Study On Clinical Significance Of Bone Metabolic Markers And Osteoblast Precursors And Osteoclast Precursors In The Diagnosis And Monitoring Of Myeloma Bone Disease

Objective:To explore the significance of bone biochemical markers, osteoblast precursors(OBPs)and osteoclast precursors(OCPs) in the early diagnosis and monitoring disease status of myeloma bone disease.Methods:Thirty-six newly-diagnosed MM patients who had achieved complete response or partial response after combination of bortezomib + dexamethasone + zoledronic acid regimen. Bone morbidity was graded into two stages according to the radiographic evaluation of the skeleton. Stage A included patients with no lytic lesions or osteoporosis alone; stage B included patients with osteolytic lesions and/or a pathological fracture due to MM. 25 aged- and gender-matched healthy individuals were enrolled in this study. The levels of serum tartrate-resistant acid phosphatase isoform 5b(TRACP-5b), carboxy-terminal cross-linking telopeptide of type I collagen(CTX), osteocalcin(OCN) and procollagen I amino-terminal propeptide(PINP) were investigated by ELISA and electrochemiluminescence immunoassay(ECLIA). The percent of circulating OBPs(CD34+OCN+) and OCPs(CD14+CD16+) were investigated by flow cytometry. Clinical data were also analyzed.Results:1.The median value of serum TRACP-5b in the newly diagnosed MM was 4.16U/L, which was significantly higher than that in the remission group(2.61U/L) and the healthy controls(2.63U/L)(P=0.037 and P=0.014, respectively). Serum level of CTX(median 1.05ng/ml) in the newly diagnosed MM patients was significantly higher than post-treatment(median 0.26ng/ml) and the the healthy controls(median 0.48ng/ml)(P=0.003 and P=0.025, respectively). Serum levels of OCN and PINP among the pre-treatment and post-treatment MM patients and the healthy controls had no obvious difference(P>0.05). The ratio of CTX/OCN and CTX/PINP in the pre-treatment and post-treatment MM patients had no significant difference(P>0.05). The median percent of circulating OBPs in the newly diagnosed MM patients was 7.14%, which was reduced compared with the healthy controls(median 12.82%) and the remission group(median 8.97%)(P=0.045 and P>0.05, respectively). There were not distinct difference of circulating OBPs between the remission group and thehealthy controls(P>0.05). Our cohort of MM patients at diagnosis had elevated median percent of circulating OCPs(2.46%), which was elevated than the post-treatment patients(median 1.87%) and the healthy controls(median 0.17%)( P=0.000 and P>0.05, respectively). There were distinct difference of circulating OCPs between the remission group and the healthy controls(P=0.000). In addition, the median percent of circulating OBPs positively correlated with the number of platelet(r = 0.427, P = 0.033). The median percent of circulating OCPs positively correlated with the number of malignant plasma cell in bone marrow(r = 0.586, P = 0.017).2.The level of serum TRACP-5b in the MM patients with or without bone damage(4.20U/L and 3.67U/L, respectively) were all higher than those of the healthy controls(2.63U/L). There were distinct difference of serum TRACP-5b between the patients with bone damage and the healthy controls(P=0.015). The level of serum CTX in the MM patients with or without bone damage(0.88ng/ml and 1.16ng/ml, respectively) were higher than those of the healthy controls(0.48ng/ml)(P=0.040 and P=0.002, respectively). The levels of serum OCN and PINP in the MM patients without bone damage were higher than the patients with bone damage, but there were not distinct difference(P>0.05). The ratios of CTX/OCN and CTX/PINP of MM patients with or without bone damage were increased than those of the healthy individuals, yet there were not distinct difference(P>0.05). The median percent of circulating OBPs in MM patients without or with osteolytic lesions(7.14% and 7.47%, respectively) were reduced significantly than the healthy persons(12.82%)(P=0.010 and P=0.041, respectively). MM patients with or without osteolytic lesions had elevated median percent of circulating OCPs(2.71% and 2.31%, respectively) compared with the healthy persons(0.17%)(P=0.001 and P=0.010, respectively).Conclusions:The median value of serum TRACP-5b, CTX and the percent of circulating OCPs in the newly diagnosed MM patients were significantly higher than that in the remission group, while the OBPs was decreased. Effective chemotherapy reduce tumor burdon and may improve bone damage, promote bone reconstruction. The percent of circulating OCPs in post-treatment MM patients was still higher than the controls. The ratios of CTX/OCN and CTX/PINP in the pre-treatment andpost-treatment MM patients had no significant difference. Disease in remission does not mean bone imbalance has fully recovered. Treatment of MBD is a long-term process and requires continuous skeletal reconstruction treatment.The median level of serum TRACP-5b, CTX and the percent of circulating OCPs in the MM patients with or without bone damage were all higher than those of the healthy controls, the OBPs was decreased. Even though the skeletal X-ray scan showed no lytic bone lesions or only osteoporosis patients also present osteolytic damage. Abnormal levels of serum TRACP-5b, CTX and percent of circulating OCPs and OBPs were found before positive X-ray findings in MBD. Once MM diagnosed,the treatment of skeletal reconstruction must begin immediately. The specific CTX/OCN and CTX/PINP ratio can reflect the imbalance of osteoclast and osteoblast in MBD, they could be used as good indices for early diagnosing and monitoring MBD.