Depletion of SIRT6 causes cellular senescence, DNA damage, and telomere dysfunction in human chondrocytes.

OBJECTIVE: SIRT6, a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases, has been implicated as a key factor in aging-related diseases. However, the role of SIRT6 in chondrocytes has not been fully explored. The purpose of this study was to examine the role of SIRT6 in human chondrocytes by inhibiting SIRT6 in vitro. DESIGN: First, the localization of SIRT6 and proliferation cell nuclear antigen (PCNA) in human cartilages was examined by immunohistochemistry. Next, SIRT6 was depleted by RNA interference (RNAi), and the effect of SIRT6 depletion on changes in gene expression, protein levels, proliferation, and senescence in human chondrocytes was assessed. Furthermore, to detect DNA damage and telomere dysfunction, γH2AX foci and telomere dysfunction-induced foci (TIFs) were examined using immunofluorescence microscopy. The protein levels of two mediators for DNA damage induced-senescence, p16 and p21, were examined by western blotting. RESULTS: Immunohistochemical analysis showed SIRT6 was preferentially expressed in the superficial zone chondrocytes and PCNA-positive cluster-forming chondrocytes in the osteoarthritic cartilage tissue samples. Real-time PCR analysis showed that matrix metalloproteinase 1 (MMP-1) and MMP-13 mRNA were significantly increased by SIRT6 inhibition. Moreover, SIRT6 inhibition significantly reduced proliferation and increased senescence associated ß-galactosidase (SA-ß-Gal)-positive chondrocytes; it also led to increased p16 levels. Immunofluorescence microscopy showed that γH2AX foci and TIFs were increased by SIRT6 inhibition. CONCLUSION: Depletion of SIRT6 in human chondrocytes caused increased DNA damage and telomere dysfunction, and subsequent premature senescence. These findings suggest that SIRT6 plays an important role in the regulation of senescence of human chondrocytes.

A radiographic analysis of alignment of the lower extremities--initiation and progression of varus-type knee osteoarthritis.

OBJECTIVE: This study aimed to investigate alignment based on age in normal knees and alignment based on deformity in osteoarthritis (OA) knees using detailed radiographic parameters. DESIGN: Various parameters were measured from weight-bearing long leg radiographs of 1251 legs (797 normal and 454 OA knees) as a cross-sectional study. Normal knees were classified by age (young, middle aged, aged, and elderly) and symptomatic OA knees on the basis of the alignment (femorotibial angle (FTA): mild, moderate, severe and profound). The mean measurements in each group were calculated and compared within each group. RESULTS: The femoral shaft showed medially bowed curvature (femoral bowing) of approximately 2° in the young normal group, which shifted to lateral bowing with age. However, OA knees showed larger lateral bowing with OA grade, which might reduce the condylar-shaft angle and subsequently shifted the mechanical axis medially. Progression of mild to moderate OA might be associated with a decreasing condylar-shaft angle (femoral condylar orientation) and widening condylar-plateau angle (joint space narrowing) rather than decreasing tibial plateau flattering. Steeping of the tibial plateau inclination due to increasing tibial plateau shift (tibial plateau compression) rather than medial tibial bowing might be the main contributor to worsening of varus deformity in knees with severe and profound OA. CONCLUSIONS: This cross-sectional study might provide the possibility of OA initiation and progression. The lateral curvature of the femoral shaft associated with aging may contribute to the initiation of varus-type OA of the knee. These changes in the femur may be followed by secondary signs of OA progression including varus femoral condylar orientation, medial joint space narrowing, and tibial plateau compression.

Akt phosphorylation in human chondrocytes is regulated by p53R2 in response to mechanical stress.

