Providing Optimal Rejuvenation to the Jawline and Perioral Area Using Neuromodulators and Hyaluronic Acid Dermal Fillers.

Including the jawline in aesthetic assessment has become increasingly popular when using both surgical and nonsurgical techniques. Facial aging processes include bone resorption, fat pad atrophy, and a breakdown of the quality of collagen and elastin in the skin. To provide optimal treatment of the jawline using nonsurgical techniques, it is important to consider all of these aspects before planning treatment. Men and women have different facial aging processes and ideal facial ratios that must be respected. The objective of this article is to discuss the use of botulinum toxin A and hyaluronic acid filler injectable treatments, deoxycholic acid injectable treatments, and cryolipolysis treatments and explain how these treatments can be utilized for optimal rejuvenation of the jawline and perioral area.

Zoledronate inhibits the differentiation potential of adipose-derived stem cells into osteoblasts in repairing jaw necrosis.

OBJECTIVE: To explore the inhibitory effects of zoledronate (ZOL) on adipose-derived stem cells (ADSCs) into osteoblasts for repairing jaw necrosis. METHODS: ADSCs were induced to differentiate into osteoblasts. The differentiation characteristics of osteoblasts was observed under inverted microscope by alizarin red staining. The transwell assay was performed to evaluate the migration of ADSCs co-cultured with osteoblasts and divided into ZOL group treated with ZOL and N-ZOL group without ZOL treatment. The differentiation and proliferation characteristics of ADSCs differentiated osteoblasts were observed respectively. The expression of CTSK (Cathepsin K) and FGFR3 (Fibroblast growth factor receptor 3) in osteoblasts were analyzed by immunofluorescence and western blot. RESULTS: The differentiation degree and proliferation of ADSCs to osteoblasts in N-ZOL group were both higher than those in ZOL group. The migratory cell number in ADSCs differentiation in ZOL group was higher than that of N-ZOL group. The protein expression of CTSK and FGFR3 in ADSCs differentiated to osteoblasts in ZOL group was higher than that in N-ZOL group. CONCLUSION: The differentiation of ADSCs into osteoblasts is significantly inhibited by ZOL. Due to this reason, it may be difficult to achieve good results by ZOL induced ADSCs into osteoblasts in repairing jaw necrosis.

Osteogenesis Differences Around Titanium Implant and in Bone Defect Between Jaw Bones and Long Bones.

The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.

Effects of probiotics, prebiotics or synbiotics on jawbone in obese-insulin resistant rats.

PURPOSE: Chronic high-fat diet (HFD) consumption results in gut dysbiosis, systemic inflammation, obese-insulin resistance, and osteoporosis of the jawbones. The probiotics, prebiotics or synbiotics alleviated gut dysbiosis and the metabolic disturbance in HFD-induced obesity. However, the effects on jawbone properties have not been investigated. This study aimed to investigate the effects of probiotic Lactobacillus paracasei HII01, prebiotic xylooligosaccharide (XOS), and synbiotics on the jawbone properties along with metabolic parameters, gut and systemic inflammation in HFD-fed rats. METHODS: Forty-eight male Wistar rats were fed with either a HFD or normal diet for 12 weeks. Rats in each group were subdivided into four subgroups to be treated with either vehicle, probiotics, prebiotics, or synbiotics for the additional 12 weeks. Blood samples, gut, bone marrows, and jawbones were collected to determine metabolic parameters, inflammation, and bone properties. RESULTS: The HFD-fed rats developed obese-insulin resistance, as indicated by increased body weight, dyslipidemia and decreased insulin sensitivity. Serum lipopolysaccharide levels and interleukin-6 mRNA expression in the ileum and bone marrows were elevated. Altered bone metabolism and the impaired jawbone properties were evident as indicated by decreased bone mineral density with increased trabecular separation. Reduced ultimate load and stiffness were observed in HFD-fed rats. Treatments with probiotics, prebiotics or synbiotics in HFD-fed rats improved metabolic parameters and reduced inflammation. However, no alterations in jawbone properties were found in all treatments. CONCLUSION: The osteoporosis of the jawbone occurred in obese-insulin resistance, and treatments with probiotics, prebiotics and synbiotics were not sufficient to improve the jawbone properties.

Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts.

