Treatment of osteoporosis in the elderly

Osteoporosis is a chronic disorder associated with a significant burden of health care cost, morbidity and mortality.
It typically affects the elderly for many reasons, including estrogen deficiency/male hypogonadism, smoke,
alcohol abuse, hypovitaminosis D, hyperparathyroidism and sarcopenia. Hip fractures are responsible of an
estimated excess mortality up to 36% within one year of fracture. Albeit fragility fractures are frequently observed
in clinical practice, many patients still remain undiagnosed and untreated. Theoretically, anti-osteoporotic
therapies should be prescribed in all patients with frailty fractures (clinical or morphometric) and/or with
low BMD levels and high fracture risk. Treatment should start with a nonpharmacological approach, encouraging
lifestyle change (i.e. outdoor physical activities, smoke/alcohol abuse cessation) and reducing the risk for
falls. Many elderlies present a hypovitaminosis D condition, so it is mandatory to correct it, preferably with colecalciferol,
to reduce negative effects of secondary hyperparathyroidism on bone.
Noteworthily, no clinical trials were exclusively focused on elderly groups as primary end-point and most of data
showing no interaction between age and drug efficacy came from post-hoc analyses. In these trials, both oral
(alendronate and risedronate) and intravenous (zoledronic acid) bisphosphonates showed relatively quickly significant
benefits, in terms of reduced incidence of (hip, vertebral and non-vertebral) fractures and in BMD
gain. Their efficacy, however, was preserved only in patients with a good compliance, which is more difficult to
reach in very medicalized patients, as elderly are. It is important to note that gastrointestinal side-effects, including
gastroesophageal irritation and esophageal erosion are another common cause of oral bisphosphonates
withdrawal. In this clinical setting, new liquid formulations of alendronate showed the same efficacy and better
compliance than first generation tablets of oral bisphosphonates, thanks to a significantly improved gastrointestinal
tolerance. The finding that the inhibitory effect on bone remodeling is prolonged even after therapeutic
discontinuation, together with the concerns about the potential risk of atypical femoral fractures and
osteonecrosis of the jaw, lay the bases in recent years for a “drug holiday” in selected patients at low fracture risk.
In both FREEDOM trial and its extension, denosumab, a fully human monoclonal RANKL antibody, significantly
reduced all fragility fractures as compared to placebo with a consistent safety profile and its effects on bone
turnover were fully reversible after withdrawal. Finally, cost, tolerability and life expectancy should always be
considered before prescribing any treatment. So, teriparatide has shown its effectiveness even in older age, but
it is a common thought that it should be reserved for more severe cases or in case of first-line therapy failure.

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