Aims

Osteofibrous dysplasia (OFD) is a rare benign lesion predominantly affecting the tibia in children. Its potential link to adamantinoma has influenced management. This international case series reviews the presentation of OFD and management approaches to improve our understanding of OFD.

PURPOSE OF THE STUDY. To assess if prolonged use of Bisphosphonates in Osteogenesis Imperfecta alters the pattern of femoral fractures. Osteogenesis Imperfecta (OI) has been treated with Bisphosphonates for many years with some clear clinical benefits. In adult cohorts there are reports of a new pattern of atraumatic subtrochanteric fractures seen with Bisphosphonate treatment. SUMMARY OF METHODS. This study assesses the location of femoral fractures in a cohort of 176 OI patients treated with Bisphosphonates over a two year period and compares it to a historical control group of 45 managed prior to the advent of this specific treatment. SUMMARY OF RESULTS. review of the radiological digital archive identified 16 femoral fractures in this time period in the Bisphosphonate treated group. All but 2 were within 5cm of the lesser trochanter, and 50% within 3cm. In comparison, the historical group, composed of 26 femoral fractures had a more widespread fracture pattern with the most frequent location being the mid-diaphysis. Many of the sub-trochanteric fractures in the treatment group occurred with minimal trauma, and in some cases without any injury. CONCLUSION. It appears that concerns in the adult osteoporotic population treated with Bisphosphonates are mirrored in Osteogenesis Imperfecta. It is possible that the high bending moments in the proximal femur together with altered mechanical properties of cortical bone secondary to the use of this group of drugs, mediated by abnormal osteoclast and osteoblast function, increase the risk of this type of injury and warrants further investigation

Background. Unicameral bone cysts (UBCs) are difficult to treat and have a high recurrence rate. Their pathogenesis is unknown making targeted therapies difficult. Attributed causes include venous and interstitial fluid obstruction, oxygen free radicals, lysosomal enzymes, prostaglandins and genetic factors. Skeletal stem cells (SSCs) are osteoblast precursors critical to bone formation and cyst fluid may influence their growth, however the association between SSCs and cyst fluid has never been investigated. Aim. To investigate the effect of UBC fluid on SSC growth. Methods. Fluid was aspirated from a UBC in the proximal femur of a nine year old boy and centrifuged to isolate the acellular supernatant. SSCs were harvested from bone marrow of a haematologically normal adult and cultured with graded concentrations of cyst fluid in culture media (0,10,25,50%). Cell growth was assessed by alkaline phosphatase staining, and cytokine levels in the fluid were measured. Results. High levels of cytokines known to be chemo-attractive for cells of the of macrophage-monocyte lineage were found, including Macrophage Chemotactic Protein-1 (1853pg/ml), Monokine Induced by γ-interferon (656pg/ml), Macrophage Inflammatory Protein (MIP)-1α (401pg/ml) and MIP-1β (34pg/ml) suggesting a role of osteoclasts in UBC pathogenesis. Furthermore, SSC growth in vitro was reduced in cyst fluid in a concentration dependent manner. Conclusion. This is the first time altered SSC and osteoprogenitor function has been associated with the fluid of a UBC. A negative effect on osteogenesis was demonstrated, the precise mechanisms of which are under investigation, and macrophage-monocyte chemokines suggest high osteoclast activity. This study has indicated a role of the cyst fluid in limiting osteogenesis and bone turnover, which may explain the high failure rate for current interventions. More patients are needed to validate these findings

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair.

Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1^+/−) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection.

When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1^+/− mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07).

These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1.

Osteofibrous dysplasia is an unusual developmental condition of childhood, which almost exclusively affects the tibia. It is thought to follow a slowly progressive course and to stabilise after skeletal maturity. The possible link with adamantinoma is controversial and some authors believe that they are part of one histological process.

We retrospectively reviewed 16 patients who were diagnosed as having osteofibrous dysplasia initially or on the final histological examination. Their management was diverse, depending on the severity of symptoms and the extent of the lesion. Definitive (extraperiosteal) surgery was localised ‘shark-bite’ excision for small lesions in five patients. Extensive lesions were treated by segmental excision and fibular autograft in six patients, external fixation and bone transport in four and proximal tibial replacement in one. One patient who had a fibular autograft required further excision and bone transport for recurrence. Six initially underwent curettage and all had recurrence. There were no recurrences after localised extraperiosteal excision or bone transport. There were three confirmed cases of adamantinoma.

The relevant literature is reviewed. We recommend extraperiosteal excision in all cases of osteofibrous dysplasia, with segmental excision and reconstruction in more extensive lesions.

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of congenital pseudarthrosis of the tibia has been investigated in only one previous study, with promising results. The aim of this study was to determine whether rhBMP-2 might improve the outcome of this disorder. We reviewed the medical records of five patients with a mean age of 7.4 years (2.3 to 21) with congenital pseudarthrosis of the tibia who had been treated with rhBMP-2 and intramedullary rodding. Ilizarov external fixation was also used in four of these patients. Radiological union of the pseudarthrosis was evident in all of them at a mean of 3.5 months (3.2 to 4) post-operatively. The Ilizarov device was removed after a mean of 4.2 months (3.0 to 5.3). These results indicate that treatment of congenital pseudarthrosis of the tibia using rhBMP-2 in combination with intramedullary stabilisation and Ilizarov external fixation may improve the initial rate of union and reduce the time to union.

Further studies with more patients and longer follow-up are necessary to determine whether this surgial procedure may significantly enhance the outcome of congenital pseudarthrosis of the tibia, considering the refracture rate (two of five patients) in this small case series.