Toward a cure for osteoporosis: reversal of excessive bone fragility.

While estrogen replacement therapy and calcium supplementation appear to be effective at preventing postmenopausal osteoporosis, therapy for established osteoporosis is far less effective. The reduction of bone fragility should be a goal of a treatment for established osteoporosis. To this end, increases in cortical bone mass by subperiosteal new bone formation may produce the greatest mechanical advantage. Anti-resorptive drugs, such as etidronate, have shown potential for reducing the incidence of osteoporotic fracture in the short term, but their ability to produce a long-term benefit may be limited. An alternative approach might be to develop drug therapies that substantially increase cortical bone strength, namely by stimulating periosteal bone formation. Although sodium fluoride has proved to be problematic, there are several other potential osteoporosis therapies. They include treatment with anabolic hormones (e.g. growth hormone and anabolic steroids) and targeted delivery of growth factors. Also, anti-resorptive and formation-stimulating drugs might be combined in a new form of ADFR (coherence) therapy where the new acronym means: Activate-Depress-Formation stimulation-Repeat.