Lasofoxifene, from the preclinical drug discovery to the treatment of postmenopausal osteoporosis.
BACKGROUND
Estrogen replacement is traditionally seen as the gold standard for preventing osteoporotic fractures in postmenopausal women as well as for the management of menopausal symptoms. However, estrogen may lead to an increased risk of breast and, when unopposed by progestins, endometrial cancers. Alternative therapies include bisphosphonates and raloxifene, a selective estrogen receptor modulator (SERM). While the former have been associated with suboptimal adherence, the latter is considerably less potent than estrogen and its effect in the prevention of nonvertebral fractures remains uncertain. Hence, there is a need for additional effective medications to prevent fractures in postmenopausal women that provide additional benefits.


METHODS
This article reviews lasofoxifene, a new SERM for the treatment of postmenopausal osteoporosis and urogenital atrophy. The medical literature is reviewed for articles containing the terms 'lasofoxifene' and 'SERMs'. The manuscript reviews the discovery strategies and preclinical development of lasofoxifene as well as its clinical development.


CONCLUSIONS
Recent evidence suggests that the ideal SERM profile for one patient may be far from ideal for another. Thus, it could be favorable that different SERMs may be available in the future, each with a somewhat different profile that may be rationally applied to various patients with a spectrum of needs. In this context, lasofoxifene, while retaining some of the adverse effects of other SERMs (i.e., hot flushes and risk of venous thromboembolic events), may offer an improved skeletal efficacy over raloxifene, addressing other postmenopausal conditions, including reduction in breast cancer risk and treatment of vaginal atrophy.
University of Siena, Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy  +39 577 585364 ;  +39 577 233446 ;  gennari@unisi.it.
Luigi
L
Gennari
Daniela
D
Merlotti
Konstantinos
K
Stolakis
Ranuccio
R
Nuti