Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

A retrospective study of osteomyelitis and osteonecrosis of the jaws and its etiologic implication of bisphosphonate in Asians.

OBJECTIVE: The objective of this study were to find the annual case trend of inflammatory jawbone diseases and to investigate the impact of medication-related osteonecrosis of the jaws (MRONJ). MATERIAL AND METHODS: A retrospective study of 372 patients diagnosed with inflammatory jawbone condition except for alveolar osteitis from 2007 to 2015 was initiated. History taking and investigation of etiologic factors MRONJ, osteoradionecrosis (ORN), odontogenic infection, foreign body, and trauma were investigated. A separate analysis showed the number of MRONJ cases in two age groups (under 70 years; 70 years and over) and serum C-terminal peptide (s-CTX) values that were found. RESULTS: The results showed that the number of MRONJ cases was significantly larger in the older age group (p < 0.05). Regarding gender and sites of lesions, MRONJ was significantly frequent in the female and the mandible (p < 0.05). The R 2 values for the regression analysis for MRONJ (R 2 = 0.9234) and odontogenic etiology (R 2 = 0.0427) signified linear increase in the number of MRONJ cases, whereas bone lesions due to traditional odontogenic etiology stayed stationary. CONCLUSION: The number of MRONJ has escalated, and most of the patients are elderly people. The current trend of inflammatory conditions of the jaw may have changed since the advent of MRONJ. CLINICAL RELEVANCE: Long-term bisphosphonate therapy became a major risk factor for the osteomyelitis and osteonecrosis of the jaws. Thorough medical history, taking would be essential and communication with prescribing physicians should be emphasized during the dental treatment planning.

Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate-related osteonecrosis of the jaws: can they be utilized as risk markers?

PURPOSE: the purpose of this retrospective study was to examine the possibility of utilizing serum C-terminal telopeptide cross-link of type I collagen (s-CTX) and serum osteocalcin (s-OC) as risk markers for oral bisphosphonate-related osteonecrosis of the jaws (BRONJ). PATIENTS AND METHODS: the s-CTX values and the s-OC values were measured from 23 patients (one male, 22 females) diagnosed with BRONJ using clinical and radiographic examinations. The two biochemical markers were evaluated during a regular checkup for osteoporosis management. For the control group of s-CTX study, s-CTX values were obtained from 61 independently recruited postmenopausal women who have been on bisphosphonate therapy for >6 months. The s-CTX values of the ONJ group and the control group were compared. Because of retrospective nature of this study, the control group for s-OC study could not be established. A single sample t-test was performed for the s-OC value from the ONJ group. RESULT: twenty-three ONJ patients had taken alendronate for osteoporosis treatment, and the s-CTX testing results were low levels of 10-192 pg/ml (mean: 93.2 ± 49.4 pg/ml). Mean of s-CTX of the control (n=61) was 125 ± 85.7 pg/ml. The duration of BP therapy ranged between 1 and 10 years (4.82 ± 2.6). The s-OC level was estimated between 0.2 and 5.4 ng/ml (1.91 ± 1.51 ng/ml). The mean s-CTX value of the control group was higher but without significance (P=0.12). The s-OC values of the ONJ group were significantly lower than the lowest value of the reference range (P<0.001). CONCLUSION: as a result of the s-CTX and s-OC testings at the diagnosis of BRONJ, the values of the two markers were decreased. The decrease of the s-OC values implies a problem during the bone-formation process. Therefore, we can assume that in this patient group, invasive dental surgery contributes to an increase in the risk of BRONJ incidence. This result may imply that, during bisphosphonate therapy, simultaneous consideration of s-CTX showing inhibition of bone resorption and s-OC indicating the degree of bone formation might be a set of risk markers assessing risk prediction for BRONJ before invasive dental surgery.

Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons.

Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.

Effects of intraluminal irradiation with Holmium-166 for TIPS stenosis: experimental study in a swine model.

