Low Testosterone Levels Are Associated with Shorter Progression Free Survival in Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4978-4978 ◽  
Author(s):  
Heather McDonagh ◽  
William Falk ◽  
Anissa Bingman ◽  
Susan Geyer ◽  
Don M. Benson ◽  
...  

Abstract Abstract 4978 Introduction: Testosterone (T) is important for maintenance of bone mineral density and muscle mass, stimulation of erythropoiesis, energy level, mood, and libido. Androgen deprivation therapy, i. e. near-complete hypogonadism, for prostate cancer is associated with type 2 diabetes, myocardial infarction, and overall mortality. In a study of male cancer patients with prostate and germ cell tumors, the prevalence of low T was 48–78% with opioid use, obesity, and being Caucasian as statistically significant covariates. Obesity increases T in women, with an associated increased breast cancer risk, and lowers T in men while raising estradiol levels. As fatigue and depression are common in multiple myeloma, we conducted a review of T in myeloma patients. None of the published literature has looked for an association between free testosterone and either characteristics of disease biology or concrete endpoints such as age of diagnosis, performance status, progression free survival, or overall survival. Methods: We retrospectively reviewed consecutive patients with plasma cell dyscrasias referred to Ohio State University that signed consent for the IRB-approved Ohio Myeloma Registry (www. ohiomyeloma. org). 343 patients were initially identified with either a total or free testosterone level available for evaluation, 171 patients with active myeloma. Results: 168 patients had a diagnosis of active myeloma and low or normal T – 44/171 (25%) were receiving opiates, 29/171 (17%) were taking anti-depressants, and 135/171 (79%) were male. 37/171 (22%) had type 2 diabetes and 92/171 (54%) had hypertension. The BMI median was 28. 9 (range 16. 9–53. 1) with 32 (19%) patients normal, 48 (28%) overweight, and 60 (35%) obese. The median time from diagnosis to T assessment was 49 days. In the entire cohort, the median free testosterone was 4. 17 (range 0. 11–16. 17) with 45 (26%) patients below the normal range, 123 (72%) within normal limits, and 3 (2%) with high T. In the subset of male patients (n=135), the median age was 61 y. o. (range 18–80). We designated two groups of male patients – 44 with low T and 91 with normal T. When comparing the two groups across hemoglobin, creatinine, calcium, stage, BMI, renal insufficiency, and anemia, there were no statistically significant differences. There was a difference between the presence or absence of lytic bone disease (p<0. 036) – less detectable bone disease on skeletal survey in the normal testosterone group. The median PFS in the low free T group was 23 months (16 events) and 35 months in the normal T group (27 events), p<0. 28. If we repeated this analysis but included women, the median PFS in the low free T group was 23 months compared to 35 months in the normal T group (p<0. 39). If we expand to include patients that had total as well as free testosterone, the median PFS was 24 months compared to 34 months with normal T (p<0. 23) (see figure). Conclusions: With approximately 30% of the cohort with severe hypogonadism (free testosterone below normal range) in a population predisposed to fractures, anemia, and depression, increased awareness of the prevalence of this diagnosis may change supportive care options for a population that often has a poor quality of life. There is a trend towards shorter PFS in patients with low free T. Disclosures: No relevant conflicts of interest to declare.

2017 ◽  
Author(s):  
Agathi Vasileiou ◽  
Ioanna Karathanassi ◽  
Parthena Navrozidou ◽  
Marianna Vlychou ◽  
Georgios Koukoulis ◽  
...  