The aim of this study was to elucidate the role of fibroblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ), evaluating the effect of zoledronate, alendronate, and ibandronate on the proliferation of fibroblasts and on their expression of genes essential for fibroblast physiology. Human CCD-1064Sk epithelial fibroblast cells were incubated in culture medium with 10-5, 10-7, or 10-9 M zoledronate, alendronate, or ibandronate. The proliferative capacity of fibroblasts was determined by spectrophotometry (MTT) at 24 of culture. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of BPs at a dose of 10-9 M on the expression of FGF, CTGF, TGF-ß1, TGFßR1, TGFßR2, TGFßR3, DDR2, α-actin, fibronectin, decorin, and elastin. Fibroblasts proliferation was significantly increased at the lowest dose (10-9M) of each BP but was not affected at the higher doses (10-5 and 10-7M). The proliferation increase may be related to the rise in TGF-ß1 and TGFßR1 expression detected after the treatment of cells with 10-9M of zoledronate, alendronate, or ibandronate. However, the expression of CTGF, DDR2, α-actin, fibronectin, and decorin decreased versus controls. The results of this in vitro study indicate that a very low BP dose (10-9 M) can significantly affect the physiology of fibroblasts, increasing their proliferative capacity and modulating the expression of multiple genes involved in their growth and differentiation.

A Novel Silicon Device for the Packing of Cutaneous Abscesses.

BACKGROUND: Superficial skin abscesses are commonly encountered in emergency medicine practice. Standard treatment includes incision, drainage, and often packing with a gauze strip. The packing component of the procedure has several negative potential outcomes, is painful, and necessitates a return visit for removal. DISCUSSION: Here we report the first case in which a novel silicon packing device was utilized. The patient presented with a facial abscess, which was incised and drained. The novel device was inserted, and removed by the patient independently, without complication. Both patient and provider reported satisfaction with the novel procedure, and noted low pain scores. CONCLUSIONS: This device has the potential to replace traditional packing, and will require further study through a controlled trial to assess for safety and efficacy.

Remodeling the neck and the lower jaw with dehoxycholate injections.

Nonsurgical cosmetic facial procedures have gained popularity in recent decades. These procedures are commonly referred to as facial rejuvenation, and only a few are performed in the neck region. Herein, the authors describe their experience with off-label use of deoxycholic acid (DC) injections on 18 patients for remodeling of the neck and lower jaw. The injection protocol was personalized for each patient, and lidocaine was always premixed with the DC. After the initial injection visit, at least 3 months passed before further injections were considered. All documented side effects, including swelling and dysesthesia, resolved spontaneously. All patients received follow-up for at least 3 months, and only 2 patients required a second session of injections. By personalizing the injection protocol for each patient, good outcomes were achieved, including aesthetic enhancement of the shape and contour of the jaw and neck. Although the study is limited by the relatively small sample size, the results are promising and warrant additional investigations.

Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability.

The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg-1·day-1) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75-150 mg·kg-1·day-1) of aspirin or acetaminophen (300 mg·kg-1·day-1) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation.NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal motor excitability has not been fully understood. We found that, during orthodontic treatment, trigeminal motor excitability is acutely increased and then decreased in a week. Because alteration of trigeminal motor function can be evaluated quantitatively by jaw-opening reflex excitability, the present animal model may be useful to search for alternative approaches to attenuate orthodontic pain.

Bone-site-specific responses to zoledronic acid.

OBJECTIVES: Bisphosphonates are widely used to treat bone diseases such as osteoporosis. However, they may cause osteonecrosis of the jaw. Here, we investigated whether in vivo exposure to bisphosphonates has a different effect on long bone and jaw osteoclasts, and on the turnover of these different bones. MATERIALS AND METHODS: Zoledronic acid (0.5 mg kg-1 weekly) was administered intraperitoneally to 3-month-old female mice for up to 6 months. The effects on the number of osteoclasts, bone mineralization and bone formation were measured in the long bones and in the jaw. RESULTS: Long-term treatment with zoledronic acid reduced the number of jaw bone marrow cells, without affecting the number of long bone marrow cells. Zoledronic acid treatment did not affect the number of osteoclasts in vivo. Yet, the bisphosphonate increased bone volume and mineral density of both long bone and jaw. Interestingly, 6 months of treatment suppressed bone formation in the long bones without affecting the jaw. Unexpectedly, we showed that bisphosphonates can cause molar root resorption, mediated by active osteoclasts. CONCLUSIONS: Our findings provide more insight into bone-site-specific effects of bisphosphonates and into the aetiology of osteonecrosis of the jaw. We demonstrated that bisphosphonates can stimulate osteoclast activity at the molar roots.

