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The FRAX calculator is a major achievement in terms of our understanding of measuring fracture risk. Along with being an easily accessible web-based tool, it is the only model based on extensive data on multiple cohorts. FRAX will help clinicians identify individuals who need osteoporosis treatments, while also screening out those who do not require osteoporosis treatments. However, FRAX is limited by a number of factors. Although it is web based, few physicians have the means to access it. It also assumes that body mass index and mortality are constant across different racial and ethnic groups. FRAX is further limited by the exclusion of variables known to be associated with fracture risk, lack of dose-response relationships for variables, increased subsequent fracture risk after initial fracture, restriction to only one bone mineral density site, racial and ethnic differences that may influence fracture risk, and availability of racial and ethnic fracture risk data to be used in the FRAX calculator. Finally, the values obtained from FRAX should not take the place of good clinical judgment.

Selective estrogen receptor modulators (SERMs) or estrogen agonists/antagonists have shown promise in osteoporosis in that they have the potential to reduce the risk of fracture, and also reduce the risk of breast cancer. SERMs maybe classified according to their core structure, which is typically a variation of the 17 beta-estradiol template and subclassified according to the side chain at the helix 12 affector region. The best known are the triphenylethylenes such as tamoxifen, used in the management of breast cancer. However, the clinical application of this class of SERMs has been limited due to endometrial stimulation. A second class is the benzothiophenes such as raloxifene and arzoxifene, which have skeletal benefit with little, if any, uterine stimulation. Indole-based SERMs such as bazedoxifene have a 2-phenyl ring system that serves as a core binding unit. Other classes include benzopyrans and naphthalenes (eg, lasofoxifene). In this review article, I will discuss raloxifene and three new SERMs—arzoxifene, bazedoxifene, and lasofoxifene—that have been recently studied. I will discuss their effect on bone, breast, and the cardiovascular system, as well as on safety.

The striking clinical benefits of intermittent parathyroid hormone in osteoporosis have begun a new era of skeletal anabolic agents. Recombinant human parathyroid hormone (rhPTH) (1–34) is the first US Food and Drug Administration–approved anabolic therapy. Its use has been limited by the need for subcutaneous injection. Newer delivery systems include transdermal and oral preparations. Newer anabolic therapies include monoclonal antibody to sclerostin, a potent inhibitor of osteoblastogenesis; and use of bone morphogenetic proteins and parathyroid hormone–related protein PTHrP, a calcium-regulating hormone similar to PTH.