Limb lengthening and correction of deformity in the lower limbs of children with osteogenesis imperfecta

We performed limb lengthening and correction of deformity of nine long bones of the lower limb in six children (mean age, 14.7 years) with osteogenesis imperfecta (OI). All had femoral lengthening and three also had ipsilateral tibial lengthening. Angular deformities were corrected simultaneously. Five limb segments were treated using a monolateral external fixator and four with the Ilizarov frame. In three children, lengthening was done over previously inserted femoral intramedullary rods. The mean lengthening achieved was 6.26 cm (mean healing index, 33.25 days/cm). Significant complications included one deep infection, one fracture of the femur and one anterior angulation deformity of the tibia. The abnormal bone of OI tolerated the external fixators throughout the period of lengthening without any episodes of migration of wires or pins through the soft bone. The regenerate bone formed within the time which is normally expected in limb-lengthening procedures performed for other conditions. We conclude that despite the abnormal bone characteristics, distraction osteogenesis to correct limb-length discrepancy and angular deformity can be performed safely in children with OI.     

Treatment of children with osteogenesis imperfecta

Children with moderate to severe forms of osteogenesis imperfecta (OI) require adequate physiotherapy, rehabilitation and orthopedic surgery. Supportive treatment with bisphosphonates can improve the effects of these nonmedicinal treatment modalities. Benefits of bisphosphonate treatment include decreased pain, lower fracture incidence, and better mobility. Among the various bisphosphonates, intravenous pamidronate has been studied in most detail. However, the optimal treatment regimen and the long-term consequences of pamidronate treatment in children are currently unknown. Given these uncertainties, treatment with bisphosphonates during growth should be reserved for patients who have significant clinical problems, such as vertebral compression fractures or long-bone deformities. Medical therapies other than bisphosphonates play a minor role at present. Gene-based therapy currently remains in the realm of preclinical research.     

Osteogenesis imperfecta--operative treatment on lower extremities in children with osteogenesis imperfecta]

The group of 141 children with osteogenesis imperfecta was treated in Orthopaedic Department of the University Children Hospital in Krakow, Poland. In 77 (54.6%) children from this group, we operated on lower extremities. Prophylactic operations, that were intramedullary Rush rodding, we performed in 19 cases (14 femurs and 11 tibias). Sofield-Millar procedures we performed in 58 children. We operated 321 times - there are 4 operations on average in one child. Average follow-up period was 6.7 years. We operated 473 long bones: 234 femurs and 239 tibias. We did 479 osteotomies. First operations were done at the age of 9 years on average (1.5-21 years). Further operations, 3 in each patient on average, we performed in period 37 months from one to another on tibias and 49 months on femurs. In all operated children we achieved full axis correction and their activity after operation improved. In order to assess that, we used the Bleck scale. In general, before operation, 54 (70%) children did not walk, and, in contrast, after operations 53 (69%) started walking. Operative treatment of the lower extremities in children with osteogenesis imperfecta improves their clinical physical abilities, quality of life and allows increase in activities.     

Modern approach to children with osteogenesis imperfecta

Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types have been described ranging from mild disease to a lethal form. In a large number of cases, mutations in one of the two genes encoding type I collagen have been found. In forms recently described (types V, VI, VII), such mutations have been excluded. In two other forms, (Bruck, and osteoporosis - pseudoglioma syndromes) defects in other proteins have been characterized. In OI, bone fragility stems from: decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). Histologic studies have shown that increased bone turnover is the rule in OI bone. This justifies using bisphosphonates in order to reduce osteoclast mediated bone resorption. Initial results are encouraging. Cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and level of ambulation, with minimal side effects. Effects on bone include increase in size of vertebral bodies and thickening of cortical bone. These results allow for more efficacious corrective surgery using intramedullary rodding of the long bones and paravertegral instrumentation. Specific occupational and physiotherapy programs are integral parts of the treatment protocol. This multidisciplinary approach will prevail until strategies aiming at the correction of the basic defect(s) will have come to fruition.     

