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.
Salmon calcitonin (Calcitonin Sandoz) was approved for the treatment of postmenopausal osteoporosis, to be administered intranasally. At a dose of 200 IU / day of salmon calcitonin reduces the risk of vertebral fractures by 33% compared to placebo. However was not observed a significant reduction in risk of fracture and increased bone mineral density also increased the dose of salmon calcitonin.
The intranasal administration of salmon calcitonin leads to an increased incidence of cases of rhinitis.
Therefore, the use of salmon calcitonin is reserved for patients with low compliance with other medications for the treatment of postmenopausal osteoporosis.
The use of teriparatide (Forsteo), active fragment of parathyroid hormone, administered daily by subcutaneous injection, stimulates the formation and bone resorption, increasing bone mineral density, thereby reducing the risk of vertebral fractures and fractures of 65-69% non-vertebral 35-40% compared to placebo.
In a comparative study with alendronate (Fosamax), the Teriparatide causes a greater increase in BMD of the spine and a lower incidence of non-vertebral fractures.
Teriparatite use of associated adverse events such as nausea, dizziness and leg cramps.
In phase II trials in women with postmenopausal osteoporosis strontium ranelate (Osseor / Protelos) at a dose of 2 g / day showed a significant increase in BMD of the spine 12 and 24 months of treatment compared to placebo .
During the second year of treatment with strontium ranelate, the proportion of patients who have suffered a vertebral fracture was reduced by 44% compared to placebo.
In the first three months of treatment can be observed between the adverse events more frequent nausea and diarrhea tend to regress over time.
By analyzing the different therapies, factors that may contribute to poor compliance, and no maintenance therapy for osteoporosis, include drug intolerance, the complexity of the regimen, and lack of understanding of the benefits and risks associated with treatment .
Emerging therapies for postmenopausal osteoporosis are represented by the new SERM (Bazedoxifene, lasofoxifene, Ospemifene, Arzoxifene) and denosumab.
The denosumab (formerly known as AMG 162) is a human monoclonal antibody, active against RANKL (Receptor Activator of Nuclear Factor Kappa B Ligand), involved in the genesis and survival of osteoclasts.
The denosumab indicated for osteoporosis, but also for other diseases of the skeleton, such as bone metastases and multiple myeloma. It is administered by subcutaneous injection every 3 or 6 months.
In a phase II study conducted in postmenopausal women with osteopenia and osteoporosis, treatment with denosumab resulted in a significant increase in BMD of the spine joint hip joint compared with placebo. These changes are similar to or greater than the results obtained with weekly dosing of alendronate.
A phase III trial confirmed these results. Hence, the data obtained from Phase II and III to indicate that the denosumab reduces the risk of fractures in the spine and articulation coxofemorale.
The Bazedoxifene (Conbriza) was approved for the prevention and treatment of osteoporosis in postmenopausal women.
In preclinical studies Bazedoxifene has been shown to reduce the risk of bone fractures caused by osteoporosis and cholesterol levels without evidence of endometrial hyperplasia and breast cancer.
The lasofoxifene (Fablyn) was approved for the prevention and treatment of postmenopausal osteoporosis and vaginal nell’atrofia.
In preclinical studies in experimental animals, the lasofoxifene has reduced the loss by maintaining the consistency of bone tissue, lowering total cholesterol levels.
In a mouse model was also demonstrated that treatment with lasofoxifene produces a low potential for proliferation of uterine and vaginal tissue.
L ‘Ospemifene (Ophena) is a drug candidate for the treatment of atrophy vaginal and prevention of osteoporosis that affects postmenopausal women. In phase II studies conducted in healthy postmenopausal women treated with different doses of Ospemifene, administered daily, we have seen a reduction of bone turnover, the Ospemifene has an effect on biochemical markers of remodeling and bone formation similar to that of raloxifene. (Xagena2009)
Source: Journal of Women’s Health, 2009
Can find more: postmenopausal osteoporosis, therapy postmenopausal osteoporosis, treatment postmenopausal osteoporosis
New post coming:
- comparative study between RALOXIFENE AND LASOFOXIFENE IN POSTMENOPAUSAL OSTEOPOROSIS