Abstract:
Paget's disease involves overactivity of both osteoblasts and osteoclasts within affected bone tissue. It is unclear in which cells the causative lesion resides, but therapies have generally been antiosteoclastic (antiresorptive) because these are the only pharmaceuticals that have been available. There is tight coupling between osteoblasts and osteoclasts, so antiresorptive therapies lead to decreases in osteoclast activity within days, followed by similar declines in osteoblast activity after a period of 2-3 months. The most commonly used test for monitoring disease activity is serum total alkaline phosphatase, which is a measure of osteoblast activity, though serum procollagen type I N-terminal propeptide is more bone-specific. The treatment of Paget's disease is now virtually always with a potent bisphosphonate, typically intravenous zoledronate since this has the highest rates of biochemical response and the greatest response longevity.