2021 ◽  
Vol 23 (5) ◽  
pp. 424-433
Author(s):  
Olga N. Fazullina ◽  
Anton I. Korbut ◽  
Maksim V. Dashkin ◽  
Vadim V. Klimontov

BACKGROUND: Type 2 diabetes and osteoporosis are widespread diseases in the middle-aged and elderly people. Most studies of osteoporosis in patients with type 2 diabetes have been performed in women; meantime risk factors for lowering bone mineral density (BMD) in men have been little studied.AIMS: to identify risk factors for decreased BMD at the lumbar spine, femoral neck and forearm in men with type 2 diabetes.METHODS: Eighty two men from 50 to 75 years old, with duration of diabetes for at least one year, were included in the study. Individuals with known risk factors for secondary osteoporosis were not included. Twenty-three men with normal BMD having no diabetes or obesity were acted as control. The T-score at the lumbar spine, femoral neck and forearm of a non-dominant arm, as well as body composition parameters, were evaluated by dual-energy X-ray absorptiometry. The levels of hormones that affect bone metabolism (parathyroid hormone, free testosterone, 25-OH vitamin D) were measured in blood serum by ELISA. Risk factors for reducing BMD were identified using multivariate regression analysis and receiver operating characteristic (ROC) curves.RESULTS: Among patients with diabetes, 49 individuals had normal BMD and 33 showed decreased T-score values (<-1 SD). Free testosterone <5.92 pg/ml was predictor for decreased BMD at the lumbar spine (OR=4.4, p=0.04). For femoral neck, the risk factors were body weight <95.5 kg (OR=2.8, p=0.04), total fat mass <27 kg (OR=3.3, p=0.03), truncal fat mass<17.5 kg(OR=4.5, p=0.006), android (central abdominal) fat mass <3.2 kg(OR=4.0, p=0.01), gynoid (hip) fat mass <3.5 kg(OR=3.3, p=0.02), and lean mass <59 kg(OR=3.0, p=0.04). Risk factors for reduced BMD at the forearm were diabetes duration>15.5 years (OR=3.7, p=0.03) and HbA1c <8.15% (OR=3.8, p=0.03). Parathyroid hormone and 25-OH-vitamin D did not predict BMD independently.CONCLUSIONS: In men with type 2 diabetes, low free testosterone is a risk factor for decreased BMD in the lumbar spine, and diabetes duration is a risk factor for decreased BMD in the forearm. The presence of obesity is associated with an increase in BMD in the femoral neck; a high HbA1c is associated with an increase in BMD in the forearm.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P &lt;0.00001), labeling index (0.25; &lt;0.0001), creatinine (0.23; &lt;0.0001), soluble IL6 receptor (0.3; &lt;0.0001), BM plasma cell percentage (0.16; &lt;0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P &lt; 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P &lt; 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P &lt; 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.


BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e034741 ◽  
Author(s):  
Jiawen Deng ◽  
Umaima Abbas ◽  
Oswin Chang ◽  
Thanansayan Dhivagaran ◽  
Stephanie Sanger ◽  
...  

IntroductionPatients with type 2 diabetes mellitus (T2DM) are at risk for a variety of severe debilitating effects. One of the most serious complications experienced by patients with T2DM are skeletal diseases caused by changes in the bone microenvironment. As a result, patients with T2DM are at risk for higher prevalence of fragility fractures. There are a variety of treatments available for counteracting this effect. Some antidiabetic medications, such as metformin, have been shown to have a positive effect on bone health without the addition of additional drugs into patients’ treatment plans. Chinese randomised controlled trial (RCT) studies have also proposed antiosteoporotic pharmacotherapies as a viable alternative treatment strategy. Previous network meta-analyses (NMAs) and meta-analyses regarding this topic did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a two-part NMA that incorporates all available RCT data to provide the most comprehensive ranking of antidiabetics (part I) and antiosteoporotic (part II) pharmacotherapies in terms of their ability to decrease fracture incidences, increase bone mineral density (BMD) and improve indications of bone turnover markers (BTMs) in adult patients with T2DM.Methods and analysisWe will search Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Chinese literature sources (China National Knowledge Infrastructure, Chongqing VIP Information, Wanfang Data, Wanfang Med Online) for RCTs, which fit our criteria. We will include adult patients with T2DM who have taken antidiabetics (part I) or antiosteoporotic (part II) therapies with relevant outcome measures in our study. We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias will be evaluated in duplicate for each study, and the quality of evidence will be examined using Confidence in Network Meta-Analysis in accordance to the Grading of Recommendations Assessment, Development and Evaluation framework. We will use R and gemtc to perform the NMA. We will report changes in BMD and BTMs in either weighted or standardised mean difference, and we will report fracture incidences as ORs. We will use the Surface Under the Cumulative Ranking Curve scores to provide numerical estimates of the rankings of interventions.Ethics and disseminationThe study will not require ethics approval. The findings of the two-part NMA will be disseminated in peer-reviewed journals and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of T2DM bone disease. Our analysis should be able to provide physicians and patients with up-to-date recommendations for antidiabetic medications and antiosteoporotic pharmacotherapies for maintaining bone health in patients with T2DM.PROSPERO registration numberCRD42019139320.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2125-2125
Author(s):  
Nika M Harutyunyan ◽  
Suzie Vardanyan ◽  
Michael Ghermezi ◽  
Jillian Gottlieb ◽  
Ariana Berenson ◽  
...  

