Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective

Abstract

Osteoclasts are unique and vital bone cells involved in bone turnover. These cells are active throughout the individual’s life and play an intricate role in growth and remodeling. However, extra-label bisphosphonate use may impair osteoclast function, which could result in skeletal microdamage and impaired healing without commonly associated pain, affecting bone remodeling, fracture healing, and growth. These effects could be heightened when administered to growing and exercising animals. Bisphosphonates (BPs) are unevenly distributed in the skeleton; blood supply and bone turnover rate determine BPs uptake in bone. Currently, there is a critical gap in scientific knowledge surrounding the biological impacts of BP use in exercising animals under two years old. This may have significant welfare ramifications for growing and exercising equids. Therefore, future research should investigate the effects of these drugs on skeletally immature horses.

Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model

“…Bisphosphonates are one of the most common drugs used to treat and prevent bone resorption via osteoclast impairment [ 1 , 3 , 4 , 75 ]. However, the effects of bisphosphonates on immature skeletal development while undergoing exercise are largely unknown [ 24 , 25 , 30 , 32 , 33 ]. Therefore, we sought to determine the effects of a single or repeated i.m.…”

“…The effect of bisphosphonates in young, active humans and animals is poorly understood [21][22][23][24]. This knowledge gap is particularly significant given the use of bisphosphonates in juvenile, high-performance animals such as racehorses where bone growth and remodeling are active [24][25][26][27][28]. Growth and adaptation to exercise depend on normal osteoclastic activity [29].…”

“…Bisphosphonate effects have been assessed in different animal models [37][38][39][40][41][42] including sheep [25]. In comparison to other large animals such as bull calves, sheep can be more easily conditioned to forced exercise [43] and a relatively uniform population can be chosen from select herds with closed breeding practices [44].…”

Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives—A Review

“…In equine medicine, tiludronate was the first bisphosphonate to be approved. It mainly acts as an antiresorptive drug, reducing the ability of the osteoclasts to degrade the bone matrix, although antiinflammatory and analgesic properties mediated by other mechanisms are also recognized and consensual [124][125][126][127][128][129][130][131][132][133][134][135]. Tiludronate disodium (Tildren ® , Ceva Animal Health LLC, Lenexa, KS, USA) and clodronate disodium (Osphos ® , Dechra, Ltd., Staffordshire, UK) are the bisphosphonate drugs that are licensed for use in horses, with its label use on horses older than 4 years old.…”

Revisiting Resveratrol as an Osteoprotective Agent: Molecular Evidence from In Vivo and In Vitro Studies

“…Bisphosphonates are major pharmacological agents that suppress osteoclast function, hence reducing bone resorption and loss. They are commonly used in clinical practice to treat skeletal disorders including osteoporosis, Paget disease of bone, and multiple myeloma [89]. Long-term bisphosphonate treatment has been linked to pathologic conditions such as osteonecrosis of the jaw (BRONJ), which impairs the bone regeneration process [90].…”