C950T and C1181G Osteoprotegerin Gene Polymorphisms In Myeloma Bone Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3128-3128
Author(s):  
Mehmet Sonmez ◽  
Nazli Kazaz ◽  
Burcu Yucel ◽  
Murat Topbas ◽  
Fahri Ucar
Keyword(s):  
Bone Disease ◽  
Haplotype Frequency ◽  
Control Group ◽  
Bone Lesions ◽  
Wild Type ◽  
Myeloma Bone Disease ◽  
Control Subjects ◽  
Polymorphic Allele ◽  
Exon 1 ◽  
And Control

Abstract Bone disease is one of the hallmarks of multiple myeloma (MM). The role of osteoprotegerin (OPG) in the RANK/RANKL/OPG signaling system is well defined in the myeloma bone disease. Polymorphisms of the TNFRSF11B gene encoding OPG have been studied in various bone diseases. However, relationship between the levels of OPG and development of bone lesions regardless of RANKL is yet unknown. In this study, the effects of OPG gene polymorphism on the development of bone lesions in MM were investigated. 52 MM patients, admitted to Karadeniz Technical University, Medical Faculty, Department of Internal Medicine, Division of Hematology between March 2011 and March 2012, were included into the study. Pathologic fracture and/or destructive bone lesions were confirmed in 36 MM patients using X-ray, computed tomography (CT), or magnetic resonance imaging (MRI). No bone lesions were noted in 16 patients. The control group consisted of 20 age and gender matched volunteers. Exon 1 of OPG gene was sequenced using DNA samples obtained from peripheral blood samples of 52 MM patients and 20 healthy control subjects. OPG gene C950T and C1181G polymorphisms were identified in 45 (33 with bone lesions) MM patients and in 16 control subjects. Polymorphic allele 1181G was higher in MM patients with bone lesions compared to MM patients without bone lesions and control group (χ2=8.629, p=0.013). Other polymorphic allele 950T was also overrepresented (73%; p=0.042) in MM patients with bone lesions compared to MM patients without bone lesions and the control group. The most frequent genotype observed in patients with myeloma bone lesions was 950 TT homozygous variant (56%, p=0.08) followed by 1181 CC homozygous wild type with 50% frequency (p=0.09). The frequency of 950 CT heterozygous genotype was higher in MM patients without bone lesions (50%, p=0.604). 1181 GG genotype showed higher frequency in MM patients with bone lesions compared to patients without bone lesions and control group (χ2=3.853, p=0.145). Of the combined haplotypes, 950 TT/1181 GG haplotype frequency is higher in patients with myeloma bone lesions (36%) compared to MM patients without bone lesions (13%) and controls (15%) (χ2=4.77, p=0.09). The frequency of TT/GG combined haplotype carriers in bone disease patients is higher than of those who do not have either polymorphic homozygous alleles (CT/CC and CC/CC haplotypes) (χ2=6.057, p=0.048). Additionally, 950 CC/1181CC wild type haplotype frequency was reasonably low in patients with myeloma bone lesions (8.3%, p=0.240). This is the first study searching for the relationship between OPG gene variants C950T (promoter), C1181G (exon 1) and myeloma bone disease. It was concluded that the presence of polymorphic 1181 G/950 T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Intermuscular Fat Content in Young Chinese Men With Newly Diagnosed Type 2 Diabetes: Based on MR mDIXON-Quant Quantitative Technique

2021 ◽  
Vol 12 ◽  
Author(s):  
Fuyao Yu ◽  
Bing He ◽  
Li Chen ◽  
Fengzhe Wang ◽  
Haidong Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fat Content ◽  
Control Group ◽  
Diabetic Patients ◽  
Diabetes Group ◽  
Control Subjects ◽  
Intermuscular Fat ◽  
And Control

ObjectiveSkeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.MethodsWe enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsWe found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p<0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p<0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p<0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.ConclusionDeposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.

