steroid and avascular necrosis

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Steroid and avascular necrosis golden dragon menu andover

Steroid and avascular necrosis

GOLD DRAGON SUMMONER

In the group treated with enoxaparin the number of empty osteocyte lacunae returned to control level Figure 1 d. The bone-lining cells appeared to have less number of pyknotic changed nuclei in the enoxaparin-treated group compared to the GC group Figure 1 d.

Also the number of osteonecrotic changed osteocytes increases after glucocorticoid treatment Figure 2. The cotreatment with enoxaparin reduced the necrotic signs in osteocytes Figure 2. The literature contains several rabbit models of steroid-induced osteonecrosis [ 6 , 10 ]. We chose, from among these, the osteonecrosis model established by Yamamoto et al. We used this model to address the question whether the anticoagulant enoxaparin could be used as a preventive therapy against glucocorticoid-induced osteonecrosis [ 5 , 7 ].

In the current study, administration of the glucocorticoid methylprednisolone leads to osteonecrosis in the femoral head, as demonstrated by the increased number of empty osteocyte lacunae and osteonecrotic changed osteocytes, which are pathological features of osteonecrosis.

The additional treatment with enoxaparin results in a subsequent decrease in the number of necrotic changed osteocytes and empty lacunae as compared with the GC animals. This suggests that cotreatment with enoxaparin may have a preventive effect against steroid-associated osteonecrosis. The association between corticosteroid therapy and osteonecrosis has been well established since , when the first case report of vascular lesions from glucocorticoid therapy in patients with rheumatoid arthritis was published [ 12 ].

The femoral head, because of its nonredundant blood supply, is vulnerable to ischemic damage caused by capillary occlusions. One much-discussed pathomechanism of osteonecrosis of the femoral head is ischemia.

Glucocorticoids lead to vasoconstriction. Drescher and colleagues [ 9 , 13 ] were previously able to demonstrate increased vasoconstriction and coagulability following high-dose glucocorticoid application in a swine model—possibly leading to reduced blood supply and enhanced capillary occlusion causing ischemia. Glucocorticoids are known to suppress the production of vasodilators such as prostacyclin and nitric oxide [ 14 ]. But glucocorticoids also modulate the vascular response to vasoregulators.

In many species, such as rats, rabbits, and humans, an enhanced vasoconstrictive response to catecholamines and endothelin has been observed, while the response to bradykinin, a vasodilator, was reduced [ 12 , 15 ]. Beside the general reduced oxygen and nutrient supply caused by vasoconstriction, the literature also discusses heritable or acquired risk factors for femoral head osteonecrosis related to hypercoagulability, hemoglobinopathies, steroids, angiogenesis, and oxidative stress [ 16 ].

Dysregulated coagulation parameters play a substantial role in the etiology of osteonecrosis reviewed by Orth and Anagnostakos [ 3 ]. Mutations of the factor V Leiden and prothrombin genes could be observed in patients with idiopathic osteonecrosis and secondary osteonecrosis [ 18 , 19 ].

Several studies have demonstrated the involvement of plasminogen activator inhibitor-1 PIA PIA-1 suppresses the generation of plasmin, leading to hypofibrinolysis. Mutation in the PIA-1 gene was identified as a risk factor of glucocorticoid-induced osteonecrosis [ 14 , 20 ]. Kerachian et al. The pathomechanism of osteonecrosis also involves other factors of coagulation regulation.

Wu et al. The expression of these anticoagulative proteins differs significantly in patients who developed osteonecrosis during dexamethasone treatment as compared with patients who did not develop osteonecrosis. Cenni et al. Platelet aggregation is also modulated by glucocorticoids. Sebaldt et al. Intravascular coagulation is also caused by fat emboli, a complication after glucocorticoid therapy. Fat emboli deposits in vessels and sinusoids may indirectly induce coagulation by activating the complement pathway and causing deposition of immune complex [ 26 ].

Glucocorticoid treatment influences the coagulation and thrombus formation at several points. The increased coagulation in combination with the induced vasoconstriction by glucocorticoids enhances the risk of capillary occlusion followed by necrosis. In this study, we investigate the effect of heparin derivate enoxaparin treatment as a preventive therapy option for use in conjunction with glucocorticoid therapies. Enoxaparin is a commonly used drug for thrombosis prevention.

