Congenital Pseudarthrosis of the Tibia

Congenital pseudarthrosis of the tibia is a rare condition in which the tibia is bowed (usually anterolaterally) at birth or in early childhood. It fractures spontaneously or after minor trauma, with failure of the fracture to heal and formation of a pseudarthrosis. It is among the most difficult orthopaedic problems of childhood.

Its incidence is about 1 in 140 000 to 250 000 live births. About 50 to 55% of patients have neurofibromatosis type 1, and 4 to 10% of children with neurofibromatosis type 1 develop it; some cases are associated with fibrous dysplasia, and the rest are idiopathic. The lesion is usually unilateral, in the distal third of the tibia, with the fibula often also involved.

The Crawford classification (anterolateral bowing) has four types:

• Type I (increased cortical density, with a normal medullary canal).
• Type II (increased density with a narrowed or obliterated canal).
• Type III (a cystic lesion).
• Type IV (a frank fracture or pseudarthrosis, with a narrow tapered end).

The Boyd classification uses time of onset and appearance.

Complications are nonunion, refracture (about 50% or more after union), limb length discrepancy, ankle valgus, stiffness, ankle and subtalar deformity, and amputation (about 10 to 30% overall).

Pathophysiology.

A band of thickened, abnormal periosteum and fibrous hamartoma tissue (rich in fibroblasts, with NF1 inactivation in the cells) surrounds the bone at the pseudarthrosis, constricts the tibia, impairs blood supply and bone formation, and raises osteoclast activity. Biallelic NF1 loss in the cells at the site (a second hit) is found in neurofibromatosis related cases. The constriction of the bone explains the failure of healing and the persistent poor bone.

Anterolateral bowing of the lower leg in a newborn or infant, before any fracture. A fracture happens in the first 2 years in most (often after minor trauma, or no trauma at all), with pain, swelling, deformity, abnormal motion, and failure to heal in a cast. Look for café-au-lait spots (6 or more, over 5 mm in children), axillary and inguinal freckling, neurofibromas, Lisch nodules and scoliosis.

Examine the limb for angulation, motion at the pseudarthrosis, limb length, ankle and knee, and the skin. Examine for the features of neurofibromatosis and take a family history.

• Radiographs of the whole tibia and fibula in two planes: anterolateral bowing with a narrowed, sclerotic, tapered segment (the "hourglass" or "sucked candy" appearance) at the junction of the middle and distal third.
• Cystic change or a fracture with tapered, rounded ends, and fibular involvement.
• MRI shows the abnormal periosteum and soft tissue and the extent of the pathological bone, and is used for surgical planning. Weight bearing long leg films for alignment and length.
• Clinical or genetic diagnosis of neurofibromatosis type 1 (NF1 testing); spinal MRI and ophthalmology review when relevant.
• Blood tests: calcium, phosphate and alkaline phosphatase to exclude metabolic bone disease; biopsy is not needed.

Differential diagnosis.

• Physiological anterior tibial bowing and fibular hemimelia.
• Osteofibrous dysplasia and fibrous dysplasia.
• Posteromedial tibial bowing (benign, corrects by itself).
• Osteogenesis imperfecta, rickets and infection.

The aim is bone union, normal alignment, and a functioning limb. Management should be in a paediatric limb reconstruction centre, and many children need several operations.

Prevention of fracture (before a pseudarthrosis, with bowing and Crawford type I to III). A total contact (clamshell) brace or knee-ankle-foot orthosis, worn full time until skeletal maturity to protect the tibia. Avoid surgery in a bowed tibia without a fracture, except for a prophylactic procedure in a few. Corrective osteotomy for the bowing is avoided because it often causes a fracture.

Fracture and pseudarthrosis (surgery, after the age of 3 to 5 years when possible).

• Excision of the abnormal periosteum and fibrous hamartoma, resection of the pseudarthrosis ends to bleeding bone, autologous bone grafting (iliac crest).
• Intramedullary rodding (a Williams or telescopic rod crossing the ankle, or an intramedullary nail), with or without a plate.
• This is the usual first line treatment, with union in 60 to 80%.
• Vascularised free fibular graft (usually the contralateral fibula) for large defects or failure of previous surgery, in children older than 4 to 5 years, with union in 70 to 90%.
• Circular external fixator (Ilizarov) with bone transport or compression distraction, used for failure, shortening and deformity.
• Biological adjuncts (off label): recombinant human bone morphogenetic protein 2 on an absorbable collagen sponge placed at the grafted site, with the dose set by the product kit volume at the surgeon's discretion.
• Avoid with infection, a tumour, an open physis at the site, and pregnancy; watch for heterotopic bone and swelling.
• Bisphosphonates and teriparatide are under investigation, and are not used outside specialist centres.
• Amputation (Syme or through knee) with prosthesis for repeated failure, severe shortening, a stiff painful foot, or family preference, with good functional results, and is not a failure of treatment.
• Ankle valgus: growth modulation or osteotomy after union. Limb length: lengthening or epiphysiodesis.

Operative antibiotic prophylaxis. Cefazolin 30 mg/kg to a maximum of 2 g intravenously (2 g in adolescents; 3 g when weight is 120 kg or over) within 60 minutes before incision as a single dose (repeat after 4 hours or blood loss over 1500 mL). With severe penicillin allergy, clindamycin 10 mg/kg (maximum 900 mg) intravenously or vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose.

Pin site care and infection (external fixation). Daily pin site cleaning with saline and dry dressing. For pin site infection, flucloxacillin 25 mg/kg orally every 6 hours (maximum 1 g a dose) on an empty stomach for 5 to 7 days (avoid with penicillin allergy and with a history of flucloxacillin cholestatic jaundice). Use clarithromycin 7.5 mg/kg orally every 12 hours (maximum 500 mg a dose) in penicillin allergy (check QT interval and interactions).

Analgesia.

• Children: paracetamol 15 mg/kg orally every 4 to 6 hours (maximum 75 mg/kg daily and not exceeding 4 g daily); avoid ibuprofen and other NSAIDs while union is awaited.
• After major surgery, oral morphine 0.1 to 0.2 mg/kg every 4 hours as needed for severe pain for up to 3 days (maximum 10 mg a dose); monitor sedation and respiration, and prescribe a laxative.

Monitoring. Radiographs every 4 to 6 weeks until union (usually 3 to 9 months), then every 3 to 6 months to maturity. Brace use after union until maturity (to reduce refracture). Limb length, ankle alignment, rod position, skin and neurological state at each visit. Annual NF1 review (blood pressure, scoliosis, eyes, learning, development).

Referral and escalation. Refer every child with anterolateral tibial bowing to paediatric orthopaedics at diagnosis, and a child with a fracture to a limb reconstruction centre. Urgent referral for a fracture in a bowed tibia, infection, neurovascular compromise, or failed union.

Special groups.

• Neurofibromatosis type 1: genetics and multidisciplinary follow up; scoliosis, hypertension and learning review.
• Failed union after several operations: discuss amputation early.
• Young children (under 3 years): brace and observe; delay surgery until older when possible.
• Families: long course; psychological and practical support.