Oral Presentation 33rd ASM of the Australian & New Zealand Bone & Mineral Society 2023

Reversing high bone porosity in NF1 bone using dietary supplements (#48)

Aaron Schindeler 1 2 , Alexandra K O'Dononhue 1 , Lucinda R Lee 1 , Charlotte Lee 1 , Emily R Vasiljevski 1 , Craig F Munns 3 4 , David G Little 1
  1. Bioengineering & Molecular Medicine, The Children's Hospital at Westmead & the Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, NSW, Australia
  3. Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia
  4. Department of Endocrinology and Diabetes, Queensland Children’s Hospital, Brisbane, QLD, Australia

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder associated with tumour susceptibility, but it can also have profound effects on bone and muscle. In children, NF1 is associated with osteopenia and focal bone dysplasias. Studies of NF1 bone microarchitecture have revealed fundamental differences in bone density and cortical porosity. Our research has found that the muscle manifestations of NF1 – low muscle tone associated with aberrant metabolism and long-chain lipid accumulation – are responsive to dietary intervention with L-carnitine + medium-chain fatty acid (MCFA) supplemented chow. This study aimed to test whether this intervention could rescue the NF1 bone phenotype in mice.

Methods: N=70 female Nf1flox/flox:Prx1-Cre (Nf1Prx1-/-) NF1 limb-KO mice were given 8 weeks of standard chow or one of six modified diets altered to reduce long-chain fatty acid intake and/or improve lipid metabolism with L-carnitine supplementation. MicroCT analysis was performed on the cortical bone to look at standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae and larger open pores). Histological staining was used to further visualize these changes.

Results: Nf1Prx1-/- bones were found to have inferior properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. The high cortical bone porosity was significantly reduced via dietary interventions including L-carnitine + MCFA chow previously shown to improve muscle histology function. Dietary intervention also produced significant increases in cortical tissue mineral density and cortical thickness. A reduction in large cortical pores was further reflected by tissue histology.

Discussion: These data support the concept that lipid metabolism may have an important mechanistic effect on bone porosity and quality in NF1. Emerging interventions for NF1 muscle health may thus produce secondary benefits in bone.

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