The role of the immune system in the physiopathology of osteoporosis.

The close anatomical relationship between the immune system, estrogen deficiency and bone loss has been recognized for centuries but the existence of a functional relationship has emerged only recently. The role of the immune system in the development of senile osteoporosis, which arises primarily through the effects of estrogen deficiency and secondary hyperparathyroidism, is slowly being unraveled. This review focuses the evidence that links immune cells, inflammation, cytokine production and osteoclast formation and their activity. The under standing of the interplay of inflammation and osteoclast can lead to the development of new drugs for prevention and treatment of bone loss.

I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study.

BACKGROUND: Total knee arthroplasty (TKA) is often associated with a severe local inflammatory reaction which, unless controlled, leads to persistent pain up to one year after surgery. Standard and accelerated rehabilitation protocols are currently being implemented after TKA, but no consensus exists regarding the long-term effects. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been demonstrated to exert an anti-inflammatory effect, to promote early functional recovery and to maintain a positive long-term effect in patients undergoing joint arthroscopy. The aim of this study was to evaluate whether PEMFs can be used to limit the pain and enhance patient recovery after TKA. METHODS: A prospective, randomized, controlled study in 30 patients undergoing TKA was conducted. Patients were randomized into experimental PEMFs or a control group. Patients in the experimental group were instructed to use I-ONE stimulator 4hours/day for 60days. Postoperatively, all patients received the same rehabilitation program. Treatment outcome was assessed using the Knee Society Score, SF-36 Health-Survey and VAS. Patients were evaluated pre-operatively and one, two, six and 12 months after TKA. Joint swelling and Non Steroidal Anti Inflammatory Drug (NSAID) consumption were recorded. Comparisons between the two groups were carried out using a two-tail heteroschedastic Student's t-test. Analysis of variance for each individual subject during the study was performed using ANOVA for multiple comparisons, applied on each group, and a Dunnet post hoc test. A p value < 0.05 was considered statistically significant. RESULTS: Pre-operatively, no differences were observed between groups in terms of age, sex, weight, height, Knee-Score, VAS, SF-36 and joint swelling, with the exception of the Functional Score. The Knee-Score, SF-36 and VAS demonstrated significantly positive outcomes in the I-ONE stimulated group compared with the controls at follow-ups. In the I-ONE group, NSAID use was reduced and joint swelling resolution was more rapid than in controls. The effect of I-ONE therapy was maintained after use of the device was discontinued. CONCLUSIONS: The results of the study show early functional recovery in the I-ONE group. I-ONE therapy should be considered after TKA to prevent the inflammatory reaction elicited by surgery, for pain relief and to speed functional recovery.

Total knee arthroplasty in elderly osteoporotic patients.

Often in daily practice the choice of a prosthesis does not rise out of considerations about literature evidences, but it seems to be related to the personal experience and "surgical philosophy" of surgeon. The choice of prosthesis in total joint replacement is usually justified by biological and mechanical parameters that the surgeon considers before surgery. Osteoporosis is a disease characterized by a reduced bone mass and a degeneration of the bone tissue; it leads to bone fragility, so to a higher risk of fractures. Bone resistance, as all the changes in the microarchitecture of the bone tissue, is linked to bone density. Because of the bone density variation and/or the changes in the bone micro-architecture, as the bone strength decreases, the risk of fractures increases. It is important to understand all the factors taking part in both normal and abnormal bone remodelling. Osteoporosis does not imply a concrete bone loss, but a change of the bone micro-architecture itself. In these cases the choice of the patient and implant design are very important. In the period between March 1997-July 2002, we implanted 100 consecutive TKA (total knee arthroplasty) Genesis II in 97 subjects (79 female); mean age was 77.1 years old. All TKA were performed because of primary osteoarthritis of the knee. All patients had complete pain relief and excellent knee score. The surgical and medical complications were in accordance with the published literature. We must consider all existing medical conditions, the state of the knee and local needs of the elderly patient. Thus, within these limits, the total knee can improve the ability of patients to manage the activities of daily living and improve their quality of life.

Hip painful prosthesis: surgical view.

