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.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between −0.1 and −2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

Type 2 diabetes (T2D) is a major contributor to morbidity and mortality largely due to increased cardiovascular disease risk. This study examined the relationships among protein consumption and sources on glycemic control and cardiovascular health in individuals with prediabetes and T2D. Sixty-two overweight or obese participants with prediabetes or T2D, aged 45–75 years were stratified into the following three groups based on protein intake: <0.8 g (gram)/kg (kilogram) body weight (bw), ≥0.8 but <1.0 g/kg bw, and ≥1.0 g/kg bw as below, meeting, and above the recommended levels of protein intake, respectively. Body mass, body mass index (BMI), hip circumference (HC), waist circumference (WC), lean mass, and fat mass (FM) were significantly higher in participants who consumed below the recommended level of protein intake as compared with other groups. Higher animal protein intake was associated with greater insulin secretion and lower triglycerides (TG). Total, low-density, and high-density cholesterol were significantly higher in participants who met the recommended protein intake as compared with the other groups. These data suggest that high protein consumption is associated with lower BMI, HC, WC, and FM, and can improve insulin resistance without affecting lipid profiles in this population. Furthermore, higher intake of animal protein can improve β-cell function and lower plasma TG.

Background/Objectives: Approximately 53.4 million U.S. adults aged 50 or older have low bone mass, yet male bone loss remains under-researched. This study evaluated the effects of one year of prune supplementation on bone health in osteopenic men. Methods: Fifty-nine men (55–80 years) were randomly assigned to one of three groups: 0 g prune (control), 50 g prune, or 100 g prune daily, along with 450 mg elemental calcium and 800 IU vitamin D₃. Dual-energy X-ray absorptiometry (DXA) scans and blood samples were collected at baseline, 3, 6, and 12 months. Results: No significant changes were observed in total bone mineral density (BMD) over one year. C-reactive protein (CRP) was significantly higher in the control group compared to the 50 g group at all time points. Osteo-protegerin (OPG) decreased significantly in all groups, however, the decrease was significantly greater in the control compared to both prune groups. Sclerostin (SOST) significantly increased over time in all groups, albeit to a greater degree in the control group. Tartrate-resistant acid phosphatase-5b (TRAP5b) increased in the 50 g and control group but remained stable in the 100 g group. Conclusions: Overall, prune supplementation did not improve BMD beyond that of the calcium and vitamin D₃ supplementation however, there was a modest effect on biomarkers of inflammation and bone metabolism.