July 27, 2011

Filed under: Uncategorized — admin @ 9:25 am

Recent research out of the University of Gothenberg indicates that increasing surface roughness of implants at the nano level speeds the integration process.

Increasing the Active Surface of Dental Implants at Nano Level Quickens Healing

Published on June 15, 2011 at 7:35 AM
By Cameron Chai

Researchers at the University of Gothenburg have conducted studies on the surface arrangement of dental implants both at the micro and nano level to enable speedy healing of patients.

Johanna Löberg from the Department of Chemistry at the University of Gothenburg stated that by causing an increase of the active surface area at the nano scale and altering the implant’s conductivity, the biomechanics of the body is influenced in such a way as to avoid discomfort and to speed up the healing process.

Scanning electron microscope images taken on the titanium samples with (from left), turned, sanded and blasted surfaces treated with oxalic acid and dilute sulfuric acid

It was evident that the surface of dental implants is often associated with the level of roughness, from the superimposed nanostructures to the thread. When the implant is placed in the bone, the bone tissue experiences a mechanical force known as biomechanical stimulation, which leads to the formation of new bone. Although roughness is not the only factor that influences healing, it is crucial for new bone formation. It is also necessary to measure and illustrate the appearance of the surface in detail.
Johanna Löberg has formulated an approach that explains the topography of the implant from nanometre to micrometre scale. This approach enables theoretical estimation of placing the implant in the bone by diverse surface topographies. It can be used to develop new dental implants and to enable optimization of properties for quick healing and increased bone formation. The results demonstrate that a small increase in conductivity delivers improved cell response and quick deposition of minerals that are essential for bone formation. Surfaces with a clearly defined nanostructure feature a larger active area and react faster to the deposition of bone-forming minerals.
The project was performed by the University of Gothenburg in collaboration with the Astra Tech AB in Mölndal, and has scope for further study.


July 23, 2011

Filed under: Uncategorized — admin @ 10:35 am

As you know, intravenous bisphosphonates and to a lesser extent oral bisphosphonates like fosamax have been associated with an increased rick of osteonecrosis of the jaw (ONJ).  Recently, Dr. Richard Wynn at the University of Maryland published on a human monoclonal antibody, bevacizumab (Avastin), used in treating metastatic carcinoma, that also appears to be associated with an increased incidence of ONJ.

About the Author

Dr. Richard L. Wynn is Professor of Pharmacology at the University of Maryland Dental School. He holds a BS degree in Pharmacy and a PhD degree in Pharmacology. He chaired the Department of Pharmacology at the University of Maryland Dental School from 1980 to 1995. He is the lead author of the Drug Information Handbook for Dentistry, a co-author on many other dental drug publications, an author of over 300 refereed scientific journal articles, a consultant to the Academy of General Dentistry, a featured columnist, and a featured speaker presenting more than 500 courses in continuing dental education. One of his primary interests continues to be keeping dental professionals informed of all aspects of drug use in dental practice.

