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Clodronate Does Not Alter Bone Remodeling in Young Horses
Author(s) -
Richbourg Heather A,
Mitchell Colin F,
McNulty Margaret A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.902.25
Subject(s) - bone remodeling , medicine , osteoclast , horse , lameness , biopsy , bisphosphonate , pathology , urology , surgery , osteoporosis , paleontology , receptor , biology
The bisphosphonate drug clodronate has been shown to treat diseases of abnormal bone remodeling (e.g., navicular disease) in horses, with the goal of systemically reducing osteoclast‐mediated bone loss. Recently FDA‐approved for use in horses, clinical trials have determined its effectiveness in reducing lameness in adult horses by 60 days post treatment. However, despite prolific clinical use, studies have not identified a systemic effect on normal bone remodeling in the horse, either in adults or young horses that are still undergoing tremendous bone growth and remodeling. Therefore, this study aimed to evaluate effects of clodronate on normal bone remodeling in young horses. In addition, the effect on bone healing was assessed using a bone defect model. Two‐ and three‐dimensional quantitative morphological evaluations of bone biopsies of the tuber coxae were utilized. We anticipated increases in bone volume, and decreases in bone remodeling and osteoclast number and function due to treatment compared to saline. Baseline biopsies were collected on Day 0 from nine horses aged 2–4 years old. Following the initial biopsy, horses were randomly assigned to a treatment group (control n=5, treated n=4) and treatment was administered intravenously. Oxytetracycline was administered at Day 47 and 57 as a fluorescent bone label. On Day 60, an additional bone biopsy was collected from the contralateral side, as well as a re‐biopsy of the initial side as a model of bone healing. Biopsies were evaluated via both micro‐computed tomography (microCT) and histomorphometry. Statistical analyses included paired and unpaired student's t‐tests. Horses tolerated surgery well with no post‐surgical complications. All biopsies were adequate for both microCT and histological evaluations. There was no significant effect of clodronate treatment on bone volume or trabecular structure parameters as evaluated by microCT. Clodronate did not significantly alter bone remodeling parameters after 60 days as evaluated by dynamic histomorphometry. Overall, clodronate does not appear to negatively affect normal bone structure and remodeling after 60 days in young horses. In addition, it appears that clodronate has little impact on bone remodeling short term, potentially due to its' relatively‐low potency compared to other bisphosphonates available. These data have significant clinical impact regarding the effectiveness of clodronate to treat diseases of bone remodeling in horses in general, and demonstrates that there is no negative effect of clodronate administration on normal remodeling processes in young horses. Support or Funding Information Louisiana State University Charles V. Cusimano Equine Health Studies Program Grant