A group of investigators is studying the process of bone remodeling in response to steroid hormones. Twenty adult female rats are randomly divided into 2 groups, with one group undergoing bilateral oophorectomy and the other undergoing sham laparotomy to serve as a control group. Eight weeks after the surgery, bone samples are obtained from all animals. Immunohistochemical evaluation shows overexpression of receptor activator of nuclear factor kappa B (RANK) on the surface of certain bone cells in the oophorectomized animals. Which of the following is the most likely effect of the observed finding?

Question

A group of investigators is studying the process of bone remodeling in response to steroid hormones.  Twenty adult female rats are randomly divided into 2 groups, with one group undergoing bilateral oophorectomy and the other undergoing sham laparotomy to serve as a control group.  Eight weeks after the surgery, bone samples are obtained from all animals.  Immunohistochemical evaluation shows overexpression of receptor activator of nuclear factor kappa B (RANK) on the surface of certain bone cells in the oophorectomized animals.  Which of the following is the most likely effect of the observed finding?

Quizplus · Accepted Answer

11ec160b_36f7_22c2_9249_5b3257ad09b1_MD0001_00 The 2 most important factors in osteoclast differentiation are macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANK-L), which stimulate the development of mature, multinucleated osteoclasts. The interaction of RANK-L with RANK (receptor) is blocked by osteoprotegerin (OPG), which acts as a decoy receptor. By binding RANK-L, OPG reduces the differentiation and survival of osteoclasts, resulting in decreased bone resorption and increased bone density. Bone turnover is therefore regulated by the ratio of OPG to RANK-L; bone turnover increases when OPG is low and RANK-L is high. Estrogen maintains bone mass in premenopausal women by inducing the production of OPG by osteoblasts and stromal cells. It also decreases the expression of RANK on osteoclast precursors. By contrast, the loss of estrogen effect (eg, menopause, oophorectomy) increases the expression of RANK-L and decreases production of OPG (Choice E). The decreased OPG to RANK-L ratio leads to increased osteoclast activity and bone resorption. Denosumab is a monoclonal antibody used in the treatment of postmenopausal osteoporosis. It works in a manner similar to OPG by binding RANK-L and blocking its interaction with RANK. (Choices A and C) RANK is not present on osteoblasts, so the decreased OPG to RANK-L ratio seen following oophorectomy does not affect bone mineralization or osteoid formation. (Choice B) Osteocytes are derived from osteoblasts. Estrogen reduces osteoblast and osteocyte apoptosis through activation of extracellular signal-regulated kinases rather than effects on RANK/RANK-L. Educational objective: The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANK-L) interaction is essential for the formation and differentiation of osteoclasts. Osteoprotegerin blocks binding of RANK-L to RANK and reduces formation of mature osteoclasts. Low estrogen states cause osteoporosis by decreasing osteoprotegerin production, increasing RANK-L production, and increasing RANK expression in osteoclast precursors. __________ References: Prevention and treatment of postmenopausal osteoporosis. (http://www.ncbi.nlm.nih.gov/pubmed/24176761)

A Group of Investigators Is Studying the Process of Bone