Zoledronic Acid Increases Bone Mineral Density in Patients with Thalassemia Intermedia-Induced Osteoporosis Regardless of the Incessant Bone Marrow Expansion.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3813-3813
Author(s):  
Ersi Voskaridou ◽  
Dimitrios Christoulas ◽  
Lito Antoniadou ◽  
Panagiotis Tsaftaridis ◽  
Eleni Plata ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Placebo Group ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Bone Pain ◽  
Bone Remodelling ◽  
Erythropoietic Activity ◽  
Mineral Density ◽  
Marrow Expansion

Abstract Osteoporosis represents an important cause of morbidity in adult patients with thalassemia. Its pathogenesis is multifactorial, and includes mainly bone marrow expansion, endocrine dysfunction and iron overload. Patients with thalassaemia intermedia (TI) seem to have a more expanded bone marrow with pressure on cortical bone, which causes pain and bone loss in several cases. The measurement of soluble transferrin receptor (sTfR) and erythropoietin (Epo) in the serum is considered as accurate marker of erythropoietic activity in thalassemia. Bisphosphonates are potent inhibitors of osteoclast activity and have been used for the management of thalassemia-induced osteoporosis. The aim of this study was to evaluate the effect of zoledronic acid, the most potent aminobisphosphonate, on bone mineral density (BMD) of patients with TI and explore possible correlations with bone marrow expansion and erythropoietic activity. Thirty-five patients with TI and osteopenia or osteoporosis (13M/22F, median age 45 years) were evaluated. Twenty-three were randomized to receive zoledronic acid, 4 mg, IV, every 3 months (n=12) or every 6 months (n=11) for one year, while 12 patients received placebo every 3 months. There was no difference in terms of the presence of gonadal dysfunction between the three studied groups. BMD of the lumbar spine (L), femoral neck and forearm was determined in all patients, using DEXA, before and 12 months after treatment. Bone marrow expansion was assessed by the measurement of sTfR and Epo serum levels, using an ELISA methodology (R&D Systems, Minneapolis, MN, USA), before and 12 months post zoledronic acid or placebo administration. In all patients markers of bone remodelling, such as C-telopeptide of collagen type-I (CTX) and bone specific alkaline phosphatase (bALP) were also measured by ELISA (Nordic Bioscience Diagnostics, Herlev, Denmark, and Quidel, San Diego, CA, USA, respectively). Patients were asked to quantify their degree of bone pain on Huskisson’s visual analogue scale and the McGill-Melzack scoring system before and 12 months post-therapy. All patients had increased values of sTfR, Epo, CTX, and bALP compared with 40 controls of similar age and gender (p<0.001). Patients who received zoledronic acid showed a significant increase in their L-BMD (p=0.01), which was accompanied by a dramatic reduction in CTX and bALP values ((p<0.001). There was no difference in terms of L-BMD changes between zoledronic acid groups. Placebo group showed an aggravation of L-BMD (p=0.041) and markers of bone remodelling at 12 months. No other changes were observed in the BMD of other sites. Zoledronic acid reduced bone pain, which remained stable in placebo group during the study period. There was only weak correlation between baseline sTfR levels and L-BMD, while there was no correlation between Epo or hemolytic parameters (indirect bilirubin, reticulocytes counts, and LDH) with BMD of all studied sites. Serum sTfR and Epo values showed a significant elevation after 12 months of therapy in all studied groups (p<0.01, p<0.02, and p<0.01, respectively); this elevation was irrespective of the L-BMD changes. This study suggests that the increase of BMD produced by zoledronic acid in TI is irrespective of the continuous increase of bone marrow expansion, which is considered a major cause of bone loss in this hemoglobinopathy.

scholarly journals Zoledronic Acid Markedly Improves Bone Mineral Density for Patients with Monoclonal Gammopathy of Undetermined Significance and Bone Loss

2008 ◽  
Vol 14 (19) ◽  
pp. 6289-6295 ◽  
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
Ralph V. Boccia ◽  
Marshall Flam ◽  
Siu-Fun Wong ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Bone Mineral ◽  
Monoclonal Gammopathy ◽  
Mineral Density ◽  
Undetermined Significance

Annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized placebo-controlled trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4515-4515 ◽  
Author(s):  
M. D. Michaelson ◽  
H. Lee ◽  
D. S. Kaufman ◽  
P. W. Kantoff ◽  
J. Finkelstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Bone Mineral ◽  
Gnrh Agonist ◽  
Gonadotropin Releasing Hormone ◽  
Mineral Density ◽  
Total Hip

