Anabolic therapy for osteoporosis has become the most desirable therapeutic 
option for menopausal osteoporosis. The anabolic agents currently in clinical 
use are reviewed. Teriparatide (recombinant human 1-34 parathyroid hormone) is 
used to treat women with menopausal osteoporosis and men at high risk for 
fractures. Despite PTH's clinical use, the mechanism underlying its anabolic 
action requires greater elucidation. Proteol (strontium ranelate) acts by 
inhibiting bone resorption and presumably promoting bone formation. Though 
clinical trials have shown that strontium ranelate reduces the frequency of both 
vertebral and non-vertebral fractures, its molecular target remains 
controversial. Lately, with the discontinuation of estrogen replacement therapy, 
phytoestrogens are gaining much attention, chiefly as prophylactic agents. 
Though ipriflavone stimulates osteoblast function in vitro and favorably 
influences bone turnover and spinal bone mineral density in peri- and 
postmenopausal women, its clinical use is currently rather limited. As with PTH 
and strontium ranelate, the mode of action of ipriflavone requires much greater 
elucidation. Since osteoporosis therapies are long-term, safety is a major 
consideration. PTH has been reported to be associated with incidence of 
osteosarcoma and strontium ranelate with DRESS syndrome. Therefore, target-based 
(and osteoblast-specific) development of molecules is expected to improve the 
safety profile of anabolics. Calcium-sensing receptor, insulin-like growth 
factor-1, members of wingless tail signaling family, and sclerostin are emerging 
concepts in bone anabolic therapy. We will cover the preclinical development of 
some bone anabolic agents under active investigation.