Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell–specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP–deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP–deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.

Study Design. A retrospective case series of surgically treated patients with adult scoliosis. Objective. The purpose of this study was to evaluate the incidence, risk factors, and natural course of proximal junctional kyphosis (PJK) in a long-term follow-up of patients with adult idiopathic scoliosis undergoing long instrumented spinal fusion. Summary of Background Data. Although recent reports have showed the prevalence, clinical outcomes, and the possible risk factors of PJK, quite a few reports have showed long-term follow-up outcome. Materials and Methods. This is a retrospective review of the charts and radiographs of 76 consecutive patients with adult scoliosis treated with long instrumented spinal fusion. Radiographical measurements and demographic data were reviewed on preoperation, immediate postoperation, 2 years postoperation, 5 years postoperation, and at follow-up. Postoperative Scoliosis Research Society scores and Oswestry Disability Index were also evaluated. Means were compared with Student t test. A P value of less than 0.05 with 95% confidence interval was considered significant. Results. The mean age was 48.8 years (range, 23–75 yr) and the average follow-up was 7.3 years (range, 5–14 yr). PJK has been identified in 17 patients. The Scoliosis Research Society and Oswestry Disability Index did not demonstrate significant differences between PJK group and non-PJK group; 2 patients had additional surgeries performed for local pain. Seventy-six percent of PJK has been identified within 3 months after surgery. Despite the fact that 53% of total degree of PJK was progressed within 3 months after surgery, PJK continuously progressed to the final follow-up. Pre-existing low bone mineral density, posterior spinal fusion (PSF), fusion to sacrum, inappropriate global spine alignment, and greater sagittal vertical axis change were identified as significant risk factors for PJK (P = 0.04, P < 0.001, P = 0.02, P < 0.0001, and P = 0.01). Conclusion. In a long-term review of minimum 5 years, 76% of PJK occurred within 3 months after surgery. Pre-existing low bone mineral density, PSF, fusion to the sacrum, inappropriate global spine alignment, and greater sagittal vertical axis change were significant risk factors for PJK. Careful long-term follow-up should be done for a patient with PJK.

Retrospective case series of surgically treated adult scoliosis patients. To assess the incidence, risk factors and clinical outcomes of proximal junctional kyphosis (PJK) in a large series of adult idiopathic scoliosis patients undergoing long instrumented spinal fusion (.5 vertebrae). A new classification is also projected. Maintaining both coronal and sagittal balance is essential in the surgical treatment of adult deformity patients. PJK is a well-recognized postoperative phenomenon in adults and adolescents after scoliosis surgery. Despite recent reports, the prevalence, clinical outcomes, and the risk factors of PJK are still controversial. This study is a retrospective review of the charts and radiographs of 157 consecutive patients with adult scoliosis treated with long instrumented spinal fusion. PJK was defined by a proximal junctional angle greater than 108 and at least 108 greater than the corresponding preoperative measurement. Radiographic measurements included sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL) and pelvic incidence (PI) on preoperative, immediate postoperative and at follow-up. Bone mineral density (BMD), Body mass index (BMI), age, sex, instrumentation type, surgery type, and fusion to sacrum were reviewed. Postoperative SRS outcome scores and Oswestry Disability Index (ODI) were also evaluated. PJK was graded by the severity and type. Means were compared with Student's t test and χ2 test. P value of less than 0.05 with confidence interval 95% was considered significant. The average age was 46.9 years (22-81 years) and the average Follow-up was 4.3 years (2-12 years). PJK occurred in 32 patients (20%) and were mostly classified as 1A (Ligamentous & mild) deformity. The SRS outcome scores and ODI did not demonstrate significant differences between PJK group and non-PJK group, four patients had additional surgeries performed for local pain. Fusion to the sacrum and posterior fusion with segmental instrumentation were significant risk for PJK (P = 0.03, P < 0.01). BMD, BMI, age, sex, and instrumentation type showed no difference. Eighty-four percent of PJK group was associated with TK 1 LL 1 PI .458 or preoperation to postoperation SVA more than 50 mm vs. 6.4% of non-PJK group (P < 0.01, P < 0.01). Despite the occurrence of PJK in 20% of adult scoliosis patients undergoing long fusion, no significant differences were found in SRS outcome scores and ODI in PJK and non-PJK patients. Fusion to the sacrum and posterior fusion with segmental instrumentation were identified as risk factors. PJK can be minimized by post-operative normalization of global sagittal alignment. A simplified classification based in severity type of PJK showed the majority in class 1A (ligamentous lesion and mild deformity).

Retrospective case series of surgically treated patients with adult spine deformity (ASD). To report the incidence of proximal junctional failure (PJF), characterize PJF and evaluate the outcome of revision surgery for PJF. A modified classification is also proposed. Although recent reports have shown the catastrophic results of PJF, few reports have shown the incidence, characteristics, and clinical outcomes of PJF in ASD. This retrospective analysis reviewed data entered prospectively into a multicenter database. Surgically treated patients with ASD with a minimum 2-year follow-up were included. PJF was defined as any type of symptomatic proximal junctional kyphosis (PJK) requiring surgery. On the basis of our previous classification, the following modified PJK classification was established: grade A, proximal junctional increase of 10° to 19°; grade B, 20° to 29°; and grade C, 30° or more. Three types of PJK were also defined: ligamentous failure (type 1), bone failure (type 2), and implant/bone interface failure (type 3). An additional criterion was added for the presence or absence of spondylolisthesis above the upper instrumentation vertebra (UIV). PJF developed in 23 of the 1668 patients with ASD. The incidence of PJF was 1.4%. The mean age was 62.3 ± 7.9 years, and the mean follow-up was 4.0 ± 2.3 years. Seventeen patients had undergone prior surgical procedures. Six patients had UIV above T8, and 17 had UIV below T9. Six patients had associated spondylolisthesis above the UIV (PJF-S), whereas 17 patients did not (PJF-N). The radiographical data show a significant difference in the preoperative sagittal vertical axis between the PJF-S and PJF-N groups, whereas no significant difference was observed in the preoperative sagittal parameters (5.2 ± 3.9 cm vs. 11.4 ± 6.0 cm, P = 0.04). The most common type of PJF was type 2N. The PJF symptoms consisted of intolerable pain (n = 17), neurological deficits (n = 6), and progressive trunk deformity (n = 1). Eleven patients had additional PJK/PJF and 9 required additional revision surgical procedures. The incidence of PJF among surgically treated patients with ASD was 1.4%. The most common type of PJF was 2N. Preoperative large sagittal vertical axis change and large amount of correction was a causative factor for spondylolisthesis above the UIV. After the revision surgery, further PJF was a commonly occurred event.

Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)–deficient (Atm^−/−) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm^−/− mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.