Generation and activity of equine osteoclasts in vitro: effects of the bisphosphonate pamidronate (APD)

Abstract

Equine osteoclast-like cells (ocl s) were generated from the bone marrow (bm) of two ponies and one horse in the presence of rankl, the receptor activator of NFκB ligand and macrophage colony-stimulating factor (m-csf). The phenotype of these cells was confirmed by demonstration of characteristics typical of osteoclasts (oc s) including: the expression of tartrate-resistant acid phosphatase (trap), the vitronectin receptor (vnr) and the calcitonin receptor (ctr), the demonstration of responsiveness to calcitonin (ct) and the ability to form resorption lacunae on ivory slices and calcium phosphate films. The bisphosphonate pamidronate (apd) dose-dependently inhibited resorption of calcium phosphate films by equine ocl s with an IC50 of 5·8×10−7M in one horse. apd also dose-dependently inhibited the number ofocl s present in bm cultures after 7 days. However, this effect is most likely attributable to increasedocl death rather than decreased ocl formation. Paradoxically, apd appeared to cause an early, transient, increase in ocl formation in bm cultures, however, this effect was reversed after 7 days. These preliminary in vitro data support the potential use of apd in clinical conditions characterised by increased bone turnover such as osteomyelitis, osteitis, septic osteoarthritis, navicular disease, cystic bone lesions and immobilisation-induced osteoporosis and provide useful information for future pharmacokinetic studies and clinical trials in vivo.