THE ANALGESIC DRUG BUPRENORPHINE INHIBITS OSTEOCLASTIC BONE-RESORPTION IN-VITRO, BUT IS PROINFLAMMATORY IN RAT ADJUVANT ARTHRITIS

We have examined the effect of the mu-opioid analgesic buprenorphine o n osteoclastic bone resorption in vitro and in the rat adjuvant arthri tis model. In the bone slice assay buprenorphine inhibited osteoclasti c bone resorption with an IC50 Of 1 mu M This effect was not mimicked by the mu-opioid agonist ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin and was not prevented by the mu-opioid antagonist naloxone. Since other agent s that inhibit osteoclastic bone resorption, such as bisphosphonates a nd calcitonin prevent bone erosion in the rat adjuvant arthritis model , we also examined the effect of buprenorphine in this model. Surprisi ngly, buprenorphine exacerbated inflammation measured by paw volume an d increased joint destruction assessed by X-ray scores, in the injecte d paws and particularly in the non-injected paws. These studies also s how that attempts to ameliorate animal suffering in this chronic model by using centrally acting analgesics such as buprenorphine may lead t o complications in interpreting screening results obtained with novel, potential anti-arthritic compounds.