Sclerostin antibodies as novel anabolic therapy for osteoporosis

Osteoporosis medications are dividedinto two groups: those inhibiting bone resorption and formation (bisphosphonates and denosumab), and those stimulating bone formation i.e. having an anabolic effect. The latter include teriparatide, parathyroid hormone 1-84 and abaloparatide, all of which stimulate bone resorption as well as bone formation, which limits their anabolic effect. The discovery of sclerostin the key inhibitor of bone formation has led to development of the concept that inhibition of this protein could stimulate bone formation. Romosozumab is a human monoclonal antibody to sclerostin that binds to sclerostin and enables Wnt-signaling pathway ligands and their co-receptors to interact with each other, which, in turn, leads to increased bone formation and bone mineral density. Unlike classical anabolic drugs in osteoporosis treatment, romosozumab stimulates bone formation and inhibits bone resorption. In clinical trials, romosozumab showed marked increase in lumbar spine and hip bone mineral density. Presented article contains information about pre-clinical and clinical studies of romosozumab

Направление в редакцию

Osteoporotic fractures are an important public health problem due to their negative impact on the quality of life and life expectancy, as well as high cost of treatment and rehabilitation. Along with the major risk factors for osteoporotic fractures, such as low bone mineral density (BMD), age, low body weight, frequent falls and previous fractures, an important secondary risk factor, especially among susceptible individuals, is taking certain medications. The difficulty in assessing fracture risk when taking various drugs, as well as the development of appropriate methods of prevention and treatment, is often due to the absence of large randomized trials with a sufficient level of evidence, as well as the heterogeneity of the main risk factors for fractures in studied groups of patients. We focus on the main groups of drugs for which there is evidence of a negative impact on bone metabolism, BMD and fracture risk. In addition to drugs, bone metabolism is also influenced by bariatric surgery, transplantation of solid organs, gonadectomy for various diseases

Iatrogenic lesions of the skeleton

Osteoporotic fractures are an important public health problem due to their negative impact on the quality of life and life expectancy, as well as high cost of treatment and rehabilitation. Along with the major risk factors for osteoporotic fractures, such as low bone mineral density (BMD), age, low body weight, frequent falls and previous fractures, an important secondary risk factor, especially among susceptible individuals, is taking certain medications. The difficulty in assessing fracture risk when taking various drugs, as well as the development of appropriate methods of prevention and treatment, is often due to the absence of large randomized trials with a sufficient level of evidence, as well as the heterogeneity of the main risk factors for fractures in studied groups of patients. We focus on the main groups of drugs for which there is evidence of a negative impact on bone metabolism, BMD and fracture risk. In addition to drugs, bone metabolism is also influenced by bariatric surgery, transplantation of solid organs, gonadectomy for various diseases

Denosumab treatment in patients with different courses of osteoporosis

We present three clinical cases of successful osteoporosis treatment with denosumab in patients with different courses of osteoporosis: postmenopausal with bisphosphonates ineffectiveness, osteoporosis of mixed etiology in patient on thyroid stimulating hormone suppression and aromatase inhibitor therapy and a case of osteoporosis in a male caused by primary hyperparathyroidism. Mechanism of denosumab action is different from bisphosphonates: denosumab prevents osteoclast differentiation by binding to receptor activator of nuclear factor kappa-B ligand (RANKL) and thus suppressing bone resorption. Clinical trials showed that denosumab promotes further increase of bone mineral density after bisphosphonate treatment. Denosumab has been used in Russian Federation since 2012. Clinical effectiveness and safety profile make denosumab one of the first-line drugs for osteoporosis treatment