Difficulties With Use of PTH and PTH, for the Prevention and Treatment of Osteoporosis 1. Mechanism of Action PTH and PTH, are stimulators of bone turnover; they affect both osteoblastic formation

sl.lg~--~~~ xwstinns with repard to clinical trials and consq@: fqrms,“~,g appropriate. However, I do not . --_,_ a--------~---~ believe that this nroblem is a-&-&or one assoc&ed -.. ------:-r------~-~ ~.I 1 With parathyroid hOhone since o$eo@i-coma, is ri me, and only occurs at high doses in the rapidly developing young animals. I have enclosed my SUI lmary of the consideratjons that n~~&to.,&_t&n~ accountmaH=, in humans -Sewso that a &$ter ,dE& %uidance can be developed. PTH and PTH, may not have the desired effect . ..,-1.-,m--n”-..“wl*~e*M* on fiacture~.re&.&~:~, and could in fact. increase..fr~~~~.-...-~~~~~~~~, these agents could have extremely serious side eff+cts bed on recent findings in hyperparathyroidism. ,.*-A. a, “. . “. ._^I_ My comments are based on 35 years of experience in .met&olic bo~~,.&~~~, which includes background in both primary and secondary hyperparathyroidism. I was a mmber .of.Ax ..EQ,A. committees that -_. .,.,. *n_l.--~~~,,.~~~-,-~.~;.~*P.~__._ ,WF,. .._ established early Guidelines for ~psteo$orosis trials. i ah haye, years of experience in measurements .of bone mineral density (BMD) by noninvasive technologies, which enables.me to . .< ., &“.,.“I. ~~““AI_~Nc.s,__~~yv/ -~.~_.. d._ ::._.-,comment on.&di.&ulties of using BMD; whether by DE&A ‘or Cj;%IT, as ?n end-point for studies _ . ,. .” l.-,~---T1-~~~ on PTH and PTH,,. ----..j~:_~ ,, ,/ -