Effect of different doses and durations of teriparatide therapy on resolution of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats.

OBJECTIVE: To evaluate the effects of different doses and durations of teriparatide therapy on MRONJ resolution in rats. SUBJECTS AND METHODS: A total of 120 rats that had been affected with MRONJ (after six weekly zoledronate injections and tooth extraction) were randomly divided into eight subgroups: 2, 10, and 20 µg/kg/day teriparatide were administered to L4, M4, and H4 for 4 weeks, and to L8, M8, and H8 for 8 weeks, respectively. C4 and C8 received saline for 4 and 8 weeks, respectively. One week after the final injection, rats were sacrificed and assessed clinically (bone exposure/fistula) and histologically (number of osteocytes in extraction socket and empty lacunae in alveolar bone). RESULTS: MRONJ was clinically improved in 72.2%, 61.5%, and 40% of stage I, II, and III experimental rats, respectively. In the control rats, the results were 20.8% for stage I and no improvement for stages II and III. Aside from L4 and L8, the experimental subgroups had a significantly higher rate of clinical and histological improvement compared with their corresponding controls. There was a significantly higher number of osteocytes and lower number of empty lacunae in M4 and H4 compared with C4, in H4 compared with L4, in M8 and H8 compared with C8, and in H8 compared with L8. CONCLUSION: Teriparatide therapy improved clinical and histological features of MRONJ in a dose-dependent manner, but clinically relevant doses of teriparatide might not be sufficient for MRONJ resolution in rats. Extending the duration of teriparatide therapy from 4 to 8 weeks did not affect treatment outcomes.

Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures.

Denosumab, a bone-modifying agent, reduces the risk of skeletal-related events in patients with bone metastases from solid tumors and is generally well tolerated. However, hypocalcemia, osteonecrosis of the jaw (ONJ) and atypical fracture are potential and important toxicities of denosumab therapy that require attention. In pivotal phase III trials in patients with bone metastases from solid tumors, the incidence of hypocalcemia was 9.6% in denosumab-treated patients, with most events being asymptomatic, grade 2 and resolving by week 4. Established hypocalcaemia requires additional short-term calcium and vitamin D supplementation and, if severe, administration of intravenous calcium. ONJ was reported in 1.8% of patients receiving denosumab over 3 years in these trials. Involvement of an experienced oro-maxillary surgeon is important if ONJ is suspected. Atypical fractures were rare in a large study of denosumab using the dose and scheduling approved for the treatment of osteoporosis. To prevent toxicities, patients should maintain calcium and vitamin D supplementation, good oral hygiene and regular dental reviews throughout treatment. This article presents case studies from our clinical practice and discusses the pathophysiology of these toxicities along with guidance on prevention, diagnosis and management.

Use of Vancomycin-Impregnated Calcium Sulfate in the Treatment of Osteomyelitis of the Jaw.

PURPOSE: The aim of this study was to describe the effect of vancomycin-impregnated calcium sulfate in the treatment of osteomyelitis of the jaw. MATERIALS AND METHODS: Twelve patients who were diagnosed with osteomyelitis of the jaw underwent treatment with vancomycin-impregnated calcium sulfate since July 2014 at the Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University (Shenyang, China). All patients underwent debridement of nonviable bone and implantation of vancomycin-impregnated calcium sulfate. The wounds were covered with an acellular dermal matrix and sutured. RESULTS: Ten patients had satisfactory wound healing. However, 2 cases of maxillary central osteomyelitis had delayed wound healing. The wounds healed after the surgical site was resutured under local anesthesia. At 3 months, the panoramic radiograph showed that most implants had been reabsorbed and replaced by new bone formation. All patients in this study had no recurrence of infection at 6 to 18 months (mean, 10.8 months) of follow-up. CONCLUSIONS: The use of vancomycin-impregnated calcium sulfate in the surgical debridement site for chronic osteomyelitis of the jaw has shown encouraging results. In addition, calcium sulfate can promote the formation of new bone to a certain extent.

[Osteomyelitis of the jaws - review of the literature and a case report].

Osteomyelitis (OM), is a rare disease in developed countries. It is defined as a progressive inflammation of the bone and the bone marrow, and characterized by formation of necrotic bone. This disease is more common in the lower jaw, which resembles the structure of a long bone. However, there are histologic and microbiologic characteristics that constitute important factors in the etiology and pathogenesis of the disease and therefore it is not possible to make an analogy from OM of long bones to OM of the jaws. The diagnosis of OM is based on a detailed anamnesis, clinical findings, laboratory tests and imaging. The treatment of OM consists of surgical treatment, which is considered the mainstay of the treatment, and antibiotic treatment, parenteral and oral which is considered as complementary therapy. There are several surgical procedures, according to the extent of the lesion, which include: drainage, curettage, sequestrectomy, saucerization, decortications and resection. A case of osteomyelitis of the lower jaw after dental treatment is presented. The patient underwent segmental resection and reconstruction.

