Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases

Berenson, James R.; Rosen, Lee S.; Howell, Anthony; Porter, Lester; Coleman, Robert E.; Morley, Walter; Dreicer, Robert; Kuross, Steven A.; Lipton, Allan; Seaman, John J.

doi:10.1002/1097-0142(20010401)91:7<1191::aid-cncr1119>3.0.co;2-0

Cited by 474 publications

(251 citation statements)

References 24 publications

Supporting

Mentioning

238

Contrasting

Unclassified

Order By: Relevance

“…Despite antiresorptive therapy, repair of existing lesions is not seen, and progressive disease is associated with new skeletal events. (8)(9)(10)(11)(12)(13) New strategies to reduce skeletal-related events and improve patient outcome are urgently required.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Chantry

Heath

Mulivor

et al. 2010

Journal of Bone and Mineral Research

135

View full text Add to dashboard Cite

Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis ( p < .01), promotes bone formation ( p < .01) and increases bone mass in vivo ( p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption ( p < .05) and suppression of bone formation ( p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis ( p < .01), prevents myeloma-induced suppression of bone formation ( p < .05), blocks the development of osteolytic bone lesions ( p < .05), and increases survival ( p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction ( p < .001) and inhibits bone metastases ( p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer. ß

show abstract

Section: Introductionmentioning

confidence: 99%

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Chantry

Heath

Mulivor

et al. 2010

Journal of Bone and Mineral Research

135

View full text Add to dashboard Cite

show abstract

“…Bisphosphonates also have antiangiogenesis properties (8,9) and can activate ␥␦ T cells (10,11). The use of bisphosphonates in patients with multiple myeloma and metastatic cancer to the bones, such as breast, prostate, lung, and renal cell carcinomas, has resulted in a statistically significant reduction in skeletal complications, including pathologic fractures, spinal cord compression, hypercalcemia of malignant disease, and the need for subsequent radiotherapy or surgery to bone (12)(13)(14). Intravenous bisphosphonates have improved bioavailability and do not produce gastrointestinal side effects, resulting in better patient adherence.…”

Section: Actions Of Bisphosphonatesmentioning

confidence: 99%

“…Ninety-four percent of patients with osteonecrosis received pamidronate or zoledronic acid. The doses for oncologic indications are often up to 12 times higher than those used for osteoporosis (13,59). Of interest, clodronate, a nonaminobisphosphonate, has not been implicated in the development of osteonecrosis (60).…”

Section: Risk Factors and Etiopathogenesismentioning

confidence: 99%

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

2006

View full text Add to dashboard Cite

Osteonecrosis of the jaws is a recently described adverse side effect of bisphosphonate therapy. Patients with multiple myeloma and metastatic carcinoma to the skeleton who are receiving intravenous, nitrogen-containing bisphosphonates are at greatest risk for osteonecrosis of the jaws; these patients represent 94% of published cases. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. Oversuppression of bone turnover is probably the primary mechanism for the development of this condition, although there may be contributing comorbid factors. All sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. Conservative débridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this condition. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, for osteoporosis is uncertain and warrants careful monitoring.

show abstract

“…The existing standard of care for the treatment of breast cancer-related bone metastasis is the bisphosphonate family of drugs that effectively inhibit the cancer-associated resorption. They are also used as therapeutic agents in clinical disorders characterised by increased osteolysis, such as osteoporosis (Berenson et al, 2001). Unfortunately, treatment with bisphosphonates is not curative, but randomised control trials have shown that zoledronate, the most potent bisphosphonate, decreases the frequency of skeletal-related events, delays the first occurrence of such an event, and reduces pain in bone-metastatic breast cancer patients (Rosen et al, 2004;Kohno et al, 2005).…”

mentioning

confidence: 99%

Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in a bone metastasis model of human breast cancer

et al. 2007

View full text Add to dashboard Cite

Bone is one of the most frequent sites for metastasis in breast cancer patients often resulting in significant clinical morbidity and mortality. Bisphosphonates are currently the standard of care for breast cancer patients with bone metastasis. We have shown previously that doxycycline, a member of the tetracycline family of antibiotics, reduces total tumour burden in an experimental bone metastasis mouse model of human breast cancer. In this study, we combined doxycycline treatment together with zoledronic acid, the most potent bisphosphonate. Drug administration started 3 days before the injection of the MDA-MB-231 cells. When mice were administered zoledronic acid alone, the total tumour burden decreased by 43% compared to placebo treatment. Administration of a combination of zoledronic acid and doxycycline resulted in a 74% decrease in total tumour burden compared to untreated mice. In doxycycline-and zoledronate-treated mice bone formation was significantly enhanced as determined by increased numbers of osteoblasts, osteoid surface and volume, whereas a decrease in bone resorption was also observed. Doxycycline greatly reduced tumour burden and could also compensate for the increased bone resorption. The addition of zoledronate to the regimen further decreased tumour burden, caused an extensive decrease in bone-associated soft tissue tumour burden (93%), and sustained the bone volume, which could result in a smaller fracture risk. Treatment with zoledronic acid in combination with doxycycline may be very beneficial for breast cancer patients at risk for osteolytic bone metastasis.

show abstract

Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases

Cited by 474 publications

References 24 publications

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in a bone metastasis model of human breast cancer

Contact Info

Product

Resources

About