Functional recovery after muscle sparing total hip arthroplasty in comparison to classic lateral approach - A three years follow-up study.

BACKGROUND: The muscle sparing total hip arthroplasty had generated a distinguishable interest, in both the patients and the surgeons, but its benefits are still often questioned. The main idea of this study was to compare the functional clinical outcome of the patients operated by the anterolateral approach with a muscle-sparing technique (modified Watson-Jones approach), and the patients operated by modified direct lateral approach without the muscle-sparing technique (Bauer/Hardinge approach). METHODS: The patients (N = 130) were divided into two groups: 68 in a standard method group (STAND) and 62 patients in a muscle sparing surgery group (MSS). The hip flexibility, mobility, the strength of the hip abduction, the pain scale, Harris hip scores, the duration of the hospital stay and the overall satisfaction were measured seven days, three months, one year and three years (in 80 patients) after the surgery. There were no differences in any of the parameters between the groups prior to the procedure. RESULTS: The statistically significant differences in first three follow-ups (up to one year) were determined between the groups in passive and active hip flexion ability but the hip abduction strength, which is a crucial parameter for functional recovery, and 50 m walk test remained better in MSS group even after three years. Patients, who underwent MSS suffered also less pain, stayed in hospital shorter and were more satisfied with the operation outcome. CONCLUSIONS: The functional recovery in patients treated with muscle sparing method was faster than in patients operated with conventional lateral approach. Based on the results, we could recommend anterolateral muscle sparing approach for a total hip replacement for its faster and fuller functional recovery.

Susceptibility to large-joint osteoarthritis (hip and knee) is associated with BAG6 rs3117582 SNP and the VNTR polymorphism in the second exon of the FAM46A gene on chromosome 6.

Family with sequence similarity 46, member A (FAM46A) gene VNTR and BCL2-Associated Athanogene 6 (BAG6) gene rs3117582 polymorphisms were genotyped in a case-control study with 474 large-joint (hip and knee) osteoarthritis (OA) patients and 568 controls in Croatian population by candidate-gene approach for association with OA. We found that BAG6 rs3117582 SNP genotypes were associated with protection (major allele homozygote) and susceptibility (major-minor allele heterozygote) to OA. BAG6 rs3117582 major allele (A) was associated with reduced risk to OA while the minor allele (C) was associated with increased risk to OA. We identified 6 alleles harboring 2 to 7 repeats making 20 genotypes for FAM46A. A rare FAM46A VNTR genotype comprising VNTR alleles with four and seven repeats (c/f) was associated with increased OA risk in both genders. The genotype with four and six repeats (c/e) was also associated with increased risk to OA in males. A polymorphic FAM46A allele with six repeats (e) was associated with reduced risk to OA in females. Our results suggest association between the FAM46A gene, BAG6 gene and OA in Croatian population, respectively. This is the first study to show associations between these genetic loci and OA.

Emerging pathways and promising agents with possible disease modifying effect in osteoarthritis treatment.

Current modalities for osteoarthritis (OA) treatment are partially safe and effective, and only alleviate the disease symptomatology, but do not modify progression and structural changes of the disease. At present, there is no approved safe and effective disease-modifying OA drug (DMOAD) for clinical application. Therefore, there is an urgent need for discovery of DMOAD in order to treat OA. Hopefully, the new DMOADs would also pave the way for better understanding of OA pathophysiology. Given the fact that there is still no adequate remedy that will modify the course of OA, a number of emerging pathways and promising agents with possible DMOAD effect arise targeting cartilage, synovial membrane, and subchondral bone, or using stem cell therapy, and gene therapy. All these methodologies will be described and discussed in this review. Available treatment methodologies for OA are unsatisfactory. In order to properly treat OA in the future, more realistic option will be the use of multiple drugs, instead of single therapy, which is likely to be ineffective in the treatment of such heterogeneous diseases. Which combination of drugs with DMOAD effect will be suitable for the treatment of OA, remains to be determined in future studies.

Levels of dipeptidyl peptidase IV/CD26 substrates neuropeptide Y and vasoactive intestinal peptide in rheumatoid arthritis patients.

Neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) have their biological half-lives controlled by dipeptidyl peptidase IV (DPP IV/CD26). Several lines of evidence suggest the involvement of NPY in the regulation of rheumatoid arthritis (RA), and VIP has already been identified as a potent anti-inflammatory factor that reduces joint inflammation. The role of DPP IV/CD26 in the pathogenesis of RA has been indicated, but its mediator actions involving NPY and VIP have not been well investigated, so the aim of this study was to find an association between NPY, VIP, and DPP IV/CD26 in RA patients. Assessment of NPY, VIP, DPP IV/CD26 as well as some other inflammatory markers was carried out in 20 RA patients being treated with different types of drugs. Control group consisted of 18 osteoarthritis patients. Synovial fluid and serum content of investigated molecules was determined by ELISA and DPP IV/CD26 activity was measured spectrophotometrically. Immunodetection showed elevated levels of NPY and VIP in RA patients, with a significant increase in synovial fluid, while concentration and activity of DPP IV/CD26 were significantly decreased in both synovial fluid and serum. Positive correlations between serum DPP IV/CD26 concentration and activity (R = 0.6961), as well as between serum and synovial fluid concentration of VIP (R = 0.7029) were found. In RA group, NPY, VIP, and DPP IV/CD26 concentrations were not affected by the administration of drugs. The results of this study indicate a connection between elevated concentration of NPY and VIP and decreased DPP IV/CD26 activity and concentration, suggesting a potential role of these molecules in the immunomodulation of RA.

Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review.

Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians' complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1ß, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the above mentioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.

IL1B -511(G>A) and IL1RN (VNTR) allelic polymorphisms and susceptibility to knee osteoarthritis in Croatian population.

Osteoarthritis (OA) is a frequent, destructive joint disease, with debilitating impact on a society regarding medical, social, and economic issues. Although causes of primary OA were still not fully elucidated, evidence points to complex genetic risk that varies among different population groups, including the interleukin-1 (IL-1) gene cluster. Here, we sought to determine allelic and genotypic frequencies of the IL-1ß (IL1B) and the IL-1 receptor antagonist (IL1RN) genes using single nucleotide polymorphism (SNP) at -511(G>A; rs16944) and the variable number tandem repeat (VNTR) in a case-control study with 238 patients that have undergone total or partial knee replacement and 495 healthy blood donors as controls in Croatia. The alleles of the IL1B gene at -511G>A were detected by Taqman real-time polymerase chain reaction (PCR) method and IL1RN VNTR by amplifying its DNA by PCR. The genotypes 1-2/1-2 and 2-1/2-2 at IL1B G -511A-IL1RN (VNTR) showed trends for association with the occurrence of the knee OA in this population (P = 0.09; P = 0.07, respectively). Furthermore, neither the alleles nor the haplotypes were found associated with the predisposition to knee OA. Our findings suggest that knee OA might have a different genetic risk in this Caucasian population. We did not found significant association of the IL1 gene cluster (IL1B-IL1RN) with severe knee OA. However, we found that two genotypes (1-2/1-2 and 2-1/2-2) show a trend toward association with susceptibility to disease.

The "cello technique": a new technique for ultrasound-assisted calcaneoplasty.

The "cello technique" is a new calcaneoplasty technique for the treatment of Haglund disease. It is an ultrasound-assisted technique for resection of the posterosuperior part of the calcaneus. It is possible to resect the posterosuperior part of the calcaneus under direct ultrasound control with the patient in the prone position, with a dorsally positioned ultrasound probe, in line with the Achilles tendon fibers (sagittal line), and with the abrader in the posteromedial working portal. We describe in detail the technique for this new procedure in foot and ankle surgery. This innovative technique offers the possibility of expanding the indications for ultrasound-guided surgery in other fields of orthopaedic surgery.

Hip osteoarthritis susceptibility is associated with IL1B -511(G>A) and IL1 RN (VNTR) genotypic polymorphisms in Croatian Caucasian population.

