Risedronate reduces postoperative bone resorption after cementless total hip arthroplasty.

UNLABELLED: Forty-three patients who had undergone cementless THA were randomly assigned to receive no osteoactive drug or oral risedronate for 6 months. Postoperative decrease of BMD in the risedronate group was significantly lower than that seen in the control group in zones 1, 2, 3, 6, and 7. INTRODUCTION: Proximal bone resorption around the femoral stem often has been observed after total hip arthroplasty (THA), could lead to late stem loosening. We previously reported the efficacy of etidronate on periprosthetic bone resorption after cementless THA. Recently risedronate is suggested to be effective for the prevention and treatment of for osteoporosis. The purpose of the present study was to evaluate the effects of risedronate on periprosthetic bone loss after cementless THA. METHODS: Forty-three patients who had undergone cementless THA were randomly assigned to receive no osteoactive drug (21 patients) or oral risedronate 2.5 mg/day (22 patients) for 6 months. Three patients were eliminated from the risedronate group because of dyspepsia. Periprosthetic bone mineral density (BMD) in seven regions of interest based on the zones of Gruen et al. was measured with dual energy X-ray absorptiometry at 3 weeks and 6 months postoperatively. RESULTS: At 6 months after surgery, postoperative decrease of BMD in the risedronate group was significantly lower than that seen in the control group in zones 1, 2, 3, 6, and 7 (p < 0.05, p < 0.01, p < 0.01, p < 0.05, and p < 0.05, respectively). CONCLUSION: These outcomes suggested that risedronate might reduce the periprosthetic bone resorption after cementless THA.

Dome (modified Chiari) pelvic osteotomy: 10- to 18-year followup study.

Ninety-six dome (modified Chiari) pelvic osteotomies in 87 patients with pain and disability because of osteoarthrosis secondary to hip dysplasia were reviewed. The mean age of the patients at the time of surgery was 29 years (range, 16-55 years). The mean followup was 13 years (range, 10-18 years). Forty-one hips were classified into a hip dysplasia stage, 32 hips into an early stage of osteoarthrosis, and 23 hips into an advanced stage of osteoarthrosis according to the radiographic grading of the Japanese Orthopaedic Association. The average preoperative Merle d'Aubigné and Postel hip score was 13.8, and the average score at final followup was 16.6. Excellent or good results with a score greater than 14 were achieved in 96% of the hips at final followup. Radiographically, signs of progression of osteoarthrosis were not seen in 87% of the hips. Osteoarthrosis progressed during the postoperative course in 13% of the hips. Four patients (four hips) eventually had a total hip arthroplasty at 13.8 years (range, 12.5-15.3 years) after surgery. The survival rate of dome pelvic osteotomy, using clinical failure as an end point, was 82% at 15 years. Using radiologic failure as an end point, 61 hips in 54 patients (survival rate, 78%) survived at 15 years. Using hip replacement as an end point, 92 hips in 83 patients (survival rate, 82%) survived at 15 years. Dome pelvic osteotomy is an excellent and effective operation for pain relief and functional maintenance of the hip.

Hip arthropathy associated with hemodialysis. Radiological and laboratory evaluation of 56 hemodialysis patients.

There were 56 consecutive patients enrolled in our study from the outpatient clinic of our institution, mean age of 59 years, who had been on hemodialysis for 2-26 years. The duration of hemodialysis was less than 10 years for 36 patients (short-term group) and 10 years or more for 20 patients (long-term group) with a mean duration of 11 years at time of the investigation. In the short-term group, plain radiography revealed bone cysts in 9 hips (17%) and joint space narrowing in 10 hips (19%), while in the long-term group, there were bone cysts in 19 hips (48%) and joint space narrowing in 6 hips (15%). Bone mineral density as determined by dual-energy X-ray absorptiometry was 0.621 g/cm2 for patients in the short-term group and 0.503 g/cm2 for patients in the long-term group. Hip arthroplasties were performed in 3 patients suffering from femoral neck fracture due to bone cysts. All of them showed marked bone loss (mean 0.380 g/cm2). In conclusion, plain radiography and dual-energy X-ray absorptiometry are useful for evaluating the hip arthropathy of hemodialysis patients, especially those who have undergone long-term hemodialysis.

