Postmenopausal osteoporosis is a skeletal disease, characterized by a silent and asymptomatic reduction in bone mineral density and bone architecture changes that can increase the risk of fractures. Often being asymptomatic osteoporosis is underdiagnosed and undertreated.
Osteoporosis is age related, with higher incidence in postmenopausal women. Roughly estimated that 200 million people worldwide are affected by osteoporosis. Osteoporotic fractures are associated with significant morbidity and mortality, and impaired quality of life. Fractures between those who have more influence on the quality of life are the total hip fracture and multiple fractures of the vertebrae, the latter associated with reduced respiratory function and limitation of movement.
Although there are several drugs on the market for the prevention and / or treatment of postmenopausal osteoporosis, they may not always be appropriate for all women, mainly because of their side effects. The basic therapy for the prevention and treatment of osteoporosis is represented after taking supplements of calcium and Vitamin-D. Some evidence suggests that supplements with vitamin D and calcium may have a positive effect on bone mineral density, reducing the risk of fractures.
Recent randomized clinical trials, however, have however not shown any effect of taking calcium supplements and vitamin D on reducing the risk of bone fractures. Calcium taken in the first 5 years of the menopausal period shows a limited effect in reducing the risk of fracture. A meta-analysis showed that the effect on reducing the risk of bone fractures is achieved by administering a dose of more than 1200 mg of calcium daily.
The oral bisphosphonates are generally considered first-choice therapy for patients with osteoporosis. Several studies conducted in postmenopausal women with osteoporosis showed that these drugs lead to an improvement in bone density and consequently the reduction of bone fractures, including those of the vertebrae, with a figure of 20% – 50% compared to placebo. The use of bisphosphonates, however, is limited by gastrointestinal side effects against which occur with: dyspepsia, abdominal pain, gastritis and oesophagitis. The low bioavailability of oral bisphosphonates and the possible gastrointestinal side effects that limit the use of high doses, have helped lead the administration of these drugs intravenously in the treatment of postmenopausal osteoporosis. The intravenous bisphosphonates have the disadvantage of being more expensive than the oral formulations of cause and sometimes flu-like symptoms and myalgia.
Other treatment of postmenopausal osteoporosis include hormone therapy, raloxifene, salmon calcitonin, teriparatide and strontium ranelate. Hormone therapy, which involves the administration of estrogen alone or in combination with progestin, is approved for the prevention of postmenopausal osteoporosis, although it is most suitable for the treatment of menopausal symptoms, such as, changes and vasomotor ‘ vaginal atrophy.
Hormone therapy has however shown efficacy in reducing the risk of fractures and spinal joint hip joint with a rate of 30-40%, compared to placebo. Results from two clinical trials suggest that long-term hormone therapy may be associated with an increased risk of myocardial infarction and thromboembolic events, whereas in a study of patients on combination therapy of estrogen / progestin has been observed a small but significant increased risk of breast cancer.
In particular, the Raloxifene (Evista), a selective estrogen receptor modulator (SERM) reduces by 30-50% the risk of vertebral fractures compared with placebo. Clinical studies have also shown that raloxifene reduces the risk of breast cancer by 50-80% compared to placebo, similar percentage to that obtained with tamoxifen (Nolvadex). Raloxifene showed also a significantly increased risk of thromboembolic events, in particular, the results of a study showed an increased incidence of 49% of events infarctions compared with placebo, raloxifene also produced an increased incidence of vasomotor symptoms such as hot flushes and leg cramps.
The use of raloxifene is not recommended for patients with a history of thromboembolic events and risk of myocardial infarction. Considering the fact that there are many clinical data in support of reducing the risk of bone fracture and considering the important side effects related to the circulatory system, the Raloxifene is generally regarded as second-choice therapy for the treatment of postmenopausal women with osteoporosis.