Olecranon apophysis fractures in children with osteogenesis imperfecta revisited

The authors reviewed 17 fractures of the olecranon apophysis in 10 children with mild osteogenesis imperfecta (OI). Seven of the 10 patients sustained the same injury to the opposite extremity 1 to 70 months (mean 15.1) after their initial fracture. Four fractures were initially treated by cast immobilization alone. Two of these eventually required operative treatment because of refracture or late displacement. In all, 15 fractures were treated operatively. All had healed at the time the cast was removed; however, two refractured. At latest follow-up (mean 53 months), no patient reported pain or limited function. Children with OI may be prone to this injury. Cast immobilization with careful follow-up may be used for minimally displaced fractures, but operative treatment is recommended for displaced fractures. The high rate of bilateral injury (70%) suggests that children with OI who sustain this fracture should be counseled regarding the risk of injury to the opposite extremity.     

Efficacy of oral alendronate in children with osteogenesis imperfecta

The purpose of this study was to investigate the efficacy of oral alendronate for children with osteogenesis imperfecta. Nine boys and seven girls of average age 9.5 years were given oral alendronate for an average of 4 years. Fracture frequency decreased, and in more than half of the patients the ambulatory/mobility status improved. Bone mineral density improved significantly, and restoration of collapsed vertebral bodies was observed. Urinary excretion of calcium and a bone resorption marker decreased significantly. Iliac crest physis biopsy showed an expanded primary spongiosa area with numerous multinucleated cells. This study reveals that oral alendronate caused biochemical, radiologic, and histologic changes along with clinical improvement. Oral alendronate treatment, which is convenient for the school-age group, was found to be a tolerable and efficacious treatment for children with moderate or severe osteogenesis imperfecta.     

Increased postoperative febrile response in children with osteogenesis imperfecta

Children with osteogenesis imperfecta (OI) often require operative management to correct limb and spinal deformities. The authors reviewed the postoperative courses of 22 children with OI and compared the febrile responses of these children with those of matched subgroups within a published historical control ( 8). The subgroups were matched for perioperative conditions including the magnitude of surgery, estimated intraoperative blood loss, transfusion status, age, and gender. In all subgroups examined, the patients with OI exhibited a significant increase in total febrile response (TFR) compared with those in the historical control group. Within the OI group, TFR correlated with estimated blood loss and magnitude of surgery. There were three fever workups in the OI group with no evidence of infection found. In children with OI, fever workups and delays in hospital discharge should be avoided if physical signs of infection are absent.     

Operative management of long-bone of the upper limb in children with osteogenesis imperfecta]

The authors present their own experiences in operative treatment of the upper extremities in 24 children with osteogenesis imperfecta (oi) among 141 treated in years 1988-2002, in whom 34 operations were performed. In one subgroup were children presented with bone fractures: olecranon six, humerus shaft five, lateral condyle of the humerus one, humerus supracondylar fracture one. In second subgroup included children with upper limb deformities following procedures were performed: correction of cubitus varus three, humerus osteoclasis two, dislocated radial head resection, forearm correction thirteen. Results after operative management of fractures were very satisfying for all the children--proper fracture healing, axis of the bones was straight and a full mobility of the joints was achieved. In second group: partial deformation recurrence after cubitus varus correction, good result on the one side and lack of correction an the other after humerus osteoclasis; bad result in terms of elbow mobility after radial head resection; good results (despite complicated healing and wires migration) in terms of axis correction after forearm bones osteotomies. Surgery of the upper limbs in osteogenesis imperfecta is very challenging but it is worth to perform, as it improves function.     

Displaced olecranon apophyseal fractures in children with osteogenesis imperfecta

Three boys with mild osteogenesis imperfecta (OI) who sustained eight apophyseal avulsion fractures of the olecranon were compared with four normal boys with a unilateral apophyseal fracture. The children with OI were younger (11 years 7 months) than the normal children (14 years 3 months). All fractures were treated with tension band wiring (TBW). The contralateral elbow fractured 1 to 12 months later in the children with OI. Refractures occurred in two elbows, 6 to 16 months after the initial fracture and after TBW removal. One refracture presented late as a nonunion and was treated with bone grafting and plate fixation. None of the normal children experienced refracture after TBW removal. Good functional results and range of movement were achieved. Surgical treatment is recommended for all displaced fractures of the olecranon apophysis. There is a high risk of bilateral injury and a risk of refracture following removal of TBW in children with OI.     