Thyroid Nodules in Patients with Acromegaly: Frequency According to the ACR TI-RADS Classification and its Relationship with Disease Activity

2021 ◽  
Author(s):  
Mustafa Can ◽  
Muhammet Kocabaş ◽  
Melia Karakose ◽  
Hatice Caliskan Burgucu ◽  
Zeliha Yarar ◽  
...  
Keyword(s):  
Disease Activity ◽  
Thyroid Nodules ◽  
Thyroid Volume ◽  
Thyroid Stimulating Hormone ◽  
Control Group ◽  
Control Subjects ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Mean ◽  
And Control

Abstract Purpose: In our study, we aimed to determine the frequency of thyroid nodules in patients with acromegaly according to the American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) classification and its relationship with acromegaly disease activity. Methods: A total of 56 patients with acromegaly and age, sex, and body mass index matched with 56 healthy control subjects were included in our study. Thyroid-stimulating hormone, free thyroxine, and anti-thyroperoxidase antibody levels of patients and control subjects were measured. In addition, patients and healthy controls were evaluated by ultrasonography to determine thyroid structure, thyroid volume, and thyroid nodules and to make ACR TI-RADS classification. Results: Thyroid nodules were present in 31 (55.4%) of 56 patients in the acromegaly group and 20 (35.7%) of 56 subjects in the control group, and the frequency of thyroid nodules was significantly higher in the acromegaly group (p=0.038). The mean number of nodules in the acromegaly group and control group was 1.27±1.43 and 0.48±0.73, respectively, and the mean number of nodules was significantly higher in the acromegaly group (p=0.003). The number of patients with TI-RADS 1, TI-RADS 2, and TI-RADS 4 nodules in the acromegaly group was higher than the control group (p=0.026, p=0.049, p=0.007, respectively). No difference was found in terms of cytological findings between those who have undergone FNAB in the acromegaly group and control group. Conclusion: In our study, we found that the frequency of thyroid nodules, the number of thyroid nodules, and the number of TI-RADS 1, TI-RADS 2, and TI-RADS 4 nodules increased in patients with acromegaly. There was no significant difference between acromegaly disease activity and thyroid nodule frequency, number of thyroid nodules, and TI-RADS classifications.

The inter-relationship of premenstrual symptoms

1995 ◽  
Vol 25 (5) ◽  
pp. 947-955 ◽  
Author(s):  
M. Mira ◽  
S. Abraham ◽  
D. McNeil ◽  
J. Vizzard ◽  
P. Macaskill ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Premenstrual Symptom ◽  
Control Group ◽  
Factor Scores ◽  
Premenstrual Symptoms ◽  
Mood Symptoms ◽  
Control Subjects ◽  
Symptom Reports ◽  
And Control

SYNOPSISThe prospective symptom reports of women seeking treatment for premenstrual symptoms and control subjects were investigated. In order to compare symptom reports from premenstrual symptom sufferers and control subjects a method of combining and analysing prospectively collected menstrual cycle symptom data is required. A technique that uses the time of onset of menses and the time of ovulation (as measured by urinary luteinizing hormone excretion) to standardize each cycle into 14 time points was developed. Summary factors were then empirically derived from data collected prospectively from 30 premenstrual symptom sufferers and 19 control subjects. Twenty-two mood symptoms were summarized into a single factor and the 29 most frequently occurring physical symptoms were summarized into two factors. Factor scores were calculated on the basis of these factors and the effect of time during the menstrual cycle on these scores examined. Both physical symptom factor scores increased significantly in the luteal phase for both the premenstrual symptom sufferer group and the control group. The single mood factor score increased significantly in the luteal phase for the premenstrual symptom sufferer group but not for the control group, suggesting that the only qualitative difference between the groups was the presence of cyclic mood symptoms in the premenstrual symptom sufferer group. The premenstrual symptom sufferer group recorded significantly higher scores on each of the three factors than the control group. The correlation between the scores on each of the factors over three cycles was high both in the follicular and luteal phase suggesting that these factor scores provide a reproducible measure of menstrual cycle symptomatology.

