572
Sequence variants in the gene encoding estrogen receptor alpha (ER-α) may
modify the effects of hormone-replacement therapy on levels of high-density lipo-
protein (HDL) cholesterol and other outcomes related to estrogen treatment in post-
menopausal women. Some clinical trials have shown that postmenopausal women
with coronary disease, who have the ER-alpha IVS1-401 C/C genotype, or several
other closely related genotypes, have an augmented response of HDL cholesterol to
hormone-replacement therapy. These point to the possibility of using genetic
screening for tailoring decisions about hormone-replacement therapy for maximiz-
ing the health and wellbeing of postmenopausal women. It is conceivable that, ulti-
mately, more comprehensive pharmacogenomic studies of HRT, in conjunction
with more detailed phenotypic markers of disease outcome will lead to effective
algorithms for individualizing HRT for postmenopausal women.
Personalized Management of Osteoporosis
Osteoporosis, a disease characterized by reduced bone mass and increased skeletal
fragility, affects 10 million Americans; another 34 million are at risk for it. Because
of a large number of causes as well as risk factors, there are wide variations in
course of osteoporosis and response to treatment. Calcium and vitamin D is used
commonly for prevention of osteoporosis in those at risk, e.g. postmenopausal
women. Once considered to be an inevitable consequence of aging, osteoporosis is
both diagnosable and treatable.
Bisphosphonates are widely prescribed for treatment of osteoporosis. Examples
include: alendronate (Fosamax), risedronate (Actonel, Atelvia), ibandronate
(Boniva), and zoledronic acid (Reclast, Zometa). All the bisphosphonates that have
been approved for the treatment of osteoporosis have shown robust effi cacy in pre-
venting fractures in clinical trials lasting 3–4 years, but data on safety have raised
concern regarding the optimal duration of use for achieving and maintaining protec-
tion against fractures. Current FDA labeling states: “The optimal duration of use has
not been determined. All patients on bisphosphonate therapy should have the need
for continued therapy re-evaluated on a periodic basis.” To optimize the effi cacy of
bisphosphonates in reducing fracture risk, decisions to continue treatment must be
based on individual assessment of risks and benefi ts. In this regard, patients at low
risk for fracture (e.g. younger patients without a fracture history and with a bone
mineral density approaching normal) may prove to be good candidates for discon-
tinuation of bisphosphonate therapy after 3–5 years, whereas patients at increased
risk for fracture (e.g. older patients with a history of fracture and a bone mineral
density remaining in the osteoporotic range) may benefi t further from continued
bisphosphonate therapy. Further investigation into the benefi ts and risks of long-
term therapy, as well as surveillance of fracture risk after discontinuation of bisphos-
phonate therapy, will be crucial for determining the best regimen of treatment for
individual patients with osteoporosis (Whitaker et al. 2012 ).
18 Personalized Approaches to Miscellaneous Problems in Healthcare