Painful hip prosthesis is the most feared immediate and remote complication of a primary implant and usually represents the failure of one or more therapeutic moments. In cases of aseptic implant failure, the causes invoked may be represented by an incorrect indication, the quality of materials, local and general condition of the patient and especially from a bad joint biomechanics. In cases of septic loosening, however, the cause of failure to be found in the location of pathogens within the implant. In planning a revision is necessary to respect many important steps. They are represented by the exact identification of the causes of failure, the correct preoperative planning, by respecting the skin incisions, the proper choice of the prosthesis, planning the surgical technique, and finally by an appropriate rehabilitation program.In the evaluation of hip failure the first diagnostic step is to recognize exactly those aseptic and septic forms anyway to exclude the diagnosis of infection.

The incidence of hip, forearm, humeral, ankle, and vertebral fragility fractures in Italy: results from a 3-year multicenter study.

INTRODUCTION: We aimed to assess the incidence and hospitalization rate of hip and "minor" fragility fractures in the Italian population. METHODS: We carried out a 3-year survey at 10 major Italian emergency departments to evaluate the hospitalization rate of hip, forearm, humeral, ankle, and vertebral fragility fractures in people 45 years or older between 2004 and 2006, both men and women. These data were compared with those recorded in the national hospitalizations database (SDO) to assess the overall incidence of fragility fractures occurring at hip and other sites, including also those events not resulting in hospital admissions. RESULTS: We observed 29,017 fractures across 3 years, with hospitalization rates of 93.0% for hip fractures, 36.3% for humeral fractures, 31.3% for ankle fractures, 22.6% for forearm/wrist fractures, and 27.6% for clinical vertebral fractures. According to the analyses performed with the Italian hospitalization database in year 2006, we estimated an annual incidence of 87,000 hip, 48,000 humeral, 36,000 ankle, 85,000 wrist, and 155,000 vertebral fragility fractures in people aged 45 years or older (thus resulting in almost 410,000 new fractures per year). Clinical vertebral fractures were recorded in 47,000 events per year. CONCLUSIONS: The burden of fragility fractures in the Italian population is very high and calls for effective preventive strategies.

A volleyball player with bilateral knee osteochondritis dissecans treated with extracorporeal shock wave therapy.

We present a case report of a 14-year-old Caucasian sport woman affected by bilateral and symmetrical knee osteochondritis dissecans (OCD) addressed to surgery, in which extracorporeal shock wave therapy determined complete healing. Shock wave is a longitudinal acoustic wave traveling with the speed of ultrasound through the water of the body tissue. Recently, this therapy has been used in the treatment of a number of musculoskeletal pathologies on the basis of the effects produced by the induction of angiogenesis, recruitment of progenitor cells and downregulation of cartilage damage. This therapy is useful, because it is non-invasive, safe, without complications or adverse effects and repeatable. Thus, it could be suggested as a useful strategy for the treatment of OCD prior starting surgery.

Extracorporeal shock waves stimulate osteoblast activities.

The extracorporeal shock wave therapy (ESWT) is an extensively applied treatment for musculoskeletal disorders because it promotes bone repair. The aim of this study was to evaluate the direct effect of ESWT on murine osteoblasts to clarify the cellular mechanism that leads to the induction of osteogenesis. Osteoblasts in culture flasks were treated with ESWT pulses (500 impulses of 0.05 mJ/mm(2)) generated by an electromagnetic device. Using western blot analysis 3h after ESWT, an increased expression of Bax was found, indicating a fast pro-apoptotic effect of treatment on some of the osteoblasts. Activation of the cyclin E2/CDK2 is the complex that regulates the G1-S transition and is essential for cell proliferation. It was evident 24 to 72h after treatment, indicating a proliferative stimulus. A decreased expression of osteoprotegerin (OPG) and receptor activator NF kappa B ligand (RANKL) 24 and 48h after ESW, followed by a later increase of OPG, paired with a much smaller increase of RANKL, was evident by real-time polymerase chain reaction (PCR). The decreased RANKL/OPG ratio suggests inhibition of osteoclastogenesis. We can conclude that ESWT induces bone repair through the proliferation and differentiation of osteoblasts and the reduction of their secretion of pro-osteoclastogenic factors.

Expression and localization of augmenter of liver regeneration in human muscle tissue.