Evaluation of periprosthetic bone-remodeling after cementless total hip arthroplasty. The influence of the extent of porous coating.

BACKGROUND: Total hip arthroplasty changes the levels of stress within the proximal part of the femur, and the femur remodels adjacent to the prosthesis. The stem size and the initial bone-mineral density around the distal portion of the stem affect postoperative bone-remodeling after the insertion of a fully porous-coated metal-cancellous prosthesis. The purpose of this study was to evaluate the influence of the extent of porous coating of this prosthesis on femoral bone-remodeling. METHODS: A longitudinal examination of sixty-one hips in fifty-four patients was performed. Thirty-one hips in twenty-seven patients with a fully porous-coated stem (Group A) and thirty hips in twenty-seven patients with a proximally porous-coated stem (Group B) were followed for twenty-four to thirty months. Periprosthetic bone-mineral density was measured with dual-energy x-ray absorptiometry at specific intervals after the operation. RESULTS: In both groups, the greatest loss of bone-mineral density, compared with the initial (three-week) value, was approximately 20 percent in zone 7 at twelve to eighteen months. In other zones, bone-remodeling appeared to cease by twelve months. At the last follow-up evaluation, the loss of bone-mineral density in the distal and middle regions in Group A was significantly greater than that in Group B (p < 0.01 for zone 3 and p < 0.05 for zone 6). In contrast, with the numbers available, there were no significant differences in loss of bone-mineral density in the proximal regions (zones 1 and 7) between the two groups at any follow-up period. CONCLUSIONS: The extent of porous coating affects bone-remodeling in the distal periprosthetic region rather than in the proximal region. The results in the present report are specific to the particular implants that were studied.

Scintigraphic assessment of the rotated femoral head after transtrochanteric rotational osteotomy for osteonecrosis.

BACKGROUND: The purpose of this study was to assess the usefulness of bone scintigraphy in predicting progressive collapse of the femoral head after transtrochanteric rotational osteotomy for the treatment of osteonecrosis of the femoral head. METHODS: We studied thirty-three hips in thirty patients with osteonecrosis of the femoral head who had undergone transtrochanteric rotational osteotomy. There were twenty male and ten female patients, with a mean age of 34.4 years at the time of the operation. The mean duration of follow-up was 10.0 years. According to the staging system of Ficat and Arlet, there were nineteen stage-2 hips and fourteen stage-3 hips at the time of the operation. Conventional anteroposterior and lateral radiographs were assessed. In addition, bone scans were performed at three weeks after the operation to predict the outcome with regard to the rotated femoral head. On the basis of the location of low scan activity within the femoral head, the scintigraphic findings were classified into one of two categories: type A if there was no low scan activity in the weight-bearing area of the femoral head or type B if low scan activity occupied the entire weight-bearing area. Six hips with collapse were studied histologically. RESULTS: Postoperative scintiscans revealed sixteen type-A hips and seventeen type-B hips. Of the type-A hips, only three exhibited progressive collapse of the femoral head after the osteotomy, whereas fourteen of the type-B hips exhibited progressive collapse. A significant association was found between the postoperative scintigraphic findings and the final radiographic result (p < 0.01). CONCLUSIONS: Bone scintiscans made three weeks after transtrochanteric rotational osteotomy were useful for predicting the final clinical result.

Pathology of femoral head collapse following transtrochanteric rotational osteotomy for osteonecrosis.

We investigated the pathology of femoral head collapse following transtrochanteric anterior rotational osteotomy. Six femoral heads were obtained during total hip arthroplasty some 2-12 years after osteotomy. In all cases, the preoperatively necrotic lesions exhibited mostly osteonecrosis with accumulation of bone marrow cell debris and trabecular bone with empty lacunae, although repair tissue such as granulation tissue and appositional bone formation were observed in limited areas in some cases. In the transposed intact articular surface of the femoral head, osteoarthritic changes such as fissure penetration to the subchondral bone and osteophyte formation were commonly observed. In newly created subchondral areas at weight-bearing sites, trabecular thickness and the number of trabecular bones had decreased, with few osteoblasts, osteoclasts, and osteocytes being present, resulting in a coarse lamellar structure of the trabecular bone. These findings suggest that transposed areas in cases of failure consist mostly of low-turnover osteoporotic lesions which could cause collapse of the femoral head.

