Validation of static and dynamic radiostereometric analysis of the knee joint using bone models from CT data.

OBJECTIVES: Static radiostereometric analysis (RSA) using implanted markers is considered the most accurate system for the evaluation of prosthesis migration. By using CT bone models instead of markers, combined with a dynamic RSA system, a non-invasive measurement of joint movement is enabled. This method is more accurate than current 3D skin marker-based tracking systems. The purpose of this study was to evaluate the accuracy of the CT model method for measuring knee joint kinematics in static and dynamic RSA using the marker method as the benchmark. METHODS: Bone models were created from CT scans, and tantalum beads were implanted into the tibia and femur of eight human cadaver knees. Each specimen was secured in a fixture, static and dynamic stereoradiographs were recorded, and the bone models and marker models were fitted to the stereoradiographs. RESULTS: Results showed a mean difference between the two methods in all six degrees of freedom for static RSA to be within -0.10 mm/° and 0.08 mm/° with a 95% limit of agreement (LoA) ranging from ± 0.49 to 1.26. Dynamic RSA had a slightly larger range in mean difference of -0.23 mm/° to 0.16 mm/° with LoA ranging from ± 0.75 to 1.50. CONCLUSIONS: In a laboratory-controlled setting, the CT model method combined with dynamic RSA may be an alternative to previous marker-based methods for kinematic analyses.Cite this article: K. Stentz-Olesen, E. T. Nielsen, S. De Raedt, P. B. Jørgensen, O. G. Sørensen, B. L. Kaptein, M. S. Andersen, M. Stilling. Validation of static and dynamic radiostereometric analysis of the knee joint using bone models from CT data. Bone Joint Res 2017;6:376-384. DOI: 10.1302/2046-3758.66.BJR-2016-0113.R3.

Saliva induces expression of antimicrobial peptides and promotes intracellular killing of bacteria in keratinocytes by epidermal growth factor receptor transactivation.

BACKGROUND: Wounds in the oral cavity, constantly exposed to both saliva and bacteria, heal quickly without infection. Furthermore, during licking of skin wounds, saliva promotes wound healing and plays a role in keeping the wound free of infection. OBJECTIVES: To investigate whether saliva induces expression of antimicrobial peptides (AMPs) in human epidermal keratinocytes and whether saliva promotes clearance of intracellular bacteria in these cells. METHODS: Expression of AMPs was investigated in the oral mucosa and ex vivo injured skin by immunohistochemistry. Human beta-defensin-3 expression was investigated in epidermal keratinocytes after saliva stimulation, using real-time polymerase chain reaction and immunofluorescence. RESULTS: We found higher expression of AMPs in the oral mucosa than in the epidermis. Saliva accelerated the injury-induced expression of AMPs in human skin ex vivo and was a potent inducer of the expression of AMPs in epidermal keratinocytes. The expression of AMPs was induced by metalloproteinase-dependent epidermal growth factor receptor (EGFR) transactivation mediated by a salivary lipid. Saliva increased the intracellular clearance of Staphylococcus aureus in keratinocytes through EGFR activation. CONCLUSIONS: These findings suggest a previously unreported role of saliva in innate immunity and demonstrate for the first time that saliva induces gene expression in epidermal keratinocytes.

Bone mineral density of the trapezium in osteoarthritic trapeziometacarpal joints.

The aim of this study was to test the precision and reliability of measurements of the bone mineral density (BMD) of the trapezium in patients with osteoarthritic trapeziometacarpal joints using dual-energy X-ray absorptiometry scans and to assess whether there is an acceptable correlation between the BMD of the trapezium and that of the distal radius, for which normative data exist. We included 66 patients (52 women, 14 men) diagnosed with Eaton-Glickel stage II-IV osteoarthritis and a mean age of 59 years (range 40-77) in a prospective study. We found good intra- and inter-observer agreement of BMD measurements. Reliability was also good in repeated measurements. There was an indication of an increase in BMD with progression in the Eaton-Glickel stage. There was only a moderate correlation between the BMD of the trapezium and that of the radius.

Computed tomography improves intra-observer reliability, but not the inter-observer reliability of the Eaton-Glickel classification.