Mitochondrial DNA (mt-DNA) disorders and abnormal regulation of nuclear-derived proteins devoted to the cross-talk between the two cellular genomes have recently interested researchers in the field of neuromuscular diseases. We have identified, isolated and sequenced a new gene, augmenter of liver regeneration (ALR) that stimulates in vivo hepatocyte proliferation and up-regulates mt-DNA expression and ATP production. ALR protein (Alrp) is mainly located, in rat, in the mitochondrial inter-membrane space and its mRNA is particularly abundant in brain, muscle, testis and liver, tissues whose activity is mostly dependent on mitochondrial metabolism. Studies on rat Alrp sequence revealed the presence of homologous amino-acid sections into proteins derived from mouse, human, Drosophyla, plants and even DNA viruses. In this article, we evaluated ALR expression in normal human muscular tissues, both as protein and as mRNA. The data, obtained by molecular biology, immunohistochemistry and electron microscopy, demonstrated that: (i) Alrp and ALR mRNA are present in human muscular tissue; (ii) Alrp is particularly expressed in muscular fibres rich in mitochondria; (iii) Alrp is localized in the mitochondrial inter-membrane space or associated to mitochondrial cristae; and (iv) in subjects younger then 35 years of age, ALR mRNA expression is different between male and female subjects. In conclusion, the present data set Alrp, as a factor associated with mitochondria also in human tissue, call for future studies aimed at establishing Alrp as an important factor involved in the molecular events that trigger neuromuscular diseases.

The management of neuropathic ulcers of the foot in diabetes by shock wave therapy.

BACKGROUND: Diabetes is becoming one of the most common chronic diseases, and ulcers are its most serious complication. Beginning with neuropathy, the subsequent foot wounds frequently lead to lower extremity amputation, even in the absence of critical limb ischemia. In recent years, some researchers have studied external shock wave therapy (ESWT) as a new approach to soft tissue wound healing. The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers. METHODS: We designed a randomized, prospective, controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies. One group was treated with standard care and shock wave therapy. The other group was treated with only standard care. The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization. RESULTS: After 20 weeks of treatment, 53.33% of the ESWT-treated patients had complete wound closure compared with 33.33% of the control patients, and the healing times were 60.8 and 82.2 days, respectively (p < 0.001). Significant differences in the index of the re-epithelization were observed between the two groups, with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group (p < 0.001). CONCLUSION: Therefore, ESWT may be a useful adjunct in the management of diabetic foot ulceration.

Assessment of the initial stability of the Symax femoral stem with EBRA-FCA: a multicentric study of 85 cases.

We report a study of 85 Symax femoral stems that were followed at regular intervals with radiographs at 6, 12, 24 and 36 months. The radiological migration of each stem was measured using the computer-assisted EBRA -FCA method. In 30 cases in which the EBRA method did not provide a complete measurement another computer-assisted method (Roman version 1.7) was employed. In all cases the distal migration of the stems was minimal, The threshold migration value used to define the stability of a stem was 1.5 mm at 24 months. The mean migration within the first two years was -0.17 mm (+/- 0.3) at 6 months, -0.31 mm (+/- 0.4) at 12 months and -0.45 mm (+/- 0.5) at 24 months. Only two cases exceeded the threshold limit of 1.5 mm at the two-year follow-up, but both values were lower than 2 mm. In the 25 cases which reached three-year follow-up the mean distal migration was -0.84 (+/-0.7). In four of them the subsidence exceeded 1.5 mm, but only one exceeded 2 mm. These data represent a positive predictive factor for the minimal risk of future aseptic loosening.

Hip fracture in a patient affected by transient osteoporosis of the femoral head during the last trimester of pregnancy.

Few cases of hip fracture in pregnant women affected by transient osteoporosis of the femoral head have been reported in the literature, but its real incidence seems to be underestimated. During pregnancy, osteoporosis manifests itself with an insidious onset of hip pain and limp without any trauma or infective episode in clinical history. Its clinical course is characterized by spontaneous recovery a few weeks to several months after delivery. This article describes the case of a 35-year-old woman with a sudden onset of bilateral hip pain during the last trimester of her first pregnancy; she had neither history of steroid therapy nor alcohol abuse; her body temperature and serological parameters were normal. Bilateral transient osteoporosis of the femoral heads was suspected and confirmed by magnetic resonance imaging. Fifteen days postpartum, she was admitted to our clinic with a displaced femoral neck fracture. A cementless total hip arthroplasty was performed to quickly begin a rehabilitative program. She underwent antiresorptive therapy with alendronic acid 70 mg/week and vitamin D for 3 months. Three months after the fracture, a dual-energy x-ray absorptiometry scan showed osteopenia (T-score, -1.5). Risedronic acid 35 mg/week and vitamin D were then prescribed. The last physical examination at 3 months postoperatively revealed a gradual recovery of the autonomy in activities of daily life.

