The invention encompasses compositions and methods for effectively treating and / or preventing
osteoporosis and related disorders such as
osteoarthritis and
rheumatoid arthritis, and for promoting overall bone and joint health. This is accomplished by totally addressing the multiple mechanisms that lead to such disorders. The invention includes compositions comprising a combination of agents that effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that increase the risk for development of
osteoporosis. The present compositions and methods simultaneously promote
bone formation and reduce
bone resorption by (a) stimulating
osteoblast formation and osteogenesis; (b) suppressing
adipocyte differentiation; (c) inhibiting
osteoclast formation; and (d) increasing
apoptosis of osteoclasts. The inventive compositions used for administration to human and other mammalian subjects having or at risk for development of
osteoporosis comprise (1) at least one agent capable of modulating expression and / or activity of one or more of
peroxisome activated
protein receptor gamma (PPAR-γ), CAAT /
enhancer binding protein-α (C / EBPα) and
Sterol Regulatory Element-
Binding Protein (SREBP-1); (2) at least one agent that activates expression and / or activity of one or more of the osteogenic transcription factors (Runx2 / Cbfα1, Dlx5, Osterix, Msx2); (3) at least one agent that activates expression and / or activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4),
alkaline phosphatase (ALP), and
osteocalcin; (4) at least one agent capable of activating Wnt / β-
catenin signaling pathway; (5) at least one agent that inhibits the activity of pro-oxidants including
reactive nitrogen species and
reactive oxygen species (ROS); (6) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and
prostaglandin E2 (PGE2); and (7) at least one agent that induces the expression of and / or activates one or more of
adenosine monophosphate-activated
protein kinase (
AMPK),
sirtuin (SIRT1) and
adiponectin (AP).