A randomized double-blind clinical trial on the treatment of knee osteoarthritis: the efficacy of polynucleotides compared to standard hyaluronian viscosupplementation.

BACKGROUND: This randomized, double-blind, parallel-group clinical trial aims to assess the equivalence of intra-articular polynucleotides compared to standard hyaluronic acid (HA) viscosupplementation in the treatment of knee osteoarthritis (OA). METHODS: 75 patients affected by knee OA were assessed for eligibility and 72 were enrolled and randomized to receive either intra-articular polynucleotides (Condrotide-36 patients) or hyaluronic acid (Hyalubrix-36 patients) at the Orthopedic Institute "Gaetano Pini" (Milan). All patients underwent three intra-articular injections of Condrotide or Hyalubrix with an interval of 1week. Participants, care givers, and investigators responsible for outcome assessment were all blinded to group assignment. Primary outcome measurements (KOOS and pain level (1) at rest, (2) at weight-bearing and (3) during physical activity) were evaluated at baseline (T0) and after one (T1), two (T2), six (T6), ten (T10), and 26 (T26)weeks. Secondary measurements included the determination of COMP serum levels at T0, T6 and T26. RESULTS: The reduction of pain and the increase of KOOS values from baseline were statistically significant for both treatments; nevertheless, for parameter KOOS "symptoms" the treatment with Condrotide showed significant results already after twoweeks (at T2 p=0.003) while the results obtained with Hyalubrix became significant only after 18 weeks (at T18 p=0.01). No significant adverse events were reported. CONCLUSIONS: Condrotide is as effective as Hyalubrix in reducing knee OA symptoms but showed an earlier response on pain reduction and can therefore be considered a valid alternative to the use of HA in the treatment of OA, avoiding the adverse events of NSAIDs and of intra-articular corticosteroids.

Revision surgery after failed ACL reconstruction with artificial ligaments: clinical, histologic and radiographic evaluation.

Synthetic ligament for anterior cruciate ligament (ACL) reconstruction has been widely used in the past. Long-term follow-up has demonstrated the unreliability of many of these devices in ACL surgery, and problems may arise for the surgeon approaching a patient with failed artificial ligament reconstruction. The aim of this study is to investigate whether revision surgery may improve clinical and radiographic outcomes in patients with failed synthetic ACL reconstruction. Fourteen patients who were treated in the past with ACL reconstruction with synthetic grafts underwent two-stage revision surgery. Follow-up averaged 4.2 years (range 2-6 years). Mean KOOS score was 75.8 (SD 10.2); IKDC score was B in two patients, C in nine and D in three. The improvement compared to preoperative status was not statistically significant (p > 0.05). Four patients were positive to Lachman and anterior drawer tests. Mean side-to-side anterior laxity averaged 4.3 mm (SD 1.2). Biopsy specimens documented the presence of foreign body granulomatous reaction, giant foreign body cells and polyethylene wear particles. The level of osteoarthritis worsened at follow-up compared to preoperative status (p < 0.05). ACL revision surgery with autografts in patients who underwent previous failed primary synthetic ligament reconstruction does not improve clinical outcomes and does not influence the natural history of knee osteoarthritis started from artificial ligament debris.

Magnesium and osteoporosis: current state of knowledge and future research directions.

A tight control of magnesium homeostasis seems to be crucial for bone health. On the basis of experimental and epidemiological studies, both low and high magnesium have harmful effects on the bones. Magnesium deficiency contributes to osteoporosis directly by acting on crystal formation and on bone cells and indirectly by impacting on the secretion and the activity of parathyroid hormone and by promoting low grade inflammation. Less is known about the mechanisms responsible for the mineralization defects observed when magnesium is elevated. Overall, controlling and maintaining magnesium homeostasis represents a helpful intervention to maintain bone integrity.

Single-bundle versus double-bundle anterior cruciate ligament reconstruction: assessment with vertical jump test.

