THERAPEUTIC STRATEGY IN PAGETS-DISEASE OF BONE

Paget's disease of bone is a localized progressive disease, characteri zed by increased bone remodeling, bone hypertrophy, and abnormal bone structure, leading to pain and deformity, Disease complications involv e the bones, joints, and central nervous system, Short-term treatment objectives are to alleviate or suppress bone pain; the long-term aim i s for the prevention of complications caused by the slow disease progr ession in affected bones, The lifetime risk of complications depends o n life expectancy, location, and activity index of Paget's disease, Th e use of potent and safe new bisphosphonates (tiludronate, pamidronate , alendronate, risedronate, and others) represents a major advance for the management of the condition: these compounds permit normalization of the biochemical indices of remodeling, and clinical doses have las ting effects without disruption to aanemineralization. Bone histomorph ometry has shown that bisphosphonates can restore normal bone structur e and an optimal therapeutic strategy should be defined, Symptomatic p atients (or asymptomatic patients at risk) should be treated, as well as any patient requiring orthopedic surgery, The optimum strategy for preventing complications is to treat as early as possible and to halt disease progression by normalizing the biochemical markers that reflec t the increased bone remodeling, There is no consensus on the threshol d values for retreatment, Few studies have evaluated the long-term eff ects of the inhibitors of osteoclastic resorption on the risk of compl ications, A recent 12 year, long-term follow-up of 41 cases of Paget's disease has shown that antipagetic therapy that did not normalize bio chemical markers-in 71% of patients did not prevent new complications in 62% of patients, These results suggest that an optimal regimen of t reatment and retreatment should target normalization of biochemical ma rkers of bone remodeling; the new bisphosphonates make this quite feas ible in most patients,