Pharmacologic modalities in the treatment of osteoradionecrosis of the jaw.

Managing osteoradionecrosis (ORN) of the facial bones is a challenge in maxillofacial head and neck surgery. Changes in understanding of ORN of the jaws has led to new studies using novel therapeutic modalities to manage this disorder. These treatment regimens may allow medical management to replace major reconstructive surgery for some patients who have already undergone chemoradiotherapy or combined modality therapy for head and neck cancer.

[The improvement of complex treatment of odontogenous periostitis in elderly patients].

The paper presents the results of clinical examination of 114 patients aged 60-88 years with acute odontogenous periostitis receiving treatment in in-patient maxillofacial surgery unit. The dynamic of clinical symptoms is used to carry out the comparative effectiveness study of several peroral antibiotics in elderly patients.

Osteoporosis of the jaw. Product evaluation: mf Odontovis Calcium®.

AIM: The aim of this study was to test mf Odondovis Calcium® as a food supplement in a 3-month product evaluation study measuring how the low jaw bone density, could be improved. The upper jaw density was tested with an ultrasound method, evaluating the grey scale median of the images (GSM). METHODS: Seventy nine subjects were enrolled; 22 normal subjects (group A) and 57 with upper jaw osteoporosis (according to DEXA values). Patients were divided into 2 groups (group B and C, respectively 28 and 29 cases). These subjects were treated with what was considered the' best treatment' and in the group B only was added mf Odontovis Calcium®, consisting of calcium salts, Vitamin D and physiological modulators with antioxidant activity. This treatment continued for 3 months. RESULTS: The GSM of osteoporotic patients was significantly lower in comparison with GSM in normal subjects. No changes were observed (between the inclusion and 3 month values) in normal subjects and minimal, non-significant changes were observed in control osteoporosis patients. Before-after treatment values of GSM in treatment patients showed a significant increase (P<0.022) at 3 months. The increase in GSM in these patients was significantly higher (P<0.05) in comparison with control patient with osteoporosis. The Tolerability of the product was very good and the compliance corresponded to 98%. CONCLUSION: the jaw density in patients with osteoporosis is increased in only 3 months with supplementation with mf Odontovis Calcium®. Long-term clinical implications should be observed in more prolonged studies.

Teriparatide and osseous regeneration in the oral cavity.

BACKGROUND: Intermittent administration of teriparatide, a drug composed of the first 34 amino acids of parathyroid hormone, has anabolic effects on bone. Although teriparatide has been evaluated for the treatment of osteoporosis and for the healing of fractures, clinical trials evaluating it for the treatment of osseous conditions of the oral cavity in humans are lacking. METHODS: A total of 40 patients with severe, chronic periodontitis underwent periodontal surgery and received daily injections of teriparatide (20 µg) or placebo, along with oral calcium (1000 mg) and vitamin D (800 IU) supplementation, for 6 weeks. The patients were followed for 1 year. The primary outcome was a radiographic linear measurement of alveolar bone level. Secondary outcomes included clinical variables, bone turnover markers in serum and oral fluid, systemic bone mineral density, and quality of life. RESULTS: Radiographic linear resolution of osseous defects was significantly greater after teriparatide therapy than after placebo beginning at 6 months, with a mean linear gain in bone at 1 year of 29% as compared with 3% (P<0.001). Clinical improvement was greater in patients taking teriparatide than in those taking placebo, with a reduction in periodontal probing depth of 33% versus 20% (2.42 mm vs. 1.32 mm) and a gain in clinical attachment level of 22% versus 7% (1.58 mm vs. 0.42 mm) in target lesions at 1 year (P = 0.02 for both comparisons). No serious adverse events were reported; however, the number of patients in the study was small. No significant differences were noted with respect to the other variables that were assessed. CONCLUSIONS: Teriparatide, as compared with placebo, was associated with improved clinical outcomes, greater resolution of alveolar bone defects, and accelerated osseous wound healing in the oral cavity. Teriparatide may offer therapeutic potential for localized bone defects in the jaw. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00277706 .).

Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment.

