Aims

To systematically review the outcomes and complications of cosmetic stature lengthening.

Background

Sclerostin is a secreted glycoprotein that inhibits the intracellular Wnt signaling pathway, which when inactivated bone formation is stimulated. This stimulation has been proven in fracture studies, showing larger and stronger calluses with accelerated fracture healing, both in sclerostin knockout and sclerostin antibody injection models. The effects of these two mechanisms have not been compared to assess the accurate effect of the Scl-Ab injections. Therefore we designed a study to compare the effect of sclerostin depletion (sclerostin knockout) and inhibition (Scl-Ab injection).

Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralisation, which is vital for normal bone development, its biomechanical competence and fracture healing. Phosphatase, orphan 1 (PHOSPHO1), a bone-specific phosphatase, has been shown to be involved in the mineralisation of the extracellular matrix in bone. It can hydrolyse phosphoethanolamine and phosphocholine to generate inorganic phosphate, which is crucial for bone mineralisation. Phospho1−/− mice show hypomineralised bone and spontaneous fractures. All these data led to the hypothesis that PHOSPHO1 is essential for bone mineralisation and its structural integrity. However, no study to our knowledge has shown the effects of PHOSPHO1 on bone fracture healing. In this study, we examined how PHOSPHO1-deficiency might affect the healing and quality of the fractured bones in Phospho1−/− mice.

We performed rodded immobilised fracture surgery on the right tibia of control wild type (WT) and Phospho1−/− mice (n=16 for each group) at eight weeks of age. Bone was left to heal for four weeks and then the mice were euthanised and their tibias were analysed using Faxitron X-ray analyses, microCT, histology and histomorphometry and three-point bending test.

Our microCT and X-ray analyses revealed that the appearance of the callus and several static parameters of bone remodeling at the fracture sites were markedly different in WT and Phospho1−/− mice. We observed a significant increase of BS/BV, BS/TV and trabecular number and decrease in trabecular thickness and separation in Phospho1−/− callus in comparison to the WT callus. These observations were further confirmed by histomorphometry. The increased bone mass at the fracture sites of Phospho1−/− mice appears to be caused by increased bone formation as there is a significant increase of osteoblast number, while osteoclast numbers remained unchanged. There was a marked increase of osteoid volume over bone volume (OV/BV) in the Phospho−/− callus. Interestingly, the amount of osteoid was markedly higher at the fracture sites than that of normal trabecular bones. The three-point bending test showed that Phospho 1 −/− fractured bone had more of an elastic characteristics than the WT bone as they underwent more of a plastic deformity before the breakage point compare to the WT.

Our work suggests that PHOSPHO1 plays an integral role during bone fracture repair. PHOSPHO1 can be an interesting target to improve the fracture healing process.

The aim was to assess the long-term impact of humeral and forearm rodding on functional ability, grip strength, joint range of motion and angular deformity in children with osteogenesis imperfecta.

A retrospective chart review was conducted on 57 children with osteogenesis imperfecta who underwent humeral rodding or forearm rodding at our institution between 1996 and 2013. Functional ability was assessed using the self-care and mobility domains of the Pediatric Evaluation and Disability Inventory (PEDI). Grip strength was measured using a dynamometer and joint range of motion with a goniometer. Deformity was measured on radiographs of the humerus or forearm. Outcomes were assessed pre-operatively and every year post-operatively. Differences between pre-operative and 1-year post-operative outcomes were compared using paired T-tests. In 44 patients with a minimum of 2 years follow-up, outcome measures at 1-year post-surgery were compared to those at the latest clinic visit (mean follow-up = 8.0 years).

Humeral and forearm rodding resulted in a significant improvement in PEDI self-care score (mean change =5.75, p=0.028 for the humerus, mean change = 6.77, p=0.0017 for the forearm) and mobility score (mean change =3.59, p=0.008 for the humerus, mean change =7.21, p=0.020 for the forearm) at 1 year post-surgery. Grip strength improved following forearm rodding (mean change = +6.13N, p=0.015) but not humeral rodding. Joint range of movement improved following humeral rodding but not forearm rodding. There was a significant improvement in radiographic angular deformity of the forearm and humerus following surgery (p<0.0001). Over 80% of improvements were maintained in the long-term.