This study aimed to evaluate whether computed tomography improves the intra- and inter-observer reliability of the Eaton-Glickel classification of trapeziometacarpal joint osteoarthritis. The osteoarthritis of the trapeziometacarpal joint was evaluated with conventional radiographs and computed tomography by two hand surgeons, two registrars and one radiologist in 50 hands of 43 patients (12 male and 31 female) who had a median age of 60 years (46-80). Using plain radiographs, we found a mean intra-observer reliability of 0.54 (0.51-0.74), and the intra-observer reliability was improved to 0.76 (0.64-0.86) using computed tomography. Using plain radiographs, the mean inter-observer reliability was poor at 0.17 (0.04-0.51) and did not improve using computed tomography with a mean inter-observer reliability of 0.22 (0.02-0.38). In particular, the agreement in the distinction between Eaton-Glickel stage III and IV and the evaluation of the degenerative changes in the scaphotrapezio joint was low using computed tomography-scans. The detection of bone cysts on computed tomography was more precise than on plain radiographs.

Evaluation of complete cytoreductive surgery and two intraperitoneal chemotherapy techniques in Pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a low-grade malignancy characterized by mucinous tumor on the peritoneal surface. Treatment involves cytoreductive surgery (CRS) to remove all macroscopic tumor and perioperative intraperitoneal chemotherapy (PIC) to eliminate remaining microscopic disease. PATIENTS AND METHODS: Between 1994 and 2009, 93 patients were treated at the Norwegian Radium Hospital with complete CRS and PIC. PIC was administered as early postoperative intraperitoneal chemotherapy (EPIC) using mitomycin C (MMC) and 5-fluoruracil (n = 48) and as hyperthermic intraperitoneal chemotherapy (HIPEC) using MMC (n = 45). Patients were classified into three histopathological subgroups: Disseminated peritoneal adenomucinosis (n = 57), peritoneal mucinous carcinomatosis (n = 21) and an intermediate group (n = 15). Tumor distribution by peritoneal cancer index (PCI) was PCI ≤ 10 (n = 31), PCI 11-20 (n = 29), PCI ≥ 21 (n = 33). RESULTS: Recurrence was diagnosed in 38 patients and 25 patients died during follow-up. Estimated 10-year overall survival (OS) was 69% and 10-year disease-free survival (DFS) was 47%. Mean OS was 154 months (95% CI 131-171) and median OS was not reached (follow-up median 85 months (3-207)). Low-grade malignant histology (p = 0.001) and female gender (p = 0.045) were associated with improved OS. Almost equal OS and DFS were observed between patients treated with EPIC and HIPEC. CONCLUSIONS: Patients treated for PMP with complete CRS and PIC achieved satisfactory long-term outcome. The most important prognostic factor was histopathological differentiation, but acceptable survival was observed even in patients with aggressive histology and extensive intraperitoneal tumor growth. Administration of EPIC and HIPEC was equally efficacious with respect to long-term outcome.

Variation in allergen content over time of acrylates/methacrylates in patch test preparations.

BACKGROUND: Acrylates/methacrylates are volatile substances. There might be a gradual decrease in acrylate/methacrylate allergen content over time in patch test preparations but this has not yet been documented. OBJECTIVES: To determine the allergen content of acrylates/methacrylates in patch test preparations over time under different storage conditions. METHODS: Five acrylate/methacrylate allergens [2-hydroxyethyl methacrylate (2-HEMA), methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), triethylene glycol diacrylate (TREGDA) and 2-hydroxypropyl acrylate (2-HPA)] in syringes and IQ™ chambers (Chemotechnique Diagnostics, Vellinge, Sweden) were analysed using gel permeation chromatography and high-performance liquid chromatography to measure the allergen content over time in samples stored in the freezer, refrigerator and under room temperature. RESULTS: The concentration of allergens in syringes decreased with time. Those stored at room temperature had the fastest rate of decrease, followed by those in the refrigerator and freezer. In most cases, in syringes or IQ™ chambers under all storage conditions, the MMA decreased most rapidly, followed by 2-HPA, 2-HEMA, EGDMA and TREGDA. The allergens in the IQ™ chambers rapidly disappeared, with almost all samples reaching nondetectable levels by day 8. MMA was the first to reach a nondetectable level--at day 2. CONCLUSIONS: Acrylate/methacrylate allergens are lost rapidly from IQ™ chambers especially if stored at room temperature. Allergens in syringes remain above 80% of their initial concentrations for longer periods compared with IQ™ chambers. In syringes and IQ™ chambers there is a slower rate of decrease in concentration when the storage temperature is lower. Allergens should be stored refrigerated, replaced regularly, and freshly applied on to test patches on the day of use.