Extensor deficiency: first cause of childhood flexible flat foot.

Childhood flexible flat foot is the most common paramorphism of the lower limb. The cause is not a bony malformation of the foot but a functional deficiency of the anatomic structures supporting the plantar arch. These structures, working as active tie rods (the tibialis anterior and posterior muscles) or passive factors of support (flexor hallucis longus and flexor digitorum longus muscles) act together to maintain the plantar arch. Their deficiency is responsible for childhood flexible flat foot, characterized by a flattening of the plantar arch and calcaneus pronation (heel valgus) and manifested in the characteristic "duck walking" in children. Hypothesizing poor extensor activity of the tibialis anterior, extensor digitorum longus, and extensor hallucis longus muscles during the heel contact phase of the gait cycle, we began a preliminary study to evaluate, through superficial electromyography (sEMG), the activation of muscle groups involved in the pathogenesis of childhood flexible flat foot, in particular the tibialis anterior and extensor hallucis longus muscles, to plan a rehabilitative program addressing the strengthening of insufficient muscles. The therapeutic program should also include the use of a medial elastic push orthosis. Data obtained by sEMG highlight a reduced activation of muscles related to the grade of flat foot, emphasizing the concept that a reduced activation of extensor muscles may be involved in determining flexible flat foot.

Shock waves in the treatment of stress fractures.

In soccer players, lower extremity stress fractures are common injuries and are the result of repetitive use damage that exceeds the intrinsic ability of the bone to repair itself. They may be treated conservatively but this may cause long-term complications, such as delayed union, muscle atrophy and chronic pain. Stress fractures that fail to respond to this management require surgical treatment, which is also not without risks and complications. Extracorporeal shock wave therapy (ESWT) has been used successfully on fracture complications, such as delayed union and nonunion. As such, we want to examine ESWT in the management of stress fractures. In this article, we present a retrospective study of 10 athletes affected by chronic stress fractures of the fifth metatarsus and tibia that received three to four sessions of low-middle energy ESWT. At the follow-up (8 wk on average), the clinical and radiography results were excellent and enabled all players to gradually return to sports activities. These reports show that ESWT is a noninvasive and effective treatment for resistant stress fractures in soccer players.

Surgical approach to bone healing in osteoporosis.

Osteoporotic fractures represent one of the most common cause of disability and one of the major voice in the health economic budget in many countries of the world. Fragility fractures are especially meta-epiphyseal fractures, in skeletal sites with particular biomechanic characteristic (hip, vertebrae), complex and with more fragments, with slow healing process (mineralization and remodeling) and co-morbidity. The healing of a fracture in osteoporotic bone passes through the normal stages and concludes with union of the fracture although the healing process is prolonged. Fractures in the elderly osteoporotic patients represent a challenge to the orthopaedic surgeons. Osteoporosis does not only increase the risk of fracture but also represents a problem in osteofixation of fractures in fracture treatment. The major technical problem that surgeons face, is the difficulty to obtain a stable fixation of an implant due to osteoporotic bone. The load transmitted at the bone-implant interface can often exceed the reduced strain tolerance of osteoporotic bone.IN THE TREATMENT OF OSTEOPOROTIC FRACTURES IT IS IMPORTANT TO CONSIDER DIFFERENT ASPECTS: general conditions of elderly patient and comorbidity, the reduced muscular and bone mass and the increased bone fragility, structural modifications as medullary expansion.The aim of surgical treatment is to obtain a stable fixation that reduces pain and permits an early mobilization.

Bone healing induced by ESWT.

It has been at least two decades since the introduction of Extracorporeal Shock-Wave Treatment (ESWT) for the treatment of non-unions; despite conflicting opinions in the literature, it is recently achieving good results also in acute fractures. This paper reports Authors' clinical experience with electromagnetic shock-waves in the treatment of delayed unions and fresh fractures. Nonunion cases experienced remarkable successful results at an average of 8-10 weeks after ESWT; high success rate is been also found for the acute fractures. It can be concluded that this therapy constitutes an important aid in treatment of non-unions and can be useful also in fresh bone fractures.

Spontaneous bilateral fracture of patella.

