Review Article
New therapies in osteoporosisNuevas terapias en osteoporosis

https://doi.org/10.1016/j.rcreue.2016.04.006Get rights and content

Abstract

Osteoporosis is a skeletal system pathology characterized by low bone mineral density and tissue structural deterioration. This condition is associated with high fracture risk that severely compromises quality of life. Osteoporosis incidence is becoming more significant with increasing lifespan worldwide.

Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and/or increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin, GKS-3b and dickkopf-1, two endogenous inhibitors of bone formation. This review discusses these new therapies.

Resumen

La osteoporosis es una patología que afecta el sistema esquelético y se caracteriza por una baja densidad mineral ósea y un deterioro estructural del tejido óseo. Esta enfermedad está asociada con un alto riesgo de fracturas que comprometen seriamente la calidad de vida. La incidencia de osteoporosis es actualmente mayor debido al aumento de la esperanza de vida en el mundo.

Numerosas investigaciones con respecto a nuevas estrategias de tratamiento han sido desarrolladas y tienen como objetivo inhibir la resorción ósea excesiva o aumentar la formación de hueso. Entre los tratamientos más prometedores están denosumab, un anticuerpo monoclonal que ejerce su acción contra el activador del receptor del ligando NF-kappa B, una citoquina clave de los osteoclastos; odanacatib, un inhibidor específico de la proteasa catepsina K de los osteoclastos; y anticuerpos monoclonales contra las proteínas antiesclerostina, la glucógeno sintasa quinasa-3b y dickkopf-1, dos inhibidores endógenos de la formación de hueso. En esta revisión se analizan y se revisan los conceptos actuales de las nuevas terapias.

Section snippets

Methodology

It was conducted a literature review, searching articles of relevance on new therapies in osteoporosis, in order to perform subsequently a broad description of the topic. The review was carried out in the MEDLINE and EMBASE databases. The search strategy did not have date limits and was conducted using MeSH terms as it follows: “osteoporosis AND antiresorptive therapies, “osteoporosis AND anabolic therapies, “osteoporosis AND denosumab, “osteoporosis AND cathepsin k inhibitors,

Denosumab

Is a fully human monoclonal antibody that has a high affinity for RANKL, a molecule known for its prominent role in osteoclastogenesis.8, 9

Its pharmacokinetic properties are superior, compared with other drugs, which results in a longer dosing interval. It is the most advanced of all the compounds under research and it has been approved in Europe for the treatment of osteoporosis and in the United States for the management of osteoporosis and bone metastases.10

It suppresses, in a dose-dependent

Anabolic therapy

Anabolic drugs improve bone formation rather than avoiding a greater loss of bone mass, and the result is a faster increase in bone mass. Special attention is being paid to the activation of the canonical Wnt bone-forming signaling pathway to achieve an anabolic effect on the bone. The canonical Wnt signaling pathway offers several objectives that may be suitable for pharmacological intervention. The main purpose of this interventions is to increase signaling in order to increase the bone mass (

Conclusions

The number of available anti-osteoporotic drugs will increase considerably in the coming years. Many of the new drugs combine efficacy with convenient administration, which could result in a better adherence. Odanacatib and to some extent saracatinib represent a different class of antiresorptive agents that inhibit the activity of osteoclasts rather than undermining their viability. The successful integration of these new compounds is based on the evidence of osteoporosis therapy that requires

Conflict of interest

The authors declare that they have no conflict of interest.

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    Please cite this article as: Posada AF, Aguirre HD, Casallas JCG, Patiño JDL, Oñate RV. Nuevas terapias en osteoporosis. Rev Colomb Reumatol. 2016;23:34–43.

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