Young-Kyun Lee

Incidence and mortality following hip fracture in Korea.

The authors evaluated the incidence of hip fracture and subsequent mortality in Korea using nationwide data obtained from the Health Insurance Review and Assessment Service. This study was performed on patient population, aged 50-yr or older who underwent surgical procedures because of hip fracture (ICD10; S720, S721). All patients were followed using patient identification code to identify deaths. Crude hip fracture rates increased from 191.9/100,000 in 2005 to 207.0/100,000 in 2008 in women and from 94.8/100,000 in 2005 to 97.8/100,000 in 2008, in men respectively. Crude mortality within 12 months after hip fracture showed a similar trend (18.8% in 2005 and 17.8% in 2007). The mean of standardized mortality ratio of hip fracture was 6.1 at 3 months, 3.5 at 1 yr, and 2.3 at 2 yr post-fracture. The increasing incidence and the high mortality after hip fracture are likely to become serious public health problems and a public health program should begin to prevent hip fractures in Korea.

Alumina-on-alumina total hip arthroplasty: a concise follow-up, at a minimum of ten years, of a previous report.

We previously reported the five-to-six-year results of the use of third-generation alumina-on-alumina bearings in a consecutive series of 100 primary cementless total hip arthroplasties. This report presents the longer-term outcomes of these same bearings, at a minimum of ten years postoperatively. Eighty-six of eighty-eight hips available for the study retained the original bearings at the time of the latest follow-up. Thirteen hips were associated with noise, and six hips demonstrated fretting of the femoral neck on radiographs. Two hips required a change of the bearings because of a ceramic head fracture. The ten-year survival rate of the alumina-on-alumina total hip prostheses, with revision of any implant for any reason as the end point, was 99.0%. On the basis of those results, we concluded that the rate of survival of primary cementless total hip prostheses with third-generation alumina-on-alumina bearings is excellent at ten years. However, the risk of ceramic fracture, noise, and impingement between the metal neck and the ceramic liner should be a concern to surgeons, and patients should be informed of these risks before surgery.

Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption

Osteoclasts differentiate from precursor cells of the monocyte-macrophage lineage and subsequently become activated to be competent for bone resorption through programs primarily governed by receptor activator of nuclear factor-κB ligand in cooperation with macrophage colony–stimulating factor. Proteins prominently expressed at late phases of osteoclastogenesis and with a supportive role in osteoclast function are potential therapeutic targets for bone-remodeling disorders. In this study, we used a proteomics approach to show that abundance of the brain-type cytoplasmic creatine kinase (Ckb) is greatly increased during osteoclastogenesis. Decreasing Ckb abundance by RNA interference or blocking its enzymatic activity with a pharmacological inhibitor, cyclocreatine, suppressed the bone-resorbing activity of osteoclasts grown in vitro via combined effects on actin ring formation, RhoA GTPase activity and vacuolar ATPase function. Activities of osteoclasts derived from Ckb−/− mice were similarly affected. In vivo studies showed that Ckb−/− mice were better protected against bone loss induced by ovariectomy, lipopolysaccharide challenge or interleukin-1 treatment than wild-type controls. Furthermore, administration of cyclocreatine or adenoviruses harboring Ckb small hairpin RNA attenuated bone loss in rat and mouse models. Our findings establish an important role for Ckb in the bone-resorbing function of osteoclasts and underscore its potential as a new molecular target for antiresorptive drug development.

CXC Chemokine Ligand 2 Induced by Receptor Activator of NF-κB Ligand Enhances Osteoclastogenesis

