Peter C. Ruenitz Pages 791 - 802 ( 12 )
Unchecked bone density loss can lead to osteoporosis. Such loss arises from a variety of metabolic imbalances, in particular hormonal insufficiency in postmenopausal women. Bone densitometry, coupled with - appropriate monitoring of bone turnover markers osteocalcin and (deoxy)pyridinoline, enables early diagnosis. This review will focus on recent advances concerning the biochemical and histomorphometric bases for clinically effective bone loss prevention by new and established medicinal agents. Estrogen replacement therapy generally has involved steroidal estrogens, given as mixed sulfate ester conjugates composed mainly of estrone and equilin. Current experimental evidence suggests no major diffe- rence in the biochemical function of these steroidal estrogens, or their respective 17 β-hydroxy counterparts. Nonsteroidal estrogen receptor ligands such as tamoxifen, raloxifene, and droloxifene, like estradiol, act as selective estrogen agonists in bone. But unlike estradiol, they are estrogen antagonists in other tissues. This selective estrogenicity might offer advantages over conventional estrogens, such as a decreased incidence of carcinogenicity. However, therapy with tamoxifen, the most widely used of these, has been associated with reproductive tract toxicity. And in laboratory rats, tamoxifen is converted to DNA-reactive hepatocarcinogenic metabolites. Prospects for bone loss suppressive drugs with a more diverse range of applications and low toxicity potential are embodied in the bisphosphonate etidronate and its analogues: risedronate, alendronate, ibandronate, pamidronate, and cimandronate. lpriflavone, an isoflavone derivative, augmented the effect of conjugated estrogens, enabling dose reduction of the latter in postmenopausal osteoporosis. Constricted analogues of parathyroid hormone hold future promise in bone restoration therapy.