OBJECTIVE: The p53 tumor-suppressor protein p53R2 is activated in response to various stressors that act on cell signaling. When DNA is damaged, phosphorylation of p53 at its Ser 15 residue induces p53R2 production. The role of p53R2 in chondrocytes remains poorly understood. In this study, we evaluated in chondrocytes, p53R2 expression and its regulation in response to mechanical stress. Furthermore, we investigated the function of p53R2 in relation to mechanotransduction. METHODS: Osteoarthritis (OA) cartilage obtained from total knee replacements and normal cartilage obtained from femoral neck fractures was used to measure p53R2 expression by using immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR). The OA chondrocytes were subjected to a high magnitude of cyclical tensile strain by using an FX-2000 Flexercell system. Next, sulfated glycosaminoglycan (sGAG) production was quantified in these cells. Protein expression of p53R2, and phosphorylation of Akt, p38MAPK, ERK1/2, and JNK was also detected using western blotting. Moreover, Akt phosphorylation was detected after transfecting the cells with p53R2-specific small interfering RNA (siRNA). RESULTS: Expression of p53R2 was significantly increased in OA chondrocytes and in chondrocytes after applying 5% tensile strain to the cells. However, Akt phosphorylation was down-regulated in OA chondrocytes after the strain, and was up-regulated after transfection of p53R2. sGAG protein as well as collagen type II and aggrecan mRNA was increased following transfection of p53R2-specific siRNA after 5% tensile strain. CONCLUSIONS: p53R2 could regulate matrix synthesis via Akt phosphorylation during chondrocyte mechanotransduction. Down-regulation of p53R2 may be a new therapeutic approach in OA therapy.

DcR3 induces cell proliferation through MAPK signaling in chondrocytes of osteoarthritis.

INTRODUCTION: Decoy receptor 3 (DcR3), a soluble receptor belonging to the tumor necrosis factor (TNF) receptor superfamily, competitively binds and inhibits the TNF family including Fas-ligand (Fas-L), lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T-cells (LIGHT) and TNF-like ligand 1A (TL1A). In this study, we investigated the functions of DcR3 on osteoarthritis (OA) chondrocytes. METHODS: Expressions of DcR3 in chondrocytes were measured by realtime Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Expression of DcR3 in sera and joint fluids was measured by enzyme-linked immunosorbent assay (ELISA). Chondrocytes were incubated with DcR3-Fc chimera protein (DcR3-Fc) before induction of apoptosis by Fas-L and apoptosis was detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling labeling (TUNEL) staining and Western blotting of caspase 8 and poly (ADP-ribose) polymerase (PARP). Chondrocytes were incubated with DcR3-Fc and the proliferation was analyzed by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. Phosphorylation of Extracellular Signal-Regulated Kinase (ERK), P38 mitogen-activated protein kinase (MAPK) and Jun N-terminal Kinase (JNK) in chondrocytes was measured by Western blotting after incubation with DcR3-Fc, Mitogen-activated protein kinase kinase (MEK1/2) inhibitor, or P38 MAPK inhibitor. Chondrocytes were treated with DcR3-Fc after pre-incubation with blocking antibody of Fas-L, LIGHT and TL1A, and proliferation or phosphorylation of ERK was analyzed. RESULTS: DcR3 was expressed in OA and normal chondrocytes. DcR3-Fc protects chondrocytes from Fas-induced apoptosis. DcR3-Fc increased chondrocytes proliferation and induced the phosphorylation of ERK specifically. DcR3-induced chondrocytes proliferation was inhibited by pre-incubation of PD098059 or blocking Fas-L antibody. DcR3 increased chondrocytes proliferation in OA chondrocytes, but did not in normal. CONCLUSION: DcR3 regulates the proliferation of OA chondrocytes via ERK signaling and Fas-induced apoptosis.

Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium.

