Treatment of osteoporoses by manipulation of coherent bone cell populations.

Up to and including the year 1979, no agent, combination of agents or other treatment has been found which, when given continuously to the intact incoherent adult human skeleton, can store in it clinically useful amounts of bone in a way which can continue with continued treatment. BMU theory suggests that failure derives from a depression by such treatments of both resorptive and formative activity, partly by depressing the naturally coupled activities of already existing 'clast and 'blast populations, and partly by reducing BMU activation. However BMU theory also suggests that selected agents given in special sequences can create a positive bone balance in repeatable increments. One such proposal, called the ADFR sequence, involves generating a pulse of increased BMU activations. The resorptive and formative activities created by that pulse will occur at predictably different periods of time, that is, they will prove coherent. By depressing the coherent resorption with a suitable agent during its lifetime, and then freeing the skeleton of treatment during the following coherent osteoblastic activity one stores an increment of new bone, because the ADF sequence causes remodeling BMU to deposit normal amounts of new bone in smaller than normal holes. The sequence is repeated as often as needed to add further increments. Other manipulations of coherent bone cell populations could remove bone or simply alter its turnover speed, as desired. Thus special sequences of simple pharmacologic actions, which have no useful ultimate effects upon global bone balance when delivered continuously and alone to the incoherent skeleton, create a simple new kind of therapy which should (and did) exert dramatic (and probably repeatably incrementable) effects in the coherent skeleton. The concept of manipulating deliberately induced coherent skeletal states for therapeutic purposes would not appear to depend for its success upon any one or 2 or even 3 special drugs.