PURPOSE: The study was designed to compare the clinical results of traditional single-bundle (SB) anterior cruciate ligament (ACL) reconstruction with those of double-bundle (DB) ACL reconstruction. METHODS: This study comprised 80 patients aged 18 to 45 years with an isolated ACL lesion: 40 patients underwent SB reconstruction, and 40 patients underwent DB reconstruction. Patients were assessed preoperatively with functional assessment including the International Knee Documentation Committee 2000 knee subjective form and visual analog scale, as well as physical examination (including the pivot-shift test and instrumented knee laxity measurement). Vertical jump assessment with the Optojump system (Microgate, Bolzano, Italy) has been introduced as a method to compare functional ability between the 2 surgical techniques. The same protocol was repeated 6 months, 12 months, and 2 years after surgery. RESULTS: No statistically significant differences were noted between the groups concerning subjective evaluation, thigh girth difference, mean visual analog scale score, range of motion, and Lachman and anterior drawer tests (P = not significant). A statistically higher number of patients in the SB group showed a positive pivot-shift test and a higher side-to-side difference when measured with the KT-1000 arthrometer (MEDmetric, San Diego, CA) than in the DB group (P < .001). Better mean jumping performance results were reported in the DB group compared with the SB group (P < .001). The average performance results for the injured limb were not significantly reduced compared with those of the uninjured limb in the DB group 12 months after surgery. At 2 years, a restoration of jumping ability in the ACL-reconstructed limb was achieved in both groups regardless of the technique used. CONCLUSIONS: DB ACL reconstruction has been proven to be superior to the SB technique with regard to knee stability and vertical jump performance. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Renal phosphate handling in Gitelman syndrome--the results of a case-control study.

BACKGROUND: Patients with Gitelman syndrome, a hereditary salt-wasting tubulopathy, have loss-of-function mutations in the SLC12A3 gene coding for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. Since the bulk of filtered phosphate is reabsorbed in the proximal tubule, renal phosphate wasting is considered exceptional in Gitelman syndrome. METHODS: We investigated the renal handling of inorganic phosphate in 12 unselected Italian patients affected with Gitelman syndrome (5 females and 7 males, aged 6.0-18 years, median age 12 years) and in 12 healthy subjects matched for gender and age (controls). The diagnosis of Gitelman syndrome among the patients had been made clinically and confirmed by molecular biology studies. RESULTS: The biochemical hallmarks of Gitelman syndrome, namely hypochloremia, hypokalemia, hypomagnesemia, increased urinary excretion of sodium, chloride, potassium and magnesium and reduced urinary excretion of calcium, were present in the 12 patients. In addition, both the plasma inorganic phosphate concentration (median and interquartile range: 1.28 [1.12-1.36] vs. 1.61 [1.51-1.66)] mmol/L) and the maximal tubular reabsorption of inorganic phosphate (1.08 [0.99-1.22] vs. 1.41 [1.38-1.47] mmol/L) were significantly lower (P < 0.001) in Gitelman patients than in control subjects. Circulating levels of 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin were similar in patients and controls. CONCLUSIONS: The results of our case-control study disclose a hitherto unrecognized tendency towards renal phosphate wasting with mild to moderate hypophosphatemia in Gitelman syndrome.

Pseudoaneurysm of the peroneal artery: an unusual complication of open docking site procedure in bone transport with Taylor Spatial Frame.

A docking site is the terminus of travel of two segments of bone that are gradually brought into approximation, normally associated with the bone transport technique in limb reconstruction. Traumatic pseudoaneurysm of the peroneal artery have been reported following different types of trauma and orthopedic procedures performed in the distal leg. One uncommon case of delayed peroneal artery pseudoaneurysm following surgical docking site is described. The diagnosis was supported by angiography. Embolization with coil was a successful method of treatment. We recommend a safe method of osteotomy with good bone exposure and adequate soft tissue protection.

Nitric oxide mediates low magnesium inhibition of osteoblast-like cell proliferation.

An adequate intake of magnesium (Mg) is important for bone cell activity and contributes to the prevention of osteoporosis. Because (a) Mg is mitogenic for osteoblasts and (b) reduction of osteoblast proliferation is detected in osteoporosis, we investigated the influence of different concentrations of extracellular Mg on osteoblast-like SaOS-2 cell behavior. We found that low Mg inhibited SaOS-2 cell proliferation by increasing the release of nitric oxide through the up-regulation of inducible nitric oxide synthase (iNOS). Indeed, both pharmacological inhibition with the iNOS inhibitor l-N(6)-(iminoethyl)-lysine-HCl and genetic silencing of iNOS by small interfering RNA restored the normal proliferation rate of the cells. Because a moderate induction of nitric oxide is sufficient to potentiate bone resorption and a relative deficiency in osteoblast proliferation can result in their inadequate activity, we conclude that maintaining Mg homeostasis is relevant to ensure osteoblast function and, therefore, to prevent osteoporosis.

