[ ISSN : 2576-5442 ]
We present two cases of symptomatic avascular necrosis of distal femur in two multiple sclerosis patients who received Methylprednisolone (15 and 10 grams respectively) for relapses treatment over a period of 28 and 29 months. Both complained knee pain after steroid treatment, in both cases we diagnosed avascular necrosis of distal femur only one year later. These cases illustrate how important is not to underestimate the event of avascular bone necrosis after steroid pulse treatment, even with low cumulative dosages, after a long time interval and in unusual necrosis sites.
Osteonecrosis is a serious condition involving trabecular bone destruction. Direct injury may result from trauma, major arterial disease, Gaucher’s and Caisson disease, sickle cell and thalassemias. Many risk factors have been listed, such as connective tissues and rheumatological diseases, haematological and vascular conditions, but it’s often difficult to determine whether the main trigger is the underlying disease or its treatment (e.g. steroids). Genetic factors may also play a role [1].
The link between corticosteroid administration and the development of osteonecrosis is well established. Thirty-five percent of non-traumatic cases are due to long-term corticosteroid treatment [2], but the pathophysiology is still controversial. Even though it is estimated that fewer than 5% of patients receiving high-dose corticosteroid present osteonecrotic lesions [3-6], the relationship between cumulative dose, treatment duration and risk of osteonecrosis development is still unknown.
A multifactorial process involves host predisposition, type and dosage of steroids, underlying diseases, concurrent medications, personal habits, such as alcohol or cigarette smoking, and younger age [7]. High dose steroid pulses (usually methylprednisolone) are a well established and efficacious treatment for Multiple Sclerosis (MS) relapses. Though administered in short-term pulses, the effect of methylprednisolone persists long after drug has dissipated from sera or tissue with an intermediate relative duration [7]. MS patients are frequently exposed to repeated pulse steroid therapy.
The incidence of Steroid Induced Osteonecrosis (SIO) in MS patients is uncertain and probably under-reported in this context. Single groups of symptomatic cases are reported about femoral head or diaphyseal necrosis [8-11], while two studies screened MS patients with femoral MRI [2,12].
We report two cases of symptomatic SIO of distal femur in two young women with a low cumulative steroid dosage.
Case Reports
Case 1: A 23-year-old Caucasian smoker woman was diagnosed relapsing-remitting MS in June 2007. Treatment with Interferon Beta 1a was started in October 2007. Before immunomodulant treatment she experienced retrobulbar optic neuritis in January 2007 and paresthesias on the right side in June 2007, both episodes were successfully treated with intravenous Methylprednisolone (1g/day for 5 days). In May 2009 she had a new spinal cord relapse again treated with Methylprednisolone (1g/ day for 5 days). One month after her last steroid pulse she began suffering articular pain in her right knee. No traumas were reported, knee X-rays and MRI were normal, pain gradually disappeared in a few weeks.
On April 2011 she complained again pain in her right knee and MRI detected an extensive infarction of the right distal femoral and proximal tibial epiphysis.(Figure 1 a. MRI at diagnosis. b. MRI after two years) She was treated conservatively with biphosphonate and cholecalciferol with only partial benefit on pain and functional articular impairment. She carried on Interferon treatment without any further MS relapses.
Figure 1: a. MRI at diagnosis, b. MRI after two years.
Case 2: A 20-year-old Caucasian woman was diagnosed relapsingremitting MS in June 2007. Treatment with Interferon Beta 1a was started in May 2009. Before immunomodulant prophylaxis she was treated with intravenous Methylprednisolone (1g/day for 5 days) for one episode of retrobulbar optic neuritis in April 2007. On September 2009 she experienced again retrobulbar optic neuritis, successfully treated with intravenous Methylprednisolone (1g/day for 5 days). In a few days after her last steroid pulse she complained mild bilateral articular pain in her knees and hips. No traumas were reported, rheumatological re-evaluation resulted negative and pain disappeared after anti-inflammatory non steroid treatment.
One year later, she began suffering severe pain in her right knee. Knee X-rays resulted normal, but MRI detected avascular necrosis in her right femoral condyle. She was treated conservatively with biphoshonate with complete benefit on the articular function and only partial benefit on pain (Figure 2). She was then switched to treatment with fingolimod without any further MS relapses.
Figure 2: MRI at diagnosis.
