Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1

Abstract

Neurofibromatosis type 1 is a genetic syndrome characterized by a wide variety of tumor and non-tumor manifestations. Bone-related issues, such as scoliosis, tibial dysplasia, and low bone mineral density, are a significant source of morbidity for this population with limited treatment options. Some of the challenges to developing such treatments include the lack of consensus regarding the optimal methods to assess bone health in neurofibromatosis type 1 and limited data regarding the natural history of these manifestations. In this review, the Functional Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration: (1) presents the available techniques for measuring overall bone health and metabolism in persons with neurofibromatosis type 1, (2) reviews data for use of each of these measures in the neurofibromatosis type 1 population, and (3) describes the strengths and limitations for each method as they might be used in clinical trials targeting neurofibromatosis type 1 bone manifestations. The Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration supports the development of a prospective, longitudinal natural history study focusing on the bone-related manifestations and relevant biomarkers of neurofibromatosis type 1. In addition, we suggest that the neurofibromatosis type 1 research community consider adding the less burdensome measurements of bone health as exploratory endpoints in ongoing or planned clinical trials for other neurofibromatosis type 1 manifestations to expand knowledge in the field.

Advancing neurofibromatosis and schwannomatosis clinical trial design: Consensus recommendations from the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration

“…9 When a single recommendation may be premature, REiNS also reviews state-of-the-art methodologies and their available evidence to provide guidance on options for clinical trial measures, as with this issue's review on potential endpoints to assess bone health in individuals with NF1. 10 And as best practices evolve over time, REiNS seeks to update its recommendations as needed. To this end, our biomarker working group has updated and expanded their 2016 recommendations for collecting and annotating biosamples in NF clinical trials.…”