Gaetano Caruso

Risk factors for development of atypical femoral fractures in patients on long-term oral bisphosphonate therapy

Bisphosphonates (BPs) are the first-line therapy for osteoporosis. In recent years, atypical femoral fractures (AFF) have been described in patients on BPs therapy. However, the relationship between BPs and AFF remains to be clarified. We evaluated clinical and hormonal characteristics of AFF patients, in order to determine AFF risk factors. We studied 11 females with AFF and 58 females with typical femoral fractures (TFF), admitted to our Department for surgical repair between January 2008 and December 2011. All AFF patients received BPs therapy for 6 to 13 yrs, whereas 36.2% (p<0.0001) of TFF patients received BPs for shorter period (TFF, 6.1±1.8 yr vs. AFF, 8.6±1.9 yr, p<0.0001). A higher prevalence of hypocalcemia was observed in AFF patients compared with TFF (p<0.02), with significantly (p<0.05) lower corrected calcium levels in AFF patients. By contrast a reduced prevalence of elevated PTH levels (p<0.05) was found in AFF patients. No significant difference in prevalence of vitamin D defect was observed between the two groups. Younger age (p<0.004), higher BMI (>30 kg/m2, p<0.03) and early menopausal age (p<0.05) were observed in AFF patients. At time of fracture, prevalence of osteopenia/osteoporosis and levels of bone turnover markers were significantly (p<0.01) lower in AFF compared with TFF patients. By multivariate analysis hypocalcemia, obesity, and younger age (<70 yr) were confirmed to be independent predictors of AFF; elevated PTH level was the predominant independent protective factor (p<0.004). In conclusion, our data indicate that clinical characteristics and metabolic factors may favor the development of AFF in BP treated patients. We identified hypocalcemia due to latent hypoparathyroidism as primary risk factor for AFF; age, obesity, early menopause, and BMD may also influence the development of AFF. An adequate clinical and metabolic assessment is suggested to prevent the development of AFF in BP treated patients.

Human leukocyte antigen-G molecules are constitutively expressed by synovial fibroblasts and upmodulated in osteoarthritis

Human leukocyte antigen (HLA)-G molecules are nonclassical HLA class I antigens expressed as membrane bound and soluble isoforms (sHLA-G) with a restricted tissue distribution and anti-inflammatory functions. Because inflammation is involved in the pathogenesis of osteoarthritis (OA), we have analyzed the expression and production of HLA-G molecules in in vitro cultured synovial fibroblasts (SFs) from OA patients and control subjects. We have analyzed the levels of sHLA-G1 and HLA-G5 isoforms by immunoenzymatic assay (enzyme-linked immunosorbent assay) in the SF culture supernatants from six OA patients and six control subjects in 70-day in vitro cultures and after the addition of lipopolysaccharide or recombinant interleukin (IL)-10 (rIL-10). We have confirmed HLA-G modulation by cytofluorimetry and immunofluorescence. The results have demonstrated the spontaneous production of sHLA-G1 molecules by both OA and control SFs. The expression was confirmed by cytofluorimetry and immunofluorescence. OA SFs produce both sHLA-G1 and HLA-G5 molecules during the first 23 days of culture and higher levels of sHLA-G1 during the first 40 days of in vitro culture and after lipopolysaccharide or rIL-10 activation compared with control SFs. The production of HLA-G1 molecules, constitutively expressed by control and OA SFs, is significantly increased in OA, suggesting a possible mechanism to counteract the inflammation of the synovial joints.

Intraosseous glomus tumor of the ankle: a case report and review of the literature.

Glomus tumors are benign vascular lesions4 composed of uniform round to oval cells, resembling normal glomus bodies that can be classified as paragangliar tissue derived from neural crest, which participates in thermal regulation.24 They usually occur in the peripheral soft tissues, most frequently in the digits, where the glomus bodies are normally present. However, they may arise in diverse locations such as bone, stomach, intestines, or neural tissue, where the glomus bodies are thought to be sparse or even absent.2,3,9,12,14,15,17 Glomus tumors can be solitary or multiple. The solitary acquired form is more common. Multiple glomus tumors are rare and are inherited as an autosomal dominant trait. The onset usually is in adolescence with a male predominance; between 30 and 60 years, the predominance is female. The tumor consists of glomus cells, vascular structures, and smooth muscle tissue in varying proportions. Glomus tumors have been divided into three groups according to the relative proportions of these components: glomus tumor proper, glomangioma, and glomangiomyoma. In case of histologic uncertainty, immunohistochemical features may be helpful for differential diagnosis, including hemangiopericytoma, leiomyosarcoma with epithelioid change, rhabdomyosarcoma, Ewing sarcoma, and nodular hidradenoma. Glomangiomas, which usually are encountered in patients with multiple lesions, constitute approximately one fifth of the cases and are predominately on the hand and forearm. Pain radiating proximally or distally

A six-year retrospective analysis of cut-out risk predictors in cephalomedullary nailing for pertrochanteric fractures: Can the tip-apex distance (TAD) still be considered the best parameter?