Among the predisposing factors to osteoarthritis (OA), a frequent destructive joint disease, is the complex genetic heritage including the interleukin-1 family members like the IL1ß (IL1B) and the IL1 receptor antagonist (IL1RN) genes. The aim of this study was to investigate allelic and genotypic frequencies of the IL1B gene single nucleotide polymorphism (SNP) at -511(G>A) and the variable number tandem repeat (VNTR) in the IL1RN gene in a Croatian Caucasian population of hip OA (HOA) cases and healthy controls. A total of 259 HOA patients with total hip replacement (THR) and 518 healthy blood donors as controls were genotyped for IL1B gene SNP -511(G>A) and the VNTR in the IL1RN gene associated with HOA. The genotype G/A (1/2) at IL1B was significantly associated with the protection of the HOA (p < 0.036, OR = 0.72, 95% CI = 0.52-0.99). The genotype G/G (1/1) had only a trend towards the susceptibility (p = 0.053, OR = 1.35, 95% CI = 0.98-1.86) to disease. None of the haplotypes IL1B -511(G>A) and IL1RN (VNTR) were found associated with the HOA. The haplotype 1-2 at these loci had only a trend to susceptibility (p = 0.065). Haplotype 1-3 had a significant male bias in diseased. Furthermore, genotype comprising 2-1/2-2 haplotypes was found significantly associated with predisposition to HOA (p = 0.027, OR = 2.23, 95% CI = 1.03-4.88), whereas genotype 1-1/2-2 with protection to disease (p = 0.028, OR = 0.65, 95% CI = 0.43-0.97). Our findings suggest that HOA in Croatian population might have a different genetic risk regarding the IL1 locus than has been reported for other Caucasian populations previously.

Long-term results of anterior cruciate ligament reconstruction: a comparison with non-operative treatment with a follow-up of 17-20 years.

PURPOSE: The aim of our study was to review the clinical and radiological outcome of patients who had undergone anterior cruciate ligament (ACL) reconstruction in comparison to a group of non-operatively treated patients. METHODS: In a retrospective study we compared ACL reconstruction using a bone-patellar tendon-bone graft with a non-operatively treated group of patients 17-20 years later. Fifty-four patients that met the inclusion criteria, with arthroscopically proven ACL rupture, were treated between 1989 and 1991. Thirty-three patients underwent ACL reconstruction, forming group one. Eighteen non-reconstructed patients continued with rehabilitation and modification of activities (group two). The International Knee Documentation Committee (IKDC) subjective and objective evaluation forms and the Lysholm and Tegner scale were used to assess the knees at follow-up. Radiographic assessment was performed using the IKDC grading scale. RESULTS: Follow-up results showed that 83% of reconstructed patients had stable knees and normal or nearly normal IKDC grade. Patients in the non-reconstructed group had unstable knees with 84% having abnormal or severe laxity. The subjective IKDC score was significantly in favour of group one: 83.15 compared to 64.6 in group two. The Lysholm and Tegner score was also significantly better in group one. Conservatively treated patients all had unstable knees and worse scores. The rate of osteoarthritis showed more severe changes in non-reconstructed patients with additional meniscus injury. CONCLUSIONS: We can conclude that 94% of patients who underwent ACL reconstruction had stable knees after 15-20 years and there was a significantly lower percentage of osteoarthritis in comparison to conservatively treated patients.

Microfracture technique in combination with intraarticular hyaluronic acid injection in articular cartilage defect regeneration in rabbit model.

Although articular hyaline cartilage typically has low potential for regeneration, numerous methods and techniques have been proposed to induce the reparation process. In our work, we used microfracture techniques in combination with intraarticular application of hyaluronic acid in rabbit knee articular cartilage defect. In comparison with the control group, after 6 and 10 weeks we observed a higher potential of healing in the experimental group, with thicker and more organized repair tissue filling the defect. In conclusion, a combination of the microfracture technique and application of hyaluronic acid might be potentially beneficial in inducing articular cartilage defect reparation.

Age-related and gender-related differences between human vertebral and iliac crest bone--a histomorphometric study on the population of the Mediterranean Coast of Croatia.

In this study, osseous tissue was examined in normal adult population that has inhabited areas by the Croatian Adriatic Sea. The most of such studies have shown that women are prone to lose bone connectedness, while men are predisposed to be a stronger constitution and they start with greater bone mass, though. Bone samples from two different anatomic sites were analyzed. The crista iliaca and the lumbar vertebra represent functionally different organs too. We wanted to consider weather the same age- and gender-related changes affect these two organs due to normal aging. Static histomorphometry was used to quantify involution changes in the trabecular bone. Results showed that involution process more severely affects women than men. Age-related structural changes were more prominent in lumbar vertebra than in iliac crest bone. Severe structural changes in lumbar vertebra could subsequently lead to a dysfunctional and deformed vertebral column. Therefore, iliac crest bone biopsies could hardly explain involution process that affects lumbar spine.