Seroprevalence of Helicobacter pylori infection in patients with chronic nonspecific pharyngitis: preliminary study

2007 ◽  
Vol 122 (1) ◽  
pp. 61-64 ◽  
Author(s):  
İ Aladag ◽  
Y Bulut ◽  
M Guven ◽  
A Eyibilen ◽  
K Yelken
Keyword(s):  
Helicobacter Pylori ◽  
Treatment Strategies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Control Groups ◽  
Chi Square ◽  
Control Subjects ◽  
The Difference ◽  
H Pylori ◽  
And Control

AbstractBackground and objectives:Chronic nonspecific pharyngitis is a chronic inflammation of the pharynx. It is found worldwide, and treatment is difficult. The underlying aetiopathogenesis is still controversial. The aim of this study was to investigate Helicobacter pylori seroprevalence in chronic nonspecific pharyngitis patients without other possible causative factors for chronic pharyngeal irritation and without H pylori gastric mucosal infection.Materials and methods:Forty-one patients with symptoms of chronic nonspecific pharyngitis and 30 healthy control subjects were enrolled in this prospective, controlled, clinical study. In both study and control groups, selected patients were shown to have gastric mucosa uninfected by H pylori, as demonstrated by the 14C-urea breath test. Comprehensive otorhinolaryngological examination did not elicit any factor contributing to the chronic pharyngeal complaint. Serum H pylori immunoglobulin G antibody titres were assayed using serum enzyme-linked immunosorbent assay. The difference between the study and control groups was analysed by the chi-square test (the likelihood ratio was used).Results:Thirty-two of the 41 patients (78 per cent) and 14 of the 30 control subjects (46.7 per cent) were found to be H pylori positive. Patients with chronic nonspecific pharyngitis were found to have a significantly higher rate of H pylori seropositivity than the control group (p = 0.016).Conclusion:These data may be important in developing future treatment strategies for chronic nonspecific pharyngitis.

Inhibition of p38α MAPK Reduces Tumor Burden, Prevents the Development of Myeloma Bone Disease, and Increases Survival in the 5T2 and 5T33 Murine Models of Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3436-3436 ◽  
Author(s):  
Karin Vanderkerken ◽  
Satya Medicherla ◽  
Les Coulton ◽  
Benjamin Van Camp ◽  
Andy Protter ◽  
...  
Keyword(s):  
Bone Disease ◽  
Critical Role ◽  
Disease Free Survival ◽  
Myeloma Cell ◽  
Bone Lesions ◽  
Myeloma Cells ◽  
Growth And Survival ◽  
Myeloma Bone Disease ◽  
Osteolytic Bone Disease

Abstract The bone microenvironment plays a critical role in supporting the growth and survival of myeloma cells and the development of osteolytic bone disease. Signalling through p38 α MAPK mediates synthesis of myeloma cell survival factors by stromal cells; whereas, inhibiting p38 α MAPK reduces myeloma cell proliferation and inhibits osteoclast formation in vitro. However, it is unclear whether p38 α MAPK inhibition will prevent the growth and survival of myeloma cells and the bone disease in vivo. The aim of this study was to determine whether SCIO-469, a selective p38 α MAPK inhibitor, would inhibit myeloma growth and prevent the development of bone disease in the 5TMM syngeneic models of myeloma. Treatment of 5TMM cells, in vitro, with SCIO-469 resulted in a clear inhibition of p38 phosphorylation, as assessed by Western blotting and an inhibition up to 35% of stromal cell induced 5T33MM proliferation. Injection of 5T2MM murine myeloma cells into C57Bl/KaLwRij mice resulted in the growth of myeloma in bone and the development of bone disease characterized by increased osteoclast surface (p<0.05), a reduction in cancellous bone (p<0.01) and the presence of osteolytic bone lesions on x-ray (p<0.01). Treatment of 5T2MM-bearing mice with SCIO-469 (150mg/kg in the diet, therapeutical treatment from paraprotein detection) resulted in a 42% decrease in serum paraprotein and prevented development of osteolytic lesions (p<0.01). Injection of 5T33MM cells into C57Bl/KaLwRij mice also resulted in the development of myeloma but not associated bone disease. Treatment of 5T33MM-bearing mice from the time of tumor cell injection with SCIO-469 resulted in a decrease in serum paraprotein (8.8+/−1.4g/dl to 0.04+/− 0.03g/dl, p<0.001) and a reduction in the proportion of tumor cells in the bone marrow (67 +/− 8.1% to 1.09 +/− 0.58%, p<0.001). Kaplan-Meier analysis demonstrated an increase in disease-free survival (veh=27.5 days vs 96 days, p<0.001) after treatment of the mice with SCIO-469. These data demonstrate that targeting p38 α MAPK with SCIO-469 is associated with an anti-myeloma effect, which indirectly prevents the development of myeloma bone disease.