Humeral and forearm rodding in children with osteogenesis imperfecta leads to long-term improvement in functional ability and angular deformity.

Purpose: Arthrogryposis Multiplex Congenita is a rare congenital disorder associated with multiple musculo-skeletal contractures which causes substantial morbidity. Knee involvement is commonly seen among children with arthrogryposis, with flexion contracture of the knee being the most frequent knee deformity. Knee flexion contractures in the paediatric population are particularly debilitating as they affect ambulation. Treatment for knee flexion contractures requires numerous orthopaedic procedures and an extensive follow-up period. The purpose of this study was to assess the effectiveness of orthopaedic procedures, namely distal femoral extension osteotomy and/or Ilizarov external fixator, on the ambulation status of children with knee flexion contracture.

Method: The medical records and radiological images of 16 paediatric patients with arthrogryposis and knee flexion contractures were reviewed. The etiology of all of them was amyoplasia except for one case of popliteal pterygium. The mean age of first surgery was 6.2 years (age range: 1–15 years). The mean length of follow-up was 83.9 months. All patients’ knee flexion contractures were treated with femoral extension osteotomy, Ilizarov external fixator, or both. Two patients previously had posterior soft tissue releases, including hamstrings lengthenings, proximal gastrocnemius release, and release of posterior capsule.

Results: Prior to the initial surgery for knee flexion contracture, 13 patients were non-ambulatory. One patient was a household ambulator with flexed knees. Two patients walked with orthoses. There was an average of 1.8 surgeries done per patient, namely distal femoral extension osteotomy and/or Ilizarov external fixator. At the latest follow-up, 12 patients were ambulatory, including 11 children ambulating with technical aids (orthosis, walker, braces, or rollator walker) and one child ambulating without any technical aid. Four patients remained non-ambulatory. The mean total arc of motion was 64.8 degrees preoperatively, 63.1 degrees postoperatively, and 52.8 degrees at the latest follow-up. A mean loss of 6.8 degrees per year in total arc of motion occurred. There were complications in four patients which consist of infected hardware, transient neurological compromise, cast change, and pressure sore.

Conclusion: Surgical correction of knee flexion deformities by distal femoral extension osteotomy and/or Ilizarov external fixator was effective in improving the ambulation status of children with arthrogryposis. At latest follow-up, the gradual loss of total arc of motion did not impact the ambulatory gains made by these procedures.

Bone Morphogenetic Protein 7 (BMP7) is a powerful osteoinductive substance that could stimulate bone formation in difficult conditions including distraction osteogenesis. However, to be effective, large unphysiological doses are required. Blocking the expression of BMP antagonists could amplify the effects of BMP7, allowing smaller doses of BMP7 to be used without altering its osteogenic potential. In this study, BMP7 antagonist Noggin was shown to be upregulated following BMP7 injection in a rabbit distraction osteogenesis model suggesting a role for Noggin in controlling BMP7 activity. Blocking Noggin expression may thus permit smaller doses of BMP7 to be used effectively.

Distraction osteogenesis (DO) is an excellent method to form new bone. However, the long duration the external fixator has to be kept on until the new bone consolidates, could lead to numerous problems. BMP7 may accelerate bone formation in DO. However, large doses of BMP7 may be necessary. In this study, we investigated the expression of BMP7 antagonist Noggin in DO.

Noggin may control BMP7 activity through a negative feedback mechanism. Blocking Noggin may amplify the effects of BMP7, thus permitting the use of smaller doses of BMP7 effectively in DO.

Using smaller doses of BMP7 – while maintaining its powerful effects – may decrease side effects and render this drug more affordable economically.

Noggin is normally expressed in DO. Its expression is upregulated by local application of BMP7. Its expression is co-localized to the same cells that express BMP7 and its receptors.