Therapeutic effect of transtrochanteric rotational osteotomy and hip arthroplasty on quality of life of patients with osteonecrosis.

We reviewed 37 patients with avascular necrosis of the femoral head (ANF). There were 23 men and 14 women with a mean age of 36 years at the time of the operation. The duration of follow-up was 9 years. Twenty patients had undergone transtrochanteric rotational osteotomy (TRO) and 17, hip arthroplasties. Assessment of their quality of life (QoL) was performed using the Rosser Index Matrix for disability and distress. Concerning TRO, the mean preoperative and postoperative QoL scores were 0.944 and 0.957, respectively. Twelve patients exhibited increases and 7 patients decreases in their scores. Regarding the arthroplasty, the mean preoperative and postoperative QoL scores were 0.949 and 0.998, respectively. All patients showed increases in QoL scores after arthroplastic surgery. Concerning heavy manual work, all five of those patients returned to their preoperative occupations. These findings suggest that hip arthroplasty has more reliable therapeutic effects than TRO on QoL improvement for patients with ANF.

Arthrographic examination of the pseudocapsule of the hip after posterior dislocation of total hip arthroplasty.

We examined the pseudocapsule in ten patients with posterior dislocation after total hip arthroplasty (THA) using arthrography to investigate the relationship between dislocation and the state of the pseudocapsule. The pattern of contrast medium pooling demonstrated on tangential views was evaluated. In five patients with early dislocation arthrography showed leakage indicating lack of pseudocapsule whereas there was no leakage in five patients with late dislocation. Repeat arthrography revealed healing of the pseudocapsule could progress by 6-8 weeks after dislocation. These findings suggest that the difference in the pseudocapsule between those who dislocate early and late may explain different clinical outcomes in the two groups.

Flow-cytometric analysis of leukocyte alkaline phosphatase in myelodysplastic syndromes.

The expression of leukocyte alkaline phosphatase (LAP) in neutrophils is reduced in some patients with myelodysplastic syndrome (MDS). We quantitatively assayed for LAP in MDS leukocytes by a flow cytometry based method using a monoclonal antibody raised against human bone alkaline phosphatase. The LAP expression was assayed in blood samples from a group of 46 MDS patients, consisting of 39 patients with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 4 patients with RAEB in transformation. The percentage of LAP-positive cells was significantly higher in the MDS patients than in the normal subjects and also higher in RA than in RAEB and RAEB in transformation. To investigate the cause of the elevated LAP expression, we measured the serum concentrations of several cytokines. The granulocyte colony-stimulating factor (G-CSF) level was significantly elevated in MDS patients, and the serum G-CSF concentration clearly correlated with the percentage of LAP-positive cells. Thus, the LAP activity in RA is higher than in normal subjects, and G-CSF is thought to be one of the causes stimulating LAP expression in MDS neutrophils.

Leucocyte alkaline phosphatase identifies terminally differentiated normal neutrophils and its lack in chronic myelogenous leukaemia is not dependent on p210 tyrosine kinase activity.