Repair of osteochondral lesions in the knee by chondrocyte implantation using the MACI® technique.

PURPOSE: Matrix-associated autologous chondrocyte implantation (MACI(®)) is an innovative therapeutic option for the treatment of chondral and osteochondral lesions of the knee. METHODS: Fifty-three patients (54 knees) with MRI-documented osteochondral lesions were treated with MACI(®). A clinical assessment was performed using VAS score, Lysholm score, and Tegner activity level after an average follow-up of 27 months (SD: 2.3). MRI scans were performed 12 and 24 months after surgery. Seventeen patients were reevaluated after an average time of 59 months (SD: 6.7) after surgery. RESULTS: Two years after transplantation, Lysholm score increased from a preoperative mean value of 70 (SD: 13.4) to 95 (SD: 6.4); the average VAS score decreased from a preoperative value of 5.2 (SD: 2.9) to 1.9 (SD: 2.1). The difference with respect to Tegner activity level did not prove to be significant. At 1 year, MRI scans documented a completely repaired defect with slight subchondral bone abnormality in 38 cases (70%). Satisfying outcomes were confirmed on 17 patients who were reevaluated 5 years after surgery. At 60 months, MRI scans showed complete integration with the surrounding native cartilage without any sign of detachment or bone marrow edema in 15 cases (88%). CONCLUSION: The MACI(®) technique is a safe and clinically effective procedure, which has been proven to be valuable in treating osteochondral defects even over the long term. LEVEL OF EVIDENCE: Therapeutic study, Level III-2 (retrospective cohort study).

Anterior cruciate ligament recostruction with bone-patellar tendon-bone autograft in Tanner 3 stage patients with open physes.

Ten skeletally immature patients were treated with an arthroscopic-assisted anterior cruciate ligament reconstruction with bone-patellar tendon bone autograft (compass, 50-55°; holes, 7-9 mm). Radiological assessments (standard radiograph), Orthopädische Arbeitsgruppe Knie (OAK) score and KT 1000, were conducted on all patients, 1 year after surgery. Skeletal maturity had been reached by all patients and no complications were observed. All patients returned to their preinjury sport level. Drilling more vertical tunnels when bone-tendon-bone autograft was chosen to avoid partial epiphysiodesis and offers good functional and isometric results.

Supracondylar humerus fractures in children: a comparison of experiences.

The most common elbow lesions found in pediatric practice are supracondylar fractures. We compared two groups of 34 patients each with a supracondylar humerus fracture grade III (Gartland classification). The first group was treated with percutaneous pinning with Kirschner wires, with patients in a supine position, sometimes preceded by transkeletal traction. The second group was treated with percutaneous pinning with Kirschner wires, with patients in a prone position, within 6 h of the trauma. No statistically significant differences with regard to clinical outcomes and neurovascular complications were revealed in the comparison. Therefore, we can state that both treatment techniques used are valid.

Achondroplasia in female twins: surgical indications.

Although in literature achondroplasia has been described profusely, reports on achondroplastic twins are limited. We present two cases of monozygotic female twins with achondroplasia, who underwent limb-lengthening surgical procedure with external fixation in the following five steps: tibia, femur, tibia; femur, homer. Both the cases presented a good limb length and an optimal correction of associated deformities after the treatment, fulfilling the indications. Surgical indications were mostly led by the axial deviations of the lower limbs, and the timing of the limb-lengthening procedures has been the same in both couples showing the importance of this aspect.

The external fixation in the treatment of humeral diaphyseal fractures: outcomes of 84 cases.

We retrospectively review 84 cases of diaphyseal humeral fractures (24 type A, 38 type B, 22 type C of the AO/OTA classification) treated with external fixation (Hoffmann II frame) between 1995 and 2007. Six of these fractures were complicated with radial nerve palsy. Four cases were open fractures. All reductions were achieved closely or through minimal open approaches. All fractures achieved consolidation with an average of 95 days (range 58-140). The six radial nerve palsies had complete spontaneous recovery. According to the Constant score excellent shoulder function was recorded in 54.6% of the cases, good results in 25%, fair in 13.6% and poor in 6.8%. The elbow function according to the Mayo elbow performance index was excellent in 81.8% of cases, good in 13.6%, fair in 2.3%, and poor in 2.3%. We observed superficial pin tract infections in 12% of the patients. There was no cases of deep infection. External fixation of humeral diaphyseal fractures as recorded in this case series, represents a management option, which allows straightforward fracture reduction and adequate stability, with a short operative time, excellent consolidation rate and good functional results with no major complications secondary to this type of surgery.