Both our patients had a brief disease history when they developed femoral osteonecrosis, the first one was exposed to 15g of Methylprednisolone over a period of 28 months, the second one to 10g of Methylprednisolone over a period of 29 months. Both complained knee articular pain in a few weeks following the last steroid pulse but both were diagnosed distal femoral osteonecrosis at least one year later. Whether previous pain in the proximity of the site of necrosis might have been an early necrosis symptom is speculative. The interval between steroid administration and the onset of symptoms is reported to be variable. Retrospective studies on different disorders rarely found an interval of less than 6 months and sometimes even more than 3 years [6].
A prospective study on autoimmune disorders requiring high-dose steroid treatment [13] detected initial changes in femoral head MRI as early as 3.6 months; in the same study MRI was repeated with a follow up of 31 months: though reducing in time, necrosis lesions persisted in the longer follow up. Establishing the exact onset of osteonecrosis radiological signs during a period without symptoms was not possible in our cases without having performed sequenced MRIs. However, in the absence of other evident risk factors for osteonecrosis, we think that steroid treatment might have had a primary role for our patients, even with a diagnosis after more than 12 months after treatment.
Our patients experienced side effects of pulse steroid treatment both over a short time frame after pulse treatment in the first case (10 grams over 6 months) and over a long time frame in the second one (10 grams over 29 months). Previous studies [2,12] tried to assess the risk for osteonecrosis in multiple sclerosis patients exposed to heterogeneous (10 to 60g) or higher cumulative dosages (more than 20 g).
They didn’t succeed in clarifying the cumulative effect of corticosteroid treatment, but they were both able to point out a higher frequency of radiographic avascular necrosis in steroid-treated patients (15.5 to 23%, including asymptomatic cases) than in nonsteroid-treated patients (0%). Ce at al [2] evaluated only femoral head MRI in MS patients, while we detected SIO in the distal femoral bone, which is well described in other diseases even if less common than femoral head [7].
Alertness on articular pain is essential for an early diagnosis of SIO before irreversible bone damage. Neurological pain may induce to underestimate the event of avascular bone necrosis after steroid pulse treatment. An early detection of SIO may grant the option of a conservative treatment such as joint rest, non steroidal anti-inflammatory drugs and biphosphonate, muscle strengthening exercises, restriction of weight load across the affected joint and mobility training. Whereas, progression of necrosis to subchondral bone collapse and destruction may follow a delayed diagnosis, leading to the need for total joint replacement. Therefore, a thorough clinical assessment, together with MRI may be advisable in case of recent or repeated history of pulsed steroid treatment in MS patients reporting articular and bone pain, even in different sites other than hips.
Considering the average disease history MS patients tend to be young and smoking may be a frequent risk factor; identification of high risk patients would be an essential issue to consider while applying repeated high dose steroids, even if nowadays risk stratification is still unclear. Furthermore, a critical point is MS relapse management after osteonecrosis diagnosis: what is the risk/benefit ratio of steroid retreatment when necessary? What is the safest dosage? How high is the risk of osteonecrosis relapse in the same area or in other locations? How much a therapeutic shift to a second or third line agent is justified before new clinical relapses? Prospective sequenced bone MRI studies after steroid treatment in MS patients are essential to better understand the risk/benefit ratio and the safest dosages.
At the moment we have no hints on the risk of osteonecrosis relapses, further prospective investigations are needed. While trying to obtain the appropriate answers, we suggest to shift to therapeutic agents with better efficacy profiles in order to minimize the risk of relapses and the consequent need of steroid re-treatment in case of history of SIO. If not viable, we recommend the use of plasma exchange or intravenous immunoglobulins as alternatives to steroid.
3. Jacobs B. Epidemiology of traumatic and nontraumatic osteonecrosis. Clin Orthop Relat Res. 1978; 130: 51-67.
Rottoli M, Barcella V, Conti MZ and La Gioia S. Steroid Induced Femoral Osteonecrosis in Multiple Sclerosis: Two Case Reports. SM Musculoskelet Disord. 2017; 2(3): 1019.
Occlusion is biologically defined as the coordinated functional interaction between the various cell populations forming the masticatory system as they differentiate, model, remodel, fail and repair
Talia Becker*
Achilles tendon is a common site of foot and ankle discomfort but its rupture is not frequent. It’s a superficial tendon and this lends it to excellent evaluation by sonography instead of magnetic resonance imaging. Recently ultrasonography has been widely used in musculoskeletal practice. We present a case of Achilles tendon ruptures diagnosed based on fundamental sonographic findings.
