Biphosphonate complications

Bisphosphonates are potent antiresorptive agents proven to be highly effective in vertebral and non-vertebral fractures. However, the reported complications associated with long-term use have led to questions on indefinite treatment. After administration of alendronate there is a high retention of the drug due to slow skeletal release as a result of bone resorption (half-life of more than 10 years), and it seems logical to propose a cessation of treatment (drug holidays) after prolonged treatment. The largest study published to date that assesses the effects on bone mineral density (BMD) and fractures with maintained or discontinued alendronate treatment is the FLEX (Fracture Intervention Trial Long-term Extension) trial...

Zolendronic acid is a nitrogenous biphosphonate commonly used as an intravenous infusion for the management of Paget's disease, osteoporosis, and hypercalcemia of malignancy. We report a rare and challenging complication of zolendronate infusion: unilateral acute anterior uveitis followed by persistently raised intraocular pressure despite being on four different classes of antiglaucoma medication. The challenge was that the patient required topical steroid to treat her uveitis in the background of known glaucoma with corresponding steroid response...

Bone is a dynamic organ, constantly changing metabolically and being remodelled through the balanced activity of osteoclast and osteoblast on trabecular surfaces. Osteoporosis represents a continuum, in which multiple pathogenic mechanisms converge to cause loss of bone mass and deterioration of microarchitecture of skeletal structure. In thalassaemia major (TM), progressive 'aging' of bone starts in early childhood, through the gradual development of an imbalance between augmented osteoclastic resorption and insufficient osteoblastic bone formation...

During the last several years the treatment of osteoporosis with bisphosphonates has become accepted as a safe and effective procedure. However, recently there have been increasing numbers of reports of rare complications in the literature. Particularly the occurrence of atypical fractures of the femur has become a focus of interest but the problem is insufficiently known and only rarely addressed in the scientific discussion. The case illustrated here and a survey of the important facts in the recent literature highlight essential aspects of long-term bisphosphonate therapy...

The number of papers reporting the occurrence of specific pathological fractures in long-term biphosphonate users has recently increased. They refer to the forms of stress fracture probably resulting from an extreme decrease in bone turnover, which may involve sub-trochanteric or isolated transverse fractures, or short transverse fractures with a unicortical beak in an area of cortical hypertrophy. At the time of prodromal signs and symptoms, cortical bone at the site of impeding fracture appears rougher on radiographs...

Fibrous dysplasia of bone or Jaffe Lischtenstein's disease is a genetic, non-inheritable disease of bone development, characterized by bone pain, deformities and fracture, mainly observed in yo ung adults. The frequency is equal between sexes. Mutations in the gene coding the Gsα, GNAS complex, results in osteoblastic differentiation defects, and bone resorption. The disease can have a monostotic or polyostotic form, or be associated with café-au-lait skin spots and precocious puberty (McCune-Al bright syndrome)...

Pregnancy-associated osteoporosis is rare and self--limiting. We report two clinical cases, with beginning of back pain during a 1st pregnancy. In the 1st case, the pain became severe after a fall, and she had other risk factors of fracture, like low calcium intake, and a treatment with thyroid hormones for weight loss. In the 2nd case, we did not find any. Both were diagnosed of osteoporosis by bone densitometry and radiology (multiple vertebral compression fractures). They had a favorable progression with life-style measures, calcium and vitamin D supplementation, and oral biphosphonate in the 2nd case...

BACKGROUND: Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. METHODS: We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT...

Multiple myeloma (MM) is an uncontrolled malignant proliferation of plasma cells. Today, it is the best studied form of hemoblastomas, but many pathophysiological and therapeutic aspects of this condition await a deeper insight. The medico-social significance of the disease is emphasized by its continuous growth, variable clinical manifestations, low quality of the patients" life, mean life expectancy of 3-5 years, and numerous complications. One clinical feature of MM is bone lesions that occur in all patients as osteolysis (OL), osteoporosis (OP), hypercalcemia, and combination of these disorders...

Osteonecrosis of the jaw is an uncommon consequence of biphosphonate therapy. This has most commonly been a bone complication with little if any soft tissue involvement. An unusual case of necrotizing fasciitis with extensive soft tissue infection stemming from a prolonged case of osteonecrosis of the jaw presented. The management of this patient (aggressive surgical debridement and prolonged wound care) is reviewed as well as the review of the underlying processes.

