Paolo Ferrata

Osteogenic growth peptide effects on primary human osteoblast cultures: Potential relevance for the treatment of glucocorticoid‐induced osteoporosis

The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vivo studies on animals have demonstrated that the synthetic peptide OGP (10–14), reproducing the OGP C‐terminal active portion [H‐Tyr‐Gly‐Phe‐Gly‐Gly‐OH] increases bone formation, trabecular bone density and fracture healing. In vitro studies performed on cellular systems based on osteoblastic‐like cell lines or mouse stromal cells, have demonstrated that OGP (10–14) increases osteoblast proliferation, alkaline phosphatase (ALKP) activity and matrix synthesis and mineralization. In view of a potential application of OGP (10–14) in clinical therapy, we have tested different concentrations of OGP (10–14) on primary human osteoblast (hOB) cultures. We have observed significant increases of hOB proliferation (+35%), ALKP activity (+60%), osteocalcin secretion (+50%), and mineralized nodules formation (+49%). Our experimental model based on mature hOBs was used to investigate if OGP (10–14) could prevent the effects on bone loss induced by sustained glucocorticoid (GC) treatments. A strong decrease in bone formation has been attributed to the effects of GCs on osteoblastogenesis and osteocyte apoptosis, while an increase in bone resorption was due to a transient osteoblastic stimulation, mediated by the OPG/RANKL/RANK system, of osteoclasts recruitment and activation. Moreover, GCs act on hOBs decreasing the release of osteoprotegerin (OPG) a regulator of the RANKL/RANK interaction. Here, we provide evidences that OGP (10–14) inhibits hOB apoptosis induced by an excess of dexamethasone (−48% of apoptotic cells). Furthermore, we show that OGP (10–14) can increase OPG secretion (+20%) and can restore the altered expression of OPG induced by GCs to physiological levels. Our results support the employment of OGP (10–14) in clinical trials addressed to the treatment of different bone remodeling alterations including the GC‐induced osteoporosis. J. Cell. Biochem. 98: 1007–1020, 2006.

Serum C-Reactive Protein and Procalcitonin Kinetics in Patients Undergoing Elective Total Hip Arthroplasty

Background. The sensitivity and the specificity of different methods to detect periprosthetic infection have been questioned. The current study aimed to investigate the kinetics of C-reactive protein (CRP) and procalcitonin (PCT) in patients undergoing uncomplicated elective total hip arthroplasty (THA), to provide a better interpretation of their levels in noninfectious inflammatory reaction. Methods. A total of 51 patients were included. Serum CRP and PCT concentrations were obtained before surgery, on the 1st, 3rd, and 7th postoperative days and after discharge on the 14th and 30th days and at 2 years. Results. Both markers were confirmed to increase after surgery. The serum CRP showed a marked increase on the 3rd postoperative day while the peak of serum PCT was earlier, even if much lower, on the first day. Then, they declined slowly approaching the baseline values by the second postoperative week. PCT mean values never exceed concentrations typically related to bacterial infections. Conclusions. CRP is very sensitive to inflammation. It could be the routine screening test in the follow-up of THA orthopaedic patients, but it should be complemented by PCT when there is the clinical suspicion of periprosthetic infection.

Rosuvastatin inhibits spontaneous and IL-1β-induced interleukin-6 production from human cultured osteoblastic cells.

OBJECTIVE Experimental and clinical data suggest that statins may protect bone by inhibiting bone resorption and/or stimulating bone formation. Interleukin-6 (IL-6) is produced by osteoblasts, and potently stimulates osteoclast activation playing a key role in normal bone resorption as well as in post-menopausal and inflammation-driven osteoporosis. Although statins inhibit IL-6 production from different cell types, currently no data exist on osteoblasts. The aim of the study was to evaluate the effect of rosuvastatin on IL-6 production by human osteoblasts. METHODS Osteoblasts from osteoarthritic patients were incubated with rosuvastatin (0.1-10 μmol/L)±IL-1β, and IL-6 production was evaluated as cytokine concentration in the culture medium (ELISA), as well as mRNA expression in the cells (qPCR). Putative intracellular mechanisms of the drug, such as blocking HMG-CoA-reductase, and interference in the prenylation process were investigated by the addition of mevalonate and isoprenoids. The effect of rosuvastatin±IL-1β on the anti-resorptive molecule osteoprotegerin (OPG) was also assessed (ELISA). RESULTS Rosuvastatin significantly reduced IL-6 levels in the osteoblast culture medium, both in unstimulated and IL-1β-stimulated cells. This effect was reversed by mevalonate or geranylgeraniol, but not farnesol. Moreover, the drug decreased both spontaneous and IL-1β-induced IL-6 mRNA expression in osteoblasts. Conversely, rosuvastatin did not affect OPG levels in the culture medium. CONCLUSION Our results show that rosuvastatin decreases IL-6 production by osteoblasts, thereby suggesting a possible inhibiting activity on osteoclast function in an indirect way. These data may provide further rationale for employing rosuvastatin to beneficially affect bone metabolism in post-menopausal women and possibly in inflammation-driven osteoporosis.