During the past 80 years a number of theories about the pathogenesis of osteoradionecrosis (ORN) have been proposed, with consequent implications for its treatment. Until recently tissue hypoxia and its consequences were accepted as the primary cause, and this led to the use of hyperbaric oxygen (HBO) for both treatment and prevention of complications of radiotherapy in the head and neck. The benefit of HBO has not been validated. A new theory for the pathogenesis of ORN has proposed that damage to bone is caused by radiation-induced fibrosis. Cells in bone are damaged as a result of acute inflammation, free radicals, and the chronic activation of fibroblasts by a series of growth factors. New treatments have therefore been devised that include pentoxifylline, a vasodilator that also inhibits fibrosis, and tocopherol (vitamin E) to reduce damage caused by free radicals. Impressive results in terms of reversing the process of ONR have been reported using these agents. It has been suggested that this theory and these agents could be the basis of future treatment and prevention of ORN.

Contemporary concepts in the treatment of chronic osteomyelitis.

Although there are relatively standard treatment approaches for chronic osteomyelitis, many avenues of investigation are being pursued to reflect contemporary concerns. The mainstays of care continue to include timely and thorough surgical débridement and culture-directed antibiotics. Sensitive diagnostic screening is essential, and advances in radiology can lead to early confirmation of disease and accurate surveillance. There is potential to greatly reduce overall morbidity, chance of recurrent infection, and treatment courses by using the local delivery systems currently researched by orthopedic surgeons. The challenges posed by multidrug-resistant bacterium may be countered by sound culturing techniques and new antibiotics. The general purpose of this article is to survey the new directions in oral surgery, orthopedics, infectious disease, immunology, and radiology that may have application to the treatment of maxillofacial osteomyelitis.

[The use of quercetin granules for treating suppurative soft-tissue wounds of the maxillofacial area and neck]. / Primenenie granul kvertsetina dlia lecheniia gnoinykh ran miagkikh tkanei cheliustno-litsevoi oblasti i shei.

Wound-healing effect of quercetin granules was examined in 20 experimental animals and in 90 patients with suppurative-inflammatory diseases of the maxillofacial and cervical soft tissue. The results evidence anti-inflammatory and wound-healing effects of quercetin granules used as 20% gel.

[Clinical and therapeutic aspects of maxillofacial lesions of Paget's disease]. / Aspects cliniques et thérapeutiques des atteintes maxillo-faciales de la maladie de Paget.

Histopathology of mandibular swellings in two women aged 68 and 73 years respectively provided a diagnosis of Paget's disease. The complementary biological tests (phosphorus-calcium metabolism, alkaline phosphatase, hydroxyprolinuria) performed showed the increase in bone metabolism, while imaging techniques (conventional radiography, scintigraphy, CT scan) demonstrated numerous subclinical bony foci. Treatment of the facial deformity, if desirable esthetically or functionally necessary (alveolitis, osteitis) can only be surgical. If there is biological bone hypermetabolism, medical (diphosphonate, calcitonin) can be discussed with the rheumatologists. Evolutive risks are represented by rare sarcomatous transformations, osteomyelitis on Paget and monstrous deformities of the face, as in one of the patients reported who had refused all treatment over 37 years.

The management of osteoradionecrosis of the jaws.

Therapeutic measures used in the management of osteoradionecrosis (ORN) of the jaws are reviewed with reference to clinical case material. The development of rational treatment regimes designed to deal with the underlying pathological problem are discussed.

[Clinical studies on TMS-19-Q.O tablets, the preparation of a new macrolide antibiotic, in the field of oral surgery].

Multicenter clinical trial or TMS-19-Q.O tablet was performed to evaluate the usefulness in oral surgery. The results obtained were as follows: Clinical efficacy was assessed by clinical points. The patients entered into the trial were 77 cases with periodontitis, 23 with pericoronitis, 92 with osteitis of jaw and 18 with other infections, and the each effective rates were 80.5, 60.9, 83.7 and 72.2%, respectively. Overall effective rate was 79.0%. Isolation frequency of organisms were 33.8% in periodontitis, 34.8% in osteitis of jaw and 17.4% in pericoronitis. Bacteria isolated were aerobic organisms (63.1%) and anaerobic organisms (36.9%). TMS-19-Q.O tablet was well tolerated, and no adverse reaction was observed.

[Clinical experience with mezlocillin in infections of mouth and jaw (author's transl)]. / Klinische Erfahrungen mit Mezlocillin bei Infektionen im Mund- und Kieferbereich.

The effectiveness and tolerance of the new semisynthetic acylureidopenicillin 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido]-penicillanic acid sodium salt (mezlocillin, Baypen) were investigated in 10 patients with bone and soft tissue infections of the mouth and jaw. The antibiotic was given in doses of 2 to 10 g/d. Indications for treatment were osteomyelitis of the jaw and/or phlegmon of the floor of the mouth and abscesses of the soft palate. 9 out of 10 infections could be cured. Due to the short treatment period one case was not assessable. In 6 patients 9 causative aerobic and anaerobic organisms were isolated which were eliminated. The clinical and laboratory control examinations did not reveal any adverse reactions.