Current research efforts, although limited, clearly indicate that the gut microbiota may be implicated in bone metabolism, and therefore, further exploration of this relationship is a promising area of focus in bone health and osteoporosis research. Although most existing studies investigate this relationship using animal models, human studies are both needed and on the horizon.

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, costs, and consequences of calcium supplementation on osteoporosis/osteoporotic fractures, cardiovascular events, kidney stones, gastrointestinal diseases, and other important diseases. In the end, we suggest that calcium supplementation should be prescribed and taken cautiously, accounting for individual patients’ risks and benefits. Clearly, further studies are needed to examine the health effects of calcium supplementation to make any solid recommendations for people of different genders, ages, and ethnicities.

BACKGROUND AND PURPOSE Intracellular pharmacokinetics of anticancer drugs in multi‐drug resistance (MDR) cancer cells is hugely important in the evaluation and improvement of drug efficacy. By using adriamycin as a probe drug in MDR cancer cells, we developed a cellular pharmacokinetic‐pharmacodynamic (PK‐PD) model to reveal the correlation between cellular pharmacokinetic properties and drug resistance. In addition, the ability of 20(S)‐ginsenoside Rh2 (20(S)‐Rh2) to reverse MDR was further investigated. EXPERIMENTAL APPROACH The cellular pharmacokinetics of adriamycin were analysed visually and quantitatively in human breast cancer cells MCF‐7 and in adriamycin‐resistant MCF‐7 (MCF‐7/Adr) cells. Mitochondria membrane potential was assayed to evaluate the apoptotic effect of adriamycin. Subsequently, a PK‐PD model was developed via MATLAB. KEY RESULTS Visual and quantitative data of the dynamic subcellular distribution of adriamycin revealed that it accumulated in cells, especially nuclei, to a lesser and slower extent in MCF‐7/Adr than in MCF‐7 cells. 20(S)‐Rh2 increased the rate and amount of adriamycin entering cellular/subcellular compartments in MCF‐7/Adr cells through inhibition of P‐glycoprotein (P‐gp) activity, in turn augmenting adriamycin‐induced apoptosis. The integrated PK‐PD model mathematically revealed the pharmacokinetic mechanisms of adriamycin resistance in MCF‐7/Adr cells and its reversal by 20(S)‐Rh2. CONCLUSIONS AND IMPLICATIONS P‐gp, which is overexpressed and functionally active at cellular/subcellular membranes, influences the cellular pharmacokinetic and pharmacological properties of adriamycin in MCF‐7/Adr cells. Inhibition of P‐gp activity represents a key mechanism by which 20(S)‐Rh2 attenuates adriamycin resistance. Even more importantly, our findings provide a new strategy to explore the in‐depth mechanisms of MDR and evaluate the efficacy of MDR modulators.