Serial dilation reduces graft slippage compared to extraction drilling in anterior cruciate ligament reconstruction: a randomized controlled trial using radiostereometric analysis.

PURPOSE: This study tested the hypothesis that serial dilation of the tibial tunnel could provide a stronger anchorage of the graft-fixation-device complex compared to traditional extraction drilling. METHODS: Forty patients (22 men and 18 women) undergoing ACL reconstruction were randomized to either extraction drilling (group ED) or compaction by serial dilation (group SD) of the tibial tunnel. Tantalum beads were placed in the tibia, femur, and in the hamstring graft. Radiostereometric analysis (RSA) was performed postoperatively and again after 6, 12, and 24 weeks. Migration of graft in the bone tunnels as well as knee laxity was assessed using RSA and a TELOS stress device. RESULTS: Six patients (three men and three women) were excluded during follow-up, which resulted in 17 patients in group ED [median age 30 years (range 20-50)] and 17 patients in group SD [median age 32 years (range 20-49)]. The mean migration of the graft in the tibial bone canal after 3 months was 1.3 (SD 0.6) mm in group ED and 0.8 (SD 0.5) mm in group SD (P = 0.02). The overall knee laxity after 3 months was 13.0 (SD 4.0) mm in group ED and 10.9 (SD 3.1) mm in group SD. CONCLUSION: This study found less slippage of the hamstring graft in the tibial bone canal in the serial dilated group compared to the extraction drilling group. The clinical relevance of the difference is unknown. No difference in stress radiographic knee laxity was found between the two groups.

The combination of radiostereometric analysis and the telos stress device results in poor precision for knee laxity measurements after anterior cruciate ligament reconstruction.

PURPOSE: Several devices for measuring knee laxity following anterior cruciate ligament ACL reconstruction exist, but the precision of the methods has never been optimal. Therefore, a new standardized protocol (NSP) was made, aiming at ensuring a reliable positioning of the Telos Stress Device (TSD) which theoretically could result in precise knee laxity measurements when using radiostereometric analysis (RSA) in combination with TSD. METHOD: The TSD was applied to the knee of 30 healthy persons, using both the NSP and the official company instructions. The position of the stress arms of the TSD was marked following each measurement. The reliability of each protocol was calculated as the difference in length between the first and second markings. The NSP for the TSD was then used in a clinical study. Thirty-five patients underwent ACL reconstruction. Double measurements of knee laxity by RSA were performed at a 3-month follow-up. RESULTS: Using the NSP for TSD positioning, the prediction interval at the marking sites ranged from ±0.4 to ±1.1 mm. Following the company instructions, the prediction interval ranged from ±0.8 to ±3.9 mm depending on marking site. Thus, the precision of positioning the stress arms of the TSD was improved at all marking sites using the NSP compared with the original company protocol. The double measurements of the knee laxity in the clinical study resulted in a mean difference of 0.0 mm and a prediction interval of ±5.2 mm. CONCLUSION: Even though the NSP improved the positioning of the TSD on patients' extremities, the combination of NSP-TSD and RSA was not able to provide acceptable knee laxity measurements in a clinical setting compared with published precision data for other devices on the market. Therefore, the Telos Stress Device is not recommendable for use in knee laxity measurements following ACL reconstruction.

Maternal plasma level of antimicrobial peptide LL37 is a major determinant factor of neonatal plasma LL37 level.