The perivascular mononuclear cell collections of the rheumatoid synovium were examined both at the light and electron microscopic level by an immunoperoxidase staining technique using monoclonal antibodies directed against T cell subsets. These accumulations were variable in composition and size, not only in specimens from different patients but in the same specimen. Some areas (lymphocyte-rich areas) contained mainly small lymphocytes in clusters and others (transitional areas) contained blast cells, macrophages, and plasma cells in addition to lymphocytes. The percentage of T4 staining cells correlated positively and the percentage of T8 staining cells correlated negatively with the percentage of lymphocytes in any given area. In contrast, the percentage of T4 cells correlated negatively and the percentage of T8 cells correlated positively with the percentage of macrophage-like cells in these areas. Approximately 80% of the total lymphocytes, both in the lymphocyte-rich areas and transitional areas, were T lymphocytes (OKT3 staining). In lymphocyte-rich areas, helper/inducer T lymphocytes (OKT4 staining) were predominent over suppressor/cytotoxic lymphocytes (OKT8 staining), and in such areas the mean T4:T8 ratio was 2.9. Macrophage-like cells were seen only in small numbers in this type of area. In the transitional areas, suppressor/cytotoxic lymphocytes (OKT8 staining) predominated over helper/inducer lymphocytes (OKT4 staining). In such areas the mean T4:T8 ratio was 0.8. The T8 cells in the transitional areas tended to be large in size and often had a blastic appearance, and the abundant macrophage-like cells infiltrating these areas were frequently in close contact with T8 lymphocytes. These findings indicate that the ratio of T4 to T8 lymphocytes in rheumatoid synovium varies with the type of area examined. In lymphocyte-rich collections, made up largely of quiescent small lymphocytes, T4 cells are predominant. In areas of apparent immunological reactivity, T8 cells are predominant. It is suggested that T8 cells proliferate in immunologically active areas of the synovium as a result of local stimulation of a T cell-mediated immune response.

Factors affecting prosthetic rehabilitation outcomes in amputees of age 60 years and over.

This retrospective, observational study was designed to investigate factors affecting successful prosthetic ambulation in elderly amputees aged > or = 60 years. The study included 64 unilateral transfemoral or hip disarticulation amputees. Patients who were able to walk > or = 100 m with prosthesis were classified as successful and those who could walk < 100 m as failures. Age, comorbidities, cause of amputation, ability to stand on one leg, patient's motivation for walking and maximum oxygen uptake as a proportion of predicted maximum oxygen uptake (%VO(2max)) during an exercise load test were examined as indicators of physical fitness. Significant differences were noted between the two groups in the number of comorbidities, ability to stand on one leg, patient's motivation for walking and mean %VO(2max). A low number of comorbidities, the ability to stand on one leg, motivation for walking and adequate physical fitness allowing an exercise intensity of > or = 50% VO(2max) were considered to be predictive factors for successful prosthetic rehabilitation.

Repair of osteochondral defects with a new porous synthetic polymer scaffold.

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group. Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p<0.05). Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.

Surgery for clavicular and humeral fractures in an osteopetrotic patient: a case report.

Osteopetrosis is a rare disease characterised by generalised sclerosis of the bone. Surgical treatment for fractures in osteopetrotic bones is difficult due to their hardness. We report successful surgical treatment of humeral and clavicular fractures in a 30-year-old osteopetrotic patient with severe multiple trauma. Two years after surgery, the patient had a full range of movement at the shoulder and elbow, with good bone union and alignment.

Osteogenic potential of cells in vitro derived from haemarthrosis of the knee induced by injury to the anterior cruciate ligament.

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with beta-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH)(2)D(3), a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced. Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury.

Effect of bubble flow velocity on drag-force and shear stress working on submerged hollow fibre membrane.

This study is aimed at elucidating the mechanism by which rising air bubbles induce shear stress on hollow fibre membrane surfaces. Shear stress on hollow fibre membrane surfaces (laterally-set and vertically-set) caused by aeration was measured directly using a two-direction load sensor. In the laterally-set hollow fibre module, time-averaged upward-direction shear stress on the membrane surface was compared to theoretical shear stress values considering the effect of water flow on membrane surface. Measured time-average shear stress values were almost 200 times larger than theoretical values implying strong interactions between bubbles and solid surface. In the vertically-set membrane module, velocity measurement of bubble flow using laser Doppler velocimeter revealed that drag force working on membrane surface was closely related to upward-direction water velocity. Also fluctuation of drag force and shear force on membrane surface was found to be related to velocity fluctuation (turbulence).

Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells.

OBJECTIVES: Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. METHODS: Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. RESULTS: Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. CONCLUSIONS: The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury.Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint Res 2016;5:602-609. DOI: 10.1302/2046-3758.512.2000582.

Donor leukocytes combined with delayed immunosupressive drug therapy prolong limb allograft survival.

Donor leukocytes administered at the time of transplantation may prolong organ allograft survival. Delayed administration of calcineurin inhibitors, such as FK506 or cyclosporine, may enhance their efficacy. Herein the effectiveness of this strategy to promote limb transplant survival was investigated in the strong histocompatibility barrier of Brown-Norway donor to Lewis recipients. Donor leukocytes (6 x 10(7) intravenously) were injected on the day of transplantation followed on day 1 to 14 with mycophenolate mofetil (MMF; 15 mg/kg/d) and prednisone, (0.5 mg/kg/d) which were then tapered by 20% each week and stopped at week 7. Administration of of FK506 (2 mg/kg/d) was started on day 4 and continued for 8 weeks, then tapered for 4 weeks to a maintenance dose of 0.8 mg/kg/d, which was continued for 12 weeks (group A; n = 8). A control group (n = 8) underwent identical treatment save for donor leukocyte injection but rather commencement of FK506 on day 1. Rejection was common during FK506 tapering in both groups. However group A showed a significantly later onset, a shorter period for reversal of the first rejection, and a significantly lower dosage of FK506 at the time of rejection. After the completion of immunosuppression, rejection occurred significantly later in group A than the control group with one animal surviving without immunosuppression on day 344. This is the first trial of a donor leukocyte injection combined with delayed FK506 administration in limb transplantation, which suggested that it could produce a modest but significant improvement in outcome.

Donor leukocytes combine with immunosuppressive drug therapy to prolong limb allograft survival.

Donor leukocytes administered at the time of transplantation may prolong organ allograft survival. This study examined the effectiveness of donor leukocyte injection combined with immunosuppression for limb transplantation across the strong histocompatibility barrier of a Brown Norway donor to a Lewis recipient. Eight animals received 6 x 10(7) donor leukocytes injected on the day of transplantation. From day 1, FK506 (2 mg/kg/d), mycophenolate mofetil (MMF) (15 mg/kg/d), and prednisone (0.5 mg/kg/d) were administered for 2 weeks. After week 2, prednisone and MMF were both tapered by 20% of the initial dosage per week. After week 7, the animals received only FK506 (2 mg/kg/d). From week 8, FK506 was tapered to the maintenance dose of 0.8 mg/kg/d at week 10 and was stopped on week 24. A control group of 8 animals underwent identical treatment except that the leukocyte injection was omitted. Rejection was observed in both groups during FK506 monotherapy; however, the onset of early rejection episodes was significantly later, the period for reversal of the first rejection was significantly shorter, and the dosage of FK506 at the time of rejection was significantly lower among leukocyte-treated recipients. After completion of immunosuppression, survival was modestly prolonged in the leukocyte-treated group. One animal is surviving without immunosuppression on day 234. This trial of donor leukocyte injection combined with immunosuppression in limb transplantation showed a modest, but significant, improvement in outcome.

Profiling microRNA expression in fracture nonunions: Potential role of microRNAs in nonunion formation studied in a rat model.

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter. Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment.

Angiosarcoma arising from skeletal haemangiomatosis in an atomic bomb survivor.

The authors report a unique case in which an angiosarcoma arose from skeletal haemangiomatosis in a 72 year old man. This patient had a history of atomic bomb irradiation more than 50 years ago. Radiographically, the patient had multiple sclerotic foci of benign haemangiomas in the pelvis, the sacrum, and the left femur. The patient developed a high grade angiosarcoma in the left pubic bone. It is thought that atomic bomb irradiation played an important role in the development of the malignant lesion.

