Osteoporosis treatment: quo vadis? (A brief overview)

What we formerly called osteoporosis includes four conditions with an osteopenia: A) osteopenias usually due to mechanical disuse, where injuries cause fractures, and in limb bones more than the spine; B) osteopenias with such fragile bone that normal activities instead of injuries can cause fractures and/or bone pain, and in the spine more than limb bones; C) a group that combines features of (A) and (B); D) temporary osteopenias while major fractures, burns or other injures heal. If belatedly, we now realize our past failure to view those conditions as separate entities compromised many past studies of the prevalence, diagnosis and ways to prevent and cure each of them. That failure also compromised many past explanations of the nature, pathogenesis and natural course of "osteoporosis", and much of the related research. This caused some confusion as well as controversies about illusory instead of genuine issues. Controlling existing osteoblasts and osteoclasts with drugs has not prevented or cured those conditions. That will require controlling the modeling drifts and remodeling BMUs that create those cells. Modeling can increase bone mass and strength, remodeling can conserve or reduce them, and neither can provide the other's functions. During normal mechanical usage modeling is OFF and remodeling works in its "conservation mode" to keep existing bone. In disuse, modeling stays OFF while remodeling works in its "disuse mode" to remove bone and cause an osteopenia. Most natural nonmechanical agents (Table 1) can help or hinder those mechanical responses, but cannot duplicate or override them. Wrist and hip fractures from falls cause the most serious problems associated with these conditions. Those fractures begin in the cortex of epiphyseal-metaphyseal regions of limb bones. They never begin in trabecular bone and rarely in the shafts of long bones. They never begin in the trabecular bone and rarely in the shafts of long bones. Since a bone's strength depends on its shape and size (architecture) as well as on the amount of bone in it (bone mineral "density" and content), treatments intended to prevent or cure these conditions should strengthen the above cortex, and absorptiometric studies should begin to account for both bone architecture and bone tissue content. "Bone anabolic" agents (parathyroid hormone and some prostaglandins) can make modeling add bone to normal and osteopenic skeletons, but when the treatment stops remodeling begins removing that bone. "Antiremodeling agents" (including estrogen and many bisphosphonates) can make remodeling tend to keep existing bone, but when such treatments stop remodeling usually resumes removing bone. Combining anabolic agents with antiremodeling agents offers an exceptionally promising prospect of effective prevention and cure of the above osteopenias. Practical problems make this approach not yet ready for human use, but it soon could be.