Zoledronic acid has been used for prevention of osteolytic and osteoblastic bone metastasis. This case report illustrates an undesirable consequence from prolonged usage of zoledronic acid in bone metastasis prevention. Periprosthetic acetabular fracture in a patient treated with zoledronic acid for 7 years was reported. The clinical presentation, radiographic and pathological results were described. This is a rare complication after total hip arthroplasty which should not be ignored especially in patients who received long term bisphosphonate.
Acetabulum/*injuries/pathology/surgery ; Aged ; Arthroplasty, Replacement, Hip/*adverse effects ; Bone Density Conservation Agents/*adverse effects/pharmacology ; Bone Neoplasms/prevention & control/secondary ; Bone Remodeling/drug effects ; Breast Neoplasms/pathology ; Diphosphonates/*adverse effects/pharmacology ; Female ; Fractures, Spontaneous/chemically induced/etiology ; Hip Prosthesis ; Humans ; Imidazoles/*adverse effects/pharmacology ; Osteoarthritis, Hip/*surgery ; Periprosthetic Fractures/*chemically induced/etiology ; Prosthesis Failure ; Reoperation

During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.
9,10-Dimethyl-1,2-benzanthracene ; Adenocarcinoma/*prevention & control ; Animals ; Apoptosis/*drug effects ; Breast Neoplasms/chemically induced/pathology/*prevention & control ; Cell Line, Tumor ; Chemoprevention ; Female ; Gene Expression Regulation, Neoplastic ; HSP90 Heat-Shock Proteins/genetics/metabolism ; Humans ; Isoflavones/chemistry ; NF-kappa B/genetics/metabolism ; Peptides/chemistry/isolation & purification/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Soybean Proteins/chemistry/*isolation & purification/*therapeutic use ; Soybeans/chemistry