Serum Concentrations of DKK-1 Correlate with the Extent of Bone Disease in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3518-3518
Author(s):  
Martin Kaiser ◽  
Maren Mieth ◽  
Peter Liebisch ◽  
Susanne Rötzer ◽  
Christian Jakob ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Serum Levels ◽  
Conventional Radiography ◽  
Bone Lesions ◽  
X Rays ◽  
Myeloma Bone Disease ◽  
Lytic Lesions ◽  
Significant Difference ◽  
First Time

Abstract Objectives: Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells was reported to cause inhibition of osteoblast precursors. DKK-1 is an inhibitor of the Wnt/β-catenin signaling, which is a critical signaling pathway for the differentiation of mesenchymal stem cells into osteoblasts. So far there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions. Methods: DKK-1 serum levels were quantified in 184 previously untreated MM patients and 33 MGUS patients by ELISA, using a monoclonal anti-DKK-1 antibody. For the evaluation of bone disease, skeletal X-rays were performed. Results: Serum DKK-1 was elevated in MM as compared to MGUS (mean 11,963 pg/mL versus 1993 pg/mL, P < 0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL versus 15,209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL versus 17,915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1–3 vs. >3 lesions: mean 3114 pg/mL vs. 3559 pg/mL vs. 24,068 pg/mL; P = 0.002). Conclusion: This is the largest study of DKK-1 serum levels in multiple myeloma patients and data show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, suggesting that DKK1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

Bone Turnover Biomarkers Are Useful In Monitoring Myeloma Bone Disease and As Early Predictor Biomarkers For Relapse Disease In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1869-1869
Author(s):  
Kay Reen Ting ◽  
Abdul Hameed ◽  
Jennifer Brady ◽  
Paul Dowling ◽  
Colin Clarke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Turnover ◽  
Bone Disease ◽  
Newly Diagnosed ◽  
Serum Free ◽  
Myeloma Bone Disease ◽  
And Control ◽  
Early Predictor