Influence of N-methyl pyrrolidone on the activity of the pulp-dentine complex and bone integrity during osteoporosis.

AIM: To analyse the effect of systemic application of N-methyl pyrrolidone (NMP) on the pulp-dentine complex and on the jawbone of ovariectomized rats. METHOD: Female Sprague Dawley rats were randomly divided into a Sham-operated group (Sham n = 6) and an oestrogen depletion by ovariectomy (OVX n = 12) group. In 6 of the ovariectomized animals, N-methyl pyrrolidone (NMP) in phosphate-buffered saline (PBS) was administered systemically weekly by intraperitoneal injection (i.p.); the other 6 were injected with PBS (Veh). After 15 weeks of injections, the jaw bones were collected and pulps extracted from the incisors teeth. Histology was used to determine pre-dentine thickness in teeth and radiography to determine alveolar bone mass. Immunohistological staining and RT-PCR were performed to verify the presence and localization of the odontoblast-specific dentine sialoprotein and to quantify its expression in the dentine-pulp complex. Mandibular cortical width and mandibular height were evaluated by means of X-ray analysis. Statistical analysis was performed with analysis of variance (anova). RESULTS: Both pre-dentine (P = 0.029) and alveolar bone structures (P = 0.049) were significantly reduced due to oestrogen deficiency in OVX Veh and OVX. NMP treatment normalized these parameters to the Sham level. DSPP expression in OVX NMP animals was significantly higher (P = 0.046) than in OVX Veh. X-ray analysis confirmed that ovariectomy significantly reduced the mandibular cortical width in the OVX Veh group compared to the Sham Veh and OVX NMP (P = 0.020). CONCLUSION: N-methyl pyrrolidone (NMP) had a remarkable anti-osteoporotic ability preserving activity in the pulp-dentine complex and preventing jawbone loss. These effects make NMP a promising candidate for the preservation of the activity of the pulp-dentine complex and jawbone thickness in post-menopausal females.

Osteonecrosis of the Jaw Developed in Mice: DISEASE VARIANTS REGULATED BY γδ T CELLS IN ORAL MUCOSAL BARRIER IMMUNITY.

Osteonecrosis of the jaw (ONJ), an uncommon co-morbidity in patients treated with bisphosphonates (BP), occurs in the segment of jawbone interfacing oral mucosa. This study aimed to investigate a role of oral mucosal barrier γδ T cells in the pathogenesis of ONJ. Female C57Bl/6J (B6) mice received a bolus zoledronate intravenous injection (ZOL, 540 µg/kg), and their maxillary left first molars were extracted 1 week later. ZOL-treated mice (WT ZOL) delayed oral wound healing with patent open wounds 4 weeks after tooth extraction with characteristic oral epithelial hyperplasia. γδ T cells appeared within the tooth extraction site and hyperplastic epithelium in WT ZOL mice. In ZOL-treated γδ T cell null (Tcrd(-/-) ZOL) mice, the tooth extraction open wound progressively closed; however, histological ONJ-like lesions were identified in 75 and 60% of WT ZOL and Tcrd(-/-) ZOL mice, respectively. Although the bone exposure phenotype of ONJ was predominantly observed in WT ZOL mice, Tcrd(-/-) ZOL mice developed the pustule/fistula disease phenotype. We further addressed the role of γδ T cells from human peripheral blood (h-γδ T cells). When co-cultured with ZOL-pretreated human osteoclasts in vitro, h-γδ T cells exhibited rapid expansion and robust IFN-γ secretion. When h-γδ T cells were injected into ZOL-treated immunodeficient (Rag2(-/-) ZOL) mice, the oral epithelial hyperplasia developed. However, Rag2(-/-) ZOL mice did not develop osteonecrosis. The results indicate that γδ T cells are unlikely to influence the core osteonecrosis mechanism; however, they may serve as a critical modifier contributing to the different oral mucosal disease variations of ONJ.