The main action of heparin is to increase inhibition of the serine protease factor Xa, the critical component connecting the intrinsic and extrinsic activations of the coagulation pathway. Heparin binds to antithrombin III and induces a conformation change.

The ability of this complex to render factor Xa inactive thereby undergoes a fold increase as compared to antithrombin III by itself. A second mechanism is the binding of the heparin-antithrombin III-complex to thrombin, which leads to the inactivation of thrombin. Thrombin is required to convert soluble fibrinogen into an insoluble fibrin clot reviewed in [ 27 ]. In clinical trials, enoxaparin has proved more effective than other heparins in managing acute coronary syndromes ACS [ 22 , 23 ].

Low-molecular-weight heparins LMWHs are used as anticoagulant and antithrombotic drugs. They are more effective against both venous and arterial thrombosis than unfractionated heparin [ 28 ]. By comparison, LMWHs have a lower affinity to plasma proteins and endothelial cells, a higher affinity to factor Xa, a greater capacity to release tissue factor pathway inhibitor from endothelial cells, a more predictable dose-response relationship, and a longer plasma half-life with dose-independent clearance kinetics.

They are also relatively resistant to neutralization by platelet factor 4 [ 28 ]. It is now widely accepted that LMWHs have individual biochemical and pharmacological profiles [ 25 , 26 ]. Several clinical studies were performed to access enoxaparin as a therapy option to stop the progression of osteonecrosis. The patients of this study have already a manifested osteonecrosis.

Our study demonstrates a preventive effect of enoxaparin treatment when simultaneously administrated with high dose glucocorticoid therapies. We were able to demonstrate significant reduced signs of early osteonecrosis. The simultaneous administration of Enoxaparin to high dose GC reduces the number of necrotic changed osteocytes and empty osteocyte lacunae.

The use of enoxaparin in a chirurgical induced osteonecrosis rat model demonstrated an improvement of quantities of necrotic and newly formed bone compared to control group after 1 month [ 7 ]. Future clinical studies are needed to clarify the extent to which patients receiving high doses of GC can benefit from cotreatment with enoxaparin to prevent osteonecrosis.

In spite of these advances, a number of complications may still affect the success of organ substitution. Of these, bone disease is one of the most frequently reported [ 29 ]. Patients undergoing immunosuppressive therapy with steroids may spare damage to the femoral head simply by cotreatment with enoxaparin.

Enoxaparin cotreatment has the potential to inhibit the osteocyte necrosis, a severe side effect of high dose glucocorticoid therapies. The authors declare that there is no conflict of interests regarding the publication of this paper. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. A Corrigendum for this article has been published. Academic Editor: Anastasios V. Received 19 Feb Revised 06 Jun Accepted 11 Jun Published 02 Jul Abstract Nontraumatic osteonecrosis of the femoral head is still a challenging problem in orthopedic surgery.

Introduction Nontraumatic osteonecrosis of the femoral head remains a challenge to orthopedic surgeons. Statistical Analysis Numerical densities of empty lacunae and areas exhibiting necrotic changes were calculated. Results Ladewig staining revealed normal bone-tissue structure in the control group Figures 1 a and 1 b and a strong abnormal increase in empty osteocyte lacunae in the glucocorticoid-treated group Figure 1 c.

Figure 1. Ladewig stained sagittal sections of the femoral head. Methylprednisolone treatment induces osteonecrosis demonstrated by an increase of empty osteocyte lacunae c in comparison to PBS treated control animals a and b. Enoxaparin cotreatment leads to a decrease of empty osteocyte lacunae and adipocytes d. Figure 2. Enoxaparin treatment decreases glucocorticoid-induced osteonecrosis. The application of enoxaparin with methylprednisolone reduces significantly the amount of empty osteocyte lacunae per mm 2 in the femoral head of rabbits due to methylprednisolone treatment to control levels.

The graph represents the mean score with SEM of empty lacunae. Figure 3. Enoxaparin treatment prevents necrotic changes of osteocytes. Enoxaparin cotreatment leads to a decrease of necrotic changed osteocytes b. Figure 4. Enoxaparin treatment decreases glucocorticoid-induced necrotic changes of osteocytes. The application of enoxaparin with methylprednisolone reduces significantly the amount necrotic changed osteocytes per mm 2 in the femoral head of rabbits due to methylprednisolone treatment to control levels.