AIM: To determine cathelicidin antimicrobial peptide LL37subcellular distribution in cord neutrophils and normal plasma LL37 levels in mothers and neonates, relate them to delivery mode and relevant biochemical markers, including 25-OHvitamin D [25(OH)D] as this molecules increases cathelicidin gene expression. METHODS: A total of 115 infants were included, n = 68 with normal delivery and n = 47 with elective Caesarean section (C-section), a subset of these being 50 mother-infant pairs. Biomarkers were determined in maternal and cord blood. Subcellular peptide LL37 distribution was analysed with immunoelectron microscopy. RESULTS: Cord plasma LL37 levels were three-times higher after normal delivery compared with C-section. A highly significant correlation was observed between maternal and cord plasma LL37 levels, regardless of delivery mode. No relationship was found between LL37 and 25(OH)D levels. Neutrophils from cord blood after normal delivery contained 10-times more cytoplasmatic cathelicidin peptide compared with corresponding cells after C-section where a strict granular localization was found. CONCLUSION: These data are consistent with a placental transfer of LL37 and identifies maternal stores as the critical factor determining neonatal plasma LL37 level. An additional enhancement of neonatal cathelicidin mobilization and release is connected to normal delivery stress.

Serial dilation versus extraction drilling in anterior cruciate ligament reconstruction: a biomechanical study.

The hamstring tendon graft has become increasingly popular in anterior cruciate ligament reconstruction because of low donor-site morbidity. However, the tibial fixation is considered difficult, mainly because of low tibial mineral bone density. Therefore, we tested whether preparation of the tibial tunnel with compaction by serial dilation provided a stronger anchorage of the graft-fixation-device complex than does traditional extraction drilling of the tibial tunnel. In 20 bovine tibiae, the bone tunnels were created with either extraction drilling (group 1) or compaction by serial dilation (group 2). Twenty bovine digital extensor tendons were fixated in the bone tunnel with an Intrafix tibial fastener. The graft-fixation-device complexes were mounted in a hydraulic test machine. The fixation strength was evaluated after cyclic loading. The difference between the serial dilation group and the extraction drilling group ranged from a mean slippage of 0 mm at 70-220 N, to a mean slippage of 0.1 mm at 70-520 N. We found no significant difference in slippage of the graft-fixation-device complex after 1,600 cycles. This study failed to show a significant difference between compaction by serial dilation and extraction drilling of the tibia bone tunnel in anterior cruciate ligament reconstruction.

Occurrence of pathogens in raw and ready-to-eat meat and poultry products collected from the retail marketplace in Edmonton, Alberta, Canada.

A total of 800 meat and poultry products were purchased from the retail marketplace in Edmonton, Alberta, Canada. The products consisted of raw ground beef, chicken legs, pork chops, and ready-to-eat fermented sausage, roast beef, processed turkey breast, chicken wieners, and beef wieners. The samples were analyzed to determine the prevalence of Shiga toxin-producing Escherichia coli, Salmonella, Campylobacter spp., and Listeria monocytogenes. Shiga toxin-producing E. coli 022: H8 was found in one raw ground beef sample. Salmonella and Campylobacter were found in 30 and 62% of raw chicken legs, respectively. L. monocytogenes was found in 52% of raw ground beef, 34% of raw chicken legs, 24% of raw pork chops, 4% of fermented sausages, 3% of processed turkey breast, 5% of beef wieners, and 3% of chicken wieners. The occurrence of pathogens in this study is similar to that in retail products in many other international locales.

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.

BACKGROUND: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. METHODS: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. FINDINGS: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. CONCLUSION: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.

Seven years of treatment with risedronate in women with postmenopausal osteoporosis.

The effects of 7 years of risedronate treatment were evaluated in a second 2-year extension of a 3-year vertebral fracture study in women with osteoporosis. For the first 5 years of the study, women received risedronate 5 mg/day or placebo according to the original randomization, with maintenance of blinding. All the women who entered into the 6-7 years extension study received risedronate 5 mg/day. Endpoints included vertebral and nonvertebral fracture assessments, changes in biochemical markers of bone turnover, and bone mineral density (BMD) measurements. A total of 164 women (placebo/risedronate group, 81; risedronate group, 83) entered the 6-7 years extension study and 136 (83%) completed the study. Annualized incidence of new vertebral fractures during the 6-7 years was similar between the 2 treatment groups (3.8%). The incidence of vertebral fractures did not change in the 7-year risedronate group during the 6-7 years as compared to 4-5 years, while a significant reduction was observed in the placebo group that switched to risedronate treatment during years 6-7. The incidence of nonvertebral fractures was 7.4% and 6.0% in the placebo/risedronate and risedronate groups, respectively, during years 6-7. Urinary N-telopeptide decreased from baseline by 54% and 63% at 3 months and 7 years, respectively, in the risedronate group. The increases in BMD from baseline after 5 years of risedronate treatment were maintained or increased further during years 6-7; lumbar spine BMD after 5 and 7 years of risedronate treatment increased from baseline by 8.8% and 11.5%, respectively, for this extension study population. Risedronate was well tolerated and the occurrence of upper gastrointestinal adverse events was low. After 7 years of continuous risedronate treatment there were significant increases in BMD and decreases in bone turnover to within premenopausal levels and there was no indication of any loss of anti-fracture efficacy.

