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

Skeletal effects of neratinib treatment and Blautia luti supplementation in tibial trabecular bone of albino Wistar rats (#30)

Micaela Quinn 1 , Helen Tsangari 1 , Bonnie Williams 1 , Joanne Bowen 1 , Tania Crotti 1
  1. School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia

Background

Cancer treatment-induced bone loss (CTIBL) is a longer-term consequence of chemotherapy and endocrine therapy1,2. However, skeletal effects of neratinib, a tyrosine kinase inhibitor approved for breast cancer3, remain unknown. Preclinical evidence of interactions between the gut microbiome (GM) and bone4, and protective effects of GM modulation in bone disorders5, suggests probiotic supplementation may mitigate CTIBL. This study aimed to determine the effect of neratinib treatment and probiotic supplementation with Blautia luti on tibial trabecular bone microarchitecture and histomorphometry in albino Wistar (AW) rats.

Methodology

Female AW rats (n=40) were randomly allocated to; vehicle control (VC; 0.5% hydroxypropyl methylcellulose; n=4), neratinib (N; 50mg/kg; n=4), Blautia luti (B; 107 CFU; n=8), neratinib and Blautia luti pre-treatment (NBp; n= 8), neratinib and Blautia luti pre- and post-treatment (NBppo; n=8), and neratinib and Blautia luti post-treatment (NBpo; n=8). Dosing schedules of neratinib and Blautia luti for each group are shown in figure 1. Tibia were scanned ex-vivo by micro-computed tomography and bone structural indices assessed; bone volume (BV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). Serial decalcified sections were stained with hematoxylin and eosin, and tartrate-resistant acid phosphatase for histomorphometric analysis of osteoblasts and osteoclasts respectively.

Results

BV (p=0.017), Tb.N (p=0.003) and Tb.Th (p=0.000) significantly decreased in N compared with VC; consistent with increased osteoclast (p=0.163) and significantly decreased osteoblast (p=0.014) numbers in N rats. BV increased in B compared to VC rats (p=0.605), whilst Blautia luti supplementation significantly increased Tb.Th in NBp (p=0.013), NBppo (p=0.011) and NBpo (p=0.001) rats, compared to N alone.

Conclusion

Loss of BV, increased osteoclast and decreased osteoblast numbers in the tibia indicates neratinib's negative effect on bone microarchitecture. Although Blautia luti alone caused an increase in BV, supplementation failed to provide a significant mitigative effect on neratinib-induced bone loss.

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