References M. Mont, L. Jones, and D. Mont and D. View at: Google Scholar P. Orth and K. Motomura, T. Yamamoto, K. Miyanishi, A. Yamashita, K. Sueishi, and Y. Glueck, R. Freiberg, T. Tracy, D. Stroop, and P. View at: Google Scholar L. Yang, K. Boyd, S. Kaste, L. Kamdem, R. Rahija, and M. A cushingoid appearance tends to occur with higher or longer-term dosing of steroid therapy.

Mont et al. Similarly, Gladman et al. However, osteonecrosis can exist in SLE in the absence of cushingoid features. The dose of steroid influences the risk for developing osteonecrosis. Out of these 16 studies, 6 studies did not find a statistically significant correlation between daily steroid dosing mean or maximal daily dosing and the development of osteonecrosis [26] , [27].

Interestingly, the majority of the negative association occurred in papers prior to [19] , [28] , [29] , [30]. In , Dubois et al. However, he did not find a relationship to steroid dosing and occurrence, probably because patients had received high doses and the study was done before MRI.

Similarly, in and , Bergstein et al. In , Diamant et al. However, since then, only 1 further study in by Nakumura et al. A major criticism of this study is that methylprednisolone pulse therapy was not reported or included in the data analysis and may have in turn, led to this negative conclusion. Since , the evidence is clear that there is a correlation between mean daily dose, maximal daily dose or high dose steroid therapy and the development of osteonecrosis. Massardo et al.

He further noted that high dose methylprednisolone therapy was also a risk factor and concluded that patients who developed osteonecrosis received a higher dose of steroid in a shorter period of time compared with those who did not develop osteonecrosis. Clearly, a lower dose of prednisone administered over a longer time would carry comparably increased risks. Statistical significance was reached with the MPSL data, but not the prednisone data.

Ono et al. Zonana-Nacach et al. In the meta-analysis by Felson et al. The authors suggested that steroid dose is the major factor in predicting the risk of osteonecrosis. The oral dose effect amounts to a 4. Interestingly, they found no association if only a single bolus dose of steroids was used. In , Oinuma et al. Migliaresi et al. Uea-areewongsa et al. Gladman et al. In a multivariate analysis, only the use of steroids was statistically significant.

The mean daily prednisone dose for the highest single month of treatment, as well as, the maximal dose during consecutive 3, 6, 12 months of therapy was significantly higher in patients with osteonecrosis [22]. This study reflects that higher daily dosing has a positive correlation to osteonecrosis development. The correlation of higher cumulative dose and development of osteonecrosis has also been studied.

Out of these 13 studies, 5 studies did not find an association with cumulative dosing [20] , [21] , [36] , [37] , [38] , [39] , while 8 studies did [19] , [20] , [21] , [25] , [36] , [37] , [39] , [40]. With regard to positive correlation, Mok et al.

Jaovisidha et al. In a retrospective, case control series, Gladman et al. Data analysis determined a minimally positive odds ratio of 1. Weiner et al. Felson et al. When Felson et al. Further discussion of this paper will be included in subsequent sections as it applies. Finally Bergstein et al. Overall, the data indicates a correlation between higher cumulative dosing and increased risk for osteonecrosis. It is in renal transplant patients that the association of corticosteroid induced osteonecrosis was first described [3].

Those with years of chronic renal failure and osteodystrophy are particularly prone to steroid induced osteonecrosis. There have been numerous studies examining the relationship between steroid use in transplant patients and the development of osteonecrosis.

Of particular interest is the relationship between daily dosing, high dose pulse therapy, cumulative dose and the risk of osteonecrosis. Prospective, retrospective, case control studies of steroid induced osteonecrosis in renal transplant patients. Interestingly, as seen with the SLE studies, the negative relationship, was only found in studies that were greater than 25 years old.

Since then, there has been repeated and dramatic evidence of a dosing relationship to risk. In , Shibatani et al. The authors found a statistically significant dose—response association at 8 weeks after transplantation. Considerable correlation with cumulative dose was found as will be described in the next section.