The aim of the present paper was to review recent developments in the management of patients with acute kidney injury or chronic kidney disease occurring secondary to either cancer itself or its therapy, with a focus on infiltration of the renal parenchyma, myeloma, tumor lysis syndrome, glomerular disease, thrombotic microangiopathy, chemotherapy-associated thrombotic microangiopathy, biphosphonate-induced renal diseases, acute kidney injury, and chronic kidney disease after hematopoietic cell transplantation...

Skeletal complications of bone metastases or secondary osteoporosis are a frequent event in patients with prostate cancer. Bisphosphonates have been widely used for both indications because of their capacity to prevent bone loss, to reduce pain and to inhibit metastatic growth. Possible side effects include acute phase reactions, osteonecrosis of the jaw and renal impairment. Therefore, the risks and benefits of therapy should be considered and informed consent obtained from the patient. Given current evidence the guidelines only allow a recommendation for use in patients with metastatic prostate cancer...

Fibrous dysplasia of bone is a skeletal disease due to a specific mutation in the GNAS1 gene with a broad spectrum of clinical presentations ranging from isolated monostotic and polyostotic forms to associations with other extra-skeletal manifestations (McCune-Albright syndrome). The main complications are bone pain, deformities and fractures and sometimes cranial nerve compression and the development of bone sarcomas. Traumatologic surgery represents the principal approach in complicated lesions. Currently, the efficacy of pharmacological therapies is fairly limited...

Osteonecrosis of the jaw associated to biphosphonate use is more common in cancer patients with bone metastases, that are using intravenous diphosphonates. When these drugs are used orally the risk of the complication is lower. We report 3 diabetic women aged 69, 76 and 82 years, receiving alendronate 70 mg every one week. The unveiling event was the extraction of several teeth without the use of antibiotics. All had bone pain, purulent discharge, loss of bone and halitosis. All improved five months after discontinuing alendronate...

The proteasome inhibitor bortezomib (Velcade) is currently approved as second-line treatment of multiple myeloma (MM). MM-related bone disease is one of the most debilitating complications of MM. Besides supportive care with biphosphonates, which have proven efficacy in reducing and delaying skeletal-related events, there is no specific treatment of lytic bone lesions. The present study investigated the effect of bortezomib alone or in combination with a hydroxamate-based histone deacetylase inhibitor, JNJ-26481585 on tumor burden, and MM bone disease in the 5T2MM model...

Since osteonecrosis of the jaw was related to biphosphonate administration by Marx, studies showing clinical symptoms, drug and surgical therapies overwhelmed the literature. Furthermore, the literature demonstrated the correlation between chronic biphosphonate adsumption and osteonecrosis of the jaw onset. Nitrogen-containing biphosphonates are widely used for the management of metastatic cancer, for prevention and treatment of osteoporosis, for the treatment of Paget's disease, and for the management of acute hypercalcemia...

Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia. Compared with the hypercalcemia of malignancy, hyperparathyroidism tends to be associated with lower serum calcium levels (< 12 mg/dL) and a longer duration of hypercalcemia (more than 6 months). The hypercalcemic symptoms are usually fewer and subtle. Hyperparathyroidism tends to cause kidney calculi, hyperchloremic metabolic acidosis, and the characteristics of metabolic bone disease osteitis fibrosa cystica, but no anemia...

PURPOSE: 1) To review the pathophysiology of osteonecrosis of the jaw in patients receiving biphosphonates. 2) To review the imaging findings of osteonecrosis of the jaw and attempt to define pathognomonic imaging features. Materials and methods. Retrospective study of 15 patients with metastatic disease treated with biphosphonates. All available imaging studies including orthopantomograms, CT and bone scans were reviewed simultaneously by two radiologists (FO, DB). RESULTS: The most frequent imaging finding was osteolysis...

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others...

Osteoporosis is induced by a disorder of the bone turnover that generates an accelerated destruction process and leads to the rarefaction of the protein matrix. The RANK-L/RANK/OPG system is the main actor of the bone remodelling regulation. Juvenile osteoporoses may have primary or secondary aetiologies. The main causes include constitutional bone fragilities, and osteoporoses, which are secondary to chronic inflammatory diseases and sustained steroid treatment. Etiologic diagnosis relies on a clinical basis, and is often made too lately when complications occur...