4515 Background: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Zoledronic acid (4 mg IV every 3 months) increases BMD in GnRH agonist treated men. Intermittent zoledronic acid (4 mg IV once annually) increases BMD in postmenopausal women with osteoporosis but the efficacy of the annual treatment schedule in hypogonadal men is unknown. Methods: In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 44) who were receiving a GnRH agonist were assigned randomly to zoledronic acid (4 mg IV × 1) or placebo. BMD of the posteroanterior lumbar spine and total hip were measured by dual energy x-ray absorptiometry at baseline and month 12. Serum N-telopeptide, a marker of osteoclast activity, was measured every 3 months. Results: Mean (± SE) BMD of the posteroanterior lumbar spine increased by 4.0 ± 0.9 in men treated with zoledronic acid and decreased by 3.1 ± 0.9 percent in men who received placebo (P < 0.001 for between-group comparison). BMD of the total hip decreased by 0.7 ± 0.6 percent in men treated with zoledronic acid and decreased by 1.9 ± 0.7 percent in men who received placebo (P = 0.005). Compared to placebo, zoledronic acid significantly decreased serum N-telopeptide throughout the 12-month study (P < 0.05). Conclusions: In men receiving a GnRH agonist for prostate cancer, a single treatment of zoledronic acid significantly increased bone mineral density of the total hip and spine at 12 months. Annual zoledronic acid may provide a convenient and effective strategy to prevent bone loss in hypogonadal men. This study was supported in part by Novartis Oncology and by the Prostate Cancer Foundation. [Table: see text]

scholarly journals Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Anoop Kapoor ◽  
Ankur Gupta ◽  
Nilay Desai ◽  
Hongshik Ahn
Keyword(s):  
Prostate Cancer ◽  
Bone Mineral Density ◽  
Placebo Group ◽  
Zoledronic Acid ◽  
Bone Turnover ◽  
Acid Group ◽  
Gonadotropin Releasing Hormone ◽  
Mineral Density ◽  
Hormone Analog ◽  
Markers Of Bone Turnover

Background. Loss of bone density with androgen deprivation therapy for prostate cancer is well recognized. We assessed the effects of quarterly infusion of zoledronic acid on bone mineral density (BMD) and markers of bone turnover over a one-year period in men receiving gonadotropin-releasing hormone analog (GnRH-a) for prostate cancer.Methods. 41 subjects were randomly assigned to treatment with zoledronic acid (4 mg) IV infusion or placebo every 3 months. The primary endpoint was the change in the lumbar spine BMD after 12 months of treatment.Results. The change in vertebral BMD in the zoledronic acid group () was significantly () greater than the change in the placebo group () as was the change in left femoral neck BMD ( for the zoledronic acid group versus for the placebo group). The decrease in biochemical markers of bone turnover was significantly () greater in the zoledronic acid group compared to the placebo group.Conclusion. Quarterly infusion of zoledronic acid for 1 year improved vertebral and left femoral neck BMD with a decrease in bone turnover markers in men on GnRH-a treatment. Zoledronic acid treatment appears to be promising in men with low BMD receiving GnRH-a treatment.

The role of bisphosphonates in breast and prostate cancers.

2004 ◽  
Vol 11 (2) ◽  
pp. 207-224 ◽  
Author(s):  
Janet E Brown ◽  
Helen Neville-Webbe ◽  
Robert E Coleman
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Bone Mineral ◽  
Bone Disease ◽  
Bone Pain ◽  
Metastatic Bone Disease ◽  
Mineral Density ◽  
Intravenous Pamidronate ◽  
Oral Clodronate

Bisphosphonate drugs are a group of pyrophosphate analogues which bind avidly to hydroxyapatite bone mineral surfaces and their major action is to inhibit osteoclast activity and thus bone resorption. In oncology, their role in metastatic bone disease is well established, but there is increasing interest in their potential role in preventing and treating cancer-induced bone loss and their possible anti-tumour effects. Metastatic bone disease is associated with a variety of skeletal complications, including pathologic fractures, bone pain, impaired mobility, spinal cord compression and hypercalcaemia. Intravenous bisphosphonates, particularly zoledronic acid, in conjunction with rehydration, are now established as the treatment of choice for hypercalcaemia. For treatment of bone pain, it has also been shown that bisphosphonates can be an effective supplementary approach to radiotherapy. In breast cancer and myeloma, bisphosphonates have now become part of standard therapy to treat and prevent skeletal-related events (SRE) and, until recently, treatment was largely with intravenous pamidronate or oral clodronate. However, large, randomised, multicentre trials using intravenous administration of the highly potent bisphosphonate zoledronic acid every 3-4 weeks have recently demonstrated a reduction of 20% in the risk of developing an SRE compared with pamidronate for patients with breast cancer. Moreover, these trials have demonstrated, for the first time, that a bisphosphonate significantly reduces the occurrence of skeletal events in hormone-refractory prostate cancer and in non-small cell lung cancer and a range of other solid tumours. Investigations into the potential of the relatively low potency bisphosphonate, clodronate, for the prevention of bone metastases in breast cancer have produced conflicting data. Further large, randomised studies with clodronate and zoledronic acid are planned and until the results are available it is not possible to identify a definite adjuvant role for bisphosphonates. Evidence is accumulating in vitro that bisphosphonates are also able to directly affect tumour cells, in addition to their effects on osteoclasts, with zoledronic acid being particularly potent. Over recent decades there has been a significant improvement in cure rates and survival times in certain cancers and the use of chemotherapy and hormone therapy has expanded greatly, leading to increasing numbers of long-term survivors who have received these treatments. Management of treatment-induced bone loss is therefore assuming a greater importance and bisphosphonates represent an attractive treatment option in such patients. Several placebo-controlled trials using oral clodronate, oral risedronate, intravenous pamidronate and intravenous zoledronic acid have all now demonstrated benefits in reducing the loss in bone mineral density.