Oromandibular dystonia: a serious side effect of capecitabine.

BACKGROUND: Capecitabine has activity against several types of cancer. In 10-15% of patients treated with capecitabine, treatment is discontinued because of serious adverse reactions, mostly within the first weeks of treatment. CASE PRESENTATION: A 56 year-old female patient presented at the emergency department after ten days of chemotherapy with progressive airway obstruction and complaints of numbness of the tongue. She also had difficulty swallowing and was unable to speak. Laboratory findings were completely normal and no co-medication was used, in particular no dopamine antagonists. CONCLUSION: The case highlights the need for awareness that capecitabine may potentially lead to severe life-threatening complaints of oromandibular dystonia. We hypothesize that capecitabine passed the blood brain barrier which led to a disruption within the basal ganglia in this case. Prompt treatment with an anticholinergic drug and cessation of capecitabine in the patient case led to disappearance of complaints.

Prospective, mono-institutional study of the impact of a systematic prevention program on incidence and outcome of osteonecrosis of the jaw in patients treated with bisphosphonates for bone metastases.

The aim of our study was to investigate the occurrence of osteonecrosis of the jaw (ONJ) after implementation of dental preventive measures before starting bisphosphonates (BPs) therapy and during treatment. All consecutive patients with bone lesions eligible for BPs treatment were prospectively evaluated. Before starting BPs, each patient underwent a strict dental preventive program with a specialized odontoiatric team. The odontoiatric evaluation identified patients with oral pathologies or inadequate oral hygiene and provided a dental preventive treatment. From April 2007 to April 2012, 254 patients were enrolled. After excluding patients due to previous BPs treatment, 212 patients with a mean age of 74 years (range 37-95) were included. On average, patients received 9.7 treatment cycles (range 1-48). No ONJ was recorded (0.0 %; 95 % confidence interval [CI] 0.0-1.4). Comparing this risk with that observed in a previous cohort who did not receive dental prevention (16/186, 8.6 %; 95 % CI 4.2-15.3 %), we observed clear efficacy in preventing ONJ (relative risk reduction: 100 %, 95 % CI 86-100 %, P < 0.0001). We developed a strict three-step prevention program that is able to decrease ONJ incidence and the need for destructive surgery with permanent sequelae. We demonstrated that ONJ could be effectively prevented. We recommend a mandatory preventive program involving a multidisciplinary team for all patients starting BPs.

The effects of bisphosphonate on the remodeling of different irregular bones in mice.

BACKGROUND: We aimed to compare the effects of bisphosphonate on the remodeling of irregular bones (the jaw and ilium) in mice after trauma. METHODS: To verify the feasibility of modeling osteonecrosis, 20 mice were injected intraperitoneally with zoledronate and dexamethasone (ZOL&DEX group), dexamethasone (DEX group), or phosphate-buffered saline (PBS) [control (CTR) group]. Mice then underwent extraction of the right maxillary first molar and creation of an artificial bony cavity in the ilium. Bone sections were stained with H&E for morphological studies. To further compare differences between the maxilla and the ilium caused by similar traumas, 80 mice were injected intraperitoneally with ZOL&DEX or PBS. Pathological progression at the injury sites was assessed at 1 day and at 1, 3, and 8 weeks after trauma using micro-computed tomography (CT), H&E and immunohistochemistry analyses, high-performance liquid chromatography-mass spectrometry, and enzyme-linked immunosorbent assay. RESULTS: Only the ZOL&DEX model group effectively developed osteonecrosis. Bony sequestra, osseous sclerosis, unhealed mucosa, and radiopaque alveolar bone were found in the maxilla. In the ilium, there was a lower frequency of osteonecrotic disease and osseous sclerosis, and less suppression of bone remodeling than in the maxilla following long-term bisphosphonate administration. Zoledronate levels were higher in the maxilla. ZOL&DEX treatment suppressed the levels of RANKL and IL-17, but induced an upregulation of osteoprotegerin and FAM20C in both bones. CONCLUSION: Accumulation of bisphosphonate may increase the incidence of osteonecrosis. The RANKL/OPG pathway and IL-17 and FAM20C cytokines play key roles in the progression of pathologically abnormal bone remodeling.