Objectives Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years. Methods A total of 571 patients were included in this study, which analysed the incidence of cut-out in relation to several clinical variables: age; gender; the AO Foundation and Orthopaedic Trauma Association classification system (AO/OTA); type of nail; cervical-diaphyseal angle; surgical wait times; anti-osteoporotic medication; complete post-operative weight bearing; and radiological parameters (namely the lag-screw position with respect to the femoral head, the Cleveland system, the tip-apex distance (TAD), and the calcar-referenced tip-apex distance (CalTAD)). Results The incidence of cut-out across the sample was 5.6%, with a higher incidence in female patients. A significantly higher risk of this complication was correlated with lag-screw tip positioning in the upper part of the femoral head in the anteroposterior radiological view, posterior in the latero-lateral radiological view, and in the Cleveland peripheral zones. The tip-apex distance and the calcar-referenced tip-apex distance were found to be highly significant predictors of the risk of cut-out at cut-offs of 30.7 mm and 37.3 mm, respectively, but the former appeared more reliable than the latter in predicting the occurrence of this complication. Conclusion The tip-apex distance remains the most accurate predictor of cut-out, which is significantly greater above a cut-off of 30.7 mm. Cite this article: G. Caruso, M. Bonomo, G. Valpiani, G. Salvatori, A. Gildone, V. Lorusso, L. Massari. A six-year retrospective analysis of cut-out risk predictors in cephalomedullary nailing for pertrochanteric fractures: Can the tip-apex distance (TAD) still be considered the best parameter?. Bone Joint Res 2017;6:481–488. DOI: 10.1302/2046-3758.68.BJR-2016-0299.R1.

Squamous cell carcinoma in chronic osteomyelitis: a case report and review of the literature

BackgroundChronic osteomyelitis is a challenging problem, and malignant transformation is a rare occurrence. We report a case of a patient with squamous cell carcinoma arising from an osteomyelitic hotbed and discuss through a literature review the etiopathogenesis, diagnosis, and treatment of this lesion.Case presentationA 69-year-old Italian man had sustained an exposed tibial fracture 40 years ago during a road accident, for which he had undergone various surgical osteosynthesis treatments with multiple antibiotic therapies. He presented to our hospital because of recurrence of a fistula at the proximal third of the anterior region of the tibia. For 2 months, we treated the lesion with antibiotics, and local medication with curettage. We saw no evidence of lesion improvement, and we advised the patient to undergo a knee amputation, which he refused. The alternative we chose was a surgical toilet of the osteomyelitic hotbed and used bioglass as a bone substitute. After 2 months of follow-up, we noticed a fulminating, budding formation in the area of the surgical wound that turned out to be a squamous cell carcinoma on biopsy. The patient again refused the amputation and underwent a wide-margin surgical debridement. After 2 months, the carcinoma recurred, and an above-the-knee amputation was performed.ConclusionsOur experience with this case indicates that amputation is the most appropriate treatment for squamous carcinoma occurring in patients with chronic osteomyelitis. To avoid risks of lymphonodular and organ metastasization, this radical surgical procedure should not be delayed. Early diagnosis and timely therapy can prevent amputation only in selected cases. Surgeons who treat osteomyelitis and chronic wounds should be aware of the risk of tumor degeneration. Squamous cell carcinoma associated with chronic osteomyelitis has a low-grade malignancy, but implications of lymphonodular involvement and organ metastasis should not be excluded.

The “Chauffeur Fracture”: Historical Origins of an Often-Forgotten Eponym

This article describes the origin of the term “chauffeur fracture” used to indicate an oblique fracture of the radial styloid process with extension into the wrist joint. This kind of fracture was originally described by the British surgeon Jonathan Hutchinson in 1866. The invention of the automobile increased the incidence of this fracture among chauffeurs and cabdrivers. Indeed, at the beginning of the 20th century, motor vehicles were started by means of a crank-handle connected to the engine, which needed to be turned vigorously clockwise by hand. If the motor started unexpectedly, the crank-handle could jerk back violently and thereby cause a wrist injury due to sudden hyperextension. We retrospectively reviewed the literature and historical articles to better define the historical origins of an often-forgotten eponym. In 1904, the French surgeon Just Lucas-Championnière first evidenced the occupational origin of this fracture, so introducing the term “chauffeur fracture” to identify this injury.

