Deog-Yoon Kim

Correlation Between Serum C-Terminal Cross-Linking Telopeptide of Type I Collagen and Staging of Oral Bisphosphonate-Related Osteonecrosis of the Jaws

PURPOSE The aim of the present study was to correlate the staging of bisphosphonate-related osteonecrosis of the jaws (BRONJ) with serum C-terminal cross-linking telopeptide of type I collagen (CTX), which is under debate as an index of risk prediction. Stage I BRONJ was defined as asymptomatic osteonecrotic bone. Stage II BRONJ includes infection, and stage III includes additional complications such as fracture or extraoral fistulas. PATIENTS AND METHODS The serum CTX values of 18 patients (mean age 74 years) who were diagnosed with osteonecrosis of the jaws caused by oral bisphosphonate were investigated. RESULTS The serum CTX values ranged from 10 to 262 pg/mL (mean 112 +/- 76.1). The mean duration of bisphosphonate therapy was 3.9 years, and 17 of the 18 patients had received once weekly 70 mg aldendronate and 1 patient once weekly 35 mg risedronate. The risk assessment was rated according to the CTX values of the individual patient (minimal risk, more than 150 pg/mL; moderate, 100 to 150 pg/mL; and high, less than 100 pg/mL). Next, the BRONJ scores were calculated according to the number of the BRONJ lesions and their stage. The risk assessment and BRONJ scores were correlated. The result was statistically significant (P = .019). CONCLUSIONS BRONJ is relatively rare but has been increasingly recognized in our clinic. The usefulness of the serum CTX value as an index of risk prediction continues to be debated. Considering the staging of lesions and the number of lesions, we found a significant correlation between the disease severity and the risk assessment using serum CTX.

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.

Changes in regional cerebral blood flow and glucose metabolism following electroacupuncture at LI 4 and LI 11 in normal volunteers.

OBJECTIVES Although numerous trials have demonstrated the clinical effects of acupuncture, the mechanism of its therapeutic effect still remains uncertain. Recent neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) have revealed that acupuncture therapy may alter brain activity. This study was performed to evaluate changes in regional cerebral blood flow and glucose metabolism following electroacupuncture (EA) in normal volunteers. DESIGN AND SETTING Twenty (20) normal volunteers were enrolled for brain SPECT and 13 normal volunteers were enrolled for (18)F-fluorodeoxyglucose PET. A few days after the baseline measurements, EA was performed at two acupoints (LI 4 and LI 11) for 15 minutes and a second brain image was acquired for each subject. We used statistical parametric mapping 2 to analyze the changes in brain perfusion and glucose metabolism. RESULTS Significant increases in perfusion were observed in the left middle frontal gyrus, the superior parietal gyrus, the right superior frontal gyrus, and the middle parietal gyrus. Following EA, glucose metabolism significantly increased in the left superior medial frontal gyrus, the middle frontal gyrus, and the right superior medial frontal gyrus (paired t-test, uncorrected p < 0.005). CONCLUSIONS There were specific increases in both regional cerebral blood flow and glucose metabolism following EA in both frontal regions. This common brain response in localized regions was induced from stimulation of specific acupoints (LI 4 and LI 11).

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 Pagets 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.

Changes in SPECT Cerebral Blood Flow Following Japanese Style, Superficial Acupuncture at LI-4 and LI-11 in Healthy Volunteers

OBJECTIVES Japanese style, superficial acupuncture (SA) has been clinically evaluated for its therapeutic benefit, yet the neurophysiologic responses associated with SA remain unclear. This study was performed to measure changes in regional cerebral blood flow (rCBF) following SA at LI-4 and LI-11 in healthy volunteers using single photon emission computed tomography (SPECT). Changes in SPECT activity following Japanese style SA were compared to previous reports of SPECT changes following electroacupuncture (EA) at the same acupoints. DESIGN AND SETTING Ten (10) healthy volunteers were enrolled for this study. A few days after the baseline brain SPECT, SA was performed at LI-4 and LI-11 for 15 minutes and a second brain perfusion image was acquired for each subject. We used SPM2 to analyze the changes in rCBF after SA through a paired t test. In addition, the differences of rCBF changes between SA and EA were compared using a two-sample t test. RESULTS Cerebral blood perfusion significantly increased after SA in the left superior frontal gyrus, left middle cingulum, left insular, right medial orbital frontal gyrus, and right middle cingulum (paired t test, uncorrected p < 0.005), while no regions showed a significant decrease. The results comparing poststimulation images between SA and EA demonstrated that the perfusion in the right lingual, both thalamus, left middle temporal gyrus, left insula, and both cerebellum were significantly increased in SA compared with EA (false discovery rate [FDR] corrected p < 0.05). CONCLUSIONS There were specific increase patterns of rCBF following SA at LI-4 and LI-11, which were similar to those following EA. However, there were significant differences in the decrease pattern of rCBF between SA and EA, which might be due to the difference of the strength of acupuncture stimulation between the two methods. These results may contribute to developing a better strategy to a select stimulation method in acupuncture therapy.