Versatility of Taylor Spatial Frame in Gustilo-Anderson III C femoral fractures: report of three cases.

Taylor Spatial Frame (TSF) combines a multiplanar external fixator and software accuracy for reduction of acute long-bone fractures. The frame gives stability, soft-tissue preservation, adjustability and functionality allowing bone to realize its full osteogenic potential. Three patients with multiple injuries and femoral Gustilo-Anderson type III C have been treated in our center. Initial surgery was performed within 6 h of injury with help of vascular surgeon. We used TSF as definitive fixation method. The results were assessed using the functional and radiological scoring system described by Paley and Maar. Fracture union occurred in all limbs and average fixation time was 151.6 days. All three patients had excellent outcome in terms of bony and functional ASAMI criteria. The TSF is a valuable tool. It is a definitive method of femoral Gustilo-Anderson type III C fracture care using external fixation with several advantages over previously used devices.

Anterior cruciate ligament reconstruction with synthetic grafts. A review of literature.

Anterior cruciate ligament (ACL) rupture, one of the most common knee injuries in sports, results in anteroposterior laxity, which often leads to an unstable knee. Traditional ACL reconstruction is performed with autograft; disadvantages of this technique are donor site morbidity and a long rehabilitation period. In the 1980s, artificial ligaments became an attractive alternative to biological grafts. The initial enthusiasm surrounding their introduction stemmed from their lack of donor morbidity, their abundant supply and significant strength, immediate loading and reduced postoperative rehabilitation. Synthetic grafts made of different materials such as carbon fibers, polypropylene, Dacron and polyester have been utilised either as a prosthesis or as an augmentation for a biological ACL graft substitute. Nevertheless, every material presented serious drawbacks: cross-infections, immunological responses, breakage, debris dispersion leading to synovitis, chronic effusions, recurrent instability and knee osteoarthritis. Recently, a resurgence of interest in the use of synthetic prostheses has occurred and studies regarding new artificial grafts have been reported. Although many experimental studies have been made and much effort has been put forth, currently no ideal prosthesis mimicking natural human tissue has been found.

Synthetic grafts for anterior cruciate ligament rupture: 19-year outcome study.

Artificial ligaments for ACL replacement have been widely used in the 1980s and early 1990s in orthopaedic surgery. Synthetic devices have been utilized either as a prosthetic material or as an augmentation for a biological ACL graft substitute. The initial enthusiasm surrounding the introduction of synthetic graft materials stemmed from their lack of donor morbidity, their abundant supply and significant strength of these devices. The disadvantages in long-term follow-up were found to be cross-infections, immunological responses, tunnels osteolysis, femural and tibial fractures, foreign-body synovitis and knee osteoarthritis. A total of 126 patients were treated with artificial ACL substitution with polyethylene terephthalate (PET) synthetic ligaments in our Institute between 1986 and 1990. Of the original group, 51 sportsmen aged 15 to 40 were followed-up at a mean of 19years (range 17.5 to 20.6years) after surgery. Assessment was made with KOOS and IKDC score, Tegner activity scale, clinical examination, KT-1000 arthrometer, and X-ray evaluation. Of the 51 patients followed-up, 27.5% were found to have ruptured their PET ligaments and 100% presented degenerative osteoarthritis at the X-ray evaluation according to Ahlbäck radiological classification of arthritis. The objective evaluation showed functional impairment in 29.4% with an average reduction of 3 points in the Tegner activity scale. The osteoarthritis observed in all patients prompted us to avoid the diffusion of this surgical technique. Although in theory well-conceived, studies have yet to substantiate the function of these augmentation devices or to show clinical better results than those achieved with isolated autograft or allograft ACL substitutes.

Stress fractures of the base of the metatarsal bones in young trainee ballet dancers.