Leucocyte alkaline phosphatase (LAP) is a marker of post-mitotic granulocytes and its activity is reduced or absent in chronic myelogenous leukaemia (CML) granulocytes as a consequence of LAP messenger RNA (mRNA) deficiency. We provide evidence that along the granulocytic maturation in normal marrow, the acquisition of LAP surface expression, identified by the monoclonal antibody 1B12.1, was restricted to CD11bbright/CD16bright positive cells. Moreover, in normal granulocytes, exposure to granulocyte colony-stimulating factor (G-CSF) in vitro and in vivo increased the cell surface expression of LAP. Although G-CSF was able to induce the LAP surface expression in CML granulocytes, the inhibition of p210 tyrosine kinase activity by genistein or CGP75148B failed to restore LAP mRNA expression and LAP protein synthesis. In conclusion, the acquisition of LAP protein on the cell surface of granulocytes follows CD16 antigen expression and can be considered as the last marker of terminally differentiated neutrophils. G-CSF is a potent regulator of the LAP mRNA expression and protein synthesis in normal and CML-derived neutrophils. The lack of direct activity of p210 tyrosine kinase on LAP mRNA expression in CML neutrophils supports the notion that the LAP defect in this disease could be related to a precocious and uncontrolled release of white blood cells from the bone marrow into the blood stream.

MR evaluation of the articular cartilage of the femoral head during traction. Correlation with resected femoral head.

OBJECTIVE: The purpose was to evaluate the articular cartilage of the hip joint with MR during traction and compare the findings with the resected specimen or arthroscopic findings. MATERIAL AND METHODS: Eight healthy volunteers, 5 patients with osteonecrosis, 5 with acetabular dysplasia, and 5 with advanced osteoarthrosis underwent MR imaging to evaluate the articular cartilage of the hip joint. Coronal fat-suppressed 3D spoiled gradient-echo (SPGR) images were obtained during traction. Identical imaging was performed of all the resected femoral heads of the osteonecrosis and advanced osteoarthrosis patients, and was correlated with the macroscopic pathological findings. RESULTS: The traction was effective and the femoral articular cartilage was clearly identified in all 8 control subjects, and in all cases of osteonecrosis and acetabular dysplasia. In 4 cases of osteonecrosis, chondral fracture was identified in the boundary between the necrosis and the normal area. In all cases of advanced osteoarthrosis, cartilage was identified only at the medial side. The MR images of osteonecrosis and advanced osteoarthrosis corresponded well with the MR images of the resected femoral heads and the macroscopic findings. CONCLUSION: Fat suppressed 3D-SPGR during continuous leg traction was useful in detecting cartilage abnormalities.

Assessment of alkaline phosphatase on the surface membrane of neutrophils by immunofluorescence.

Expression of alkaline phosphatase (ALP) on the surface membrane of neutrophils (mNAP) was studied by immunofluorescence using an anti-ALP monoclonal antibody. Fluorescent intensity distribution of mNAP was analyzed using FACS (fluorescence-activated cell sorter). The mean fluorescent intensity (MFI) of the mNAP in this assay was well correlated with the neutrophil ALP (NAP) score demonstrated cytochemically (r = 0.832). mNAP levels in various hematological disorders were evaluated by % mNAP+ cells and MFI. The levels in aplastic anemia and polycythemia vera were significantly higher, and in chronic myelocytic leukemia and paroxysmal nocturnal hemoglobinuria (PNH), the levels were significantly lower compared with the levels in healthy volunteers. Two-color immunofluorescence with anti-ALP and anti-CD16 showed that the PNH clone was essentially negative for mNAP, whereas residual normal neutrophils (CD16+) had levels slightly higher than those in normal individuals. Highly reproducible results were obtained in the blood samples which were stored at 4 degrees C for at least 24 hr without any treatment prior to immunofluorescent staining. No degradation of fluorescent intensity was seen 4 days after staining and fixation. The mNAP assay is simple, without subjective evaluation for quantification, and is useful for differential diagnosis of hematological disorders.

Population pharmacokinetics and pharmacodynamics of cisplatin in patients with cancer: analysis with the NONMEM program.

