Novel Antiangiogenic Effects of the Bisphosphonate Compound Zoledronic Acid

Wood, Jeanette M.; Bonjean, Karine; Ruetz, Stephan; Bellahcène, Akeila; Devy, Laetitia; Foidart, Jean Michel; Castronovo, Vincent; Green, Jonathan R.

doi:10.1124/jpet.102.035295

Cited by 724 publications

(468 citation statements)

References 25 publications

(28 reference statements)

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“…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).…”

Section: Actions Of Bisphosphonatesmentioning

confidence: 99%

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

2006

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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.

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Section: Actions Of Bisphosphonatesmentioning

confidence: 99%

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

2006

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“…(67) An effective stress fracture healing response requires an increase in periosteal vascularity. Although some observations identify a direct suppression of vasculogenesis by BPs, (68) it can be difficult in bone to distinguish between inhibition of new vessel growth and suppression of osteoclastic activity because both are coupled. However, dissociation between the two is possible during skeletal development in animal models, and studies of growing animals showed no antiangiogenic effect of clodronate.…”

Section: Insights Into the Pathogenesis Of Atypical Femoral Fracturesmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

967

646

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Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

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“…Osteonecrosis of the jaw is usually painful and preceded by a dental procedure in 60% of cases. Oversuppression of bone turnover and antiangiogenic effects of BP are considered to be contributing factors [39,40].…”

Section: Post-treatment Changesmentioning

confidence: 99%

Magnetic resonance imaging of bone marrow in oncology, Part 2

Hwang

Panicek

2007

Skeletal Radiol

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Magnetic resonance imaging plays an integral role in the detection and characterization of marrow lesions, planning for biopsy or surgery, and post-treatment followup. To evaluate findings in bone marrow on MR imaging, it is essential to understand the normal composition and distribution of bone marrow and the changes in marrow that occur with age, as well as the basis for the MR signals from marrow and the factors that affect those signals; these points have been reviewed and illustrated in part 1 of this two-part article. Part 2 will emphasize the practical application of MR imaging to facilitate differentiation of normal marrow, tumor, and treatment-related marrow changes in oncology patients, and will review complementary MR techniques under development.

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Novel Antiangiogenic Effects of the Bisphosphonate Compound Zoledronic Acid

Cited by 724 publications

References 25 publications

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Magnetic resonance imaging of bone marrow in oncology, Part 2

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