Bevacizumab (Avastin®): Another Drug Associated With Osteonecrosis of the Jaw

First it was the intravenous bisphosphonates, zoledronic acid (Zometa®) and palmidronate (Aredia®), then the oral bisphosphonates (the Fosamax® family of drugs), then the anti-RANKL drug, denosumab (Prolia®, Xgeva®). Now it’s a human monoclonal antibody known as bevacizumab (Avastin) that is associated with osteonecrosis of the jaw (ONJ) syndrome.
Bevacizumab (Avastin) belongs to a class of drugs known as antiangiogenic agents, used with increasing frequency in treating cancer. Bevacizumab is indicated for the treatment of metastatic colorectal cancer, and metastatic nonsquamous, nonsmall cell lung cancer. Angiogenesis in tumor cells involves the formation and growth of new blood vessels which help tumor growth. Bevacizumab acts to block angiogenesis through inhibition of cell proliferation and vessel sprouting, as well as by decreasing circulating vascular endothelial growth factor (VEGF) levels. This action is similar to the antiangiogenic action ascribed to the bisphosphonates. There are literature reports on patients receiving bevacizumab who developed ONJ. These reports are described in this month’s newsletter.
A case of ONJ associated with bevacizumab exposure was reported in a letter to the editor in 2008 (Greuter S, Schmid F, Ruhstaller T, et al, “Bevacizumab Associated Osteonecrosis of the Jaw,” Ann Oncol, 2008, 19(12):2091-2).
A 63-year old woman was treated for breast cancer. Bone scans were normal and she had never taken bisphosphonates. While being treated with liposomal doxorubicin and bevacizumab, the patient experienced left-sided maxillary pain after one-month therapy. A tooth infection was diagnosed and numbers 25 and 26 were extracted. One month later, a mouth-antrum fistula was surgically revised and occluded. Soon afterward, the patient suffered from a trigeminal neuralgia. Imaging showed maxillary sinusitis and signs of ONJ. The jaw lesion was extirpated and the sinus drained. Histology verified the clinical diagnosis of ONJ and an infiltration from the cancer was excluded. At 3 months of follow-up, the patient remained free of lesions and symptoms.
The authors commented that bevacizumab acts to block angiogensis through inhibition of cell proliferation and vessel sprouting, as well as by decreasing circulating vascular endothelial growth factor (VEGF) levels. This action is similar to the antiangiogenic action described for the bisphosphonates.
The authors stated that this was the third published case of ONJ associated with bevacizumab therapy. The doxorubicin the patient was taking is an anthracycline antineoplastic agent that has been on the market for many years and has never been known for causing ONJ. The authors suspected that bevacizumab, which hampers wound healing and possibly bone remodeling, was the causative agent in this case.
The other two published cases were included in a report by Estilo, et al (Estilo CL, Fornier M, Farooki A, et al, “Osteonecrosis of the Jaw Related to Bevacizumab,” J Clin Oncol, 2008, 26(24):4037-8).
A 51-year-old female with a history of infiltrating ductal carcinoma of the right breast was diagnosed in late 2001 and treated with mastectomy in 2002. She subsequently underwent treatment with chemotherapy, doxorubicin, cyclophosphamide, and letrozole for various cycles over a 3-year period. Since 2006, she underwent additional chemotherapy, capecitabine therapy, and radiation. In late December 2006, she was started on bevacizumab at a dose of 15 mg/kg every 3 weeks for a total of 8 doses, the last dose given in May 2007. Six weeks after the last dose, the patient presented with a 2-month history of complaints of lower jaw discomfort and protruding bone in the lower jaw. Examination revealed an area of bone exposure in the left posterior lingual mandible approximately 1 X 1 mm in diameter. The area appeared necrotic. The surrounding tissue had no evidence of infection. The exposed bone was smoothed with a bone file and the patient prescribed chlorhexidine 0.12% oral rinse. The bevacizumab and capecitabine were then discontinued. The area of exposed bone had resolved within a few weeks. The overlying mucosa appeared normal. At that time, a new area of exposed bone appeared in the right posterior lingual mandible of 1 X 1mm in area. Histology showed devitalized necrotic bone with a scalloped “moth eaten” appearance. Bacterial colonies occupied the demineralized areas.
The other case was a 33-year-old woman with a history of glioblastoma multiforme diagnosed in November 2006. She underwent surgery followed by radiation therapy and temozolomide from December 2006 through January 2007. The patient started bevacizumab therapy in Feb 2007 at a dose of 10 mg/kg every 2 weeks. Thirteen weeks later, she was referred to the dental clinic for evaluation of a 2-week history of spontaneous mucosal breakdown overlying her right mandible. The patient complained of gingival pain. On examination, there appeared a 1 X 2 cm dehiscence at the junction of the unattached/attached gingiva in the mucobuccal fold overlying the lower right first and second premolar and first molar teeth. There was exposed necrotic bone visible through the dehiscence extending inferiorly and posteriorly. There was no evidence of infection. Other than that, the oral mucosa appeared healthy with intact dentition. The patient continued on biweekly bevacizumab. In August 2007, she returned with a small mucosal defect posterior to the original lesion. There was soft tissue dehiscence with no evidence of exposed bone.
The authors commented that the clinical features of bone exposure in the two cases were compatible with ONJ in patients exposed to bisphosphonate therapy. The two patients had no history of bisphosphonate use. The authors suggested that bevacizumab contributed to the oral mucosal breakdown with exposed necrotic mandibular bone in the two patients. The antiangiogenic property of bevacizumab could compromise microvessel integrity in the jaw and lead to subclinical compromise of the osteonecrosis. Trauma from tooth brushing or chewing could also increase the demand on this compromised bone to repair itself and result in localized bone necrosis, periosteal death, and eventual exposed necrotic bone.
Estilo et al went on to explain that angiogenesis is a critical step in tumor growth, invasion, and metastasis. VEGF is a family of cytokines that exert important functions in tumor angiogenesis. VEGF is overexpressed in various human tumors and overexpression of VEGF is associated with tumor progression. VEGF is also essential for osteogenic differentiation and bone formation. Thus bevacizumab, used as a VEGF inhibitor to suppress tumor progression, could also suppress the osteogenic differentiation and bone formation. This could result in failure to repair bone trauma.
In the two patients described, additional factors possibly contributing to the development of ONJ were the advanced cancer and chemotherapy. The authors cautioned that clinicians involved in the care of patients treated with bevacizumab should be aware of the potential complication of ONJ.

