Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing.</p> <p>Methods/Design</p> <p>A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use.</p> <p>Discussion</p> <p>This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws.</p

Risks and benefits of bisphosphonates

Bone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers due to the prevalence of these diseases. Bone metastases result in considerable morbidity and complex demands on health care resources, affecting quality of life and independence over years rather than months. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma as well as a wide range of solid tumours affecting bone by 30–50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain

Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

<p>Abstract</p> <p>Purpose</p> <p>Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient.</p> <p>Methods</p> <p>Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque^®centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ.</p> <p>Results</p> <p>A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0) was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ.</p> <p>Conclusion</p> <p>To our knowledge this is the first case of BRONJ successfully treated with autologous stem cells transplantation with a complete response.</p

Osteonecrosis of the jaw as a possible rare side effect of annual bisphosphonate administration for osteoporosis: A case report

<p>Abstract</p> <p>Introduction</p> <p>Osteonecrosis of the jaw is a serious side effect in patients receiving nitrogen-containing bisphosphonates intravenously due to malignant diseases. Albeit far less frequently, osteonecrosis of the jaw has also been reported to occur due to the oral administration of nitrogen-containing bisphosphonates due to osteoporosis. Annual infusions of zoledronic acid have been recommended in order to improve patient compliance, to optimize therapeutic effects and to minimize side effects. To date, osteonecrosis of the jaw has not been linked to the annual administration of bisphosphonates.</p> <p>Case presentation</p> <p>We report the case of a 65-year-old Caucasian woman suffering from osteoporosis who developed early stage osteonecrosis of the jaw in two locations, with chronic infections, after two months of oral bisphosphonate treatment and three annual administrations of zoledronic acid. Our patient was treated by fluorescence-guided resection of the necrotic jaw bone areas; local inflammation was treated by removal of a wisdom tooth and repeat root resections. Histopathology revealed typical hallmarks of osteonecrosis of the jaw.</p> <p>Conclusion</p> <p>Osteonecrosis of the jaw may occur as a consequence of annual administrations of zoledronic acid. It is conceivable that, due to the pharmacological properties of bisphosphonates, a jaw bone that encounters frequent local inflammations is more likely to develop osteonecrosis.</p

Metastatic breast carcinoma in the mandible presenting as a periodontal abscess: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tumors can metastasize to the oral cavity and affect the jaws, soft tissue and salivary glands. Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Because of their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. The purpose of this report is to present a rare case of a metastatic breast carcinoma mimicking a periodontal abscess in the mandible.</p> <p>Case presentation</p> <p>A 55-year-old Caucasian woman was referred to our clinic for evaluation of bisphosphonate-induced jaw osteonecrosis. She had undergone modified radical mastectomy with axillary lymph node dissection for invasive ductal carcinoma of the left breast. Her clinical examination showed diffuse swelling and a periodontal pocket of 6 mm exhibiting suppuration in the posterior right mandible. Moreover, paresthesia of the lower right lip and chin was noted. There were no significant radiographic findings other than alveolar bone loss due to her periodontal disease. Although the lesion resembled a periodontal abscess, metastatic carcinoma of the breast was suspected on the basis of the patient's medical history. The area was biopsied, and histological analysis confirmed the final diagnosis of metastatic breast carcinoma.</p> <p>Conclusion</p> <p>The general dentist or dental specialist should maintain a high level of suspicion while evaluating patients with a history of cancer. Paresthesias of the lower lip and the chin should be considered ominous signs of metastatic disease. This case highlights the importance of the value of a detailed medical history and thorough clinical examination for the early detection of metastatic tumors in the oral cavity.</p

Internet-based treatment for older adults with depression and co-morbid cardiovascular disease: protocol for a randomised, double-blind, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression, cardiovascular disease (CVD) risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD.</p> <p>Methods/Design</p> <p>This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months.</p> <p>Discussion</p> <p>Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on depressive symptoms and adherence to treatment among patients at risk of CVD. In addition it will also precisely and reliably define the effects of the intervention upon aspects of cognitive function that are likely to be affected early in at risk individuals, using sensitive and responsive measures.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12610000085077.aspx">ACTRN12610000085077</a></p