To stop or not to stop, that is the question

Abstract

Treatment aimed at preventing fractures should be stopped if evidence of continued antifracture efficacy is lacking, if continued treatment increases bone fragility by adversely affecting matrix properties, and if stopping does not increased bone fragility. Credible evidence of antifracture efficacy beyond 5 years is lacking because of attrition of the cohort originally allocated to treatment or placebo and lack of controls. Prolonged suppression of remodeling is associated with accumulation of microdamage, advanced glycation products and increased tissue mineral density in animal studies but the structural benefits appear to out weight these adverse effects. Atypical minimal trauma subtrochanteric fractures are associated with prolonged treatment in human subjects but these are exceedingly rare. Stopping treatment does result in the reemergence of remodeling, rapidly with some drugs, more slowly with others while fracture rates are increased in poor compliers to treatment. Thus, within the constraints of limited evidence, I infer that stopping therapy is more likely to do net harm than continuing therapy - treatment should be continued in the majority of individuals.