Bilateral patellae fractures represent a rare entity, accounting for approximately 2.9% of all lesions interesting in this anatomical district. In most cases found in the published work, they are described as stress fractures or as complications of chronic diseases such as osteoporosis, renal failure and secondary hyperparathyroidism. Although many pathogenetic mechanisms have been supposed, none have been proved for certain. Insufficiency fractures of the patellae are rare events and no data has been published on their incidence. We present a case of bilateral fracture of the patellae due to an indirect trauma occurring in an 85-year-old patient affected by Parkinson's disease, osteoporosis and diffuse degenerative osteoarthritis. X-ray of the knees (anteroposterior and lateral) and magnetic resonance imaging evaluation confirmed the fractures. The patient was treated conservatively. She had a good result, returning to her previous autonomous ambulation. This case is unusual because there was no direct trauma to the knees because of bilaterality, but confirmed previous observations about insufficiency fractures of patellae in the presence of comorbidity. Insufficiency fractures of patellae can be an insidious condition in elderly people. Prepatellar pain, a common symptom in the relapse phase of degenerative arthritis of the knee, should not be underestimated, particularly in patients with diseases influencing metabolism of bone and with an elevated risk of fall. A periodical clinical and instrumental follow up should be done in these patient. Moreover, we underline the necessity of a multidisciplinary approach.

Nora's lesion. Clinical and therapeutic considerations.

In this article we report a case of bizarre paraosteal osteochondromatous proliferation (BPOP), also known as Nora's lesion, arising on the distal phalanx of the fifth finger of the hand in a young-adult subject. In this paper, we discuss the possible therapeutic programme related to the grade of severity of the clinical features and underline the rarity of this lesion and the difficulty of diagnosis, which is exclusively histological.

Spontaneous bilateral patellar tendon rupture: a case report and review of the literature.

Bilateral rupture of the patellar tendon is a very rare injury. It occurs in association with chronic systemic diseases or corticosteroid medications. We report a case of a 13-year-old child with Ehlers-Danlos syndrome presenting a bilateral patellar tendon disruption of proximal insertion that occurred with a trivial trauma. Surgical management consisting in tendon repair with a suture anchor technique protected temporarily with a cerclage wiring gives a good outcome.

Extracorporeal shock waves down-regulate the expression of interleukin-10 and tumor necrosis factor-alpha in osteoarthritic chondrocytes.

BACKGROUND: The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and particularly on the expression of IL-10, TNF-alpha and beta1 integrin. METHODS: Human adult articular cartilage was obtained from 9 patients (6 male and 3 females), with primary knee osteoarthritis (OA), undergoing total joint replacement and from 3 young healthy donors (HD) (2 males, 1 female) with joint traumatic fracture. After isolation, chondrocytes underwent ESW treatment (electromagnetic generator system, MINILITH SL1, STORZ MEDICAL) at different parameters of impulses, energy levels and energy flux density. After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta1 integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry. RESULTS: At baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies. CONCLUSION: Our study confirmed that osteoarthritic chondrocytes express low beta1 integrin and high TNF-alpha and IL-10 levels. Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. However, further in vivo and in vitro studies are necessary to establish if ESW can represent a viable option in the treatment of OA.

Wound necrosis after total knee arthroplasty.

Quickly evolutive skin necrosis and deep infection after total knee arthroplasty (TKA) are not uncommon. Several predisposing factors, such as immunosuppression, malnutrition, steroid use, rheumatoid arthritis, multiple scars, and vascular disease can be involved in the onset of wound complications, as well as long tourniquet time and early knee flexion. Skin necrosis after TKA can be treated in different ways, including local wound care, debridement, and soft tissue coverage with muscle or skin grafts. This article presents a rare case of skin necrosis occurring in a patient without any other apparent risk factor after TKA. A 78-year-old woman affected by primary osteoarthritis of the right knee who had no comorbidities and who had already undergone TKA for primary osteoarthritis on the left knee underwent a cemented TKA. Three days postoperatively, she developed a fever and wound problems, which soon after turned into skin necrosis. This complication was first treated surgically with a debridement of the wound with antibiotic therapy and local wound care, then with vacuum-assisted closure (Kinetic Concepts Inc, San Antonio, Texas) therapy and soft tissue coverage using skin grafting. She had a complete recovery in the next 3 months; the skin grafting was well tolerated and the range of motion and functional outcome were good.