scholarly journals Icariin Prevents Diabetes-Induced Bone Loss in Rats by Reducing Blood Glucose and Suppressing Bone Turnover

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1871 ◽  
Author(s):  
Shanshan Qi ◽  
Jia He ◽  
Hongxing Zheng ◽  
Chen Chen ◽  
Shiqiang Lan
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Blood Glucose ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Histomorphometry ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Mineral Density ◽  
Diabetic Osteoporosis

Diabetic Osteoporosis (DOP) is a common metabolic bone disease, characterized by decreased bone mineral density (BMD) and destruction of bone microstructure. It has been reported that icariin is beneficial for estrogen deficiency-induced osteoporosis, and alcohol-induced osteoporosis; whether icariin has protective effects on diabetes-induced osteoporosis has not been reported. In this study, a rat model of diabetic osteoporosis was established by streptozotocin injection, the bone protective effects and potential mechanism of icariin on diabetes-induced bone loss was observed. Thirty 8-week-old female Sprague Dawley rats were divided into control group (vehicle treatment), T1DM (diabetic) group and T1DM-icariin (ICA) group (diabetic rats treated with icariin), 10 rats in each group. The bone histomorphometry parameters, bone mineral density (BMD), serum bone turnover markers, and bone marrow adipogenesis were analyzed after 8 weeks of icariin administration. The results showed consumption of icariin at a doses of 100 mg kg−1 decreased blood glucose, and increased the BMD of diabetic rats. Icariin effectively decreased serum bone turnover marker levels, including CTX-1, ALP, TRACP 5b, osteocalcin, and PINP. Meanwhile, the bone histomorphometry parameters, the number of osteoclasts per bone perimeter were turned to be normal level, and the icariin treatment suppressed bone marrow adipogenesis. The runt-related transcription factor 2 (RUNX 2), as well as the osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) ratio in serum and bone tissues were increased significantly after icariin treatment in diabetic rats. All of the above indicate that oral administration of icariin can prevent diabetic osteoporosis; the effect is mainly related to its ability to reduce blood glucose, inhibit bone turnover and bone marrow adipogenesis, as well as up-regulate bone RUNX 2, and OPG expression.

Osteoporosis in Sickle Cell/β-Thalassemia Is Primarily Caused by an Imbalance at the RANKL/OPG Pathway.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3173-3173
Author(s):  
Ersi Voskaridou ◽  
Ioannis Papassotiriou ◽  
Evangelos Premetis ◽  
John Meletis ◽  
Dimitris Loukopoulos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Renal Function ◽  
Bone Resorption ◽  
Bone Loss ◽  
Sickle Cell ◽  
Type I ◽  
Mineral Density ◽  
T Score ◽  
Tracp 5B ◽  
Marrow Expansion