OBJECTIVE: We wanted to evaluate the effectiveness of intraluminal irradiation with Holmium-166 ((166)Ho) for reducing the pseudointimal hyperplasia (PIH) in the transjugular intrahepatic portosystemic shunt (TIPS) tract in a swine model. MATERIALS AND METHODS: TIPS was performed in 12 domestic pigs, after the creation of portal hypertension by intraportal injection of a mixture of N-butyl-2-cyanoacrylate (NBCA) and lipiodol. Five pigs first underwent intraluminal irradiation (30 Gy) in the parenchymal tract with using a (166)Ho solution-filled balloon catheter, and this was followed by the placement of a nitinol stent in the TIPS tract. For the seven control pigs, the balloon was filled with saline and contrast media mixture. Two weeks later, follow-up portography and histological analysis were performed. RESULTS: TIPS was successfully performed in all twelve pigs with achieving artificially induced portal hypertension. Portography performed two weeks after TIPS showed the patent tracts in the TIPS tracts that were irradiated with (166)Ho (5/5, 100%), whereas either completely (5/6, 83.3%) or partially (1/6, 16.7%) occluded TIPS were seen in the seven pigs of the nonirradiated control group, except in one pig that experienced periprocedural death due to bleeding. Histological analysis showed a statistically significant difference for the maximal PIH (irradiated: 32.8%, nonirradiated: 76.0%, p < 0.001) between the two groups. CONCLUSION: Intraluminal irradiation with 30 Gy of (166)Ho for TIPS significantly improved the TIPS patency in a swine model of portal hypertension during a 2-week period of follow-up.

Short-Term Teriparatide and Recombinant Human Bone Morphogenetic Protein-2 for Regenerative Approach to Medication-Related Osteonecrosis of the Jaw: A Preliminary Study.

Our objective was to examine whether adjunct teriparatide administration and local application of recombinant human bone morphogenetic protein-2 (rhBMP-2) is beneficial for the regeneration of jaw bone in patients with medication-related osteonecrosis of the jaw (MRONJ). This study enrolled 17 patients diagnosed with MRONJ. All patients received sequestrectomy under general or local anesthesia with suspension of bisphosphonate. The bone regeneration ratio was compared on cone beam computed tomography (CBCT) scans, acquired immediately post-operation and after 6 months. The patients were divided into groups, based on their treatment regimens: teriparatide combined with rhBMP-2 (parathyroid hormone [PTH]+BMP), rhBMP-2 (BMP), and the control. Biochemical markers were also evaluated at the baseline (T0), 1 month (T1), and 3 months (T2) after surgery. Significant increase was observed in the values of the biochemical markers, serum osteocalcin, and serum C-terminal telopeptide cross-link of type I collagen, within 3 months of surgery in the PTH+BMP group, whereas the mean value in the BMP group did not show a significant change. In all groups, the MRONJ lesions were healed and new bone formation was detected in the CBCT images. The regeneration ratio was significantly greater in the group PTH+BMP than in the BMP and control groups. Significantly greater amount of bone formation was observed in the group PTH+BMP than in the BMP and control groups. Local application of rhBMP-2 alone also had a beneficial effect on bone regeneration but was not more significant than control. Based on these findings, administration of short-term teriparatide with rhBMP-2 in MRONJ patients may maximize the regeneration of bone after surgery. © 2017 American Society for Bone and Mineral Research.

Bisphosphonate related osteonecrosis of the jaws (BRONJ) in osteoporotic males.

BACKGROUND: The purpose of this study was to describe the clinical characteristics of bisphosphonate related osteonecrosis of the jaws (BRONJ) in osteoporotic males. METHODS: The medical records of BRONJ patients from 2007 to 2014 were reviewed. The data from only the male patients was extracted, and demographic data was collected and biochemical markers were measured. RESULTS: 11 Patients out of 210 (5 %) being males. Among the 11 patients, the indication of bisphosphonate (BP) was osteoporosis in 9 patients, and cancer in two. In one of the osteoporosis patients, osteoporosis was thought to be secondary to hypogonadism after testicular tumor resection. Serum c-terminal telopetide crosslink of type I collagen (s-CTX) values ranged from 60 to 165 pg/mL (mean: 84.6 ± 36.8, median: 70). Serum osteocalcin (s-OC) ranged from 0 to 5.06 ng/mL (mean: 1.83 ± 1.66, median: 1.5) and vitamin D ranged from 0 to 11.9 (mean: 5.02 ± 4.92, median: 3.5). CONCLUSION: BRONJ can be overlooked in male patients with osteoporosis. Although the incidence of BRONJ in males may be low, dentists should also check if their male patients are on osteoporosis treatment since osteoporosis in males can be manifested as a secondary disease to hypogonadism.