The right tibia of sixteen rabbits was lengthened using a uniplanar fixator. The rabbits were divided into two groups: one received seventy-five micrograms recombinant BMP7 and the other placebo. All injections were performed one week after start of distraction. Rabbits were sacrificed ten minutes, one day, two days and two weeks following the injections. The expression of Noggin was studied in the distracted tissue by immunohistochemistry.

Noggin may play a role in DO. Blocking its action may have huge clinical implications, by permitting the use of smaller – but equally effective – amounts of BMP7.

Funding: CIHR, FRSQ and Shriners of North America

The different pathways by which bone morphogenetic protein 7 (BMP-7) could exert its osteogenic function in distraction osteogenesis (DO) were investigated. Using immunohistochemistry, the temporal and spatial expression of markers for angiogenesis, cell proliferation, Indian hedgehog pathway, osteogenic growth factors and their receptors were investigated in a rabbit model of DO. Our results showed that local injection of BMP-7 at the lengthened site caused up-regulation of expression of growth factors and their receptors, cell proliferation and vascular markers and Indian hedgehog gene in a temporal fashion. By knowing these pathways, manipulation of DO by pharmaceutical agents may be possible.

Based on preliminary data, BMP-7 can accelerate the consolidation of newly formed bone if locally injected early in the distraction phase; however, the exact mechanism remains unknown.

The purpose of this study was to investigate the different pathways through which BMP-7 exerts its effects in DO.

The right tibia of twenty-four rabbits was lengthened 2.0 cms. The rabbits were divided into three groups : control, placebo and treated groups. The rabbits received no injection (control), buffer (placebo) and 75 micro grams BMP7 (treated) in the distracted zone one week after the start of distraction. The rabbits were sacrificed ten minutes, one day, two days and two weeks following the injections. Using immunohistochemistry, the different pathways of bone formation were assessed by analysing the expression of markers for angiogenesis (VGEF, Vascular Endothelial Growth Factor and PECAM , platelet endothelial cell adhesion molecule) , cell proliferation markers (PCNA, proliferation cell nuclear antigen), osteogenic growth factors (TGFβ, IGF, FGF and their receptors) and Indian hedgehog gene as part of the parathyroid hormone related peptide pathway.

BMP-7 may stimulate bone formation through several pathways in a temporal fashion early after local injection, by up-regulating the expression of numerous osteogenic growth factors and their receptors and Indian hedgehog, and late two weeks after the injection, by up-regulating cell proliferation and vascular markers.

Our results showed the possible mechanisms of action of BMP-7 in DO and more importantly the various pathways through which pharmacological agents could be used in the manipulation of DO.

Purpose: The goal of this study was to evaluate the use of dual energy x-ray absorptiometry (DEXA) to subjectively assess distraction osteogenesis callous regenerate strength to aid in the determination of when to remove the external fixator device in patients undergoing distraction osteogenesis for limb length discrepancies.

Methods: All patients that underwent distraction osteogenesis with either an Ilizarov or Orthofix frame from 1984 to 2005 at the Montréal Shriners Hospital Canada that had monthly DEXA scans prior to removal of their external fixators were included. The fixators were removed once two consecutive DEXA scans showed that the bone mineral density (BMD) had plateaued with a less than 10% successive increase in BMD. A retrospective chart and radiographical review was performed to assess the healing index and post fixator removal complications.

Results: 30 patients underwent 32 corrections. There were 29 lengthenings and 3 lengthenings with angular corrections. The average lengthening was 5.4 cm (3.6–9.1). The healing index average was 49 days/cm (20–77). All patients were progressed from partial to full weightbearing within 6 weeks of fixator removal. There were 2 post removal fractures. One patient fractured through the regenerate and another fractured through a proximal pin site.