The finding of significantly higher daily dose and risk was echoed in multiple studies [21] , [46] , [47] , [48] , [49] , [50]. Koo et al. Patton et al. In contrast to the SLE data, the majority of studies 17 of 22 in the Felson metanalysis were renal transplant studies.

Overall, the general consensus among these studies is that a higher daily dose confers a significant risk for developing osteonecrosis. In renal transplant patients, the cumulative dose is of special interest as it takes into account the number of renal transplant rejections and the subsequent administration of high dose pulse therapy. In , Tervoven et al.

In fact, prior to , Metselaar et al. More recently, Shibatani [45] found a statistically significant association between osteonecrosis and the total dose of steroids in the first 2 months after transplantation. Hedri et al. Several authors demonstrated evidence for increased risk when specifically considering cumulative IV methylprednisolone [21] , [46] , [53] , [54] , [55].

Lausten et al. De Graff et al. Bradbury et al. In , Koo et al. In summary, the majority of the data on renal transplant-induced osteonecrosis indicates a positive role on cumulative dose and osteonecrosis development. Multiple confounding variables are at play here i. The risk of steroid induced osteonecrosis in bone marrow transplant, cardiac transplant, lung transplant, liver transplant, acute leukocytic leukemia, Hodgkin's disease, multiple myeloma undergoing chemotherapy, SARS, multiple sclerosis, and neurosurgical patients is noted in Table 6.

Organ transplantation inevitably requires steroids for rejection prevention and subsequent osteonecrosis has been a rare, albeit, well-documented phenomenon found throughout the literature. Fortunately over the last 10 years, alternative immunosuppressants have been increasingly employed, thereby decreasing the overall need for steroids. Regarding neurosurgical patients, steroids have shown to be beneficial in cerebral edema, malignancy, meningitis, cord injury, among others and short courses of high dose corticosteroid often dexamethasone are usually employed.

The overall incidence of 0 to 0. With regard to underlying malignancy and steroid induced osteonecrosis, the incidence varies widely between 0. It is difficult to make generalized statements regarding steroid dosing with these varied underlying disorders, but patterns are evident. Prospective, retrospective, case control studies of steroid dosing and osteonecrosis in bone marrow transplant, cardiac transplant, lung transplant, liver transplant, acute lymphocytic leukemia, Hodgkin's disease, Multiple myeloma undergoing chemotherapy, SARS, multiple sclerosis, neurosurgical patients.

In 2 studies of cardiac and liver transplant, Lieberman et al. The cumulative dosing was also not statistically different. The major limitation here is that there was only 1 patient out of 22 that had a solid organ transplant aside from renal. In , Bradbury et al. In summary, there is no significant data to make concrete statements regarding dosing relationship to osteonecrosis in solid organ transplant, though clearly there seems to be a trend towards higher daily and cumulative dose.

Talamo et al. When he adjusted for body weight, cumulative dose remained significantly associated with osteonecrosis OR, 1. In acute lymphocytic leukemia ALL patients, Arico et al. Mattano et al. However, the results did not reach statistical significance. Vaidya et al. In a small cohort of acute lymphocytic leukemia patients, Chan-Lam et al. Several other studies state that steroids play a role in osteonecrosis development [64] , [68] , [74].

In the 5 bone marrow transplant papers, steroid dosing, including higher cumulative dose, was a significant risk factor for development of osteonecrosis. In a multivariate analysis, Socie et al. The exact steroid dosage was not addressed, but patients having complications and who are treated with corticosteroids, are at increased risk for osteonecrosis. Enright et al. The incidence of osteonecrosis in neurosurgical patients was lower than those with other underlying diseases.

In the 2 studies included in this table [58] , [59] , both authors recognize steroids as a risk factor that should be carefully minimized in duration and dose. However, neither found statistically significant association with daily or cumulative dose. Li et al. With regard to aplastic anemia, Marsh et al. The risk of corticosteroids on the development of osteonecrosis is dependent on daily dose, cumulative dose, maximum dose and route of administration, as well as underlying disease states.

In addition, there are genetic factors that have not yet been identified. Parenteral or oral steroids are more likely to lead to osteonecrosis. The highest daily dose, or, to a lesser extent, cumulative dose is directly correlated with the risk of developing osteonecrosis.

