Amnion vs Bisphosphonates

Much has been written lately about the use of bisphosphonates in horses, particularly in young racehorses.  In a recent article written by Ed Krane, Ph.D. on February 26, 2019, for DVM360, Dr. Krane speaks to several veterinarians about bisphosphonates outlining the mechanisms of action and the clinical use in racing.  The article also looks at the challenges in using these products on younger horses, particularly racehorses and the possible degeneration of bone that could occur.  Also in fairness, Heather A. Richbourg on April 1, 2017, published in FASEB Journal an article to the contrary that bisphosphonates did not alter bone remodeling in young horses.

Due to the recent breakdowns at Santa Anita, we have been asked about the differences between Amnion and Bisphosphonates like tiludronate disodium and clodronate disodium as related to bone growth. Amnion regenerates and remodels bone very differently from bisphosphonates because amnion is the natural material that grew the bones to begin with.  Amnion is the material and membrane that surround the fetus during pregnancy and is responsible for most of the material required to grow the fetus.  Rich in collagen, lamin, proteoglycans, cytokines, growth factors, and hyaluronic acid, amnion promotes angiogenesis through neo-vascularity of the tissue and upregulating progenitor cells to the damaged area.  Additionally, the introduction of amnion responds to the inflammation by stimulating cellular signaling through MicroRNA and exosomes encouraging osteoblast activity to support osteogenesis.

In a study completed at the Autonomous University of Juarez in 2017, Amnion was used to stimulate bone growth in rams with a 1 cm side perforation of the tibial crest.  As a result, substantial bone regeneration occurred with over 70% of the bone being regenerated in the first 60 days.

This is very different from the mechanism of action by which bisphosphonates respond.  According to Daniel Ross’s article published October 3, 2017, bisphosphonates work by suppressing the osteoclast activity responsible for remodeling and removing damaged or old bone tissue.  Osteoclasts are the cells responsible for the absorption of that material thereby preventing the bone from being lessened in any way.  Osteoblasts, the cells that build bone, are able to proliferate in building new bone over the top of existing dead tissue which is the reason bisphosphonates work so well in various lameness indications such as navicular.     

Below are some other comparisons between the two technologies:

Bisphosphonates

• Inhibits osteoclast activity thereby prevents bone resorption
• Does not stimulate osteogenesis
• Mechanism of action is osteoclast suppression
• Designed by human beings
• Drug used to prevent bone loss
• Not safe in all instances

Based on the above research, veterinarians are using AniCell’s AniMatrX and StemWrap lines prophylactically on horses during training in order to strengthen their bones naturally by improving blood flow to the legs and thereby decreasing healing time of training. 

1. Bisphosphonates: A dense issue in equine veterinary care; Ed Kane, Ph.D, February 26, 2019  http://www.dvm360.com/bisphosphonates-dense-issue-equine-veterinary-care

2. The bone disease treatment drugs that may be putting young horses at risk; Daniel Ross, October 3, 2017 https://www.thoroughbredracing.com/articles/bone-disease-treatment-drugs-may-be-putting-young-horses-risk/

3. Isolation and Characterization of Equine Amniotic Membrane-Derived Mesenchymal Stem Cells; Min-Soo Seo, et-al, June 2013 https://www.ncbi.nlm.nih.gov/labs/pubmed/23388430-isolation-and-characterization-of-equine-amniotic-membrane-derived-mesenchymal-stem-cells/

4. Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells; Natasha Topoluk, et-al, September 2017 https://www.ncbi.nlm.nih.gov/labs/pubmed/28541092-amniotic-mesenchymal-stromal-cells-exhibit-preferential-osteogenic-and-chondrogenic-differentiation-and-enhanced-matrix-production-compared-with-adipose-mesenchymal-stromal-cells/?from_term=amniotic+cells+and+osteogenesis&from_pos=2

5. Acellular preserved or morselized liquid amnion accelerated bone regeneration in rams;  Rivera-Barreno R, et-al, October 2017 https://anicellbiotech.com/stemwrap-for-bone-regeneration-studied-autonomous-university-of-city-juarez/

6. After a rash of horse deaths, Santa Anita Park bans race day medications; Eliott C. McLaughlin & Stella Chan, CNN, March 14, 2019 https://www.cnn.com/2019/03/14/us/santa-anita-park-22-horse-dies/index.html

7. Clodronate Does Not Alter Bone Remodeling in Young Horses; Heather A. Richbourg, Colin F Mitchell, and Margaret A. McNulty, April 1 2017 https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.902.25

The purpose of this article is not to in any way discredit the effectiveness of bisphosphonates for FDA-approved diagnosis, but to highlight the benefits of amnion, its mechanism of action, and its known safety for a wide-spectrum of indications.