The population pharmacokinetics and pharmacodynamics of cisplatin (CDDP) were evaluated based on a mixed-effect model using the NONMEM program. Unchanged CDDP in plasma was measured as a biologically active platinum species during CDDP chemotherapy, using high-performance liquid chromatography. Plasma concentration measurements (157) of unchanged CDDP from 26 patients with cancer receiving 80 mg/m2 CDDP by infusion over 2 hours, 3.5 hours, or 4 hours were analyzed according to a one-compartment model. The influences of individual characteristics such as body weight, dose schedule, course, and clinical laboratory values (renal function markers, albumin) on total body clearance (Cl) and volume of distribution (Vd) were examined. In the final pharmacokinetic model, body surface area and dose schedule affected Cl of unchanged CDDP. The Cl of CDDP was increased by 27.3% after the 2-hour infusion schedule compared with Cl after the longer infusions. The Vd was estimated as 13.4 L/m2. The interindividual variability for Cl and Vd and residual variability were 22.9%, 30.9%, and 35.5%, respectively. The relationships between maximum concentration (Cmax) of unchanged CDDP and maximum blood urea nitrogen (BUNmax), or minimum creatinine clearance (ClCr,min) over a 1-month period after CDDP administration were evaluated according to linear, exponential, or maximum response (Emax) models. The linear or Emax model described pharmacodynamics most successfully, with relatively large interindividual variability for both slope and EC50 (more than 25%). Residual variability was 15.3% and 17.1% in BUNmax and Clcrmin, respectively. The population means and interindividual and residual variability of pharmacokinetics and pharmacodynamics of CDDP were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic and pharmacodynamic approach could be useful to manage CDDP nephrotoxicity using sparse data in a clinical setting.

The Metal-Cancellous Cementless Lübeck total hip arthroplasty. Five-to-nine-year results.

We implanted 51 Metal-Cancellous Cementless Lübeck (MCCL) prostheses into 45 patients with dysplastic hips and followed 49 hips (96.1%) for five to nine years. One had needed revision for stem fracture and one for infection; the clinical outcome of the other 47 hips was assessed using the Merle d'Aubigné and Postel hip score. All hips were either excellent (63%) or good (37%). Three patients (6%) had mild thigh pain at six months, but this had settled within two years. Serial radiographs showed stable fixation with bone ingrowth in all hips, with increased density of the cancellous bone in contact with the implant and some trabecular ingrowth. There was early varus shift of the stem in one hip, but this stabilised in three months. Osteolysis of the femoral cortex was seen in one hip at seven years after surgery, and mild bone resorption due to stress shielding in 31 (63%). Acetabular bone grafting with autogenous bone from the femoral head gave successful support to the socket in 13 hips. The MCCL prosthesis gave satisfactory mid-term results in patients with osteoarthritis secondary to hip dysplasia.

The herbal medicine unkei-to stimulates cytokine-induced neutrophil chemoattractant production in the pituitary folliculo-stellate-like cell line (TtT/GF).

PROBLEM: We previously reported that a cytokine-induced neutrophil chemoattractant (CINC) was produced in the pituitary gland and that it influenced anterior pituitary hormone release. In this study we investigated the effect of Unkei-to, a Japanese herbal medicine, on CINC production in the rat anterior pituitary gland and the pituitary folliculo-stellate-like cell line (TtT/GF). METHOD OF STUDY: Dispersed normal anterior pituitary cells and the folliculo-stellate-like cell line TtT/GF were used to test the effect of Unkei-to on CINC secretion and CINC mRNA accumulation. Concentrations of CINC in the conditioned media were measured by an enzyme-linked immunosorbent assay, and levels of CINC mRNA were analyzed by Northern blot analysis. RESULTS: Unkei-to (20 micrograms/ml) significantly increased the secretion of CINC by normal anterior pituitary cells within 12 hr of incubation. Unkei-to also stimulated CINC secretion from TtT/GF cells in a time- and dose-dependent manner. Unkei-to (20 micrograms/ml) increased CINC mRNA accumulation in TtT/GF cells within 3 hr of incubation and also caused a 13-fold increase in the secretion of CINC from TtT/GF cells compared with the vehicle group within 24 hr of incubation. Finally, we found that some of the Unkei-to's ingredients, Evodiae fructus and Pinelliae tuber, markedly stimulated CINC secretion from TtT/GF cells. CONCLUSIONS: Our results will help to elucidate the mechanism behind the clinical effect of Unkei-to on the anterior pituitary gland. They also suggested the presence of special substances, which stimulate CINC secretion, within Unkei-to's ingredients such as E. fructus and P. tuber.