Bone morphogenetic protein-7 (osteogenic protein-1) promotes tendon graft integration in anterior cruciate ligament reconstruction in sheep.

BACKGROUND: Bone morphogenetic proteins induce new bone both in patients with bone defects and at extraskeletal sites in animals. After anterior cruciate ligament rupture, tendon graft fixation into a bone tunnel is a widely used method for anterior cruciate ligament reconstruction. HYPOTHESIS: Bone morphogenetic protein-7 applied to the bone-tendon interface enables better integration of a free tendon graft into the surrounding bone. STUDY DESIGN: Controlled laboratory study. METHODS: The anterior cruciate ligament was reconstructed using a free tendon graft in the right rear knees of 30 one-year-old male sheep. Recombinant human bone morphogenetic protein-7 (25 microg) was applied randomly to the bone-tendon interface in 15 animals, and a vehicle was applied in 15 control animals. At 3 weeks, 10 animals from each group were sacrificed, and the remaining sheep were sacrificed at 6 weeks after surgery. Subsequently, histologic analysis and mechanical testing were performed. In another group of 20 sheep, the same procedure was used and mechanical testing was performed after 3 weeks. RESULTS: More new bone was formed at the bone-tendon interface in the knees treated with bone morphogenetic protein-7 as compared histologically with similar areas in control animals, creating areas of dense trabecular network with significantly greater invasion of the tendon fibrous tissue into the bone marrow space. Mechanical testing showed greater strain resistance to force (368 N) in the knees treated with bone morphogenetic protein-7 than in control specimens (214 N). There was no difference between mechanical testing of samples from 3 and 6 weeks after surgery. CONCLUSION: Bone morphogenetic protein-7 promotes complete tendon graft integration into the newly formed surrounding trabecular bone in the reconstruction of the anterior cruciate ligament. CLINICAL RELEVANCE: Bone morphogenetic protein-7 in tendon graft integration might be successfully used in reconstructive surgery of ligaments.

Study of the healing process after transplantation of pasteurized bone grafts in rabbits.

Different bone allografts (pasteurized, autoclaved, and frozen) were compared based on their osteoinductive properties. Our primary purpose was to examine the biologic qualities of pasteurized allografts, as pasteurization inactivates most viruses transmitted by transplantation. Frozen, pasteurized, and autoclaved allografts were packed into a standard defect of rabbit ulna. The animals were sacrificed at 2 and 4 weeks after surgery. The parts of bones with experimental defects were explored en bloc, and a roentgenogram was carried out. Ulna bone samples were then embedded in methyl-methacrylate. Roentgenograms showed that after 2 weeks, calluses were well-formed, but irregular in shape in all 3 types of allografts. After 4 weeks, the calluses were regular in shape in all but the autoclaved grafts. After 2 weeks, the healing processes had begun in the frozen and pasteurized grafts, with the reaching approximately the same stage, while in the autoclaved grafts these processes were not seen and the bone particles were surrounded by connective tissue without any changes. After 4 weeks, osteoinductive processes were very strong, with the first signs of complete bone remodeling at the bone edges of the defect in pasteurized and frozen allografts. The osteoinductive values of these 2 types were very high and similar. Autoclaved allografts, on the other hand, had very low osteoinductive values, as they were still at the very beginning of the healing process. Histomorphometric analysis revealed a significant difference in both newly formed osteoid thickness and osteoblast number per microm of bone surface in all experimental groups (P < 0.005). Values of osteoid thickness and osteoblast number were significantly higher in both frozen and pasteurized grafts when compared with the autoclaved ones (P < 0.005). Osteogenic properties of pasteurized bone allografts were preserved, and the allografts have been gradually replaced with newly formed bone. As such, pasteurized bone grafts from a bone bank have approximately the same biologic validity as frozen grafts, while autoclaved grafts impair bone healing.