膳食钙能否预防骨髓瘤的发生？

Multiple myeloma (MM) is the second most common blood cancer. It remains an incurable disease due to relapsing and developing treatment resistance. Treatment resistance and disease progression are not solely due to intrinsic MM characteristics but are also fostered by alterations within the surrounding BM microenvironment. The bone serves as a home for growing myeloma but is also a target organ for myeloma cells. The MM-bone disease (MMBD) is one of the defining features of MM. A previous report showed that myeloma cells colonize the endosteal niche, enter a dormant state, and are activated by bone-lining cells. We previously found that bone anabolic agent exhibited marginal effects on MM progression with bone formation. Furthermore, we found that the surviving mice from myeloma transplants become tolerable to subsequent tumor transplantation. The Sigma Anti-Bonding Calcium Carbonate (SAC) is a chemically modified form of calcium carbonate with unique weak bonding and a potent dietary calcium supplement. We found that the SAC is a highly reactive in chemical reaction and the dietary supplement increases serum calcium ion concentration, osteogenic potential of bone marrow progenitors, and increase bone mass. Due to its exceptional bone anabolic capability, we decided to test the SAC to multiple myeloma bone disease (MMBD) mouse model. We pretreated mice with SAC for 4 weeks before 5TGM1-transplanted mice (TbT) and then tested myeloma growth. It may mimic a treatment in the pre-emerging or -relapsed period of MM . We divided the 8-12-week-old NOD SCID gamma mice into PBS, TbT, and TaT. SAC was gavaged twice daily, five days/week, for four weeks before the transplantation (TbT) or two weeks after transplant (TaT), while PBS was gavaged to the control group when TbT started. The 1x106 luciferase-expressing 5TGM1 cells were injected into the mice via the tail vein. Mice were imaged weekly by IVIS imager to assess the myeloma progression and terminated when endpoint criteria were met. All surviving mice were sacrificed one week after all PBS group mice died. We found that the median survival of PBS-treated mice was 39 days, while 45 days in the TaT group. To our surprise, >60% of TbT group mice survived until the end of the study. The bioluminescence image analysis showed that myeloma slowly progressed in both treated group mice. DEXA results demonstrated that bone minerals significantly increased in the spine of SAC-treated mice compared to the control mice. Trabecular thickness and bone volume density were significantly higher in the SAC-treated group at the lumbar spine compared to the PBS group. We also tested 14 PBS-treated or 20 SAC-treatment at TbT on 5TGM1-transplanted immune competent C57BL/KaLwRij mice. We found a significant bone matrix increase and improvement of median survival on SAC treatment with <40% mice lost until 70 days post-transplantation, while 39 days of median survival on PBS-treated with 80% mice lost due to MM phenotype. In summary, we discovered that pretreatment of potent calcium, SAC, significantly prevents MM progression in both immune deficient and competent mice. We conclude that improving the bone microenvironment with potent calcium pretreatment prevents myeloma cell engraftment and/or growth in mice. These results may suggest a novel therapeutic regimen for MM during pre-emerging or -remission of multiple myeloma patients when treatment safety is ensured.