• Restorative Dentistry and Endodontics
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• v.44 no.4
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• pp.42.1-42.16
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• 2019

Antiresorptive drugs (ARDs), such as bisphosphonates or denosumab, that prevent bone resorption are widely used in patients with osteoporosis or with cancer that has metastasized to the bones. Although osteonecrosis of the jaw (ONJ) is a well-documented complication of ARD use, the benefits ARDs outweigh the complication. Thus, research has focused on finding ways to prevent or reduce the risk of developing ONJ. Dentists, as part of a multi-professional team, have a critical role in preventing ONJ. However, many dentists tend to hesitate to provide dental care to patients with ONJ, or tend to think that it is a problem to be dealt with by oral surgeons. This review gives an overview of ARD-related ONJ and provides the guidelines for dental care in patients taking ARDs to lower the risk of developing ONJ.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.155-168
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• 1999

Osteoporosis is one of the most important public health problems facing the aging population. Drug therapy for osteoporosis can be divided operationally into two main categories: drugs that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Antiresorptive agents such as estrogens, calcitonin, and bisphosphonates are most effective in the prevention of osteoporosis. Formation-stimulating agents such as sodium fluoride or monofluorophosphate, parathyroid hormone fragments, and anabolic steroids are of potential value in the treatment of established osteoporosis, where bone mass is already low and benefit from antiresorptive drugs is likely to be small Recently, raloxifene, a selective estrogen receptor modulator, has become available in various countries for clinical use in the treatment of involutional osteoporsis. This paper will review the use of these drugs in postmenopausal woman.

• Journal of Oral Medicine and Pain
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• v.47 no.1
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• pp.1-9
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• 2022

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents and bone-modifying agents. It is of the utmost importance to know the management of the MRONJ to improve the patient's quality of life. This study comprehensively reviews the current definitions of MRONJs, and antiresorptive medications, clinical manifestation and staging, risk factors, treatment strategies, and prevention methods of MRONJ. The disease is defined as an exposure of bone and osteonecrosis of the jaw in the oral cavity for at least 8 weeks in patients taking antiresorptive drugs or antiangiogenic agents and with no history of radiotherapy treatment of the jaws. Many articles have reported risk factors associated with MRONJ such as systemic diseases, antiresorptive medication, oral infection, and poor oral hygiene. Osteonecrosis and antiresorptive medications including bisphosphonate and denosumab have been strongly associated, but the pathology of MRONJ is only limited. Hence, an effective and appropriate management and treatment for MRONJ is still to be defined. The objectives of MRONJ treatment are to minimize osteonecrosis and relieve symptoms, and many treatments are suggested from conservative treatment to marginal resection, but this remains controversial. Appropriate treatment of MRONJ remained difficult, although many studies are being covered.

• Imaging Science in Dentistry
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• v.50 no.4
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• pp.273-279
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• 2020

This review presents an overview of some diagnostic imaging-related issues regarding medication-related osteonecrosis of the jaws(MRONJ), including imaging signs that can predict MRONJ in patients taking antiresorptive drugs, the early imaging features of MRONJ, the relationship between the presence or absence of bone exposure and imaging features, and differences in imaging features by stage, between advanced MRONJ and conventional osteomyelitis, between oncologic and osteoporotic patients with MRONJ, and depending on the type of medication, method of administration, and duration of medication. The early diagnosis of MRONJ can be made by the presence of subtle imaging changes such as thickening of the lamina dura or cortical bone, not by the presence of bone exposure. Most of the imaging features are relatively non-specific, and each patient's clinical findings and history should be referenced. Oral and maxillofacial radiologists and dentists should closely monitor plain radiographs of patients taking antiresorptive/antiangiogenic drugs.

• Molecules and Cells
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• v.37 no.8
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• pp.628-635
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• 2014

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.2
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• pp.65-75
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• 2021

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.2
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• pp.108-115
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• 2019

Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a well-known side effect of certain drugs that are used to influence bone metabolism to treat osteometabolic disease or cancers. The purpose of our study was to investigate how high-concentration and low-concentration bisphosphonate (BP) intake affects the disease severity. Materials and Methods: Data collected from the medical records of 52 patients treated with BPs, antiresorptive, antiangiogenic drugs and diagnosed with MRONJ were included in this study. Age, sex, type of systemic disease, type of drug, duration of drug treatment, jaw area with MRONJ, drug administration protocol, and MRONJ clinical and radiological findings were obtained. Patients were divided into two groups: anti-neoplastic (Group I, n=23) and anti-osteoporotic (Group II, n=29). Statistical evaluations were performed using the IBM SPSS ver. 21.0 program. Results: In both groups, more females had MRONJ. MRONJ was found in the mandibles of 30 patients (Group I, n=14; Group II, n=16). When we classified patients according to the American Association of Oral and Maxillofacial Surgeons staging system, significant differences were seen between groups (${\chi}^2=12.23$, P<0.01). More patients with advanced stage (stage 2-3) MRONJ were found in Group I (60.9%). Conclusion: According to our results, high-concentration BP intake, age and duration of drug intake increased disease severity.

• Journal of Korean Neurosurgical Society
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• v.54 no.6
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• pp.461-466
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• 2013

Objective : Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats. Methods : Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test. Results : High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015). Conclusion : The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1566-1571
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• 2008

Bone is a dynamic tissue that is constantly resorbed by osteoclasts and then replaced by osteoblasts. Osteoclasts, multinucleated cells of monocyte/macrophage lineage, are responsible for bone disorders, including osteoporosis and rheumatoid arthritis. In this study, we examined the effect of the curcumin on osteoclast survival and bone resorption. We found that curcumin significantly inhibited RANKL-mediated osteoclast survival. DAPI stainingrevealed that curcumin induced the apoptotic features of osteoclasts. Although curcumin did not suppress the phosphorylation of Akt and ERK in osteoclasts treated with RANKL, curcumin induced the cleavage of pro-caspase-9 and -3 its active forms. Also, curcumin inhibited the formation of actin rings of osteoclasts. RANKL-mediated bone resorption was inhibited by the addition of curcumin. Together with the results of this study, these findings suggest that the curcumin inhibited the survival of osteoclasts by activating caspase-9 and -3 and suppressed the bone resorptive activity. Thus, curcumin may be developed as antiresorptive drugs for the treatment of bone-related disorders.