Abstract Introduction: The levels of serum monoclonal immunoglobulins (M-Igs) are used to monitor multiple myeloma (MM) patients. However, these assessments do not discriminate between normal polyclonal immunoglobulins (uninvolved) and M-Igs since they cannot determine the type of light chain associated with each immunoglobulin class (i.e. IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ). The HevyLite® +(HLC) assays are able to accomplish this but the usefulness of these results for MM patients needs to be further established. We evaluated the levels of involved and uninvolved HLC levels, their ratios and differences and their relationship to outcomes among MM patients. Materials and Methods: Serum samples (n=189) from MM patients were analyzed using the HLC assays. Manufacturer’s HLC normal reference ranges were used. HLC results were correlated with clinical status as determined at the time of sampling and divided into groups according to clinical status (complete response (CR), ≥ partial response (PR) , < partial response, and progressive disease (PD)). Normality was assessed using the D’Agostino-Pearson omnibus normality test. Statistical comparisons were made using t-student’s or Mann-Whitney tests as appropriate as well as Fisher’s test. Progression-free survival (PFS) was calculated using Kaplan--Meier analysis for specific regimens received during the time the samples were taken. All tests were double-tailed and p-values lower than 0.05 were considered to be statistically significant. Results: All MM serum samples analyzed had IgG (62%) or IgA (38%) isotypes. Results from the involved HLC/uninvolved HLC ratios and their differences demonstrated that samples from patients with PD had significantly both higher ratios and differences (P<0.0001) compared with patients with ≥ PR. Similar results were also observed for the involved HLC values (P<0.0001). The uninvolved HLC values were significantly lower (P<0.0001) for patients with PD compared with patients with ≥ PR. Similar results were obtained when we examined the percentage of patients who were in > PR compared with those with < PR so that patients in > PR were more likely to have normal uninvolved HLC levels than among patient with <PR (P<0.0001). In addition, we evaluated the proportion of patients in CR or PR based on their levels of uninvolved HLC being in the normal or below the normal range. The results showed that patients in CR were much more likely to have normal uninvolved HLC levels than among those with below normal uninvolved HLC levels (P < 0.0001). Similarly, patients in CR also were more likely to have normal uninvolved HLC levels than among those in PR (P=0.0040). Next, PFS was determined for patients with normal and below normal uninvolved HLC values. Patients with normal uninvolved HLC levels showed a much longer PFS (45 months) than among patients with less than normal uninvolved HLC levels (11 months; P=0.0019). Similarly, PFS was calculated for patients with normal and above normal involved HLC levels. Patients with normal involved HLC levels had a much longer PFS (33 months) than among patients with involved HLC levels that were above the normal range (11 months; P=0.0405). Conclusion: This study shows that involved HLC/uninvolved HLC ratios, differences between the involved and uninvolved HLCs, higher absolute levels of involved HLC, and lower levels of uninvolved HLC correlate with clinical status for MM patients. In addition, MM patients with normal uninvolved HLC levels have a longer PFS whereas those with involved HLC levels above the normal range show a shorter PFS. These results demonstrate the usefulness of the HLC assay for determining outcome for multiple myeloma patients. Disclosures No relevant conflicts of interest to declare.


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