The Warburg effect in osteoporosis: Cellular signaling and epigenetic regulation of energy metabolic events to targeting the osteocalcin for phenotypic alteration

ABSTRACT
Osteoporosis is a silent disease of skeletal morphology that induces fragility and fracture risk in aged persons
irrespective of gender. Juvenile secondary osteoporosis is rare and is influenced by familial genetic abnormalities.

Despite the currently available therapeutic options, more-acute treatments are in need. Women suffer from oste-
oporosis after menopause, which is characterized by a decline in the secretion of sex hormones in the later phase of

life. Several studies in the past two decades emphasized hormone-related pathways to combat osteoporosis. Some
studies partially examined energy-related pathways, but achieving a more vivid picture of metabolism and bone
remodeling in terms of the Warburg phenomenon is still warranted. Each cell requires sufficient energy for cellular
propagation and growth; in particular, osteoporosis is an energy-dependent mechanism affected by a decreased
cellular mass of the bone morphology. Energy utilization is the actual propagation of such diseases, and narrowing
down these criteria will hopefully provide clues to formulate better therapeutic strategies. Oxidative glycolysis is a
particular type of energy metabolic pathway in cancer cells that influences cellular proliferation. Therefore, the
prospect of utilizing collective glucose metabolism by inducing the Warburg effect may improve cell propagation.
The benefits of utilizing the energy from the Warburg effect may be a difficult task. However, it seems to improve
their effectiveness in the osteoblast phenotype by connecting the selected pathways such as WNT, Notch, AKT, and
Insulin signaling by targeting osteocalcin resulting in phenotypic alteration. Osteocalcin directs ATP utilization
through the sclerostin SOST gene in the bone microenvironment. Thus, selective activation of ATP production
involved in osteoblast maturation remains a prime strategy to fight osteoporosis.