Abstract Bone involvement is the commonest clinical manifestation of sickle cell disease (SCD) including chronic disorders, such as osteopenia/osteoporosis. The aim of the present study is to evaluate the bone mineral density (BMD) of patients with SCD/β-thalassemia (S/β-th) in parallel with markers of bone turnover in an attempt to better understand the pathophysiology of bone loss in these patients. We studied 52 patients with S/β-th (23M/29F; median age 40 y). The BMD of the lumbar spine (L) and femoral neck (F) was evaluated by DEXA. Bone remodeling was assessed using the following serum indices: (a) bone resorption markers [C-telopeptide of type-I collagen (CTX), tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], (b) bone formation markers [bone-alkaline phosphatase (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP)], and (c) osteoclast stimulating factors [soluble receptor activator of nuclear factor κB ligand (sRANKL), and osteoprotegerin (OPG)]. Moreover, all patients had a thorough evaluation of their renal function (creatinine clearance, and cystatin-C serum levels), bone marrow expansion (soluble transferin receptors, sTfR), serum erythropoietin (Epo) and parathyroid hormone (PTH) levels. The same biochemical parameters were also determined in 25 age- and gender-matched controls. According to WHO criteria, 17 patients (32.6%; 8M/9F, median age 45 y) had osteopenia or osteoporosis (median L/T-score: −2.26; L/BMD: 0.9 g/cm2; F/T-score: −1.86; F/BMD: 0.68 g/cm2). In contrast, 30 patients (57.6%; 12M/18F, median age 40 y) had osteosclerosis (median L/T-score: +3.15; L/BMD: 1550.5 g/m2; F/T-score: +0.52; F/BMD: 1113.5 g/cm2). Renal function, Epo, Hb and sTfR levels and the number of crises/year were similar between both groups. All patients displayed increased levels of OPG, bALP, and CICP compared with controls (p&lt;0.02). CTX levels in the osteosclerotic patients were significantly lower than those of both controls (p&lt;0.0001) and osteopenic/osteoporotic patients (p&lt;0.003); this finding implies a diminished bone resorption. Moreover, bALP and PTH in the osteopenia/osteoposis group were higher than those of the osteosclerosis group (p&lt;0.01, and &lt;0.03, respectively). BMD of the osteopenic/osteoporotic patients showed a strong correlation with OPG and CTX levels (p=0.01, and 0.008, respectively). This result, in combination with the significant correlations observed between OPG and sRANKL, TRACP-5b, and bALP in these patients suggests that osteopenia/osteoporosis in S/β-th results mainly from an imbalance at the RANKL/OPG axis. Conversely, considering the absence of correlation between BMD and sTfR in the same patient group, the potential contribution of bone marrow expansion in the development of osteopenia appears much weaker. No correlation between BMD and bone indices observed in osteosclerotic group. In conclusion, this study suggests that the development of bone loss in S/β-th patients is mainly due to an imbalance in RANKL/OPG pathway. Novel agents that target this system, as well as bisphosphonates, maybe useful in the management of this common SCD complication.

Bone mineral density in women with non-metastatic breast cancer: Effect of intravenous bisphosphonates given before adjuvant therapies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11038-11038
Author(s):  
B. Alonso ◽  
R. Aleman ◽  
L. Rodríguez ◽  
M. Llanos ◽  
J. Cruz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Metastatic Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Adjuvant Therapy ◽  
Metastatic Breast ◽  
Mineral Density ◽  
Adjuvant Therapies ◽  
Intravenous Bisphosphonates

11038 Background: Adjuvant therapies shown survival improve of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). Bisphosphonates are effective agents for the management of osteoporosis. Intravenous zoledronate, which is approved for the treatment of malignant hypercalcemia, multiple myeloma, and skeletal metastases, can suppress bone resorption and are often considered first-line therapy for the treatment of osteoporosis. We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before adjuvant therapies intravenous bisphosphonates (zoledronic acid). Methods: We prospectively studied the effects of a single intravenous zoledronic acid dose (4 mg), on BMD of 74 women with NMBC (stage I-III), administred previous to the adjuvant therapies. The patients were referred to the Medical Oncology Service of University Hospital of Canary Islands between 2003 y 2006. Lumbar and hip BMD (g/cm2) was measured at diagnosis and after chemotherapy. The results were compared with a group of 80 patients with NMBC who received adjuvant therapy without intravenous bisphosphonates. Results: Breast cancer patients the median age was 52 ± 10 years old and the body mass index was 28,2 ± 5.5 kg/m2. At baseline there were not differences in BMD between the group that received bisphosphonates and the group with only chemotherapy at any of lumbar or femoral bone sites. In our study, the BMD after chemotherapy and intravenous bisphosphonates (n=74) significantly increased at femoral neck (0.805 ± 0.01, 0,826± 0.12; p=0.002) and trochanter (0.709 ± 0.01, 0.724 ± 0.01; p=0.002) and remained stable at lumbar, intertrochanter, total hip and Ward’s triangle; whether the group without bisphosphonates significantly decreased at lumbar (1.014 ± 0; 0.995 ± 0, p=0.0001), trochanter (0.701± 0; 0.690 ± 0, p=0,046), intertrochanter (1,095 ± 0; 1.078 ± 0, p=0.0001) and total hip (0,924 ± 0; 0.915 ± 0, p=0.046) areas (table). Conclusions: Women with NMBC are affected by early bone loss after adjuvant chemotherapy. Bisphosphonates intravenous (zoledronic acid) given before adjuvant therapy might be an effective treatment for this bone loss, increasing BMD or remaining stable. No significant financial relationships to disclose.

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