The initial values of densities of bone cells and MM cells in the MM-bone model.

Note 1: BMSC is 1/2.5×105 of total bone marrow cells in adults [21]; the estimated number of total cells in leg bone marrow is 4.4×1011 (#) (http://bloodguys.com/blood-education); the volume of bone marrow in leg is 8.6% of total bone marrow volume [76]; By assuming that cells in bone marrow are evenly distributed in different bone types, the number of BMSC in adults is 2.05×107 (#) ( = 4.4×1011/8.6%/2.5×105). Given that MM is generally occurred in the elder people and BMSC percentage in bone marrow decreases to 1/2×106 in elder people aged 80 [21], the estimated BMSC number is corrected to ¼ of the number in adults, namely 5.12×106 (#).Note 2: It is assumed to be 1.2-fold greater than the number of active osteoblasts (OBa).Note 3: There are 1∼2×106 BMU [77] in the total body while there are about 102∼103 active osteoblasts (OBa) per BMU [78]. Hence, we estimate OBa numbers as 1×109 (#).Note 4: Active osteoclasts (OCa) includes 9 nuclei [8] because they are fused by osteoclast precursors (OCp) differentiated cells. By assuming that OCp is 12-fold of OCa, The estimated OCp number is 2×109 (#).Note 5: There are about 10∼102 active osteoclasts (OCa) per BMU [78]. Hence, we estimate OCa number as 1.67×108 (#).Note 6: Synthesis rate of M-protein by MM cells is 0.5∼1.2×10−11 g/day/MM cell; the half-life of M-protein is 11.6∼17 days [79]; the volume of total blood in the adult is 5L; the diagnosis of MM is required the concentration of M-protein is greater than 30 g/L [57]. As a result, the estimated MM cell number at the diagnosis is 5.1×1011 (#) ( = 30×5× (log(2)/17)/1.2×10−11).Note 7: All the estimated cell numbers (#) are based on the total human body. They are converted into density (pM) by divided by Avogadro number (6.02×1023 #/mol) and the volume of total bone marrow, which is estimated 2.6L because the estimated mass of total bone marrow is 2.6 kg (http://en.wikipedia.org/wiki/Bone_marrow) and the marrow density is assumed to be close to water.