Total hip arthroplasty with a ribbed anatomic HA coated stem

In total hip arthroplasty, a straight stem seems to provide better results than an anatomic one. A new generation of anatomic stems is under evaluation, so the follow-up is still short and cannot compare with studies of straight stems. The clinical and radiographic results of 176 patients who underwent 189 primary total hip arthroplasties using an anatomic, collared, proximally hydroxyapatite (HA)-coated femoral component were prospectively determined from 1 to 6 years follow-up. The stem is ribbed in the metaphyseal region, allowing to decrease the elasticity modulus, to augment the surface for bone ingrowth and to preserve the space needed for the circulation of the inner half side of the corticalis. The average postoperative Harris hip score was 96.7 points. All femoral components had radiographic evidence of bone ingrowth fixation at the final follow-up. There were no cases of loosening for any reason. The strength of the study is limited by the short follow-up, but our preliminary excellent clinical results with stable bone ingrowth fixation allow us to continue to use this stem following patients over time.

Management of Displaced Intracapsular Femoral Neck Fracture in Young Adult:hy Complications Are Still So High? Case Report of Posttraumatic Avascular Necrosis in a 30-Year-Old Man and a Brief Review

A careful and anatomic or slightly valgus reduction, followed by stable fixation is mandatory for the correct treatment of displaced femoral neck fracture in young adult.1 Although the management of these fractures has become standard in young patients, the rate of complications continues to be unacceptably high.2 The incidence of nonunion and osteonecrosis after intracapsular femoral neck fracture has been well documented. Although for the former, a decreasing occurrence has been registered by paying particular attention to the accuracy of the reduction,3 the incidence of avascular necrosis (AVN) of the femoral head still remain the same as in the 1930s.4 Complications such as AVN and osteoarthritis can be physically, socially, and economically devastating to these young patients. We report a case of a young man who developed AVN even though every possible indication in the management of his fracture has been followed. We also perform a brief review of the current knowledge on the treatment of this type of fracture.

The orthopedic damage control in pelvic ring fractures: when and why-a multicenter experience of 10 years' treatment

Abstract Objectives To report our experience of regional referral center for the pelvis. Methods We treated 526 pelvic fractures from January 2004 to December 2014 in three regional reference centers for pelvic trauma. Men were 480 and women were 46 and ages ranged from 16 to 93 years old. Car (65%) and farm (20%) crashes were the most frequent causes of pelvis fractures. Injury severity scores ranged from 9.0 to 75.0, with a mean of 37.5. A defined algorithm for fracture management has been in place and employed to assure adequate resuscitation and fracture care. Results There were 24 deaths in total (4.56%). Sixty three (11.98%) patients underwent angio-embolization for control of bleeding (12 deaths). The average amount of blood transfused was 8.3 IU. Hospital lengths of stay ranged between 1-35 days. Among the 502 alive patients, 55.98% were able to be discharged at home while the remaining 44.02% being transferred to various rehabilitation facilities or extended care facilities. Conclusions The goal of initial management is to restore vital indicators, urinary excretion function and protect the patient from infectious complications. An emergency decisional algorithm helps manage hemodynamic instability. Initial bone and ligament procedures should reduce displacement and make it possible for the patient to wait until his condition is stable enough for definitive surgical fixation.

The Biological Metallic versus Metallic Solution in Treating Periprosthetic Femoral Fractures: Outcome Assessment.

Introduction. The periprosthetic fracture of the femur is, in order of frequency, the fourth leading cause (5.9%) of surgical revision. Our study aims to demonstrate how the grafting of bone splint betters the outcomes. Materials. We treated 15 periprosthetic femoral fractures divided into two groups: PS composed of 8 patients treated with plates and splints and PSS involving 7 patients treated only with plates. The evaluation criteria for the two groups during the clinical and radiological follow-up were the quality of life measured by the Short Form (36) Health Survey (SF-36), Harris Hip Score (HHS), Modified Cincinnati Rating System Questionnaire (MCRSQ), bone healing measured by the Radiographic Union Score (RUS), postoperative complications, and mortality. The evaluation endpoint was set at 24 months for both groups (p < 0.05). Results. The surgery lasted an average of 124.5 minutes for the PS group and 112.6 minutes for the PSS. At 24 months all clinical and radiographic scores were p < 0.05 for the PS group. During follow-up 4 patients (2 in each group) died of causes not related to surgery. Conclusions. The use of the metal plate as opposed to cortical allogenic splint should be taken into consideration as a noteworthy point for periprosthetic femoral fractures.