Incidence and Risk Factors of Osteonecrosis of the Jaw in Advanced Cancer Patients after Treatment with Zoledronic Acid or Denosumab: A Retrospective Cohort Study.

Zoledronic acid and denosumab are two antiresorptive drugs currently in use for treating osteoporosis. They have different mechanisms of action, but both have been shown to delay the onset of skeletal-related events in patients with advanced cancer. However, medication-related osteonecrosis of the jaw (MRONJ) has been reported in cancer patients treated with zoledronic acid or denosumab. We studied 155 patients with several types of advanced cancer who were treated with zoledronic acid or denosumab in our hospital during the period from April 2010 through March 2013. Thirteen of these 155 patients (8.4%) developed MRONJ. MRONJ development was significantly associated with the number of zoledronic acid or denosumab infusions (p<0.001) and the duration of zoledronic acid or denosumab therapy (p<0.001). Logistic regression analysis showed that diabetes [odds ratio (OR)=6.699, 95% confidence interval (CI), 1.435-31.277, p=0.016], anemia [OR=14.559, 95% CI, 2.161-98.069, p=0.006], and pus discharge [OR=6.491, 95% CI, 1.514-27.835, p=0.012] significantly increased the risk of developing MRONJ. However, the risk of MRONJ was significantly lower [OR=0.137, 95% CI, 0.020-0.944, p=0.043] when patients received periodical dentistry maintenance. Diabetes, anemia, and pus discharge may also play roles in its development. These findings suggest that the active inclusion of dentistry maintenance in bisphosphonate or denosumab treatment of cancer patients can reduce MRONJ development.

Biocompatibility of pure and mixed hydroxyapatite and α-tricalcium phosphate implanted in rabbit bone.

Calcium phosphates and hydroxyapatite, in particular, are used as substitute materials in experimental implantology. These materials are primarily used in hard tissue replacement because their chemical and crystallographic characteristics are considered to be similar to the mineral content, osteoconductivity and bioactivity of normal bone. Cytokines, such as interleukin (IL)-1, IL-6, IL-8, IL-10 and antimicrobial protein ß-defensin-2 (ßDef-2), are used as biomarkers of non-specific reactogenicity. Other biomarkers, including bone morphogenetic protein-2/4 (BMP-2/4), bone regeneration protein osteoprotegerin (OPG), bone matrix protein osteopontin (OP) and osteocalcin (OC), are regarded as specific factors of reactogenicity in bone substitution. The aim of our study was to assess the changes in the distribution and expression of the aforementioned proteins in the lower jaws of rabbits following implantation with pure hydroxyapatite (HAP), α-tricalcium phosphate (α-TCP) or a mix of the two (HAP/α-TCP) manufactured under different temperatures. Our results reveal osteoblast proliferation and regions of granulation tissue formation between biomaterial granules close to the original implantation site, but in the control tissue these changes were less noticeable. Our study showed low variability in the distribution of ßDef-2, OPG and all of the tested interleukins and these proteins were less expressed than BMP2/4, OP and OC. But across all experiments, no statistically significant difference in mean ßDef-2, IL-1, IL-6, IL-8, IL-10, OP, OC, BMP-2/4 and OPG expression in osteocytes was detected between experimental and control groups. We concluded that pure and mixed HAP and α-TCP sintered at different temperatures do not affect the production of cytokines and bone-specific proteins; regions with osteoblast proliferation and low levels of anti-inflammatory cytokines IL-6 and IL-10 indicates better biocompatibility for HAP/α-TCP and α-TCP-2 biomaterials and the moderate number of BMP-2/4- and a prevalence of OC- and OP-positive osteocytes in experimental tissues implanted with HAP at 3 months after implantation indicates potential bone regeneration stimulated by pure HAP.

Involvement of astroglial glutamate-glutamine shuttle in modulation of the jaw-opening reflex following infraorbital nerve injury.

