Osteoporosis is a significant health burden compromising the strength of bones and

increasing the risk of fracture. Menopause is a key turning point in skeletal health of
women. Following menopause declined in estrogen often lead to excessive bone
remodeling activity and accelerated bone loss.
Bone loss following menopause results from the imbalance of osteoclast and
osteoblast activities. Osteoclast are the specialized cells that resource bone and
osteoblasts are the cells that form new bone.

Rank ligand pathway :

RANK ligand is a protein expressed by osteoblast

Plays a key role in osteoclast formation function and survival through
interaction with its receptor that is expressed on the surface of the
osteoclasts
OPG, another protein secreted by osteoblasts is a natural inhibitor of RANK
ligand
Plays a role in regulating bone resorption.

NORMAL
At the initiation of bone remodeling, lining cells move apart to expose the bone
surface, becomes osteoblasts and begin expressing rank ligand. Rank ligand binds
to rank on osteoclast precursors, which initiates cell fusion and formation of mature
multinucleated osteoclast. RANK Ligand continues to bind to RANK on mature
osteoclast. The binding of RANK ligand to its receptor is essential for osteoclast
formation function and survival. Following bone resorption, osteoblasts migrate into
the pit.
Osteoblast fill the pit with new bone matrix, some osteoblast become embedded
within the matrix and eventually turns into osteocytes while others become new
lining cells on the bone surface. In the final stage of remodeling, newly created bone
matrix mineralizing and the bone returns to arresting state
MENOPAUSAL
The process of bone remodeling is regulated by factors including estrogen and OPG.
Estrogen limits the amount of RANK ligand expression by osteoblast and OPG blocks
the binding of RANK ligand to RANK. Thereby reducing osteoclast activity.
In post-menopausal women, reduced levels of estrogen lead to increased expression
of RANK ligand by osteoblast. Expressive RANK ligand overwhelms OPG, lead to
more osteoclast, increase bone remodeling activity greater bone lost. Osteoblast
continue to deposit new bone matrix, but they cannot replace all of the resort
development. Therefore, resorption pits may not be completely refilled, which over
time. Leads to thinning and weakening of bone.
SUMMARY

As estrogen declines, RANK ligand expression increases

Elevated RANK ligand levels lead to increased osteoclast formation, function,
and survival.
Greater osteoclast activity increases bone loss, weakens bone architecture,
and can ultimately lead to fracture.