Bone status in rheumatoid arthritis assessed at peripheral sites by three different quantitative ultrasound devices.

Rheumatoid arthritis (RA) is characterized by periarticular and generalized loss of bone mass. Quantitative ultrasound (QUS) has been introduced as a method for the assessment of bone status and fracture risk. In this cross-sectional study bone status was assessed by QUS at different peripheral sites in 27 women with RA (mean disease duration 15 years) and in 36 healthy women matched for age, height and weight. Speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness of the calcaneus were assessed by a Lunar Achilles device. Amplitude-dependent SOS (Ad-SOS, m/s) of the second to fifth phalanx was measured by a DBM Sonic 1200, and SOS of the distal forearm and third phalanx was measured by a Omnisense multisite scanner. Bone mass (g/cm2 or g) of the hip, spine, distal forearm and total body was measured by dual-energy X-ray absorptiometry. QUS values were significantly reduced in RA at most sites ( p<0.005-0.001), but between-group differences were small, and large overlaps between the groups were noticed. After correction for bone mass, the observed differences remained statistically significant for the calcaneus and distal radius ( p<0.05). Independent associations between ultrasound measures and markers of disease activity were not demonstrated. In conclusion, bone status as assessed by QUS was compromised in RA, but whether ultrasound transmission may serve as a marker of disease progression and fracture risk in the individual patient remains to be clarified in prospective studies.

Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype: validation of an in vitro model for human bone marrow-derived primary osteoblasts.

In vitro models of bone cells are important for the study of bone biology, including the regulation of bone formation and resorption. In this study, we have validated an in vitro model of human osteoblastic cells obtained from bone marrow biopsies from healthy, young volunteers, aged 20-31 years. Osteoblast phenotypes were induced by either dexamethasone (Dex) or bone morphogenetic protein-2 (BMP-2). Bone marrow was obtained from biopsies at the posterior iliac spine. Cells were isolated by gradient centrifugation and grown to confluence. Cells were treated with 1 nM 1,25-dihydroxyvitamin D (vitamin D), 100 nM Dex, and/or 100 ng/ml BMP-2. The osteoblast phenotype was assessed as alkaline phosphatase (AP) activity/staining, production of osteocalcin and procollagen type 1 (P1NP), parathyroid hormone (PTH)-induced cyclic adenosine mono-phosphate (cAMP) production, and in vitro mineralization. AP activity was increased by Dex, but not by BMP-2 treatment. P1NP production was decreased after Dex treatment, while BMP-2 had no effect on P1NP levels. Osteocalcin production was low in cultures not stimulated with vitamin D. Dex or BMP-2 treatment alone did not affect the basic osteocalcin levels, but in combination with vitamin D, BMP-2 increased the osteocalcin production, while Dex treatment completely suppressed osteocalcin production. Further, PTH-induced cAMP production was greatly enhanced by Dex treatment, whereas BMP-2 did not affect cAMP production. Finally, in vitro mineralization was greatly enhanced in cultures enriched with either BMP-2 or Dex. Cell proliferation was only increased significantly by Dex treatment. In conclusion, the model described produces cells with an osteoblastic phenotype, and both Dex and BMP-2 can be used as osteoblast inducers. However, the two treatments produce osteoblastic cells with different phenotypic characteristics, and a selective activation of some of the most important genes and functions of the mature osteoblast can thus be performed in vitro.

Chemical analysis of monomers in epoxy resins based on bisphenols F and A.