Augmentation of anterior cruciate ligament reconstruction in dogs with prostheses of different stiffnesses.

The purpose of this study was to investigate the biological and biomechanical properties of anterior cruciate ligament (ACL) reconstruction augmented with Dacron prostheses of three different stiffnesses. The ACLs of 36 adult mongrel dogs were removed and the ligament was reconstructed. In 18 dogs, one knee was reconstructed with patellar tendon alone, and the contralateral knee with Dacron augmented patellar tendon. In the remaining 18 dogs, reconstruction was with Dacron augmented patellar tendon with Dacron alone being used for the contralateral control knee. Death was 3 months after surgery, and the reconstructions were examined biologically and biomechanically. The mechanical data were compared with immediate postoperative data obtained from 45 reconstructed fresh cadaveric knees. Tensile testing demonstrated that an increase in failure load was found when the implanted patellar tendon graft was compared with the cadaveric reconstruction. The strength of the Dacron augmented reconstruction showed little change while the Dacron alone graft decreased in strength during the period of implantation. No clear difference was found between the performance of augmentation devices of different stiffnesses. Microangiography showed that grafts were totally revascularized in patellar tendon alone, but not well revascularized in Dacron augmented patellar tendon and Dacron alone reconstruction. The presence of the Dacron appeared to have an adverse effect on revascularization.

Meralgia paresthetica occurring 40 years after iliac bone graft harvesting: case report.

OBJECTIVE AND IMPORTANCE: Meralgia paresthetica is an entrapment neuropathy involving the lateral femoral cutaneous nerve. We describe an unusual case in which meralgia paresthetica occurred many years after iliac bone graft harvesting. CLINICAL PRESENTATION: An 81-year-old man presented with a 1-year history of pain, dysesthesia, and hypesthesia in the anterolateral aspect of the right thigh. This patient had undergone iliac bone grafting when he sustained a calcaneal fracture 40 years previously. Radiographs and computed tomographic scans of the pelvis revealed a bony excrescence in the anterosuperior iliac spine. INTERVENTION: The patient underwent neurolysis of the lateral femoral cutaneous nerve and excision of the bony excrescence. At surgery, the nerve was densely adherent to the bony excrescence. CONCLUSION: The etiology of meralgia paresthetica in this patient is considered to be heterotopic ossification on the anterosuperior iliac spine and pubic symphysis degeneration. A significant relationship between pubic symphysis degeneration with increasing age and meralgia paresthetica has been reported. One should be aware of meralgia paresthetica as a late complication of iliac bone graft harvesting.

Sacral radiculopathy secondary to multicentric osteosarcoma.

STUDY DESIGN: A case of multicentric osteosarcoma presenting with sacral radiculopathy is reported. OBJECTIVE: To present unusual clinical and radiologic findings of multicentric osteosarcoma. SUMMARY OF BACKGROUND DATA: Multicentric osteosarcoma is a rare variant of osteosarcoma. To the authors' knowledge, no cases of multicentric osteosarcoma presenting as sacral radiculopathy have been reported previously. METHODS: A 14-year-old boy had a large sacral tumor extending into the spinal canal, which was found to account for the initial symptoms, which mimicked those of herniated nucleus pulposus. At diagnosis, a bone survey showed multiple foci of osteosarcoma in the long bones. RESULTS: The patient was treated with chemotherapy, but died of the disease 8 months after the initial presentation. CONCLUSION: Multicentric osteosarcoma should be considered in the differential diagnosis for a pediatric patient with low back pain and sciatica.

Developmental and dynamic canal stenosis as radiologic factors affecting surgical results of anterior cervical fusion for myelopathy.

STUDY DESIGN: The correlation between preoperative and postoperative lateral functional radiograms and clinical results was analyzed in 74 cases of myelopathy treated by anterior cervical fusion. OBJECTIVES: To clarify the correlation between clinical results and radiologic findings (developmental and dynamic stenosis). SUMMARY OF BACKGROUND DATA: Although radiologic changes have been reported at the disc level adjacent to anterior cervical fusion, the question of whether these radiologic findings affect the clinical results of anterior fusion has not been resolved. METHODS: The "deteriorated" results group (28 cases) was composed of cases with deterioration of 2 points or more in the Japan Orthopedic Association score at follow-up compared with the postoperative best score. The "good" results group (46 cases) exhibited a recovery rate of > or = 50%. The two groups were compared in lateral functional roentgenograms on which the sagittal canal diameter in each vertebra and the diameter between the inferoposterior lip of the vertebral body and the anterior margin of the lamina of the distal vertebra in the extended neck were measured. A diameter of less than 12 mm was defined as developmental canal stenosis or dynamic canal stenosis. RESULTS: Fifty-four percent of the cases in the deteriorated results group had developmental canal stenosis, whereas the same findings were identified in only 2% of the cases in the good results group (P < 0.01). Preoperative dynamic canal stenosis at the disc level adjacent to the fusion was found in 64% of the patients in the deteriorated results group and in only 4% of the patients in the good results group (P < 0.01). CONCLUSIONS: Patients in the deteriorated results group showed a higher incidence of preoperative developmental and/or dynamic canal stenosis at the adjacent disc level than those in the the good results group. These results indicate that patients with preoperative developmental canal stenosis are not suitable candidates for anterior cervical fusion. When dynamic canal stenosis is found below or above the level of fusion, simultaneous fusion is recommended to avoid deterioration of the myelopathy.

Minimum 10-year outcome of decompressive laminectomy for degenerative lumbar spinal stenosis.

STUDY DESIGN: A retrospective follow-up study was conducted in patients who underwent decompressive laminectomy for degenerative lumbar spinal stenosis. OBJECTIVES: To describe the long-term outcome of decompressive laminectomy performed for degenerative lumbar spinal stenosis, and to investigate preoperative factors that influenced outcomes, especially risk factors predisposing patients to poor results. SUMMARY OF BACKGROUND DATA: The success rate of surgical treatment of decompressive laminectomy for lumbar spinal stenosis varies. Long-term follow-up investigations have indicated deterioration of outcome; however, the causes of deterioration have not been fully investigated, and there have been no reports with a minimum 10-year follow-up. METHODS: Of 151 patients who underwent decompressive laminectomy from 1980 through 1989, 37 were followed up for a minimum of 10 years. The mean age at surgery was 60.9 +/- 8. 2 years (range, 43-76), and the average follow-up period was 13.1 +/- 2.1 years (range, 10.1-17.4). The results were evaluated by the criteria of the Japanese Orthopedic Association Lumbar Score, and the outcome was classified as excellent at more than 75% improved score; good, 50-75%; fair, 25-49%; and poor, 0-24% or less. Information about impairment of activities of daily living was also obtained at follow-up. Associations between preoperative clinical and radiographic variables and clinical outcome were evaluated statistically. RESULTS: In all patients, the average score improvement of 55.2 +/- 31.6% was regarded as acceptable. The postoperative score and percentage of improvement of low back pain were lower than those of leg pain and walking ability. No impairment in activities of daily living was found in 62.2% of the patients. Rate of improvement was evaluated as excellent in 13 (35.1%), good in 8 (21.6%), fair in 8, and poor in 8 patients. Three patients required additional surgery because of disc herniation at the laminectomied segments. The patients with multiple laminectomy (P = 0.034) and more than 10 degrees preoperative sagittal rotation angle (P = 0.018) showed a significantly poorer outcome than the remainder of the patients. CONCLUSIONS: Long-term follow-up showed that even without spinal fusion, more than half the patients were evaluated as excellent or good. Patients with more than a 10 degrees sagittalrotation angle who need multiple laminectomy, should be given information about the possibility of earlier deterioration of the outcome, and alternative or additional treatment such as concomitant spinal fusion with decompression may be considered.