Effect of alendronate therapy in children with osteogenesis imperfecta

OBJECTIVE: To evaluate the effect of orally administered alendronate in children with osteogenesis imperfecta. METHODS: Thirty children (16 girls and 14 boys; mean age at baseline 10.7 +/- 6.0 years; range 4-16 years) with osteogenesis imperfecta type I (n = 22), III (n = 2), or IV (n = 6) were treated with alendronate (5 mg/day in patients aged 4-10 years and 10 mg/day in children >10 years of age) for 3 years. RESULTS: After 1 year of alendronate therapy we observed a significant increase in areal and volumetric bone mineral density Z-scores (from -2.03 +/- 1.51 to -1.04 +/- 1.20, and from -1.91 +/- 1.38 to -1.33 +/- 1.30, respectively, P < 0.001), together with a significant drop in fracture rate (from 3.77 +/- 1.57 to 0.13 +/- 0.57, P < 0.000001), relief of chronic pain (from 3.83 +/- 1.44 days of pain/week to 0.73 +/- 0.77, P < 0.000001) and improvement in ambulation/mobility (P < 0.00002). After additional 2 years of therapy there were no further significant changes in these parameters, however the improvement was still remarkable in comparison to the pretreatment values (P < 0.003, P < 0.004, P < 0.000001, P < 0.000001 and P < 0.00001, respectively). A significant drop in markers of bone turnover (urinary deoxypyridinoline and serum osteocalcin) occurred after 3 years of therapy (P < 0.003 and 0.004, respectively). No adverse reactions were observed throughout the treatment. CONCLUSIONS: Alendronate has positively influenced quality of life in paediatric patients with osteogenesis imperfecta. Bisphosphonate therapy should be used only in the context of a well-defined protocol.     

Hyperplastic callus formation in patients with osteogenesis imperfecta]

The paper present a child with osteogenesis imperfecta in whom hyperplastic callus formation after a femur fracture and also after an osteotomy with intramedullary nailing of the tibia. An overview of available literature, with special attention given to differentiation with a malignant neoplasm is also presented.     

Bone healing in children with osteogenesis imperfecta treated with bisphosphonates

The long-term effects of bisphosphonate treatment in children with osteogenesis imperfecta (OI) are unknown. The aim of this study was to evaluate whether treatment with bisphosphonates interferes with the healing of fractures in a group of children with OI. Seven subjects (6 boys), aged 11.4 +/- 5.95 years, were followed for 2.5 +/- 0.84 years after the start of treatment with intravenous pamidronate (9 mg/kg/y) and/or oral alendronate (5 or 10 mg/d). Orthopaedic surgery of 24 bones was performed after 2.33 +/- 4.14 months of treatment, with 1.6 +/- 0.84 osteotomies per bone. Ambulation was started after 26.1 +/- 32.28 days. Reoperation was required in 8% of the bones due to fracture below primary fixation. Pseudoarthrosis was seen in one fracture, an osteotomy of the proximal femur (14% of the patients, as expected in an OI population). These results suggest that treatment with bisphosphonates at the administered doses does not interfere with fracture healing. Larger and longer studies are warranted.     

Limb lengthening with simultaneous correction of deformities]

In congenital malformation of the limbs the shortening of the extremity appears frequently together with its deformity. With Ilizarov's apparatus the limb may be lengthened simultaneously with the correction of the deformity. In spite of the fact that the use of the apparatus is rather complicated and complications are frequent, in 75 cases out of 102 excellent, in 23 good results were achieved. The various indications and results are demonstrated in 7 cases.     

