tacrolimus and Osteonecrosis

The success of organ transplantation allows many transplant recipients to return to life similar to nontransplant patients. Their need for regular health care, including preventive medicine, has switched the majority of responsibilities for their health care from transplant specialists to primary care physicians. To take care of transplant recipients, it is critical for primary care physicians to be familiar with immunosuppressive medications, their side effects, and common complications in transplant recipients. Ten subjects are reviewed here in order to assist primary care physicians in providing optimal care for transplant recipients.

Topics: Adrenal Cortex Hormones; Contraceptive Agents, Female; Cyclosporine; Diarrhea; Drug Interactions; Drug Monitoring; Elective Surgical Procedures; Female; Graft Rejection; Humans; Immunosuppressive Agents; Male; Medication Adherence; Mycophenolic Acid; Organ Transplantation; Osteonecrosis; Polycythemia; Pregnancy; Pregnancy Complications; Primary Health Care; Sirolimus; Tacrolimus; Transplant Recipients; Urinary Tract Infections

To compare the effect of two immunosuppressive agents, cyclosporin A and tacrolimus, in terms of the development of osteonecrosis after renal transplantation, a cohort study was done. The cyclosporin A group and the tacrolimus group consisted of 32 patients each, and were matched for age, gender, and renal allograft (cadaveric or living). Four patients with osteonecrosis of the femoral head and one patient with osteonecrosis of the knee were observed in the cyclosporin A group, whereas none of the patients in the tacrolimus group had osteonecrosis. All five patients with osteonecrosis were diagnosed on magnetic resonance imaging within 2 years after renal transplantation, and were followed up for more than 3 years after diagnosis. Significant differences were observed in the number of patients with acute rejection (cyclosporin A, 16 patients versus tacrolimus, seven patients). Significant differences also were found in the dose of pulse corticosteroids at 2 weeks (cyclosporin A, 1161.1 +/- 939.6 mg versus tacrolimus, 674.3 +/- 587.5 mg) and 4 weeks after transplantation (1727.5 +/- 1399.9 mg versus 965.0 +/- 861.9 mg). The risk of osteonecrosis after renal transplantation was reduced in the patients who used tacrolimus for immunosuppression, which reduced the number of acute rejection episodes and the dose of pulse corticosteroid administration.

Topics: Acute Disease; Adult; Anti-Inflammatory Agents; Cyclosporine; Drug Therapy, Combination; Female; Femur Head Necrosis; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Knee; Magnetic Resonance Imaging; Male; