Influence of Diabetes Mellitus on Surgical Outcomes in Patients with Cervical Myelopathy: A Prospective, Multicenter Study.

STUDY DESIGN: Multicenter, prospective study. PURPOSE: To investigate the effects of diabetes mellitus (DM) on surgical outcomes in patients with cervical myelopathy. OVERVIEW OF LITERATURE: To date, few studies have investigated the influence of postoperative blood glucose or glycated hemoglobin (HbA1c) levels on surgical outcomes. METHODS: The participants were patients who underwent surgery for the treatment of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. The 61 cases were evaluated preoperatively and 1 year postoperatively using the Japanese Orthopaedic Association (JOA) scores and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The study variables included fasting blood glucose and HbA1c levels measured preoperatively and at 1 week, 4 weeks, and 1 year postoperatively; the F-wave conduction velocity, latency, rate of occurrence, and M-wave latency in the ulnar and tibial nerves were measured preoperatively and at 1 year postoperatively. The patients were divided into a group without diabetes (N group, 42 patients) and a group with diabetes (DM group, 19 patients). We then assessed the associations between the surgical outcomes and each of the study variables. RESULTS: JOA scores significantly improved in both groups; however, no significant between-group differences were found. There was no significant improvement in the JOACMEQ scores, which assessed cervical function, upper and lower limb function, and bladder function in both groups. We then subdivided the DM group into those with a good control of HbA1c after 1 year (DMG group, 12 patients) and those with HbA1c deterioration after 1 year (DMB group, seven patients), prior to comparing the surgical outcomes. The JOACMEQ scores for upper and lower limb function significantly improved in the DMG group (p<0.01). Compared with the DMB group, there were no significant increases in upper or lower limb function scores in the DMG group. CONCLUSIONS: Poor glycemic control might prevent postoperative functional recovery of the spinal cord.

Significance of Stabilometry for Assessing Postoperative Body Sway in Patients with Cervical Myelopathy.

STUDY DESIGN: Prospective study. PURPOSE: To examine the changes in body sway using stabilometry in patients who underwent cervical laminoplasty for cervical myelopathy. OVERVIEW OF LITERATURE: Although the patients of cervical myelopathy complain body sway there are few report to examine body sway objectively. METHODS: Patients who received treatment for cervical myelopathy between October 2010 and February 2013 were included. Twenty-one patients underwent cervical laminoplasty (myelopathy group). Body sway was assessed using stabilometry, wherein patients stood on a stabilometer with their eyes closed for 30 seconds. The Romberg ratio, outer peripheral area (OPA) with eyes closed (cm2), and total locus length per unit area (L/A) with eyes closed (/cm) were examined. Examinations were performed preoperatively (at baseline) and at 8 weeks postoperatively. Examination results of patients in the myelopathy group were compared with those of 17 healthy individuals (control group). Clinical symptoms were evaluated using the Japanese Orthopaedic Association scale score (JOA score) and the timed up and go (TUG) test. RESULTS: In the myelopathy and control groups, the mean baseline Romberg ratio, OPA, and L/A were 2.3±1.2, 8.9±5.5 cm2, and 14.2±5.3/cm and 1.4±1.0, 4.3±2.8 cm2, and 23.7±10.1/cm, respectively. Eight weeks after laminoplasty, only L/A showed significant improvement from baseline in the myelopathy group (23.2±10.1 to 16.8±7.9; p=0.03). The Romberg ratio and OPA showed improvement in the myelopathy group, but the changes were not statistically significant. JOA scores and TUG test results in this group significantly improved from baseline to 8 weeks after laminoplasty (12.7 to 13.4 and 10.8 to 8.0 seconds, respectively; both p<0.05). CONCLUSIONS: L/A is a useful parameter for measuring body sway to assess the recovery of body sway after laminoplasty.

Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry.

The influence of glucocorticoid (GC) on bone in rats at different ages was investigated in order to provide insight into human glucocorticoid induced osteoporosis (GCOP). Three-, 6-, and 12-month-old female Wistar rats were divided into four groups: Zero-time control (ZT), vehicle (Cont), prednisolone (PSL) 2 mg/kg (P-L), PSL 20 mg/kg (P-H). PSL was subcutaneously administered every day for 4 weeks. Bone mineral density (BMD) at the proximal metaphysis and diaphysis of the tibia was measured by peripheral quantitative computed tomography. Histomorphometry of the tibia was performed for 3- and 6-month-old rats. GC increased trabecular and cortical BMD at the metaphysis in all 3-month-old rats with time. Trabecular BMD at the metaphysis in the P-L and P-H groups was significantly higher than in the control group. Histomorphometric parameters for both bone formation and resorption were also increased by GC treatment. In the 6-month-old rats, the metaphyseal trabecular BMD did not significantly change in any group, but the diaphyseal trabecular BMD significantly increased in the control group with time. The trabecular BMD of the metaphysis and diaphysis was significantly lower in the P-L and P-H groups than in the control group at week 4. Histomorphometric parameters for bone formation and resorption were both reduced by GC treatment. The BMD remained unchanged in all 12-month-old rats. Six-month-old rats treated with 20 mg/kg GC are suitable models for GC-induced osteoporosis with dominant cancellous bone decrease and reduced bone turnover. The pathology induced by 20 mg/kg prednisolone in 6-month-old female rats seems to be most similar to glucocorticoid-induced osteoporosis in humans.

Minodronic acid influences receptor activator of nuclear factor kappaB ligand expression and suppresses bone resorption by osteoclasts in rats with collagen-induced arthritis.

We investigated the inhibitory mechanism of bone resorption by minodronic acid in collagen-induced arthritis (CIA) in rats. Four groups of female Sprague-Dawley rats, aged 7 months, were studied: three groups of collagen-sensitized rats, including one placebo-administered group (CIA-P), and two minodronic acid-administered groups at 0.2 mg/kg/2 day (CIA-BIS) and 2.0 mg/kg/2 day (CIA-BIS10). These were studied with an additional untreated observation group (Cont group). Minodronic acid was administered orally a day after the initial sensitization. The femoral posteromedial condyle was analyzed histologically and immunohistologically 4 weeks after the initial sensitization. Western blotting was also performed to assess the receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression of the knee joints. In CIA-P rats, many tartrate-resistant acid phosphatase (TRAP)-positive cells were found at the pannus-lining layer and the epiphyseal medulla. The bone-lining cells in the epiphyseal medulla and the cells in the pannus strongly expressed RANK and RANKL. In the minodronic acid-administered group, the number of TRAP-positive cells and the severity of arthritis were reduced. The reduction in the CIA-BIS10 group was significant compared with the CIA-P group (P < 0.05). Dosage-dependent reduction of RANK and RANKL expression was confirmed by immunohistology and Western blotting. With or without minodronic acid administration, no apoptotic cells were found in any groups using the TdT-mediated dUTP-biotinnick end labeling (TUNEL) method. The expression of OPG was not clear in all groups. These results demonstrated that minodronic acid inhibited the differentiation and the activation of osteoclasts not by inducing apoptosis but by inhibiting the RANKL-RANK system, and thereby suppressing bone resorption.

Effect of intermittent administration of human parathyroid hormone on bone mineral density and arthritis in rats with collagen-induced arthritis.

OBJECTIVE: To investigate the effect of intermittent administration of human parathyroid hormone (PTH) on bone mineral density (BMD) and arthritis in rats with collagen-induced arthritis (CIA). METHODS: Seven-month-old female Sprague-Dawley rats were divided into 4 groups: rats without CIA (control), rats with CIA treated with vehicle, rats with CIA treated with PTH for 4 weeks, and rats with CIA treated with PTH for 6 weeks. PTH (20 mug/kg) was injected subcutaneously 3 times per week. BMD in the proximal metaphysis and the diaphysis of the tibia was measured by peripheral quantitative computed tomography every 2 weeks until week 8. Eight weeks after initial sensitization, the animals were killed, and the BMD and mechanical properties of excised limbs were evaluated. Histomorphometric analysis of tibiae and histologic evaluation of arthritis were also performed. RESULTS: In the PTH-treated rats with CIA, the incidence and severity of arthritis were macroscopically and histologically similar to the findings in the vehicle-treated rats with CIA. The decrease of BMD caused by CIA was suppressed by treatment with human PTH, in a manner that was dependent on the duration of administration. In the histomorphometric analysis, bone formation parameters were higher and bone resorption parameters were lower in the PTH-treated arthritic rats compared with vehicle-treated arthritic rats. Mechanical properties were also maintained in the PTH-treated rats. CONCLUSION: Our findings indicate that, in an animal model of arthritis, intermittent PTH administration activates bone formation, resulting in increased BMD and preventing deterioration of mechanical properties. However, PTH has no effect on the arthritis itself.

Bone response to mechanical loading in adult rats with collagen-induced arthritis.

To elucidate the effects of inflammation on the response of bone to mechanical stress, we performed experiments using a rat with collagen-induced arthritis (CIA) model. Six-month-old female Wistar rats were used in the experiment. Bovine type II collagen sensitization and additional sensitization after 1 week were preformed in all CIA groups. Loads were applied using a four-point bending device. The right tibia was loaded in both CIA and control (CONT) groups at 35 N (low groups), 40 N (medium groups), or 47 N (high groups) for 36 cycles at 2 Hz three times per week for 3 weeks. Histomorphometrical data were collected from the periosteal and endosteal surfaces of the tibia in all rats. The tibia periosteal surface was subdivided into lateral and medial surfaces. Formation surface (FS), mineral apposition rate (MAR) and bone formation rate (BFR) were calculated. At lateral surface of periosteal surface, all three parameters showed significant differences between the loaded and nonloaded tibiae. All these parameters were significantly lower in CIA groups than in CONT groups, and interaction was seen between applied loading and CIA. There was a significant correlation between peak strain and the right-left difference of FS in the CONT groups. At medial surface of periosteal surface, there were force-related increase in FS, MAR, and BFR on the loaded side in both CIA and CONT groups, except MAR in the CONT group. All three parameters showed significant differences between the loaded and nonloaded tibiae. At endocortical surface, force-related increase was observed only in FS on the loaded side in CONT groups, and FS was significantly higher on the loaded side than the nonloaded side. CIA lowered all three parameters significantly. We examined the response to mechanical loading on the tibia in untreated CONT rats and rats with CIA by bone histomorphometry, and found that arthritis suppressed bone formation induced by mechanical loading.