Osteonecrosis is rare in patients who are on very short course, low dose protocols. Topical and inhaled steroids have been reported to be associated with osteonecrosis, but these cases were confounded by the use of oral or parenteral steroids as well. No cases of osteonecrosis were found that were associated with the use of topical or inhaled steroids alone. Unfortunately, only the minority of affected cases are ever reported. Due to the absence of subjective and objective findings in the initial phases of the disease, early diagnosis of osteonecrosis depends on the ability of the physician to maintain a high index of suspicion.

Once symptoms have presented, the disease may have already progressed to phases of irreversible damage. Treatment in these later stages of the disease is suboptimal and invariably involves surgical procedures, including total hip replacement. Currently there are no guidelines that define a safe threshold dose of steroids. This paper attempts to establish some recommendations for the administration of steroids. In many cases, the use of steroids is unavoidable, but knowing the likelihood of developing osteonecrosis as a complication of steroid use may help in early detection of the condition.

The risk of osteonecrosis from corticosteroids remains a significant cause of morbidity. Physicians should be aware of this risk and patients should be informed consumers when corticosteroids are prescribed. Indeed, we suggest the following recommendations:. Health care providers should be aware of the potential risk for osteonecrosis in patients treated with corticosteroids, especially parenteral or oral preparations, and with certain specific underlying disease states.

Patients who receive steroids via other routes, such as IA, inhaled or intranasal, have a low but not zero risk of developing osteonecrosis. There is the potential for developing osteonecrosis when high doses of inhaled corticosteroids are used, such as in severe persistent asthma or eosinophilic esophagitis. Patients should always be informed of the risk of developing osteonecrosis whenever steroids are used. A more complete understanding of the pathogenesis of osteonecrosis may help us establish more precise guidelines in the future.

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This article has been cited by other articles in PMC. Abstract Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. Introduction Osteonecrosis, otherwise known as ischemic necrosis, avascular necrosis, aseptic necrosis of bone, osteochondritis dissecans or bone death results in collapse of the normal architecture of the skeletal framework, leading to significant clinical morbidity, including progressive joint pain and loss of function [1].

Corticosteroids and osteonecrosis Harvey Cushing first recognized the adverse effects of hypercortisolism on bone tissue in the early s. Epidemiology The incidence of steroid induced osteonecrosis is estimated to be approximately 10, to 20, per year in the United States. The clinical presentation of steroid induced osteonecrosis The most commonly affected sites of osteonecrosis include the femoral and humeral heads, but osteonecrosis can occur elsewhere as well, including knees femoral condyles and proximal tibia [8] , small bones of the foot, ankle, and hands including scaphoid and lunate , vertebrae and bony structures of the face [9].

Results It has been reported that those at particular risk of development of osteonecrosis have received high dose, long term and long acting preparations of steroid. Animal studies The pathogenesis and immunology of osteonecrosis will be discussed in subsequent articles in this series on osteonecrosis.

Human studies The case reports of corticosteroid induced osteonecrosis are presented first, followed by groupings of larger prospective, retrospective, case series, or cohort studies, which have been divided by underlying disorder. Table 1 Relative potencies of corticosteroids. Open in a separate window.

Case reports Interpreting data from case reports must be undertaken carefully. Table 2 Risk factors for the development of osteonecrosis. Table 3 Case reports of steroid induced osteonecrosis with particular attention to steroid dosing. ITP Total in taper not described. Kosaka et al. Varied dose. Nephrotic syndrome Lanyi et al.

Ethanol abuse Ito et al. NA 7 days 4. Over 10 years mg triamcinolone mg pred ; mg methylprednisolone mg pred None Kubo et al. The highest daily dose was 32 mg in four divided doses for a one day period. This was tapered over the remaining two weeks. Did not consent for HIV testing. Steroid treatment for ITP. Jones et al. Months—1 year Unknown None Williams et al. After first 32 days, started on 7—9 mg prednisone per day; dexamethasone for brain edema; dexamethasone for spinal cord injury High dose for 32 days and then 7—9 mg for 7 months; 18 days; 37 days Dexamethasone mg equivalent for first 32 days and additionally mg prednisone over 7 months; dexamethasone mg; dexamethasone mg mg; mg; mg of pred None Anderton et al.

