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Sasso GRS et al.
524 Rev Assoc Med Bras 2015; 61(6):524-529
REVIEW ARTICLE
Elevated serum osteoprotegerin levels in women: friend or foe?
Gisela Rodrigues da Silva Sasso1*, Rinaldo Florencio-Silva2, Ricardo Santos Simões3, Maria Cândida P inheiro Baracat4,
José Maria Soares Júnior5, Edmund Chada Baracat6
1PhD – Post-Doctoral Fellow – Department of Morphology and Genetics, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brazil
2PhD – Post-Doctoral Fellow – Department of Morphology and Genetics, Unifesp, São Paulo, SP, Brazil
3PhD – Physician – Department of Obstetrics and Gynecology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil
4MSc student – Physician – Department of Obstetrics and Gynecology, FMUSP, São Paulo, SP, Brazil
5Prof. Dr. Habilitation (BR: Livre Docência) – Associate Professor in the Division of Gynecology, Department of Obstetrics and Gynecology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, SP. Brazil
6Dr., Full Professor in the Division of Gynecology, Department of Obstetrics and Gynecology, FMUSP, São Paulo, SP. Brazil
Summary
Study conducted at Universidade Federal
de São Paulo, Escola Paulista de
Medicina (Unifesp/EPM), Faculdade de
Medicina da Universidade de São Paulo
(FMUSP), São Paulo, SP, Brazil
Article received: 8/7/2015
Accepted for publication: 8/7/2015
*Correspondence:
Address: Disciplina de Histologia e Biologia
Estrutural, Departamento de Morfologia e
Genética da Universidade Federal de São
Paulo – Escola Paulista de Medicina –
UNIFESP/EPM – São Paulo (SP), Brasil
Disciplina de Ginecologia, Departamento
de Obstetrícia e Ginecologia da Faculdade
de Medicina da Universidade de São Paulo
– FMUSP – São Paulo (SP), Brasil
Introduction: osteoprotegerin has emerged as a new candidate for the treat-
ment of osteoporosis. However, high levels of osteoprotegerin have been linked
to vascular calcification, an independent and well-defined risk factor for cardio-
vascular disease (CVD) and mortality. Thus, the action of osteoprotegerin in
these situations has been questioned.
Objective: to evaluate the effect of osteoprotegerin (OPG) on the human body,
especially in bone tissue and in vascular diseases.
Methods: the scientific databases consulted were PubMed-Medline and Co-
chrane, using keywords (MeSH terms) grouped into the following syntaxes: (Os-
teoprotegerin OR Osteoclastogenesis Inhibitory Factor OR Receptors, Tumor
Necrosis Factor, Member 11b OR Tumor Necrosis Factor Receptor Superfami-
ly, Member 11b OR FDCR-1 Protein OR FDCR 1 Protein OR OCIF Protein OR
Follicular Dendritic Cell-Derived Receptor-1) AND (Bones AND Bone OR Bones
AND Bone Tissue OR Bones OR Bone Tissue OR Cardiovascular Diseases).
Results: Osteoprotegerin is present in various organs and binds to two ligands:
nuclear factor kB (RANKL) related to the differentiation of osteoclasts, and tu-
mor necrosis factor related to the apoptosis-inducing ligand (TRAIL). OPG in-
hibits the regulation effects of nuclear factor kB on inflammation and on the
skeletal and vascular systems, preventing the apoptosis induced by TRAIL, be-
ing related to the preservation of bone tissue.
Conclusion: a deeper knowledge of the mechanisms involved in the association
between OPG serum levels, bone integrity and cardiovascular disease can pro-
vide important data for future therapeutic interventions.
Keywords: osteoprotegerin, RANK ligand, receptors, TNF-related apoptosis-in-
ducing ligand, bone.
Introduction
Bone remodeling is a continuous physiological process
that maintains skeletal integrity through bone resorp-
tion by osteoclasts, followed by bone formation by osteo-
blasts. This remodeling results from a time sequence that
lasts six months on average. The remodeling process can
be divided into four stages: 1) activation of osteoclasts
(multinucleate cells responsible for bone resorption) and
their precursors; 2) the resorption of old bone by the os-
teoclasts – which takes about three weeks; 3) end of bone
resorption and 4) bone neoformation by osteoblasts.1
Osteoporosis is a disorder characterized by decreased
bone strength and increased risk of fracture, which oc-
curs due to an imbalance in the bone remodeling process,
where bone resorption exceeds bone formation. Preven-
tion and treatment currently available for osteoporosis
include bisphosphonates and selective estrogen receptor
modulators (SERMs), which are antiresorptive agents, as
well as parathyroid hormone analogues such as teripara-
tide, which are the only anabolic agents currently ap-
proved for the treatment of osteoporosis. On the other
hand, side effects and the low efficacy of the treatments