Antiangiogenic Agents and the Risk of ONJ

Christodoulou et al reported that a combination of bisphosphonates and antiangiogenic factors induces ONJ more frequently than bisphosphonates alone (Christodoulou C, Pervena A, Klouvas G, et al, “Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently Than Bisphosphonates Alone,” Oncology, 2009, 76(3):209-11). Their introduction in the report stated that antiangiogenic agents may add to the risk of ONJ, especially when used in combination with bisphosphonates. The purpose of the study was to do a back review of data of patients receiving bisphosphonates with or without antiangiogenic factors for osseous metastases from various tumors between June 2007 and June 2008.
Among 116 patients being treated for various malignancies, 25 received concurrent treatment with antiangiogenic agents at some point. Twenty-two were taking bevacizumab, two were taking a drug called sunitinib, and one was taking a drug called sorafenib. The median duration to exposure to bisphosphonates was 28.5 months for the 25 patients taking the antiangiogenic drugs and 24 months for those not taking any antiangiogenic drugs. There were no significant differences between the two groups regarding treatment duration with the bisphosphonate.
Of the 25 patients receiving concurrent treatment with bisphosphonates and the antiangiogenic drug, 4 developed ONJ (incidence of 16%). Of the 91 patients receiving bisphosphonates without antiangiogenic factors, 1 developed ONJ (incidence 1.1%). This difference was statistically significant.
In this study, the diagnosis of ONJ was according to the clinical diagnoses made by dentists specializing in treating cancer patients and consisted of pain in the jaw with exposed, necrotic bone, some with purulent discharge. The authors commented that bisphosphonates have also been reported to possess antiangiogenic activity, particularly zoledronic acid (Zometa®) — a widely popular bisphosphonate used as an adjunct agent in cancer treatment.
Greuter et al (above) summed it up best by stating “if more cases of bevacizumab-associated ONJ are reported, special dental management (jaw x-ray, optimal dental health, and good oral hygiene) should become standard before patients start bevacizumab.”

Dental Management to Reduce the Risk of ONJ

The importance of special dental management to reduce the risk of ONJ in patients taking bevacizumab was shown in a recent report (Francini F, Pascucci FF, Francini E, et al, “Osteonecrosis of the Jaw in Patients with Cancer Who Received Zoledronic Acid and Bevacizumab,” J Am Dent Assoc, 2011, 142(5):506-13). They looked at cancer patients on zoledronic acid and chemotherapy combined with bevacizumab who underwent a dental exam before starting treatment. They found that none of the patients developed ONJ.
The study included 59 patients with either breast cancer or nonsmall cell lung cancer who received 4 mg zoledronic acid I.V. every 4 weeks and 15 mg per kg bevacizumab every 3 weeks. The median time of receiving zoledronic acid was 18 months and the median time of receiving bevacizumab was 16 months. All subjects received a dental exam and panoramic x-rays before starting treatment and every three months thereafter until the patient died or was lost to follow-up. If needed, patients received periodontal disease treatment and underwent tooth extraction before they received any drug.
None of the patients required dentoalveolar surgery while undergoing cancer treatment. After a median follow up of 19.7 months, none of the participants developed ONJ. The conclusion was that a bisphosphonate combined with an antiangiogenic drug did not predispose to ONJ in participants with cancer that metastasized to the bone, who underwent a baseline dental examination and preventive dental measures.