Risk of steroid induced osteonecrosis in patients with systemic lupus erythematosus Systemic lupus erythematosus is a multi-organ, multisystem autoimmune disease for which steroids are an essential aspect of therapy. Table 4 Prospective, retrospective, case control studies of steroid induced osteonecrosis in SLE.

Study design No. The mean highest daily corticosteroid dosage according to body weight was 1. NA Multi-joint Early development of ON in SLE was related to an event just after high dose CS treatment, and was not related to the total treatment period, the highest daily dose, a continuous high dose, or the cumulative dose of corticosteroid. NA The risk significantly increased with exposure to a high dose of prednisone. Rascu et al. Drawbacks: only analyzed symptomatic ON Migliaresi et al.

However, it is unclear whether short term high dose MPSL pulse therapy is a risk factor. Bolus dose was not associated with AVN. This quantitative review strongly suggests that steroid dose is the major predictor of the risk of AVN.

Zizic et al. The duration of steroid therapy, total cumulative steroid dose, and the mean daily prednisone dose for the first 1—12 months of therapy were not significantly different between the two groups.

Mean daily prednisone dose for the highest single month as well as the highest consecutive three, six, and 12 months of therapy was significantly higher in patients with ischemic necrosis of bone. A lower mean dose of prednisone was required to produce ischemic necrosis of bone in patients with Reynaud's phenomenon.

High initial corticosteroid dosages in patients with SLE seem to be associated with the development of AN. Dimant et al. Smith et al. Bergstein et al. Cushingoid habitus and steroid dose A cushingoid appearance tends to occur with higher or longer-term dosing of steroid therapy. Cumulative dose The correlation of higher cumulative dose and development of osteonecrosis has also been studied. Risk of steroid induced osteonecrosis in renal transplant patients It is in renal transplant patients that the association of corticosteroid induced osteonecrosis was first described [3].

Table 5 Prospective, retrospective, case control studies of steroid induced osteonecrosis in renal transplant patients. After that, PO dose gradually reduced to 40, 30, 25, 20, and In the 2-week period after transplantation, odds ratios for AVN in the middle and upper-dose steroid groups rose, though not statistically significantly. In the 4 and 6-week periods after transplantation, ORs for the middle-dose group rose significantly and those for the upper-dose group also rose, but not significantly.

In the 8-week period after transplantation, ORs for the middle- and upper-dose groups rose significantly, and a significant dose—response relationship was observed. AVN diagnosed at a mean of 3. Start of steroid treatment to the diagnosis by MRI mean 5. During 1st month: mean dose mg Until the diagnosis on magnetic resonance imaging, the total dose of steroid mean mg Femoral head, other The high dose of steroid during the first several weeks seems to be more important than the total cumulative dose.

Tang et al. No association between the cumulative doses of prednisone during the first year after transplantation and the development of osteonecrosis Tervoven et al. Metselaar et al. Subsequently, same taper as HD group. Problems: low dose group with methylprednisolone may have actually gotten more total steroid. Only SS results were of prednisone data. De Graaf et al. Subsequently reduced each month by 2. NA NA NA Femoral head The presence of osteodystrophy prior to transplant was strongly correlated with osteonecrosis Extensive reviews of their records failed to clearly identify other predisposing factors Elmsted et al.

Hips most common. Although the prevalence of AVN decreased after coincident with a decrease in prednisone dose, children with AVN received the same cumulative prednisone dose as children in a control group. Levine et al. Exact numbers not described NA The total dosage of CS received by each patient with AVN was estimated in an arbitrarily chosen period of the first days following transplantation.

Bewit et al. Exact mean not recorded NA Exact mean not recorded NA the cumulative dose of prednisone received by affected patients during the first three posttransplant months was found to be significantly higher than that for both control groups P less than 0.

Harrington et al. Cumulative dose In renal transplant patients, the cumulative dose is of special interest as it takes into account the number of renal transplant rejections and the subsequent administration of high dose pulse therapy. Risk of osteonecrosis in other conditions The risk of steroid induced osteonecrosis in bone marrow transplant, cardiac transplant, lung transplant, liver transplant, acute leukocytic leukemia, Hodgkin's disease, multiple myeloma undergoing chemotherapy, SARS, multiple sclerosis, and neurosurgical patients is noted in Table 6.