CXCL2 has been known to regulate immune functions mainly by chemo-attracting neutrophils. In this study, we show that CXCL2 can be induced by receptor activator of NF-κB ligand, the osteoclast (OC) differentiation factor, through JNK and NF-κB signaling pathways in OC precursor cells. CXCL2 in turn enhanced the proliferation of OC precursor cells of bone marrow-derived macrophages (BMMs) through the activation of ERK. Knockdown of CXCL2 inhibited both the proliferation of and the ERK activation in BMMs. During osteoclastogenesis CXCL2 stimulated the adhesion and the migration of BMMs. Moreover, the formation of OCs from BMMs was significantly increased on treatment with CXCL2. Conversely, the CXCL2 antagonist repertaxin and a CXCL2 neutralizing Ab potently reduced receptor activator of NF-κB ligand-induced osteoclastogenesis. Furthermore, CXCL2 evoked fulminant bone erosion in the in vivo mouse experiments. Finally, prominent upregulation of CXCL2 was detected in synovial fluids and sera from rheumatoid arthritis patients, suggesting a potential involvement of CXCL2-mediated osteoclastogenesis in rheumatoid arthritis-associated bone destruction. Thus, CXCL2 is a novel therapeutic target for inflammatory bone destructive diseases.

Bisphosphonate use and increased incidence of subtrochanteric fracture in South Korea: results from the National Claim Registry

SummaryWe evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the Health Insurance Review and Assessment Service (HIRA).IntroductionRecently, atypical hip fractures in the subtrochanteric region have been reported among patients on bisphosphonate. However, the association between atypical hip fracture and bisphosphonate is controversial. We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the HIRA.MethodsAll new visits or admissions to clinics or hospitals for a typical and atypical hip fractures were recorded nationwide by HIRA using the ICD-10 code classification. Typical and atypical hip fractures were defined as femoral neck/intertrochanteric and subtrochanteric fracture, respectively. Bisphosphonate prescription data were also abstracted from the HIRA database.ResultsThe absolute number of typical and atypical hip fracture increased during the study period. Although age-adjusted incidence rates of typical hip fractures were stable in men and women, those of atypical hip fractures increased in women. Nationally, the annual numbers of prescriptions of bisphosphonate also increased during the study period.ConclusionsThe results of this study suggest a possible causal relationship between bisphosphonate use and the increased incidence of atypical hip fracture in Korea.

Dislocation After Total Hip Arthroplasty: A Randomized Clinical Trial of a Posterior Approach and a Modified Lateral Approach

We compared the dislocation rate of total hip arthroplasty between posterior approach and lateral approach in a prospective randomized trial. One hundred ninety-six hips were randomly chosen for a posterior approach with a posterior soft tissue repair (99 hips) or a lateral approach (97 hips). The average duration of follow-up was 37.9 months. Three hips (3%) dislocated in the lateral group, whereas none from the posterior group dislocated. At the final follow-up, the Harris hip score and limping were similar in the 2 groups. The joint stability obtained by the posterior soft tissue repair in the posterior approach group seemed to produce more favorable result when compared to the stability obtained from the lateral approach group.

Does early administration of bisphosphonate affect fracture healing in patients with intertrochanteric fractures

This prospective multicentre study was undertaken to determine whether the timing of the post-operative administration of bisphosphonate affects fracture healing and the rate of complication following an intertrochanteric fracture. Between August 2008 and December 2009, 90 patients with an intertrochanteric fracture who underwent internal fixation were randomised to three groups according to the timing of the commencement of risedronate treatment after surgery: Group A (from one week after surgery), Group B (from one month after surgery), and Group C (from three months after surgery). The radiological time to fracture healing was assessed as the primary endpoint, and the incidence of complications, including excessive displacement or any complication requiring revision surgery, as the secondary endpoint. The mean time to fracture healing post-operatively in groups A, B and C was 10.7 weeks (SD 4.4), 12.9 weeks (SD 6.2) and 12.3 weeks (SD 7.1), respectively (p = 0.420). At 24 weeks after surgery, all fractures had united, except six that had a loss of fixation. Functional outcomes at one year after surgery according to the Koval classification (p = 0.948) and the incidence of complications (p = 0.386) were similar in the three groups. This study demonstrates that the timing of the post-operative administration of bisphosphonates does not appear to affect the rate of healing of an intertrochanteric fracture or the incidence of complications.