Classical ballet is an art form requiring extraordinary physical activity, characterised by rigorous training. These can lead to many overuse injuries arising from repetitive minor trauma. The purpose of this paper is to report our experience in the diagnosis and treatment of stress fractures at the base of the second and third metatarsal bones in young ballet dancers. We considered 150 trainee ballet dancers from the Ballet Schools of "Teatro Alla Scala" of Milan from 2005 to 2007. Nineteen of them presented with stress fractures of the base of the metatarsal bones. We treated 18 dancers with external shockwave therapy (ESWT) and one with pulsed electromagnetic fields (EMF) and low-intensity ultrasound (US); all patients were recommended rest. In all cases good results were obtained. The best approach to metatarsal stress fractures is to diagnose them early through clinical examination and then through X-ray and MRI. ESWT gave good results, with a relatively short time of rest from the patients' activities and a return to dancing without pain.

Increased p21 expression in chondrocytes of achondroplasic children independently from the presence of the G380R FGFR3 mutation.

BACKGROUND: Achondroplasia (ACH) represents the major cause of dwarfism and is due to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. The cellular mechanisms involved in the reduced growth have been mainly described for in vitro or in vivo models, but few data have been obtained for humans. METHODS: Thirteen children with ACH were enrolled in the study; the presence of FGFR3 mutations was determined by restriction fragment length polymorphism analysis and sequencing, whereas protein expression in cartilage biopsy was assessed by immunohistochemistry. RESULTS: Chondrocytes in cartilage biopsies of ACH children were characterized by the presence of growth arrest mediated by STAT activation (both STAT1 and STAT5) and increased expression of p21 and cyclin D1, whereas no expression of either p53 or cyclin D3 could be detected. This mechanism was present in ACH children carrying the G380R mutation but also in a patient in whom no mutation could be detected in the entire coding region of the FGFR3 gene. CONCLUSIONS: These data thus demonstrate the presence of a common final mechanism involving p21 and possibly leading to a block in chondrocyte proliferation.

Clinical evaluation and treatment of posterior impingement in dancers.

Os trigonum impingement is a frequent cause of posterior ankle pain in ballet dancers because they need extreme plantar flexion during the execution of relevé in demipointe and en pointe positions. Clinical examination and standard and modified x-rays should be carried out to clearly identify the site and entity of the impingement. If a posterior impingement is clinically diagnosed, standard and modified magnetic resonance imaging should be also performed. From September 2005 to September 2006, we considered 186 young trainee ballet dancers. Twelve suffered from posterior ankle pain, and six of these had os trigona. We treated all the ballet dancers nonoperatively, and nine of them had good results. Conservative treatment failed in only three cases after 1-4 mos of physical and medical therapies, and, in these cases, good results were obtained through surgical excision of the accessory ossicle. Modified x-ray and magnetic resonance imaging help to determine the site and entity of the posterior impingement. If this is properly diagnosed, good results can be obtained through a nonoperative approach in a majority of cases.

Osteogenic differentiation of human adipose-derived stem cells: comparison of two different inductive media.

Human mesenchymal stem cells (MSCs) have the potential to differentiate into cells of connective tissue lineages, including bone, cartilage, fat, muscle and also neurons. In our study we have examined the phenotypic profile of human adipose tissue-derived stem cells (hASCs) and compared different osteogenic-inductive media to assess hASC differentiation. Cells were enzymatically isolated from adipose tissues derived by liposuction from several adult human donors, purified and then expanded in culture. We obtained an abundant yield of hASCs with a constant proliferative trend, a doubling time of about 68 h and a mild variable clonogenic capacity. At passage 4, hASCs expressed MSC-related cell surface antigens (CD13, CD105, CD54, CD90, CD44), and subsequently hASCs were induced to differentiate into the osteogenic lineage for at least 3 weeks of culture in two distinct media, OM1 and OM2, differing in dexamethasone and ascorbic acid concentrations. Osteogenic differentiation of OM1- and OM2-cultured cells was assessed by evaluating cell morphology, osteopontin expression, alkaline phosphatase activity and calcium deposition. OM2 medium showed a higher osteogenic potential than OM1, as assessed by increased levels of calcium deposition, alkaline phospatase activity and osteopontin expression in comparison with OM1-differentiated cells. We conclude that hASCs efficiently differentiate into osteogenic lineage, particularly when cultured in inductive medium supplemented with 10 nM dexamethasone and 150 microM ascorbic acid.