Arash Babaei-Ghazani¹,², Safoora Ebadi¹,², Bijan Forogh¹,³, and Bina Eftekharsadat⁴*
Osteoarthritis (OA), one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed to apply approaches from mouse genetics. Although proteinases like matrix metalloproteases and aggrecanases have now been proven to be the principal initiators of OA progression, clinical trials of proteinase inhibitors have not been successful for the treatment, turning the interest of researchers to the upstream signals of proteinase induction. These signals include under graded and fragmented matrix proteins like type II collagen or fibronection that affects chondrocytes through distinct receptors. Another signal is pro inflammatory factors that are produced by chondrocytes and synovial cells; however, recent studies that used mouse OA models in knockout mice did not support that these factors have a role in the central contribution to OA development. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease.
Hiroshi Kawaguchi
Estimating the Knee Functional Axis (KFA) is crucial to both correctly implanting the prosthesis and accessing the joint kinematics. Researchers have mainly reported KFA by manual management of flexion extension movements, which are passively performed without any voluntary movements. Active touch and movement refers to what is ordinarily called as touching, which is defined as variations in skin stimulation caused by variations in a person’s motor activity.
The difference is very important for the individual. However, it has not been emphasized in the biomechanical literatures. This study aims to confirm the distinction between touching and being touched. We are particularly interested in measuring the Instantaneous Axes of the Knee (IAK) during locomotion. This geometrical “pattern” of the IAK is altered along with the touch pattern by the mechanical necessities of terrestrial movement.
Wangdo Kim¹, Young Choi², and Hong-Gi Lee³*
Although fractures of the epiphyseal cartilage injuries are common in childhood, epiphyseal fractures involving the proximal tibia entities are very rare and are usually caused by high-energy trauma, with an incidence ranging between 0.5 and 3.1% of patients; peak incidence between the ages 12-14 years in male patients. The aim of this report is describe a case of fracture of the epiphyseal cartilage of a 13 year old boy, a victim of sports trauma showing lateral tibial plateau fracture and epiphyseal cartilage fracture at the same side, not compatible with the classifications of fractures in children.
Omar Ferreira Miguel
In the last few years, clinical applications of regenerative medicine have been increasing their way in medical practice.
Valerio Di Nicola¹,² and Mauro Di Pietrantonio³*
The twentieth century epidemic of low back pain has continued unabated into the 21st century. Up to 20% of the Australian population will experience low back pain at some stage of their lives
J Saunders¹, M Cusi¹,³ and H Van der Wall¹,²*
Music is the most essential ingredient of any entertainment. In order to create successful entertaining event musicians plays an imperative role. Musicians are wizards who spread the fragrance of joy by absorbing woes, in the form of Playing Related Musculoskeletal Disorders (PRMDs), for themselves. Like other occupations, musicians also suffer from work related musculoskeletal disorders which are often disabling
Wricha Mishra
Dupuytren’s Contracture (DC) is a fibro-proliferative tumor according to ICD 10 - fascial fibromatosis of unknown etiology (M 720), accompanied by a stable bending contracture of fingers. In CD in the postoperative period extremely high rate of surgical complications is observed: intraoperative (injury of blood vessels, nerves, tendons), general postoperative (hematoma, necrosis, odema, stiffness, etc.), late postoperative (recurrence, spread, progression). In the last case according to the data of different authors, complications frequency is depend upon the degree (from partial up to the total) and the accuracy of excision of the affected aponeurosis ?almaris. One of the problems in choosing the type of operation and technology is the complexity of the cutoff determination boundaries of the affected CD. Up to now there is no suitable for use in the practical CD surgery algorithm of the affected aponeurosis ?almaris spread non invasive visualization in a particular patient. The most appropriate method for the solution of this problem is a method of MRI. The technology of identifying the boundaries of surgery of the affected aponeurosis palmaris in Dupuytren’s contracture by means of MRI has been elaborated. It has been shown that MRI is a highly informative method in the assessment of topographic anatomy of aponeurosis palmaris in normal and CD states. PD, T1, T2 - weighed images allow objectively to visualize the border areas of the affected aponeurosis in I - III stages of CD. PD fsat (fat tissues signal saturation) MRI mode is not recommended for use.
Baikeev RF¹, Mikusev GI², Osmonaliyev IZh², Zakirov RH² and Afletonov EN²*
Metallosis is an aseptic fibrosis, local necrosis, inflammation, or loosening of an implant device secondary to metallic corrosion and release of wear debris. The condition has been highlighted recent years due to the clinical complications caused by metal-on-metal (MoM) hip replacement. Although some major types of MoM hip prostheses have been recalled from the market, metallosis is far from over as not only there are still a million implanted MoM hip prosthetic cases worldwide, but also it has been found in non-MoM hip prostheses and other metal implants. This mini review aims to provide recent findings of implants related metallosisin skeletal tissue.
Zhidao Xia