The Use Of Selected Parameters Of Bone Microenvironment For The Assessment Of Skeletal Involvement and Activity In Multiple Myeloma and Monoclonal Gammopathy Of Undetermined Significance
Authors: Minarik Jiri , Pusciznova Petra , Petrova Pavla , Herman Miroslav , Pika Tomas , Hrbek Jan , Bacovsky Jaroslav , Zapletalova Jana , Scudla Vlastimil 
Published: October 2019

Abstract

Aims
The aim ouf our project was to correlate serum levels of selected parameters of bone microenvironment to the extent of skeletal involvement assessed by conventional X-ray and magnetic resonance imaging in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).

Material and methods
Our cohort consisted of 75 patients with monoclonal gammopathies. There were 57 patients with active multiple myeloma (32 patients at the time diagnosis and 25 patients in relapse/progression) and 18 patients with MGUS. Skeletal involvement was assessed using conventional radiography and whole-body magnetic resonance imaging (WB-MRI). We assessed following parameters of bone marrow microenvironment: osteocalcin (OC), bone alkaline phosphatase (bALP), parathormone (PTH), carboxyterminal telopeptide of collagen type-I (ICTP), N-terminal propeptide of procolagen type-I (PINP), insulin like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), syndecan-1/CD138 (SYN), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG), osteopontin (OPN), endostatin (ES), macrophage inflammatory protein 1α and 1β (MIP-1α, MIP-1β), interleukin-17 (IL-17) and angiogenin (ANG). For statistical estimation we used Spearman correlation analysis, Fisher exact test, and Kruskal-Walis test, p < 0,05.

Results
We found positive significant correlation between the extent of skeletal involvement using X-ray and WB-MRI (correlation coefficient, cc = 0,386, p = 0,004). In 40,63% of patients WB-MRI showed higher skeletal involvement ≥ grade 2 in comparison with X-ray. There were significant differences in skeletal involvement between active phase MM and MGUS. WB-MRI had 17% less „false-positive“ findings in MGUS, and in active MM it showed only 3,6% negative skeletal involvement in comparison with 21,1% „false negative“ cases using conventional X-ray. Assessing serum levels of bone metabolism parameters we found significant positive correlation with skeletal involvement in ICTP (cc = 0,306, p = 0,023), PINP (cc = 0,274, p = 0,039), and OPN (cc = 0,331, p = 0,013). Six of the parameters had significantly higher levels in active MM in comparison with MGUS: ICTP (median, M = 9,1 vs 4,5 ug/l, p = 0,003), HGF (M 1921 vs 1251 ng/l, p = 0,019), SYN (M 81,8 vs 39,5 ng/l, p =0,016), OPN (M 92,9 vs 49,1 ug/l, p =0,001), and ANG (M 410288 vs 195140 ng/l, p = 0,011). In the rest of the parameters the differences were not statistically significant.

Conclusions
WB-MRI is more sensitive and specific in the assessment of myeloma bone disease. It can reveal false-positive cases of osteolytic involvement as well as false false-negative finding in MGUS in significant number of patients with monoclonal gammopathies. Serum parameters of bone microenvironment correlate with both the activity of the disease as well as with the extent of myeloma bone disease. The best discriminators of the activity were ICTP, HGF, syndecan, osteopontin and angiogenin. The most sensitive parameters of skeletal involvement were ICTP, PINP and osteopontin. Positive correlation of bone microenvironment parameters suggest their wider utility in clinical practice.
With support of the grant IGA MZ CR NT14393 and NT12451/5.

Disclosures:
No relevant conflicts of interest to declare.