Efficacy of denosumab therapy for neurofibromatosis type 1 with osteoporosis and history of fractures: a case report

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Abstract

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 D ₃, 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.

Most cited references 13

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Bisphosphonates for osteoporosis--where do we go from here?

Jia Guo, Timothy G. Benson, Vance M. Whitaker … (2012)

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Generalized metabolic bone disease in Neurofibromatosis type I.

Nicola Brunetti-Pierri, Stephen B. Doty, M. John Hicks … (2008)

Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1) but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical and pathological level the bone involvement in NF1 patients. Using dual energy X-ray absorptiometry (DXA) we analyzed bone status in 73 unselected NF1 subjects, 26 males and 47 females, mainly children and adolescents (mean age: 16.6 years). In a subgroup of subjects with low bone mass, we measured indices of calcium-phosphate metabolism, bone turnover, and bone density before and after vitamin D and calcium treatment. We found statistically significant and generalized reduction in bone mass with the mean lumbar bone mineral density (BMD) z-score being -1.38+/-1.05 (CI 95% -1.62 to -1.13), and whole body bone mineral content (BMC) z-score -0.61+/-1.19 (CI 95% -0.94 to -0.29), both significantly reduced compared to normal controls (p<.001). PTH was moderately elevated and after 4 months of supplemental therapy with calcium and vitamin D, it decreased to the normal range. However, BMD z-scores did not significantly improve after 2 years of follow-up. Histological analysis of bone samples from NF1 patients revealed substantial alteration of bone microarchitecture due mainly to reduced trabecular bone. Our observations are consistent with a generalized bone metabolic defect due to loss of the function of neurofibromin. Early identification of patients with osteoporosis may permit more timely and aggressive treatments to prevent the likely substantial morbidity associated with increased fracture risk later in life.

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Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1).

V Mautner, Annette M. Hartmann, P Kruse … (2009)

Patients with neurofibromatosis 1 (NF1) are shorter than expected and often have low bone mineral density (BMD), but the pathogenesis of these bony problems is poorly understood. We performed an exploratory study of BMD, 18 laboratory measures of bone metabolism, and fracture history in 72 adult NF1 patients. Eight of the 18 clinical biochemical measures of bone health had at least 10% of NF1 patients outside the standard reference range. Serum 25-hydroxy-vitamin D concentrations were low in 56% of the NF1 patients, serum parathyroid hormone (PTH) concentrations were high in 34%, and urine deoxypyridinoline cross-link concentrations were high in 50%. Mean serum 25-hydroxy-vitamin D concentrations were significantly lower in people with NF1 than in season matched controls in both summer (p = 0.008) and winter (p<0.001). 36 (50%) of the 72 people with NF1 studied had BMD consistent with osteopenia, and 14 (19%) had BMD consistent with osteoporosis. High serum PTH concentration, high serum bone tartrate resistant acid phosphatase concentration, and high serum calcium concentration were associated with lower BMD among the NF1 patients. Males were more likely than females to have low BMD. The reported frequency of fractures in individuals with NF1 was much higher than in their unaffected siblings and spouses (p<0.001), and pathological fractures were reported only in NF1 patients. People with NF1 often have a generalised abnormality of bone metabolism. Further studies are needed to determine the biochemical and molecular basis of this abnormality.

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Author and article information

Journal

Journal ID (nlm-ta): Ther Clin Risk Manag

Journal ID (iso-abbrev): Ther Clin Risk Manag

Journal ID (publisher-id): Therapeutics and Clinical Risk Management

Title: Therapeutics and Clinical Risk Management

Publisher: Dove Medical Press

ISSN (Print): 1176-6336

ISSN (Electronic): 1178-203X

Publication date Collection: 2018

Publication date (Electronic): 16 July 2018

Volume: 14

Pages: 1243-1246

Affiliations

[1 ]Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi, Matsumoto, Japan, yxn14@ 123456aol.jp

[2 ]Center for Osteoporosis and Spinal Disorders, Kamimura Orthopedic Clinic, Kotobuki, Matsumoto, Japan

[3 ]Department of Medical Genetics, Shinshu University School of Medicine, Asahi, Matsumoto, Japan

[4 ]Center for Medical Genetics, Shinshu University Hospital, Asahi, Matsumoto, Japan

[5 ]Department of Orthopedic Surgery, Okaya City Hospital, Honmachi, Okaya, Japan

Author notes

Correspondence: Yukio Nakamura, Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan, Tel +81 26 337 2659, Fax +81 26 335 8844, Email yxn14@ 123456aol.jp

Article

Publisher ID: tcrm-14-1243

DOI: 10.2147/TCRM.S159668

PMC ID: 6052922

SO-VID: be4767cf-7db5-4a03-9508-13c03c93f2cf

License:

The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

Efficacy of denosumab therapy for neurofibromatosis type 1 with osteoporosis and history of fractures: a case report

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Abstract

Background

Methods

Case presentation

Conclusion

Most cited references 13

Bisphosphonates for osteoporosis--where do we go from here?

Generalized metabolic bone disease in Neurofibromatosis type I.

Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1).

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