Pharmacological management of osteogenesis

Abstract

Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases.

Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis <i>via </i>increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis

“…A dearth of estrogen disrupts the skeletal homeostasis and results in a high rate of bone remodelling (15), with bone resorption exceeding bone formation. Currently available drugs for the treatment of osteoporosis can be divided into two categories: anti-resorptive agents and bone-forming agents (16). Anti-resorptive agents like estrogen are usually recommended as first-line therapy, which is also called HRT, for women with PMO.…”

ENDOCRINOLOGY AND ADOLESCENCE: Osteoporosis in children: diagnosis and management

“…Anabolic agents such as synthetic parathyroid hormone (teriparatide) used in adults to directly stimulate bone formation (130) is currently contraindicated in children due to the risk of osteosarcoma reported in rodent models (131). Also, antibodies against inhibitors of the WNT signaling pathway (sclerostin and dickkopfrelated protein 1) looks promising (132). Growth hormone is another anabolic agent, known to increase cortical thickness and improve muscle mass (27).…”

Os efeitos da atividade física na remodelação óssea

“…A força mecânica, quando aplicada sobre o tecido ósseo, forma sinais endógenos que interferem nos processos de remodelação óssea. Esses sinais são captados por um sistema mecanossensorial, no qual o osteócito é a principal célula responsável por traduzir a força mecânica em sinais bioquímicos que regulam o turnover ósseo (NOMURA; YAMAMOTO, 2000;CHERIAN et al, 2003). Acredita-se que a deformação celular causada pela força direta sobre a célula, o aumento da pressão intracanalicular provocado pela força dinâmica e o incremento da velocidade do fluxo do fluido intersticial sejam fatores que afetam diretamente o osteócito, sendo esse último o maior estímulo à referida célula, em resposta à carga mecânica.…”

“…A coordenação desses processos é denominada de remodelação óssea e ocorre ao longo da vida, exigindo uma constante comunicação entre osteoclastos, osteócitos e osteoblastos, para que haja equilíbrio entre os processos de reabsorção e formação ósseas e, consequente, manutenção da densidade mineral óssea (DMO) (MORAES et al, 2002;RAISZ, 2005;NARDONE et al, 2014).…”