Conclusions: Current methods of assessing distraction osteogenesis callous prior to removal of fixator are objective methods based on plain radiographs that have been shown to have poor interobserver reliability. Fractures occurring after fixator removal range between 10–15%. Using DEXA to determine when the regenerate bone mineral density and thus bone strength has plateaued yielded a post fixator removal regenerate fracture rate of 3% in our review. This new method of subjectively assessing the regenerate as compared to other objective radiological methods is a reliable alternative that safely predicts when to remove the fixator with a low post removal fracture rate while maintaining an acceptable bone healing index.

In osteogenesis imperfecta (OI) because of bone fragility, deformities in load bearing regions of the body such as femoral neck and proximal femur are expected. The purpose of this study was to determine the prevalence and clinical presentation of coxa vara in two hundred and ninety-two patients with different types of OI. More than half of the patients were OI type III (55%) and the highest prevalence of coxa vara was seen in OI type VI (44,5%). The children suffering from coxa vara had also a significant limitation of range of motion in their hips.

The charts and x-rays of one hundred and fifty-four girls and one hundred and thirty-eight boys with OI were reviewed. The patients were classified according to the Sillence classification modified by Glorieux: eighty-seven Type I, sixty-nine Type IV, sixty-two Type III, eighteen Type V, nine type VI, four types VII, and forty-three unclassified. The mean age was nine, four years (0, 3–23, 3).

Twenty-nine patients (9, 9%) had coxa vara (twenty-three left, twenty right). 55% of them were type III, 17% type IV, 13, 8% type VI and three, 4% each of types I, V, VII and unclassified OI. The prevalence of coxa vara was 1% in type I, 5,5% in type V, 7 % in type IV, 25% in type VII , 26% in type III and 44,5% in type VI (p< 0,001 for difference between types I, III and IV). Coxa vara was less frequent in patients with blue sclera (p=0,007). The mean neck-shaft angle was 99° (80°–110°) and the mean Hilgenreiner-epiphyseal angle was 68° (40°–90°). Twenty-five of coxa vara patients (thirty-six hips) had femoral rodding before diagnosis and six hips (all type III) had no history of rodding; however, 26 % of five hundred and thirty-one hips without coxa vara, had previous history of femoral rodding (p=0,004).

Abduction, extension and internal rotation were restricted in the hips with deformity. The abductors and extensors of the hips were weak in some that resulted in limping and Trendelenburg gait.

Special attention including clinical and radiological follow-up should be given to type III and VI patients particularly in the presence of previous femoral rodding.

The charts and X-rays of one hundred and fifty-nine consecutive children with Osteogenesis imperfecta (OI) were reviewed to evaluate the functional outcome of OI patients with upper limb deformities.

The patients were classified according to Sillence classification modified by Glorieux (Type I: 51, Type III: 33, Type IV: 54 and Type V: 21).

The functional outcome was measured using Pediatric Evaluation of Disability Inventory (PEDI) based on self care and mobility scores, and results were compared between the patients with upper limb deformities and the ones without upper limb deformities. There was significant negative correlation between the functional outcome and the total deformity angle.

Osteogenesis imperfecta is a genetic disorder of bone fragility. There are also some angular deformities of upper and lower limbs secondary to fracture and abnormal structure of bones in many OI patients depending on the severity of their condition.

Corrective surgeries to the lower extremities are established interventions and used extensively but surgical correction of upper limb deformities is less frequent.

The purpose of this study was to measure the severity of upper limb deformities in children with OI and the child’s functional level in order to answer the question: “Do upper limb deformities significantly affect function and therefore require surgical intervention?”

Upper limb deformities were measured and classified using AP and lateral Xrays of the arms and forearms. The site and direction of deformities were recorded. Total deformity angle was calculated as the sum of right and left arm and forearm deformity angles. Upper limb deformities were classified into four groups according to the severity of deformity angles.

The mean self care scores of PEDI were significantly low only in the group with severe and bilateral deformities but mobility scores were dramatically decreased in both the moderate and severe deformity groups.

Deformities of the upper limbs in OI limit not only mobility but also self care functions. Therefore they require more attention and it may be necessary to broaden the indications for surgery.