Efficacy of denosumab therapy for neurofibromatosis type I with osteoporosis and history of fractures: a case report

Masashi Uehara,1 Yukio Nakamura,1 Jun Takahashi,1 Mikio Kamimura,2 Fumihiro Isobe,1 Tomomi Yamaguchi,3,4 Tomoki Kosho,3,4 Shigeharu Uchiyama,1,5 Takako Suzuki,1 Hiroyuki Kato1 1Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi, Matsumoto, Japan; 2Center for Osteoporosis and Spinal Disorders, Kamimura Orthopedic Clinic, Kotobuki, Matsumoto, Japan; 3Department of Medical Genetics, Shinshu University School of Medicine, Asahi, Matsumoto, Japan; 4Center for Medical Genetics, Shinshu University Hospital, Asahi, Matsumoto, Japan; 5Department of Orthopedic Surgery, Okaya City Hospital, Honmachi, Okaya, Japan Background: The natural history and pathogenesis of the skeletal abnormalities found in neurofibromatosis type 1 (NF1) are poorly understood, and the therapeutic options for these manifestations remain limited. This report first describes the clinical outcomes of denosumab treatment for a patient with NF1 suffering from osteoporosis. Methods: We enrolled a patient with NF1 under denosumab treatment for osteoporosis, prior fractures, and no improvement in bone mineral density (BMD) over 3 years of alendronate therapy. BMD was monitored by dual-energy X-ray absorptiometry. Tested laboratory data included bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, tartrate-resistant acid phosphatase 5b, 1-alpha, 25-dihydroxyvitamin D3, and parathyroid hormone. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of treatment. Case presentation: During 2 years of denosumab therapy for osteoporosis in a 58-year-old female NF1 patient with prior fractures, BMD increased by 6.5% in the lumbar spine and 10.6% in the total hips, and bone turnover markers were notably improved. No fractures occurred during the latter half of treatment. Conclusion: Denosumab represents an effective treatment option for osteoporosis in NF1 patients. Keywords: denosumab, fracture, neurofibromatosis type 1, osteoporosis