The invention encompasses compositions and methods for effectively treating and / or preventing the development and / or progression of 
osteoporosis and related disorders such as 
osteoarthritis and 
rheumatoid arthritis, and for promoting overall bone and joint health. This is accomplished by addressing multiple key mechanisms that lead to such disorders. The invention includes compositions comprising a combination of agents having biological activities that effectively suppress, regulate or interfere with the various key biochemical processes and mechanisms that increase the risk for development and / or progression 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).