Can Clinical and Surgical Parameters Be Combined to Predict How Long It Will Take a Tibia Fracture to Heal? A Prospective Multicentre Observational Study: The FRACTING Study

Background Healing of tibia fractures occurs over a wide time range of months, with a number of risk factors contributing to prolonged healing. In this prospective, multicentre, observational study, we investigated the capability of FRACTING (tibia FRACTure prediction healING days) score, calculated soon after tibia fracture treatment, to predict healing time. Methods The study included 363 patients. Information on patient health, fracture morphology, and surgical treatment adopted were combined to calculate the FRACTING score. Fractures were considered healed when the patient was able to fully weight-bear without pain. Results 319 fractures (88%) healed within 12 months from treatment. Forty-four fractures healed after 12 months or underwent a second surgery. FRACTING score positively correlated with days to healing: r = 0.63 (p < 0.0001). Average score value was 7.3 ± 2.5; ROC analysis showed strong reliability of the score in separating patients healing before versus after 6 months: AUC = 0.823. Conclusions This study shows that the FRACTING score can be employed both to predict months needed for fracture healing and to identify immediately after treatment patients at risk of prolonged healing. In patients with high score values, new pharmacological and nonpharmacological treatments to enhance osteogenesis could be tested selectively, which may finally result in reduced disability time and health cost savings.

Chondroprotective effects of low-frequency lowenergy pulsed electromagnetic fields on human cartilage explants

Objective To investigate the effects of low-frequency low-energy pulsed electromagnetic fields (PEMFs) on proteoglycans (PG) metabolism [1-2] of human articular cartilage explants derived from patients with different osteoarthritis (OA) grades in the presence and in the absence of anabolic and catabolic stimuli for cartilage. Design Human knee cartilage explants derived from lateral and medial femoral condyles of OA patients were exposed to PEMF (1.5 mT; 75 Hz) for 1 and 7 days with and without insulin-like growth factor-I (IGF-I) (50 ng/ml) and interleukin-1β (IL-1β) (0.01-50ng/ml). Histological analysis was used to classify cartilage according to the score developed by the International Cartilage Repair Society (ICRS). PG synthesis was determined by 35S-sulfate incorporation. PG release into culture media was determined by the dimethylmethylene blue assay. Results By histological evaluation, cartilage explants derived from lateral and medial condyles were classified as OA ICRS grade I and III, respectively. After 7 days treatment, in OA grade I cartilage explants, PEMF and IGF-I alone significantly increased 35S-sulfate incorporation respect to control and counteracted the effect induced by IL-1β (0.01 ng/ml) of 26% and 24% respectively. The combination of PEMF and IGF-I resulted additive in all conditions. Similar results were obtained in OA grade III cartilage, although basal 35S-sulfate incorporation was lower than in OA grade I. No effect was observed on medium PG release. Conclusions PEMF exerts chondroprotective effects on human articular cartilage. The biological responsiveness of chondrocyte to PEMF was similar in different OA grades cartilage, suggesting that human chondrocytes maintain susceptibility to PEMF during OA progression.

HLA-G molecules are costitutively expressed by human synovial fibroblasts and up-modulated in osteoarthritis

Objective HLA-G molecules are non classical HLA class I antigens expressed as membrane bound and soluble isoforms (sHLA-G) with a restricted tissue distribution and anti-inflammatory functions [1]. Osteoarthritis (OA) is a complex degenerative disease that affects articular cartilage components and causes damage to the entire joint structure including synovium [2]. Since inflammation is involved in the pathogenesis of OA, we have analyzed the expression and the production of HLA-G molecules in “in vitro” cultured synovial fibroblasts (SFs) from OA patients and control subjects. Design We have analyzed the levels of sHLA-G1 and HLA-G5 isoforms by immunoenzymatic assay (ELISA) in the SFs culture supernatants from six OA patients and six control subjects during a 70 day “in vitro” cultures in the presence and in the absence of lipopolysaccharide (LPS) or recombinant IL-10 (rIL-10). We have confirmed HLA-G modulation by cytofluorimetry and immunofluorescence. Results Data in ELISA have demonstrated the spontaneous production of sHLA-G molecules by both OA and control SFs. The expression has been confirmed by cytofluorimetry and immunofluorescence. OA SFs produce higher levels of sHLA-G1 and HLA-G5 molecules during the first 23 days of culture in comparison to control SFs. The sHLA-G1 levels further increase over the next 20 days of “in vitro” culture. Atfer LPS and rIL-10 treatments, sHLA-G secretion increases in a similar manner in both OA and control SFs. Conclusions The production of sHLA-G1 molecules, constitutively expressed by control and OA SFs, is significantly higher in OA than in control SFs, suggesting that these molecules represent a possible molecular target to counteract the synovial joints inflammation.

Consideration on disadvantages and problems of resurfacing

The concept of resurfacing the hip joint is not new, it is a bone conserving alternative to total hip replacement that restores normal joint biomechanics and load transfer and ensures joint stability.