Consumption of legumes improves certain bone markers in ovariectomized rats

Soybeans are known to protect against osteoporosis, but other legumes frequently consumed in Asia have not been studied to learn if they have a similar protective effect. This study investigated the hypothesis that consumption of soybean, mung bean, cowpea, and adzuki bean has beneficial effects on bone biomarkers in ovariectomized rats. Female Sprague-Dawley rats were either sham operated (sham; n = 7) or surgically ovariectomized and then fed a regular AIN-93M diet (OVX; n = 7) or AIN-93M containing soybean (n = 7), mung bean (n = 7), cowpea (n = 7), or adzuki beans (n = 7) for 10 weeks. No bean consumption significantly altered the body, subcutaneous fat, or uterus weight; however, consumption significantly increased the serum calcium/phosphorous ratio and decreased urinary calcium excretion compared with those of the OVX group. Serum concentration of 17β-estradiol was significantly lower in the OVX group compared with that of the sham group and was lowest in the group fed OVX diet containing soybean. Serum osteocalcin concentration was significantly higher in all OVX rats given a diet with beans compared with the same diet without, but urinary deoxypyridinoline excretion was lowest in the group fed OVX diet containing cowpea. There were no significant differences in bone mineral density or bone mineral content of the right femur, tibia, or lumbar spine or in the trabecular bone volume of the tibia among the diet groups. In conclusion, the consumption of soybean, mung bean, cowpea, and adzuki bean in OVX rats improved osteocalcin, but only those fed cowpea showed decreased bone resorption biomarker, suggesting that cowpea may have the most protective effect on bone in OVX rats.

18F-fluorodeoxyglucose PET/CT in a patient with esophageal and genital leiomyomatosis.

Diffuse esophageal leiomyomatosis is a rare benign tumor, which can be associated with leiomyoma in female genital tracts involving the uterus, vagina, and vulva. Alport syndrome, an inherited disorder that includes the kidneys, eyes, and sensorineural hearing loss, is also rarely associated with these multiple leiomyomatosis. In our case, 18F-fluoroseoxyglucose positron emission tomography/computed tomography was used to distinguish esophageal and genital leiomyomatosis from malignant masses.

Measurements of bone mineral density in the lumbar spine and proximal femur using lunar prodigy and the new pencil-beam dual-energy X-ray absorptiometry

ObjectiveWe evaluated the correlation of the absolute bone mineral density (BMD) values of the lumbar spine and standard sites of the proximal femur obtained from a Lunar Prodigy and the newly developed pencil-beam dual-energy X-ray absorptiometry (Dexxum).Materials and methodsBetween June 2008 and December 2008, 79 Korean volunteers were enrolled. Measurements were obtained on the same day using both densitometers. The absolute BMD values (g/cm2) from the two densitometers were evaluated using Pearson’s correlation analysis with Bonferroni’s correction for the three clinically important sites. In order to evaluate precision, we performed duplicate Dexxum measurements, and calculated the within-subject coefficient of variation (WSCV).ResultsThe Pearson’s correlation coefficient (r) of BMD values for the total proximal femur, femoral neck, and lumbar spine by the two densitometers were 0.926, 0.948, and 0.955 respectively, and the null hypotheses of r = 0.8 were all rejected (p < 0.001 by one-sided Z-test with Fisher’s z-transformation for each site). The T-scores (r ≧ 0.842) and Z-scores (r ≧ 0.709) also showed strong positive correlations. The duplicate BMD values of Dexxum showed a high level of precision (WSCV ≦ 4.27%).ConclusionDexxum measurements of BMD, T-scores, and Z-scores showed a strong linear correlation with those measured on Lunar Prodigy.

Collagen telopeptide (serum CTX) and its relationship with the size and number of lesions in osteonecrosis of the jaws in cancer patients on intravenous bisphosphonates

Bisphosphonate has clearly become one of the major risk factors of ONJ. Concerns about ONJ are also seen in Asian countries including Korea. The use of serum CTX is not yet evidence based but the marker will be usable as a reference laboratory test in evaluating the risk of ONJ in the near future. Bagan et al. did a very interesting study with their valuable data. In their article, they correlated the raw value of serum CTX and the number and size of ONJ lesions of the investigated patients and there was no significant correlation. Basically, these two parameters were separately considered. It would have been interesting if these two parameters (size and number) had been considered simultaneously. The staging of the individual ONJ lesions should be considered when we evaluate ONJ lesions. Regarding the serum CTX values, the authors seemed to use raw value of serum CTX to conduct this study. Compared with uninary CTX and NTX, serum CTX is a relatively stable marker of telopeptide but it has also day-to-day variability, so it may be more logical to categorise the values into range values that were proposed by Marx. In this way, their correlation might have been significant. Based upon our data of oral bisphosphonate related osteonecrosis patients, which are submitted to be published, we found significant correlation between risk assessment according to serum CTX and the severity of ONJs which considered the number and staging of the ONJs. By means of such simultaneous consideration of the number and the staging of ONJ lesions of each patient, it might be possible for us to set up a system for a stratified evaluation of our patients.

Scintigraphic findings of growth arrest lines after bisphosphonate administration in a steroid-induced osteoporosis patient: a case study.

Bisphosphonates inhibit bone resorption, and are used to treat patients who have low bone mineral density. This treatment results in the development of growth arrest lines, which typically appear parallel sclerotic lines to the growth plate on radiographs. We describe the case of a 14-year-old boy with steroid-induced osteoporosis, who was treated by pamidronate. This patient exhibited linearly increased bilateral uptake in the shafts of his femora, tibiae, radii, and ulnae that were parallel to the growth plates. A simple radiograph corresponding bone scan demonstrated linear sclerotic lines at the same sites.