#CBD slows #bone remodeling in study of #osteoporosis

19.12.17: news.health/osteo/cbd/
GPR55 antagonist reduced mouse bone resorption:
12.23: summary:
. bone strength is maintained by remodeling,
where bone is removed by osteoclasts
to make way for new bone by osteoblasts.
. CBD appears to inhibit osteoclast function
and might be of use against osteoporosis;
but it also increases the number of osteoclasts,
so that if you ran out of CBD for a time,
the osteoclasts would be reactivated,
and there would be many more of them.
. as seen with the Bisphosphonates
the strategy of stopping resorption is flawed,
and should rarely be used [Dr.Ott]
because while the bone may remain dense,
the bone is not maintaining its strength.

. interestingly, this is another situation
where CBD and THC counteract each other.

. as a strategy to control bone loss,
a person's hormone function is key;
[J Osteoporos. 2010]
but, never take hormones orally,
or when modified in some patented way;
that is how Hormone Replacement Therapy
got a bad reputation.
. see Dr.Lee about progesterone cream
for bone health as summarized by Dr.Jo.

GPR55 (G protein-coupled receptor 55):
affects bone remodeling.
. agonists or activators include Δ9-THC;
Antagonists include Cannabidiol (CBD).

Proc Natl Acad Sci U S A. 2009:
The putative cannabinoid receptor GPR55
affects osteoclast function in vitro and bone mass in vivo.
[
. this study found a role for GPR55 in bone physiology
by regulating osteoclast number and function,
with major implications for the development of
GPR55- and CBD-related therapeutics.

. there is considerable evidence for
a role of non-CB1/non-CB2 receptors in
mediating some of the effects of
certain cannabinoid ligands
that are antagonized by CBD (4).
Recently, the receptor GPR55 has been
shown to be antagonized by CBD
(IC50 = 445 nM) (5–8).
GPR55 is activated by the bioactive lipid,
L-α-lysophosphatidylinositol (LPI) (11, 12).

. GPR55 was expressed in human and mouse
osteoclasts and osteoblasts;
expression was higher in human osteoclasts
than in the macrophage they come from.
. a GPR55 agonist (13), had no effect
on the total number of αvβ3-positive osteoclasts
generated from human peripheral blood monocytes.
However, treatment of cultures with the
GPR55 antagonist CBD (6)
significantly increased osteoclast number.

GPR55 agonists inhibited osteoclast's
increases in number;
but stimulated osteoclast polarization
and [their rate of bone] resorption;
while causing activation of Rho and ERK1/2.
[ Rho is one of the key small GTPases
required for cytoskeletal reorganization
and MAPK activation during [bone cell] migration.
. ERK1/2 is a key signaling pathway
involved in chondrocyte differentiation;
long bones are formed through
endochondral ossification,
in which chondrocytes undergo a series of
proliferation and differentiation processes.
]
These stimulatory effects on osteoclast function
were attenuated by the GPR55 antagonist
cannabidiol (CBD). Furthermore,
treatment of mice with CBD
significantly reduced bone resorption in vivo.

Consistent with the ability of GPR55 to
suppress osteoclast formation
but stimulate osteoclast function,
analysis of the long bones from [CBD-treated] mice
revealed a significant increase in
the volume and thickness of trabecular bone
and the presence of unresorbed cartilage.

refs.
]-Proc Natl Acad Sci U S A. 2009.