To evaluate the mechanisms underlying orofacial motor dysfunction associated with trigeminal nerve injury, we studied the astroglial cell activation following chronic constriction injury (CCI) of the infraorbital nerve (ION) immunohistochemically, nocifensive behavior in ION-CCI rats, and the effect of the glutamine synthase (GS) blocker methionine sulfoximine (MSO) on the jaw-opening reflex (JOR), and also studied whether glutamate-glutamine shuttle mechanism is involved in orofacial motor dysfunction. GFAP-immunoreactive (IR) cells were observed in the trigeminal motor nucleus (motV) 3 and 14 days after ION-CCI, and the nocifensive behavior and JOR amplitude were also strongly enhanced at these times. The number of GS- and GFAP-IR cells was also significantly higher in ION-CCI rats on day 7. The amplitude and duration of the JOR were strongly suppressed after MSO microinjection (m.i.) into the motV compared with that before MSO administration in ION-CCI rats. After MSO administration, the JOR amplitude was strongly suppressed, and the duration of the JOR was shortened. Forty minutes after m.i. of glutamine, the JOR amplitude was gradually returned to the control level and the strongest attenuation of the suppressive effect of MSO was observed at 180 min after glutamine m.i. In addition, glutamine also attenuated the MSO effect on the JOR duration, and the JOR duration was extended and returned to the control level thereafter. The present findings suggest that astroglial glutamate-glutamine shuttle in the motV is involved in the modulation of excitability of the trigeminal motoneurons affecting the enhancement of various jaw reflexes associated with trigeminal nerve injury.

Implications of high-dosage bisphosphonate treatment on bone tissue in the jaw and knee joint.

Bisphosphonates are bone antiresorptive agents traditionally used on a relatively large scale for treatment of bone metabolic diseases and on a smaller scale for bone metastasis treatment. A study on the effects of bisphosphonate treatment on healthy instead of diseased animals will give more insight into the basic mechanisms of bisphosphonates and their effects on different bone sites. We aimed to assess the effect of BP on the mouse knee and jaw joint. Three-month old female C57BL/6 mice were used (twenty-four and eighteen control and experimental group, respectively). At baseline and after treatment with zoledronic acid (ZA) for one, three or six months, we combined bone assessment via µCT and additional histology. Our results showed that, in the knee joint, ZA treatment increased TMD, bone volume, trabecular thickness but did not influence cortical thickness. In both control and ZA group, a higher trabecular TMD compared to cortical TMD was seen. Unseen in the knee joint, ZA treatment in the jaw joint resulted in bone-site specific changes in mineralization; a significant time-dependent higher TMD was evident in the subchondral bone compared to the most distal region of the condyle. MicroCT images revealed the presence of mineral in this region and histology showed that this region did not contain mature bone tissue but cartilage-like tissue. Our data indicate the possibility of site-specific negative side effects, i.e., disturbing normal mandibular development under the influence of bisphosphonate therapy.

Is bone turnover of jawbone and its possible over suppression by bisphosphonates of etiologic importance in pathogenesis of bisphosphonate-related osteonecrosis?

PURPOSE: The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood. The most popular hypothesis has suggested that the bone turnover (BT) in the jawbone is greater than that in other sites and that this turnover will be overly suppressed by bisphosphonates. Using bone scintigraphy, a simple tool for the quantitative evaluation of bone metabolism and blood flow, the goals of the present study were to determine whether the rate of bone remodeling is greater in the jaw and whether the bone BT in the jaw is differentially altered after bisphosphonate intake compared with that in other skeletal sites. MATERIALS AND METHODS: The bone scintigraphies of 90 female patients with breast cancer were retrospectively analyzed (n = 45 with bisphosphonate intake; n = 45 without bisphosphonate intake [control group]). All patients in the study group had undergone bone scintigraphy before therapy and during the treatment (course after 12 and 24 months). The data were quantitatively analyzed using 6 predetermined regions of interest. RESULTS: The bone BT of the mandible was similar to that of the femur and significantly reduced compared with that of the maxilla (P < .01). None of the investigated bone regions (including the mandible and maxilla) were significantly altered after bisphosphonate administration (P > .05). CONCLUSIONS: The finding that the mandible had significantly lower bone BT than that of the maxilla and that two thirds of BRONJ cases occur in the mandible were inconsistent with the investigated hypothesis. Furthermore, the bone BT in the jawbone was not overly suppressed by bisphosphonates. Thus, it is unlikely that over suppression of bone BT is the exclusive causation playing a role in the pathomechanism of BRONJ.