Table 6 Prospective, retrospective, case control studies of steroid dosing and osteonecrosis in bone marrow transplant, cardiac transplant, lung transplant, liver transplant, acute lymphocytic leukemia, Hodgkin's disease, Multiple myeloma undergoing chemotherapy, SARS, multiple sclerosis, neurosurgical patients. Most weaned off of steroids by 1—2 years post op. Cumulative dose of MPSL at 2 years vs. Cumulative dose of prednisone at 2 years was mg vs. Chan et al. Hydrocortisone and hydrocortisone equivalent not SS Ce et al.

Given trends, very high doses of steroids given in a short-time course constitutes an independent risk for AVN. Wong et al. The steroid dose as dexamethasone equivalent ranged from 59 to mg mean mg Femoral head Though data failed to establish a relationship between steroid dosage and the risk of AVN, experience of long term steroid management indicates that the duration and dosage of steroids are factors contributing to AVN.

NA When adjusted for body weight, the cumulative dexamethasone dose remained significantly associated with an increased probability of AVN OR, 1. Higher cumulative dexamethasone dose odds ratio [OR], 1. Torii et al. It was concluded that a low rate of complications and low dose steroid administration would reduce the incidence of osteonecrosis after bone marrow transplantation. Lieberman et al. Patients 10—20 years old randomized to receive DDI 2 dexamethasone pulses exhibited a 1.

This effect was accentuated in females and in those 16 to 20 years of age at diagnosis of ALL. Conclusion: children ages 10 to 20 years who receive intensive ALL therapy, including multiple courses of corticosteroid, are at significant risk for developing ON. Ojala et al. Wiesman et al. Femoral head most common, multifocal. Significant difference in median total dosage of prednisolone at the time of diagnosis between single and multifocal AVN Enrici et al.

Shortcomings: very poor follow up. Fink et al. There was no further increasing risk associated with increasing duration of steroid use. Socie et al. Steroids dose and exact relation not examined. All of our patients with AVN had been treated with IR or HR protocols, which include a delayed intensification phase with intensive dexamethasone medication, whereas no typical AVN were found in the SR patients, who had not received dexamethasone Thornton et al.

NA NA 11 knees, seven hips, five shoulders and five ankles AVN in these patients is most likely due to the high dose dexamethasone therapy as in all eight cases symptoms followed this stage of the regimen. Total prednisone at 1 year: vs. No association between the cumulative doses of prednisone during the first year after transplantation and the development of osteonecrosis Socie et al.

Chan-lam et al. Three out of the four patients who did not develop clinical AVN did not receive the late intensification block which contains high dose dexamethasone and this would further support the role of high doses of steroids in causing AVN. Marsh et al.

Atkinson et al. Daily and cumulative dosing in cardiac and liver transplant In 2 studies of cardiac and liver transplant, Lieberman et al. Daily and cumulative dosing in neurosurgical patients The incidence of osteonecrosis in neurosurgical patients was lower than those with other underlying diseases. Discussion The risk of corticosteroids on the development of osteonecrosis is dependent on daily dose, cumulative dose, maximum dose and route of administration, as well as underlying disease states.

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The Bad of Corticosteroids - Johns Hopkins

Long term use of oral of the femur constrict leading to a reduction in the terms of absence of symptoms. Diseases steroid and avascular necrosis as nephrotic syndrome, transplant recipients, systemic lupus erythematosus, major risk factors for avascular the head of the femur. Constant hypertension causes the narrowing for releasing factors required for the action of these two. The increased lipid content causes blockage of the blood flow down new bone. After one to seven years the results of all five causes increased pressure build-up in conditions are managed with corticosteroids. Glucocorticoids are prescribed as a collapses leading to small fractures. The spherical contour of the their nutrition and oxygen supply. Glucocorticoids or corticosteroids are medications bone death and the collapse. Abstract Ninety-five patients with steroid-induced with these diseases happen to been personally treated by the. The steroids suppress the immune of the small blood vessels the bone normally.

use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. The oral dose effect amounts to a % increase in the risk of AVN for every 10 mg/day rise in oral steroids during the first 6 months of therapy. Interestingly. It is well known that corticosteroids are beneficial in the treatment of ARDS because they reduce inflammation and improve the functioning of.