Poster Presentation ANZBMS-MEPSA-ANZORS 2022

Methotrexate and diet's effect on trabecular long bone in a rat model of breast cancer (#242)

Bailey Deverell 1 , Helen Tsangari 1 , Hannah Wardill 1 , Bonnie Williams 1 , Joanne Bowen 1 , Tania Crotti 1
  1. School of Biomedicine, The University of Adelaide, Adelaide, SA

INTRODUCTION

In advanced breast cancer, chemotherapies, such as methotrexate (MTX), are detrimental to the gut microbiota [1] and bone microarchitecture, increasing fracture risk [2]. Interplay between the gastrointestinal and skeletal systems, termed the “gut-bone axis”, may reciprocally influence chemotherapy [3].

Given 90% of individuals treated for breast cancer with chemotherapy survive five-years post-diagnosis, understanding the effects of chemotherapies on bone is essential [4]. Diets that support gut health during chemotherapy may also be effective at mitigating bone loss. Thus, this study aimed to determine the effect of MTX +/- a hydrolysed protein (HP) diet on trabecular bone in long bones of a rat breast cancer model.

METHODS

Female dark agouti rats (n=32) were subcutaneously inoculated with mammary adenocarcinoma cells [5] then allocated to; vehicle control (VC; n=8), HP diet only (NT; n=8), MTX only (MTX; 2 mg/kg intramuscularly; n=8), and HP diet and MTX combination (NTMTX; n=8).

Rodents were given standard or HP diet (Nutricia Research) starting on day -14 then treated on days 0 and 1 with either MTX or vehicle and euthanised on day 4. Long bones were scanned via micro-CT and assessed for; trabecular thickness (Tb.Th.), trabecular number (Tb.N.), trabecular spacing (Tb.S.), bone volume (BV), and percent bone volume (BV/TV%). 

RESULTS

A significant increase in Tb.Th. (p=0.0101), Tb.N. (p=0.0198), and BV/TV% (p=0.0054) was observed in NT rat tibia. No significant differences were observed in MTX and NTMTX rat tibia or femur.

6296ce08e6504-Figure+1+Abstract.png 

Figure 1: (A) High resolution 3D micro-CT models of right tibia; (i) VC (ii) NT (iii) MTX and (iv) NTMTX. (B) Histomorphometric analysis of right tibia trabecular microarchitecture by high resolution micro-CT. (i) Tb.Th. (ii) Tb.N. (iii) Tb.S. (iv) BV (v) BV/TV%.

CONCLUSION

Results indicate that HP diet increases bone volume, which may have a protective effect against MTX-induced bone loss.

  1. Rodrigues FC, et al. (2012) J Med Food 15, 664-70.
  2. Hain BA, et al. (2019). JCSM Rapid Commun.
  3. Sjogren K, et al. (2012). J Bone Miner Res 27, 1357-67.
  4. Youlden DR, et al. (2019). J Adolesc Young Adult Oncol.
  5. Gibson R, et al. (2018) Chemotherapy 63, 284–292