Abstract Background Multiple myeloma is a plasma cell disorder characterised by bone marrow infiltration with clonal plasma cells that secrete monoclonal immunoglobulin which is detected in serum or urine samples. Bone disease is a well-known devastating complication. It has a significant impact to the quality of life and morbidity in multiple myeloma. The uncoupling effect of osteoblast and osteoclast activity is the major element in development of myeloma bone disease (MBD). Imaging techniques are used as the current standard method for detection of bony lesions. They have limitations as they cannot provide a real-time assessment of bone turnover. Early detection of relapse disease is crucial to allow preventative therapeutic intervention as it could significantly impact on quality of life. Aims Bone biomarkers such as C-terminal telopeptide of type 1 collagen (CTX-1) and procollagen type 1 N-propeptide (P1NP) can be used as an early predictor marker for MBD relapses and a monitor for MBD at different stages of the disease. Methods CTX-1 and P1NP were measured by chemiluminescent immunoassay on fasting plasma samples from 111 patients including newly diagnosed multiple myeloma (n=28), remission (n=34), relapses (n=22) and control (n=27). These were measured at regular intervals over a 30 month study period. Relapse disease was identified by conventional biomarkers like paraprotein and serum free light chains, and confirmed by imaging and bone marrow biopsy. In a subset of patients with disease relapse, the Mann-Whitney test was used to compare bone markers pre-relapse and at relapse. Results CTX-1 levels were significantly higher in newly diagnosed multiple myeloma compared to remission and control groups (p < 0.0001). In relapse group, CTX-1 rose significantly at the time of pre-relapse to relapse state (p=0.0001). A rise of ≥ 2.0 fold rise in the level of CTX-1 from remission to relapse disease was noted. The median time between the pre-relapse sample and relapse disease was 3 months (range 1-14 months). Most of them had new bone lesions at relapse. This proves that it has potential as an early predictor of relapse or progressive bone disease. A case showed CTX-1 level was the only biochemical parameter to rise significantly prior to relapse as compared to the other conventional biomarkers (ie. paraprotein and serum free light chain). As for P1NP, the rise in P1NP from pre-relapse to relapse was not significant (p=0.0810). Conclusion Osteoclast biomarker serum CTX-1 correlates accurately with the disease burden in newly diagnosed multiple myeloma patients as compared to the rest of the groups. It is a more sensitive early predictor of relapse/progressive disease than established biomarkers. It is a more robust marker than P1NP. The rise in P1NP goes against the theory that there is an uncoupling of bone turnover in MBD and requires further study. CTX-1 is more cost effective and accessible than imaging and should be used routinely when monitoring bone disease activity in multiple myeloma patients, facilitating early intervention when relapse occurs. Disclosures: No relevant conflicts of interest to declare.

Ibandronate Reduces Osteolytic Lesions but not Tumor Burden in a Murine Model of Myeloma Bone Disease

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1697-1706 ◽  
Author(s):  
Sarah L. Dallas ◽  
I. Ross Garrett ◽  
Babatunde O. Oyajobi ◽  
Mark R. Dallas ◽  
Brendan F. Boyce ◽  
...  
Keyword(s):  
Murine Model ◽  
Bone Disease ◽  
Bone Destruction ◽  
Myeloma Cell ◽  
Tumor Burden ◽  
Clinical Findings ◽  
Bone Lesions ◽  
Detectable Effect ◽  
Myeloma Cells ◽  
Myeloma Bone Disease

We determined the effects of the potent bisphosphonate ibandronate in a murine model of human myeloma bone disease. In this model, bone lesions typical of the human disease develop in mice following inoculation of myeloma cells via the tail vein. Treatment with ibandronate (4 μg per mouse per day) significantly reduced the occurrence of osteolytic bone lesions in myeloma-bearing mice. However, ibandronate did not prevent the mice from developing hindlimb paralysis and did not produce a detectable effect on survival. There was no significant effect of ibandronate on total myeloma cell burden, as assessed by morphometric measurements of myeloma cells in the bone marrow, liver, and spleen, or by measurement of serum IgG2b levels. These results support clinical findings that bisphosphonates may be useful for the treatment of myeloma-associated bone destruction, but suggest that other therapies are also required to reduce tumor growth.

scholarly journals An Improved Animal Model of Multiple Myeloma Bone Disease

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4277
Author(s):  
Syed Hassan Mehdi ◽  
Carol A Morris ◽  
Jung Ae Lee ◽  
Donghoon Yoon
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Myeloma Bone Disease ◽  
Nsg Mice ◽  
Morphometric Analyses ◽  
Imaging Results ◽  
Nsg Mouse

