Effect of naproxen on cancellous bone in ovariectomized rats

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Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) affect bone metabolism in vitro and in vivo. They delay but do not alter the outcome of healing processes in bone. In some bone loss models, they block bone resorption and slow the rate of loss. We studied the effect of naproxen, a potent NSAID, on cancellous bone of the proximal tibial metaphysis of 6-month-old adult female ovariectomized rats. Animals were ovariectomized, divided into groups, and fed standard diets differing only in naproxen content for 42 days. The rats of the groups ate 2.0, 5.5, 12.7, and 32 mg naproxen per kg body weight per day, respectively. Serum levels of naproxen were determined. Bone volume, mineralizing surface, osteoblast activity, osteoclast surface, and bone resorption rate were determined by bone histomorphometric techniques. The rats' dose-related serum naproxen levels ranged from 4 to 28 μg/ml. Naproxen inhibited up to 70% of the bone loss occurring after ovariectomy at a serum level of 4 μg/ml. We deduced that naproxen blocked bone resorption in ovariectomized rats by slowing osteoclast activity at all doses. In contrast, naproxen slowed bone formation only at serum levels > 20 μg/ml in ovariectomized rats. These findings may have clinical relevance in helping to prevent postmenopausal bone loss in women.