scholarly journals Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases

Author(s):  
Fatih Göksel ◽  
Müge Akmansu ◽  
Ertuğrul Şentürk ◽  
Fatih Demircioğlu

Objectives: In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern. Patients and methods: A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT. Results: A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements. Conclusion: Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

Author(s):  
Deepa Soibam ◽  
Amumacha T. Singh ◽  
Parvati Nandy ◽  
Ankur Baruah

Background: Osteoporosis being a silently progressing disease, the real challenge is to identify the individual at high risk of osteoporosis. Many bone turnover marker have been associated with bone loss even before occurrence of any changes in bone structure. Therefore, this study was aim to evaluate the predictive value of bone turnover marker by correlating with low bone density.Methods: This was a case control study conducted in Sikkim Manipal Institute of Medical Sciences, India. A total of 300 subjects (150 case and 150 control) both male and female between the age group of 35- 65 were enrolled. We measure one bone formation marker serum osteocalcin and two resorption marker urine hydroxyproline (OHP) and urine N- terminal telopeptides of type I collagen (NTX). Calcaneal QUS device (GE Lunar Achilles Express heel- densitometer) was used to determine the bone density.Results: A significant difference of the bone markers i.e. hydroxyproline, NTx and osteocalcin were observed between cases and control of men and women with P<0.001. These variables statistically significantly predicts bone density with F (3, 71) = 5,671, P= 0.002, R2= 0.193 and F (3, 71) = 5.292, P= 0.002, R2= 0.183 in women and men respectively.Conclusions: Study showed that bone turnover markers are able to predict low bone mass. Resorption markers NTx and OHP were the main predictor in men whereas OHP and formation marker Osteocalcin in women. Therefore, BTM measurement along with BMD can provide useful information about the changes in the bone mass which will help to predict the risk of osteoporosis.


2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Lowell L. Hart ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  

102 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to nonsteroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J et al. NEJM2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effects of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers (BMs) were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a preexisting bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (p < 0.0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively), and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade 1-2 and occurred with similar frequency in EVE (2.9%)- and PBO (3.8%)-treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jakob Kau Starup-Linde ◽  
Rikke Viggers ◽  
Bente Langdahl ◽  
Soeren Gregersen ◽  
Simon Lykkeboe ◽  
...  

ObjectiveCirculating osteoglycin may facilitate the crosstalk between bone and pancreas to empower adaptation of bone mass to whole body energy balance. We aimed to examine whether osteoglycin is associated with bone and metabolic parameters and if osteoglycin levels differ between patients with type 1 and 2 diabetes (T1D and T2D).Design and methodsA cross-sectional study of 190 patients with diabetes mellitus and stable hemoglobin A1c (HbA1c) (97 T1D and 93 T2D) was conducted. S-osteoglycin was analyzed by ELISA. Unpaired t-tests were performed to test differences between patients with T1D and T2D and linear regression analyses were performed to investigate associations between osteoglycin, glycemic markers, bone turnover markers and characteristics.ResultsS-osteoglycin did not differ between patients with T1D and T2D (p=0.10). No associations were present between osteoglycin and age, gender, microvascular complications, HbA1c, or plasma glucose in T1D or T2D patients (p&gt;0.05 for all). S-osteoglycin was not associated with levels of bone turnover markers (C-terminal cross-linked telopeptide of type-I collagen (CTX), P-procollagen type 1 amino terminal propeptide (P1NP), P-osteocalcin (OC), P-sclerostin, S-osteoprotegerin (OPG) or S-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL)) in neither T1D or T2D patients (p&gt;0.05 for all).ConclusionOsteoglycin levels were similar in T1D and T2D patients. Osteoglycin did not correlate with glucose, HbA1c or any other biochemical marker of bone turnover. Thus, we did not find evidence supporting the existence of an osteoglycin-bone-pancreas axis.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01870557.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Michael Gnant ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  

512 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to non-steroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J, et al. NEJM. 2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effect of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation, and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a pre-existing bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (P < .0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO, but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively) and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade1/2 and occurred with similar frequency in EVE- (2.9%) and PBO- (3.8%) treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 523-523
Author(s):  
Atsushi Ishiguro ◽  
Michio Nakamura ◽  
Tetsuhito Muranaka ◽  
Satoshi Yuki ◽  
Taichi Murai ◽  
...  

523 Background: Although intravenous glucocorticoid (GC) premedication (GCP) before chemotherapy (CTx) are frequently used to prevent nausea and vomiting for continuing comfortable CTx, the side effects of intermittent GCs on bone health have not yet been reported. So we designed a multicenter, prospective, observational study to evaluate the impact of periodic GCP on bone metabolism in gastrointestinal cancer (GIC) patients (pts). Methods: The eligibility criteria were as the follows: (i) histologically proven GIC. ; (ii) The duration of periodical GCP is weekly, biweekly, and triweekly. More over 4 weeks GC free intervals is not permissible. ; (iii) age over 20. The primary endpoint was to investigate the variations of bone mineral densities (BMD) at lumbar spine measured by dual energy x-ray absorptiometry (DEXA) and bone turnover biomarkers, cross-linked N-telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP), between baseline (BL) and 16 weeks after starting CTx (16w). Results: From June 2013 to April 2015, 98 pts were enrolled. Two pts were not proven as GIC histologically. One patient (pt) was not measured on baseline DEXA. One pt was taken bisphosphonates already on BL point. Four pts were not administered CTx or GCP, and 16 pts were not measured BMD on 16w due to several reasons such as pts refusal, discontinuation of CTx, death and so on (74 pts were full analysis set). In 55 pts (74.3 % of FAS), the levels of BMD at 16w were decreased compared with BL and the average amount of BMD reduction rate was 5.83 % (-38.8 % to 31.1 %). Although no significant difference was found in the level of NTX between BL and 16w (p = 0.118), there was the significant increase of BAP level statistically (p = 0.006). There were also significant correlations between percent change in BMD and NTX, BMD and BAP, NTX and BAP (p = 0.037, 0.029, and 0.003, respectively). Conclusions: We found that periodic GCP in GIC pts caused the reduction of BMD and some influences for bone turnover. These results indicate that GCP might generate more serious osteoporosis of GIC pts during CTx. Further studies are necessary to illustrate the need to prevent GC induced osteoporosis in using GCP. Clinical trial information: 000011054.


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