with fibrodysplasia ossificans progressiva. MATERIALS AND METHODS: Lateral feet radiographs in nine children who fulfilled the diagnostic criteria of fibrodysplasia ossificans progressiva were reviewed. The studies were obtained during infancy or early childhood. RESULTS: Fourteen lateral foot radiographs of fibrodysplasia ossificans progressiva were available for this study (ages at examination: 1-104 months). Four children ages 2 months to 11 months showed double calcaneal ossification centers; 7 children had plantar calcaneal spurs that decreased in size with age. Overall, eight of nine children with fibrodysplasia ossificans progressiva demonstrated double calcaneal ossifications and/or plantar calcaneal spurs in infancy or childhood. CONCLUSION: Double calcaneal ossification centers in early infancy and plantar calcaneal spurs in childhood are frequently seen in children with fibrodysplasia ossificans progressiva and may be a useful radiologic indicator for early diagnosis.

Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters.

Endochondral ossification is an essential process for reparative phase of fracture healing, which starts with the differentiation of mesenchymal cells into chondrocytes followed by substitution of bone tissue. It is strictly controlled by the expression of crucial transcriptional factors: SOX9 in the early phase and RUNX2 in the late phase. Screening of FDA-approved compounds revealed that an anti-allergic drug, tranilast, that has been used for more than 30 years in clinical practice, enhanced the SOX9 promoter in chondrogenic cells and the RUNX2 promoter in osteoblastic cells. We observed that tranilast increased mRNA expression of both Sox9 and Runx2 in differentiating ATDC5 chondrogenic progenitor cells. Tranilast upregulated mRNA expression of chondrogenic marker genes (Col2a1, Acan, Col10a1, and Mmp13) in differentiating ATDC5 cells. Moreover, tranilast upregulated mRNA expression of essential signaling molecules involved in endochondral ossification (Pthrp, Ihh, and Axin2). In the later phase of differentiation of ATDC5 cells, tranilast increased synthesis of matrix proteoglycans, induced the alkaline phosphatase activity, and tended to accelerate mineralization. Tranilast is a potential agent that accelerates fracture repair by promoting the regulatory steps of endochondral ossification.

Low bone mineral density in achondroplasia and hypochondroplasia.

BACKGROUND: Achondroplasia (ACH) and hypochondroplasia (HCH) are the most common form of short-limb skeletal dysplasias caused by activated fibroblast growth factor receptor 3 (FGFR3) signaling. Although decreased bone mass was reported in gain-of-function mutation in Fgfr3 mice, both disorders have never been described as osteoporotic. In the present study, we evaluated bone mineral density (BMD) in ACH and HCH patients. METHODS: We measured spinal BMD (L1-L4) in 18 ACH and four HCH patients with an average age of 19.8 ± 7.5 years (range, 10-33 years). BMD Z-score in each individual was calculated for normalizing age and gender. Correlation between body mass index (BMI) and BMD was analyzed. Moreover, BMD and Z-score were compared between ACH patients and HCH patients. RESULTS: The average BMD of ACH/HCH patients was 0.805 ± 0.141 g/cm(2) (range, 0.554-1.056 g/cm(2) ), resulting in an average Z-score of -1.1 ± 0.8 (range, -2.4 to 0.6) of the standard value. A slightly positive correlation was observed between BMI and BMD (r = 0.45; P = 0.13). There was no significant difference in BMD and Z-score between ACH and HCH patients. CONCLUSION: Spinal BMD was reduced in ACH/HCH patients, and was mildly correlated with individual BMI. We should carefully monitor BMD and examine osteoporosis-related symptoms in adolescent and adult ACH/HCH patients. © 2016 Japan Pediatric Society.

Prediction of Clinically Significant Leg-Length Discrepancy in Congenital Disorders.

Leg-length discrepancy greater than 2 to 2.5 cm can potentially have an adverse effect on our walking and standing mechanisms and requires proper correction involving surgical treatment. However, for minor leg-length discrepancy in childhood, decision making for the indications for and timing of epiphysiodesis is difficult because of unpredictable final discrepancy. The purpose of this study was to analyze longitudinal changes of minor leg-length discrepancy in congenital disorders and to determine earlier predictive values for the clinically significant discrepancy. Twenty-one patients with congenital disorders who had minor leg-length discrepancy less than 2 cm at the first presentation were retrospectively evaluated. The patients were divided into 2 groups according to leg-length discrepancy at latest follow-up: the significant group (n=11) had 25 mm or more of leg-length discrepancy and the minor group (n=10) had less than 25 mm of leg-length discrepancy. The authors evaluated longitudinal changes of leg-length discrepancy within the first 10 years by mixed-effects regression model. All patients showed monotonically increasing leg-length discrepancy with age, except for 2 (neurofibromatosis type 1 and macrodactyly of the foot) who demonstrated fluctuating leg-length discrepancy. Mean annual rate of leg-length discrepancy change in the significant group was 2.1 mm across the first decade of life and was significantly larger than that in the minor group (difference in slope, 1.3 mm; P<.0001). In minor leg-length discrepancy associated with congenital disorders, the incidence of clinically significant leg-length discrepancy can be predictable by the annual rate of leg-length discrepancy change in the first decade of life.