A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1)

Exclusion Criteria

• •Lack of documentation for a diagnosis of NF1
• •Tibial fracture without evidence of pseudarthrosis or tibial dysplasia
• •Tibial dysplasia/bowing without fracture or pseudarthrosis
• •Plexiform neurofibroma of any size, or nodular neurofibroma of \> 3 cm diameter involving the ipsilateral leg, including the hip
• •If presence of plexiform is suspected but not certain on physical exam, MRI of the leg may be indicated to rule this out.
• •History of MPNST (malignant peripheral nerve sheath tumor) or any malignancy other than asymptomatic and stable optic nerve glioma
• •Optic nerve glioma that has resulted in precocious puberty or visual impairment of any degree
• •Visual impairment from any cause
• •Precocious puberty from any cause
• •Hypertension other than mild essential hypertension controlled with medication
• •Metastatic disease of any kind
• •Inadequate neurovascular status in the involved limb that may jeopardize healing
• •Active or known prior infection at the pseudarthrosis site
• •Active systemic infection
• •Other injury or condition that prevents ambulation or completion of study assessments
• •Two or more prior surgeries for tibial pseudarthrosis
• •Bilateral tibial dysplasia
• •Selection of a surgical approach that does not include prescribed surgical intervention, which must include removal of pseudarthrosis tissue, placement of an intramedullary rod using the Williams approach, and autogenous bone graft from the iliac crest distributed at the osteotomy site
• •Normal ipsilateral fibula without planned fibular osteotomy at time of surgery
• •Allergy to bone morphogenetic protein
• •Allergy to bovine collagen products
• •Positive antibody titers to BMP-2, bovine collagen, or BMP-2 neutralizing antibodies prior to surgery
• •History of using any of the following medications, regardless of dose, for at least 1 month, within 3 months of enrollment: Anabolic agents, Glucocorticoids (does not include inhaled glucocorticoids), Growth hormone, Parathyroid hormone (PTH)
• •Need for postoperative medications that could interfere with bone healing of the implant, such as steroids, (but not including low-dose aspirin or routine perioperative anti-inflammatory drugs)
• •Untreated endocrine abnormality, such as hypothyroidism, parathyroid hormone disorder
• •Severe Vitamin D deficiency with serum 25-OH (hydroxy) Vitamin D \< 10 ng/ml (25 nmol/l) Patients with Vitamin D levels \< 10 ng/ml may be treated with Vitamin D and reconsidered for enrollment when levels are sufficient
• •Females who are sexually active without use of effective contraception
• •Females who are pregnant or breastfeeding