Osteogenesis imperfecta--upper limb in osteogenesis imperfecta]

The authors of this paper discuss upper extremity in children with osteogenesis imperfecta: fractures frequency, presence of the deformity, radiological data as well as ability to use the limb. Fractures of the upper extremity and shoulder ring occurred in 93 (66%) among 141 children with oi that were treated in the ward in years 1988-2002. Most of the fractures occurred in children with type III oi in Sillence classification, this was a group were deformities appeared most frequently. Generally, deformities were found in 33% of the children with oi. Typical arm deformity was posterior bending, in forearm dorsal bending. Varus elbow occurred often (11%). We found in the x-rays capitis radius dislocation (3.5%), interosseus membrane ossification (2.1%), pseudoarthrosis of the forearm bones (2.1%). The causes of the deformities and opportunities to prevent them were discussed.     

Limb lengthening in children and osteogenesis using the technics of Wagner and Ilizarov and their modifications

Different methods of lower limb lengthening are reviewed, related to delays in strengthening and type of callus: Wagner's technique (5 cases), decortication 3 weeks before osteotomy (1 case), and Ilizarov's technique (10 cases on 8 tibiae and 6 femurs). In 5 cases, decortication with osteotomy-closure and waiting 2 weeks before beginning lengthening, was performed. This was carried out at 1 mm/day. The type of fixator is unimportant. This technique allows a restitution of the tubular bone structure in 3 or 4 months in a periosteo-cortico-medullary callus.     

Osteogenesis imperfecta--lower limb in osteogenesis imperfecta]

The author of this paper asses lower extremity in 141 children with osteogenesis imperfecta, treated in University Children Hospital in Krakow in years 1988-2002: number of fractures, presence of the deformation, radiological findings, possibility of walking. Only 3 from this group did not suffer from lower extremity long bone fractures. In remaining patients, the number of fractures was 4 on average with type I and IV, and 46 fractures in children with type III osteogenesis imperfecta in each patient. Perinatal fractures appeared in 26 children with type II or III oi. In remaining, first fracture happened at the age of 23 months on average. 21% of the children had never walked before, and the rest of them started pionisation at the age of 20 months on average. Lower extremities deformations appeared in 113 children (80%). We assessed typical deformity pattern, based on clinical and radiological findings: varisation of femur and antecurvation of the tibia. The movement limitations in hips or knees was found in 29 children. Radiological changes in growth cartilage, so-called "popcorn calcification" were found in 15 children with type III of osteogenesis imperfecta.     

Static and dynamic bone histomorphometry in children with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass. Four clinical types are commonly distinguished. Schematically, type I is the mildest phenotype, type II is usually lethal, type III is the most severe form compatible with postnatal survival, and type IV is moderately severe. Although mutations affecting collagen type I are responsible for the disease in most patients, the mechanisms by which the genetic defects cause abnormal bone development have not been well characterized. Therefore, we evaluated quantitative static and dynamic histomorphometric parameters in tetracycline-labeled iliac bone biopsies from 70 children, aged 1.5 to 13.5 years, with OI types I (n = 32), III (n = 11), and IV (n = 27). Results were compared with those of 27 age-matched controls without metabolic bone disease. Biopsy core width, cortical width, and cancellous bone volume were clearly decreased in all OI types. Decreased cancellous bone volume was due to a 41%–57% reduction in trabecular number and a 15%–27% lower trabecular thickness. Regression analyses revealed that trabecular number did not vary with age in either controls or OI patients, indicating that no trabecular loss occurred. The annual increase in trabecular thickness was 5.8 μm in controls and 3.6 μm in type I OI, whereas no trabecular thickening was evident in type III and IV OI. Wall thickness, which reflects the amount of bone formed during a remodeling cycle, was decreased by 14% in a subgroup of 17 type I OI patients, but was not determined in the other OI types. The remodeling balance was less positive in type I OI than in controls, and probably close to zero in types III and IV. Surface-based parameters of bone remodeling were increased in all OI types, indicating increased recruitment of remodeling units. No defect in matrix mineralization was found. In conclusion, there was evidence of defects in all three mechanisms, which normally lead to an increase in bone mass during childhood; that is, modeling of external bone size and shape, production of secondary trabeculae by endochondral ossification, and thickening of secondary trabeculae by remodeling. Thus, OI might be regarded as a disease in which a single genetic defect in the osteoblast interferes with multiple mechanisms that normally ensure adaptation of the skeleton to the increasing mechanical needs during growth.