Suppression of Osteoclastogenesis by N,N-Dimethyl-D-erythro- sphingosine: A Sphingosine Kinase Inhibition-Independent Action

N,N-Dimethyl-d-erythro-sphingosine (DMS) competitively inhibits sphingosine kinase (SPHK) and has been widely used to assess the role of SPHK during cellular events, including motility, proliferation, and differentiation. In the present study, the effect of DMS on the differentiation of bone marrow macrophages (BMMs) to osteoclasts was investigated. When the osteoclast precursor cells were treated with DMS, the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis was completely blocked. We were surprised to find, however, that knock-down of SPHK by small interfering RNA (siRNA) in BMMs did not reduce osteoclastogenesis. Furthermore, both overexpression of SPHK and exogenous addition of sphingosine-1-phosphate, the product of SPHK activity, failed to overcome the antiosteoclastogenic effect of DMS. These results suggest that DMS inhibited osteoclastogenesis independently of SPHK. Subsequent characterization of the DMS-mediated suppression of osteoclastogenesis revealed that DMS did not affect RANKL-induced activation of JNK, p38, NF-κB, and Ca2+ oscillation. On the other hand, DMS strongly inhibited two separate signaling pathways, the RANKL-induced activation of ERK and Akt, which eventually converged on the transcription factors c-Fos and NFATc1. There was significant increase in the osteoclast formation in the presence of DMS when BMMs were overexpressed with c-Fos, suggesting that c-Fos was a critical downstream target of DMS for the inhibition of osteoclastogenesis. Taken together, our data demonstrate that DMS has an antiosteoclastogenic function independently of its SPHK inhibitory activity. Considering previously reported anticancer properties of DMS, our study may also propose that DMS is an ideal drug candidate for bone metastases, for which osteoclastic bone-resorption is crucial.

Caffeic acid phenethyl ester inhibits osteoclastogenesis by suppressing NFκB and downregulating NFATc1 and c-Fos

Osteoclasts are multinuclear cells of myeloid lineage responsible for bone resorption. The anti-inflammatory property of caffeic acid phenethyl ester (CAPE), an active component of the propolis of honeybee hives, has been revealed. Since the regulatory mechanism of differentiation and activation of osteoclasts shares many well-known signaling pathways with that of inflammation, we investigated whether CAPE has any effect on osteoclastogenesis. CAPE potently suppressed osteoclastogenesis in cultures of bone marrow-derived precursor cells with the osteoclast differentiation factor, receptor activator of nuclear factor kappaB ligand (RANKL). While the RANKL-stimulated activation of the ERK, JNK, and p38 MAPK signaling pathways was not affected, the DNA binding and transcription activity of NF kappaB were reduced by CAPE treatment. In addition, CAPE blocked the induction of NFATc1 and c-Fos following RANKL stimulation. Forced expression of c-Fos could reverse the inhibitory effect of CAPE on osteoclastogenesis. Finally, CAPE significantly inhibited the RANKL-induced osteoclast formation in mouse calvariae in vivo. We propose that CAPE might be useful as a therapeutic agent for treatment of bone destructive diseases.

Recurrence rate of lumbar disc herniation after open discectomy in active young men.

Study Design. A retrospective clinical study. Objective. To estimate the recurrence rate of lumbar disc herniation after open discectomy in active young men using survival analysis. Summary of Background Data. There are few reports on the recurrence rate of lumbar disc herniation in young adults, even though this age group shows a higher incidence of disc herniation than the other age groups. In addition, most of the studies on the recurrence rate of disc herniation have reported percentages without regard to the effect of the time course. Methods. Medical records were retrospectively reviewed and phone call surveys were undertaken for 241 patients aged from 20 to 39 who had undergone open discectomies over a period of 14 years. A diagnosis of recurrence was based on the development of new symptoms and magnetic resonance imaging showing compatible lesions in the same segment as the initial diagnosis. The recurrence rate was calculated using a survival analysis based on the Kaplan-Meier product-limit method and the log-rank test was used to evaluate the effect of patient age, level of occurrence, and type of herniated disc on the recurrence rate. Results. The overall recurrence rate was 7.1% (17 patients) at a mean follow-up of 8.55 years, and the cumulative survival rate was 91.5% at a follow-up of 14 years. Survival analysis estimated a higher rate of recurrence at longer follow-up, although there was no recurrence after ninth year from the primary surgery. The recurrence rate was significantly higher for protruded discs compared with other types. Conclusion. Survival analysis provides a more accurate estimation of true recurrence rate. Protruded discs are more likely to show recurrence than other types.