Over 200 million people suffer from osteoporosis worldwide. Individuals with osteoporosis have increased rates of bone resorption while simultaneously having impaired osteogenesis. Most current treatments for osteoporosis focus on anti-resorptive methods to prevent further bone loss. However, it is important to identify safe and cost-efficient treatments that not only inhibit bone resorption, but also stimulate anabolic mechanisms to upregulate osteogenesis. Recent data suggest that macrophage polarization may contribute to osteoblast differentiation and increased osteogenesis as well as bone mineralization. Macrophages exist in two major polarization states, classically activated macrophages (M1) and alternatively activated macrophage (M2) macrophages. The polarization state of macrophages is dependent on molecules in the microenvironment including several cytokines and chemokines. Mechanistically, M2 macrophages secrete osteogenic factors that stimulate the differentiation and activation of pre-osteoblastic cells, such as mesenchymal stem cells (MSC’s), and subsequently increase bone mineralization. In this review, we cover the mechanisms by which M2 macrophages contribute to osteogenesis and postulate the hypothesis that regulating macrophage polarization states may be a potential treatment for the treatment of osteoporosis.
Based upon knowledge that the body creatine pool in normal males undergoes a constant fractional conversion rate to creatinine and that 24-hr urinary creatinine excretion is dependent upon creatine and protein intakes, we developed a mathematical model with feedback which describes the creatine pool size and, consequently, the 24-hr urinary creatinine excretion as a function of time after change in diet. Validity of the model was tested by comparing calculated with experimental changes in 24-hr urinary creatinine excretion rates of male volunteers who were participating in studies of effects of "high" and "low" protein diets on mineral requirements. The model was further verified by comparing published changes in creatinine excretion rates with changes predicted by the model. It is concluded that the effects of changes in creatine and protein intakes upon the body creatine pool size in healthy males can be described mathematically by a model with a feedback component. It is also cautioned that 24-hr urinary creatinine excretion may not be a good reference for quantifying other urinary substances under circumstances where the creatine or protein intakes are not constant.
Hyperlipidemia associated with cardiovascular health, and bone loss with regard to osteoporosis contribute to increased morbidity and mortality and are influenced by diet.
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