Medication Related Osteonecrosis of the Jaw: 2015 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons.

Bisphosphonates are the most widely prescribed drugs for the treatment of osteoporosis, and are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that occurrence of osteonecrosis of the jaw (ONJ) could be related with bisphosphonate exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research (ASBMR) and American Association of Oral and Maxillofacial Surgeons (AAOMS) reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects a consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of nuclear factor-kappa B ligand (RANKL) antibody family, and bevacizumab, an anti-angiogenesis inhibitor. In 2009, a statement on ONJ was also reported locally by a relevant organization, which has served as basis for clinical treatment in Korea. In addition to the new official stance of the AAOMS and ASBMR, with an increasing pool of ONJ clinical experience, a revised version of the 2009 local statement is needed. As such, the Korean Society for Bone and Mineral Research (KSBMR) and the Korean Association of Oral and Maxillofacial Surgeons (KAOMS) have collectively formed a committee for the preparation of an official statement on MRONJ, and have reviewed recent local and international data to propose guidelines customized for the local Korean situation.

Salivary gland dysfunction after radioactive iodine (I-131) therapy in patients following total thyroidectomy: emphasis on radioactive iodine therapy dose.

PURPOSE: The purpose of this study was to retrospectively evaluate symptoms, images of salivary gland dysfunction, and related clinical factors in thyroid cancer patients with total thyroidectomy followed by radioiodine therapy (RIT). METHODS: We included 164 patients who underwent thyroid ultrasonography or contrast-enhanced neck computed tomography more than 6 months later after RIT. Correlation between subjective symptoms and various RIT doses was also evaluated. RESULTS: Swelling and decreased salivary volume were the most common symptoms and images. RIT dose was the only factor with a positive correlation (P<.001). CONCLUSION: The dose of RIT should be carefully determined to minimize gland dysfunction.

Survey of Korean dentists on the awareness on bisphosphonate-related osteonecrosis of the jaws.

AIM: This survey evaluates the awareness of bisphosphonate-related osteonecrosis of the jaws among Korean dentists. METHODS: We prepared a questionnaire based on bisphosphonate-related osteonecrosis of the jaw guidelines, suggested by The American Association of Oral Maxillofacial Surgeons. Among 13,405 dentists, we randomly selected 264 (2%) practitioners. RESULTS: A total of 56.5% of respondents had heard of bisphosphonates as medication related to osteonecrosis, but only 31.4% routinely recorded bisphosphonate medication history. The cross-sectional analysis demonstrated that most dentists were unaware of The American Association of Oral Maxillofacial Surgeons' guidelines. Dentists with <5 years' clinical experience were significantly more aware than those with >5 years' experience. Experience with treating osteonecrosis of the jaw patients and recording medication histories were significantly greater in dental hospitals with >300 beds or university hospitals. Awareness of the severity of bisphosphonate-related osteonecrosis of the jaws was greatest among oral surgeons. CONCLUSION: Dentists should thoroughly check patients' medical histories, including bisphosphonate intake. With the exception of oral surgeons, most Korean dentists were not adequately aware of bisphosphonate-related osteonecrosis of the jaws and its seriousness, making it a potential risk in Korean dentistry. Therefore, it is important to educate clinicians regarding the potential risk of bisphosphonate medication in dentistry through education programs.

Uncaria rhynchophylla induces angiogenesis in vitro and in vivo.

Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine the angiogenic properties of Uncaria rhynchophylla. Uncaria rhynchophylla significantly enhanced human umbilical vein endothelial cells (HUVECs) proliferation in a dose-dependent manner. Neutralization of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) by monoclonal antibody suppressed the Uncaria rhynchophylla stimulatory effect on proliferation. In addition, Uncaria rhynchophylla significantly increased chemotactic-migration on gelatin and tubular structures on Matrigel of HUVECs in a dose-dependent manner. Interestingly, Uncaria rhynchophylla dose-dependently increased VEGF, and bFGF gene expression and protein secretion of HUVEC. The angiogenic activity of Uncaria rhynchophylla was confirmed using an in vivo Matrigel angiogenesis model, showing promotion of blood vessel formation. These results suggest that Uncaria rhynchophylla could potentially used to accelerate vascular wound healing or to promote the growth of collateral blood vessel in ischemic tissues.