Indications for Bevacizumab (Avastin®) Approved by FDA:

Treatment of metastatic colorectal cancer; treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous, nonsmall cell lung cancer; treatment of metastatic HER-2 negative breast cancer (who have not received chemotherapy for metastatic disease); treatment of progressive glioblastoma; treatment of metastatic renal cell cancer (not an approved use in Canada).
Note: For the treatment of metastatic breast cancer, effectiveness is based on improvement in progression-free survival; not indicated for the treatment of breast cancer with metastatic disease that has progressed following anthracycline and taxane treatment. For the treatment of glioblastoma, effectiveness is based on improvement in objective response rate.

Unlabeled/Investigational Use:

Treatment of recurrent ovarian cancer; recurrent cervical cancer; soft tissue sarcomas (angiosarcoma or hemangiopericytoma/solitary fibrous tumor); age-related macular degeneration (AMD).

Drug information is constantly changing. Promote medication safety in your practice with Lexicomp Online for Dentistry.


July 20, 2011

Filed under: Uncategorized — admin @ 10:11 am

A recent survey was done and asked this very question.  here are the results.


Filed under: Uncategorized — admin @ 10:06 am

In our teaching courses, we are often asked by beginning implatologists what to charge for implant placement.  Here is a recent survey which asked that very question.

Philadelphia’s Implant Information Central!: STEM CELLS WHAT ARE THEY, AND HOW CAN THEY HELP?

July 19, 2011

Filed under: Uncategorized — admin @ 11:09 am

Philadelphia’s Implant Information Central!: STEM CELLS WHAT ARE THEY, AND HOW CAN THEY HELP?: “Dr. Bruce Freund recently wrote a brief summary about stem cells and what they can do for us in dentistry and in implantology. They certain…”


Filed under: Uncategorized — admin @ 11:08 am

Dr. Bruce Freund recently wrote a brief summary about stem cells and what they can do for us in dentistry and in implantology.  They certainly hold a great deal of promise for the future.  The article can be accessed here:


July 9, 2011

Filed under: Uncategorized — admin @ 9:56 am

A recent article in the Journal of Oral Implantology has identified a combination of genes that when present may adversely affect dental implants.  This could change the way we evaluate patients for dental implant reconstruction.  


gary l henkel dds magd

horsham dental elements 

Gene combination identified as risk factor in success of dental implants


Jun 29, 2011
Journal of Oral Implantology — The health of the surrounding tissue affects the success of a dental implant. Identifying and reducing risk factors is therefore a key step in the implant process. Now a combination of genes has been identified as a possible indicator of greater tissue destruction, leading to negative outcomes for implants.
The authors of an article in the current issue of the Journal of Oral Implantology report on a study of individuals with the combination of interleukin (IL)-1 allele 2 at IL-1A-889 and IL-1B+3954. These people are “genotype positive” and are susceptible to increased periodontal tissue destruction.
Peri-implantitis, or the process of tissue inflammation and destruction around failing implants, is very similar to periodontal disease. The researchers sought to find any association of these genotypes with the severity of peri-implantitis progression and the effect of this combination on treatment outcomes.
This study compared two groups of patients, all of whom had implants. The first group consisted of 25 patients with peri-implantitis, while the second group of 25 patients had healthy tissue. Seventeen patients from the first group and five from the second group were genotype positive.
Patients in the first group, those with peri-implantitis, took part in a treatment and maintenance program. The genotype-positive patients in this group experienced greater periodontal tissue destruction and, increased discharge from tissues. The genotype-negative patients responded better to treatment. Statistically significant differences were noted between the groups.
The combination of these two alleles in patients with inflamed periodontal tissues denotes a risk factor that can lead to further tissue destruction. Patients with the specific genotype can have exaggerated local inflammation. Gene polymorphism may affect the outcomes of treatment for peri-implantitis in genotype-positive people and affect the long-term success of implants.
Full text of the article, “The Effect of Interleukin-1 Allele 2 Genotype (IL-1a-889 and IL-1b+3954) on the Individual’s Susceptibility to Peri-Implantitis: Case-Control Study,” Journal of Oral Implantology, Vol. 37, No. 3, 2011, is available by clicking here.
The Journal of Oral Implantology is the official publication of the American Academy of Implant Dentistry and of the American Academy of Implant Prosthodontics. It is dedicated to providing valuable information to general dentists, oral surgeons, prosthodontists, periodontists, scientists, clinicians, laboratory owners and technicians, manufacturers, and educators. The JOI distinguishes itself as the first and oldest journal in the world devoted exclusively to implant dentistry. For more information about the journal or society, click here.