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

The researchers developed equine osteoclast-like cells in a lab and tested the effects of a medicine called pamidronate (APD) on these cells, finding that the substance can inhibit their reproduction and resorption activities. The team’s findings suggest that pamidronate could be used for treating diseases associated with increased bone turnover in horses.

Development and Confirmation of Equine Osteoclast-Like Cells

The study commenced with the generation of equine osteoclast-like cells from the bone marrow of two ponies and one horse. The cells developed successfully in the presence of two essential elements:

• RANKL, the receptor activator of NF kappa B ligand: It plays a pivotal role in osteoclast differentiation and activation.
• Macrophage colony-stimulating factor (M-CSF): This promotes the survival, proliferation, and differentiation of osteoclast precursors.

To confirm the cells’ authenticity, the team observed the following osteoclast properties:

• The expression of tartrate-resistant acid phosphatase (TRAP): An enzyme that serves as a marker for osteoclasts.
• The expression of the vitronectin receptor (VNR) and the calcitonin receptor (CTR): These markers indicate osteoclast potential.
• Responsive to calcitonin: This hormone has significant effects on osteoclasts, inhibiting their activity.
• The ability to form resorption lacunae on ivory slices and calcium phosphate films, demonstrating the cells’ capacity to dissolve and absorb bone tissue.

The Influence of Pamidronate on Equine Osteoclast-Like Cells

The focus of the study was to observe the effects of the bisphosphonate pamidronate on these laboratory-created osteoclast-like cells. The researchers discovered that pamidronate:

• Inhibited the natural process of the cells absorbing calcium phosphate films. This inhibitive effect was dose-dependent, showing increased interruption of this process with an increase in the dosage of pamidronate.
• Decreased the number of osteoclast-like cells in bone marrow cultures after a week. The study suggests that this effect is primarily due to induced cell death rather than reduced formation of cells.
• Caused a temporary increase in the formation of osteoclast-like cells but reversed this effect after a week. This suggests a complex interaction between pamidronate and osteoclast activity.

Future Implications

The study’s findings provide preliminary support for the use of pamidronate in clinical conditions involving increased bone turnover, such as osteomyelitis, osteitis, septic osteoarthritis, navicular disease, cystic bone lesions, and immobilization-induced osteoporosis in horses. The information gained from this in vitro study should also be beneficial for the development of future pharmacokinetic studies and in vivo clinical trials.