Norepinephrine stimulates mitogen-activated protein kinase activity in GT1-1 gonadotropin-releasing hormone neuronal cell lines.

The GT1-1 GnRH neuronal cell lines exhibit highly differentiated properties of GnRH neurons. We have used GT1-1 cells to study the roles of norepinephrine (NE), membrane depolarization, calcium influx, and phorbol esters in the regulation of mitogen-activated protein (MAP) kinase. NE, which is known to stimulate the release of GnRH, induced MAP kinase activity, the tyrosine phosphorylation of MAP kinase, and MAP kinase kinase activity. Forskolin led to activation of MAP kinase comparable with that induced by NE, and a selective inhibitor of cAMP-dependent protein kinase, H8, attenuated the NE-induced activation of MAP kinase. On the other hand, elimination of extracellular calcium by EGTA completely blocked NE-induced tyrosine phosphorylation of MAP kinase, and a selective inhibitor of calcium/calmodulin-dependent protein kinase, KN-62, attenuated the NE-induced activation of MAP kinase. Furthermore, depolarization of GT1-1 cells with 75 mM KCl, 10 microM BayK 8644, or 1 microM calcium ionophore (A23187) induced rapid tyrosine phosphorylation of MAP kinase. The omission of calcium from the extracellular medium completely abolished these effects of tyrosine phosphorylation of MAP kinase. Phorbol 12-myristate 13-acetate (PMA) also induced MAP kinase activity, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the activation of MAP kinase by NE. In addition, although phosphorylation of Raf-1 kinase was stimulated by PMA, this phosphorylation was not induced by either NE or A23187. These results demonstrate that NE activates MAP kinase directly in GT1-1 cells, and that the effect of NE is mediated by increase in the cAMP level and by calcium influx, but not by PMA-sensitive protein kinase C or Raf-1 kinase.

Prolactin stimulates mitogen-activated protein kinase in human leiomyoma cells.

The effects of prolactin (PRL) on proliferation of cultured human uterine leiomyoma-derived smooth muscle cells (SMC) and its mechanism of action were investigated. PRL stimulated DNA synthesis and the expression of PRL receptor was identified by ribonuclease protection assay. Moreover, the regulation of mitogen-activated protein (MAP) kinase by PRL in leiomyoma-derived SMC was investigated. PRL stimulated MAP kinase activity, as detected by 32P incorporation into MAP-2, in a dose-dependent manner. PRL also rapidly stimulated MAP kinase phosphorylation as detected by in vivo phosphorylation using 32P labeling and phosphotyrosine immunoblotting. These results suggest that PRL stimulates the proliferation of human leiomyoma cells via the MAP kinase cascade.

Role of mitogen-activated protein kinase pathway in prostaglandin F2alpha-induced rat puerperal uterine contraction.

In this study, prostaglandin (PG) F2alpha was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2alpha stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2alpha induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase 1 (betaARK1), which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP kinase. Ritodrine (1 microM), which is known to relax uterine muscle contraction, attenuated PGF2alpha-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2alpha-induced calcium mobilization, this inhibitor partially inhibited PGF2alpha-induced uterine contraction. These results provide evidence that PGF2alpha stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gbetagamma protein, suggesting that this new pathway may play an important role in the biological action of PGF2alpha on these cells.

Interleukin-1 beta enhances and tumor necrosis factor-alpha inhibits bone morphogenetic protein-2-induced alkaline phosphatase activity in MC3T3-E1 osteoblastic cells.

The modulatory effects of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha on bone morphogenetic protein (BMP)-2- and -4-induced alkaline phosphatase (ALP) activity were examined in cultures of mouse MC3T3-E1 osteoblastic cells. Both BMP-2 and -4 significantly induced ALP in these cells. IL-1 beta alone had no effect on ALP activity, but it significantly enhanced BMP-2- and -4-induced ALP activity. TNF-alpha suppressed the induction of ALP by BMP-2 or -4. The results suggest that the action of BMP on osteogenic differentiation may be regulated by such immuno/inflammatory cytokines as IL-1 beta and TNF-alpha.