Differentiating overlapping symptoms of vulvodynia and pudendal neuralgia

Context: Vulvodynia is defined as a chronic vulvar pain non-associated with infectious, inflammatory, neoplastic or hormonal disorders. Objectives: To present a case demonstrating the difficulty in assessing concomitant disease in vulvodynia. Methods: A 26-year-old woman, presented with persistent vulvodynia. She received oral and topical medications and behavioural interventions to lessen sexual pain and restore sexuality. As sexual pain decreased, the patient reported symptoms previously not mentioned: continuous, intense periclitoral pain and numbness at the perineum when sitting for a long time. These new symptoms suggest the involvement of the peripheral neural system. The physical evaluation confirmed right-side pelvic distortion, and pathological increase in lumbar lordosis, which caused neuralgia radiating to the external genitalia and perineum, and overlapping with sexual pain. After diagnosing pudendal neuralgia according to the Nantes criteria, physical treatment and relaxation exercises to de-contract the spine were added to the vulvodynia regimen. Results: During treatment, vulvodynia was sometimes present but never unbearable, allowing satisfactory sex. With physical therapy, the symptoms of pudendal neuralgia decreased. Conclusion: Differentiating the presence of two conditions with overlapping symptoms is difficult because the vestibular pain had shadowed pudendal neuralgia symptoms at initial assessment. Syndromes of chronic pain tend to associate with each other and one syndrome may shadow symptoms of the concomitant condition affecting adjacent anatomical areas. Only the accurate identification of all the syndromes involved allows adopting the correct treatment.

Is the short posterior stabilization by TLIF and cages a good way for a correct spinal alignment in the de novo scoliosis? A case report

De novo scoliosis is becoming one of the most prevalent findings in the aging spine, and this condition is associated not only with severe back or leg symptoms but also with complicated surgical outcomes. The most common surgery is a posterior spinal fusion with metal implants and bone graft (from the pelvis or the bone bank), with or without decompression of the nerve roots. Sometimes the surgery may need to be performed anteriorly (from the front of the spine) for better stability, correction, and healing. After 1 years of follow, up we presented a case report of a 74 year old man treated for De Novo Scoliosis with a spinal short posterior stabilization, TLIF and Cages.

SAT0510 Ultrasound versus Synovial Fluid Analysis for the Diagnosis of Calcium Pyrophosphate Dihydrate Deposition Disease: is IT Cppd? Ask Us!

Background The diagnosis of calcium pyrophosphate crystal (CPP) deposition disease (CPPD) is mainly based on the synovial fluid analysis and Xrays. US has demonstrated high sensitivity and specificity values for diagnosing CPPD compared to synovial fluid analysis as the gold standard (1), but less is known about sensitivity and specificity of synovial fluid analysis itself. Objectives to compare ultrasonography and synovial fluid analysis performances in the diagnosis of CPPD using a real gold standard. Methods We enrolled in our study all patients waiting to undergo knee replacement surgery due to severe osteoarthritis. Each patient underwent US examination of the knee, focusing on the menisci and the hyaline cartilage, the day prior to surgery, scoring each site according to the presence/absence of CPP as defined previously (1). The day of the surgery, synovial fluid of the knee (if present) was aspirated by the surgeon. After surgery, the menisci, condyles and the synovial fluid were retrieved and examined microscopically. Synovial fluid analysis was performed on wet preparations. For the meniscus and cartilage microscopic analysis, six samples were collected, either from the surface and from the internal of the structure trying to cover a large part of it. All slides were observed under transmitted light microscopy and by compensated polarised microscopy. A dichotomous score was given for the presence/absence of CPP. US and microscopic analysis were performed by different operators, blind to each others findings. Sensitivity and specificity of US and synovial fluid were calculated using microscopic findings of the menisci and cartilage as the gold standard. Results we enrolled in the study 32 patients (9 males), mean age of 74 years old (±7). Synovial fluid has been collected from 24 patients. If we consider all the structures examined with US (both menisci and cartilage of both condyles), were positive for CPP 22 patients while synovial fluid analysis was positive for 11 patients. At microscopic examination of the speciments, 21 patients were positive for CPP in at least one of the structures examined. US demonstrated a sensitivity of 95% (CI95: ±0.01) with PPV =0.91 and specificity of 81% (CI95: ±0.23) and a NPV =0.90 while respective values for synovial fluid microscopic analysis were 73% (CI95: ±0.22) with PPV of 1 and 100% (CI95: ±0) with NPV of 0.69. Conclusions US demonstrated higher sensitivity values for identifying CPP deposits in the knee joint than synovial fluid analysis. Specificity values on the other had were higher for the microscopic analysis as expected. Globally we believe that for its intrinsic characteristics, the non invasive nature, for the high values of both specificity and specificity, and last but not least, for the capability to address differential diagnosis US should be the first exam ti be performed when CPPD disease is suspected. As this study demonstrates, the presence of CPP crystals in the synovial fluid, definitely confirms the diagnosis but a negative microscopic exam does not exclude it. References Frediani B, Filippou G, Falsetti P, Lorenzini S, Baldi F, Acciai C, et al. Diagnosis of calcium pyrophosphate dihydrate crystal deposition disease: ultrasonographic criteria proposed. Ann Rheum Dis. 2005 Apr;64(4):638-40 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1621