Diglycidyl ether of bisphenol A (DGEBA) is the monomer and most important contact allergen in epoxy resin(s) based on bisphenol A (DGEBA-R). Both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) methods are available for the analysis of products containing DGEBA-R. With respect to detection and quantification, epoxy resins of the bisphenol F-type, i.e. epoxy resins containing the isomers of diglycidyl ethers of bisphenol F (DGEBF), are not as well investigated as DGEBA-R. The isomers of DGEBF are p,p'-DGEBF, o,p'-DGEBF and o,o'-DGEBF. Both p,p'-DGEBF and o,p'-DGEBF have been shown to be contact allergens in humans, and all 3 isomers are sensitizers in the guinea pig maximization test. We aimed (i). to develop HPLC methods for separation and purification of the individual DGEBF isomers, (ii). to detect and quantify the DGEBF isomers in epoxy resins of the bisphenol F-type and (iii). to evaluate and develop the TLC as a method for the detection of the DGEBF monomers. We found the total content of the DGEBF isomers in the investigated epoxy resins of the bisphenol F-type to vary from 17.0 to 81.7% w/w. Some of them also contained 0.1-2.4% w/w DGEBA. The HPLC method showed a sensitivity that was 2000-20 000x higher than that obtained with the TLC method for the DGEBF monomers. We concluded that the range of the DGEBF isomer content in epoxy resins of the bisphenol F-type is approximately the same as the monomer content in liquid compared to solid DGEBA-R. The relevance of contact allergy to DGEBA-R can remain unrecognized if the suspected product is an epoxy resin of the bisphenol F-type, which is analysed with the TLC method.

Convalescence after inguinal herniorrhaphy.

BACKGROUND: Convalescence after inguinal herniorrhaphy is usually 3-4 weeks and is an important outcome parameter of hernia surgery. The aim of this study was to describe in detail the consequences of recommending a short convalescence, including the risk of recurrence. METHODS: This was a multicentre prospective questionnaire study in patients given a recommendation for short convalescence (1 day); information was recorded on expected length of convalescence, employment status, physical workload and limiting factors. The reoperation rate in patients included in the study (group 1, n = 1059) was compared with that for comparable patients treated in participating departments but not part of the study group (group 2, n = 1306) and patients in the Danish Hernia Database (group 3, n = 8297). RESULTS: The median time off work was 7 days and the time interval before carrying out the most strenuous leisure activity was 14 days. After 30 days, 6.8 per cent of patients had not resumed employment and 17.0 per cent had not yet resumed strenuous leisure activity. Important reasons for not resuming work and leisure activity were pain (approximately 60 per cent of patients) and wound problems (approximately 20 per cent). The reoperation rate in group 1 at the median observation time was 0.7 per cent, which was no different to that in group 2 (1.6 per cent) (P = 0.186) or group 3 (1.4 per cent) (P = 0.092). CONCLUSION: Reduced convalescence after inguinal herniorrhaphy may be recommended without incurring a risk of higher reoperation rates. Pain and wound problems remain the most important factors for not resuming work or leisure activity as recommended.

Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience.

Limited placebo-controlled data are available to assess the long-term fracture efficacy of bisphosphonates. In order to determine the effects of 5 years of risedronate treatment, we extended a 3-year, placebo-controlled vertebral fracture study in osteoporotic women for an additional 2 years; women who entered the extension study continued to receive 5 mg risedronate or placebo according to the original randomization, with maintenance of blinding. End points included vertebral and nonvertebral fracture assessments, bone mineral density measurements, and changes in biochemical markers of bone turnover. A total of 265 women (placebo, 130; 5 mg risedronate, 135) entered the study extension and 220 (83%) completed the additional 2 years. Fracture results observed in the study extension were consistent with those observed in the first 3 years. The risk of new vertebral fractures was significantly reduced with risedronate treatment in years 4 and 5 by 59% (95% confidence interval, 19 to 79%, P = 0.01) compared with a 49% reduction in the first 3 years. Rapid and significant decreases in markers of bone turnover observed in the first 3 years were similarly maintained in the next 2 years of treatment. Increases in spine and hip bone mineral density that occurred in the risedronate group during the first 3 years were maintained or increased with a further 2 years of treatment. The mean increase from baseline in lumbar spine BMD over 5 years was 9.3% (P < 0.001). This study demonstrates that the effects of risedronate over 3 years on vertebral fracture and BMD are maintained with a further 2 years of treatment.