Oral Therapeutics Post Menopausal Osteoporosis

Abstract

Osteoporosis affects a significant number of postmenopausal women in the United States. Screening is performed using clinical assessments and bone mineral density scans via dual x-ray absorptiometry. Oral therapy is indicated to prevent pathologic fractures in those deemed at increased risk following screening. Bisphosphonates including alendronate, ibandronate, and risedronate are currently first-line oral therapeutics in fracture prevention following the diagnosis of osteoporosis. Hormonal therapies include estrogen-containing therapies, selective estrogen receptor modulators, and other compounds that mimic the effects of estrogen such as tibolone. Lifestyle modifications such as supplementation and physical activity may also contribute to the prevention of osteoporosis and are used as adjuncts to therapy following diagnosis. These therapeutics are limited primarily by their adverse effects. Treatment regimens should be tailored based on significant risk factors demonstrated by patients, adverse effects, and clinical response to treatment. The most severe risk factors relevant to pharmacological selection involve hormone replacement therapies, where concern for venous thrombosis, coronary artery disease, breast, and uterine cancer exist. Bisphosphonates are most commonly associated with gastrointestinal discomfort which may be mitigated with proper administration. Although adverse effects exist, these medications have proven to be efficacious in the prevention of vertebral and non-vertebral fractures in post-menopausal women. Fracture risk should be weighed against the risk of adverse events associated with each of the regimens, with clinical judgment dictating the treatment approach centered around patient goals and experiences.

Molecular and Cellular Mechanisms of Osteoporosis

“…Selectively inhibit the enzyme farnesyl pyrophosphate synthase in osteoclasts, leading to their apoptosis [131] Gastrointestinal adverse effects [132] Atypical fractures [133] Not recommended for patients with low creatinine clearance [134] RANKL inhibitors Inhibits the binding of RANKL to its receptor, inhibits osteoclastogenesis [135,136] Duration of denosumab administration increases the rate of bone resorption after treatment cessation [137] PTH analogues Binds the PTH receptor (PTH1R), activates protein kinase A, enhances the formation of osteoblasts [138,139] Decreases bone mineral density after withdrawal [140] Antisclerostin antibodies Slow down the binding of sclerostin to LRP5/6, reduce blocking of the osteogenic Wnt pathway, increases the number of osteoblasts [141] Increase the risk of cardiovascular events [142] Hormone therapy Binds to estrogen receptors [143] Used for postmenopausal osteoporosis [143] Calcitonin Inhibit osteoclast activity [144] Used for postmenopausal osteoporosis, low efficiency [144,145] Targeting STING Activation of STING/IFN-β [146] It is a potential target Targeting semaphorins Modulate plexin receptors, enhanced bone formation, and reduced bone resorption [147] It is a potential target…”

“…However, the main side effects of raloxifene, such as hot flashes and venous thromboembolism, limit its use in some patients [169,170]. However, SERM preparations are successfully used in postmenopausal osteoporosis [145].…”