Multiple myeloma (MM) is a plasma cell malignancy that causes an accumulation of terminally differentiated monoclonal plasma cells in the bone marrow, accompanied by multiple myeloma bone disease (MMBD). MM animal models have been developed and enable to interrogate the mechanism of MM tumorigenesis. However, these models demonstrate little or no evidence of MMBD. We try to establish the MMBD model with severe bone lesions and easily accessible MM progression. 1 × 106 luciferase-expressing 5TGM1 cells were injected into 8–12 week-old NOD SCID gamma mouse (NSG) and C57BL/KaLwRij mouse via the tail vein. Myeloma progression was assessed weekly via in vivo bioluminescence (BL) imaging using IVIS-200. The spine and femur/tibia were extracted and scanned by the micro-computer tomography for bone histo-morphometric analyses at the postmortem. The median survivals were 56 days in NSG while 44.5 days in C57BL/KaLwRij agreed with the BL imaging results. Histomorphic and DEXA analyses demonstrated that NSG mice have severe bone resorption that occurred at the lumbar spine but no significance at the femur compared to C57BL/KaLwRij mice. Based on these, we conclude that the systemic 5TGM1 injected NSG mouse slowly progresses myeloma and develops more severe MMBD than the C57BL/KaLwRij model.

scholarly journals PROGNOSTIC VALUE OF THE BONE TURNOVER MARKERS IN MULTIPLE MYELOMA

2017 ◽  
Vol 39 (1) ◽  
pp. 53-56 ◽  
Author(s):  
D Auzina ◽  
S Lejniece
Keyword(s):  
Multiple Myeloma ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Bone Disease ◽  
Diagnostic Marker ◽  
Control Group ◽  
Bone Lesions ◽  
Bone Resorption Marker ◽  
Baseline Values ◽  
Turnover Markers

Background: Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and reduced osteoblast function. Aim: The aim of our research was to determine connection between bone turnover markers and presence of bone lesions, their degree of severity, to monitor MM bone disease and to assess effectiveness of anti-myeloma treatment. Materials and Methods: Serum samples and clinical data from 123 patients with newly diagnosed MM were collected at Riga East Clinical University Hospital (Riga, Latvia) from June 2014 to June 2016. Bone lesions detected by radiography, CT scans, MRI, and PET/CT were divided into degrees from 0 to 3 (0 — no bone involvement, 1 — ≤ 3 bone lesions, 2 — ≥ 3 bone lesions, 3 — fracture). Staging was performed applying Durie/Salmon (DS) and International Staging System classifications. Progressive disease was defined as development of one or more new bone lesions. The levels of bone metabolic markers β-isomerized C-terminal telopeptide of collagen type I (β-CTX) and bone-specific alkaline phosphatase (bALP) were monitored regularly in the year. Results: Bone lesions were found in 86 (69%) patients. From these 6 (4%) patients had 1st degree, 11 (9%) had 2nd degree and 69 (56%) had 3rd degree bone lesions. Level of the bone resorption marker β-CTX in the control group was 0.41 ng/ml, which is lower than in MM patients (p < 0.001). Spearman correlation coefficient analysis found a positive and statistically significant correlation (rs = 0.51, p < 0.001) between bone lesions degree and β-CTX levels. Mean β-CTX for patients without bone lesions was 0.72 ng/ml (SD = 0.64), but for patients with 3rd degree bone lesions it was 1.34 ng/ml (SD = 0.65) difference being 38% (p < 0.001). In patients who responded to therapy after 6 months of treatment reduction of β-CTX was found compared to baseline values (M = –0.65). In contrast, in patients who did not respond to therapy, there was a statistically significant (p < 0.001) increase in β-CTX values after six months of treatment compared to baseline values (M = 0.42). Exact cutoff value of β-CTX is 0.79. When analyzing mean bALP, no significant difference between MM patients and control group was found. ANOVA statistical analysis showed no statistically significant differences in bALP levels at different degrees of bone lesions (p = 0.95) in MM patients. Analysis of bALP suitability as MM diagnostic marker using receiver operating characteristics curve showed that bALP is not applicable for clinical diagnosis of MM (AUC 0.5, p > 0.05). However, β-CTX was found to be an excellent diagnostic marker for MM (AUC 0.91; 95% confidence interval, 0.88–0.94; p < 0.001). Conclusions: Patients with MM and bone lesions have increased value of bone resorption marker β-CTX. There is a correlation between bone resorption marker and degree of bone lesions. Changes in β-CTX levels may be used to monitor the effectiveness of myeloma treatment.

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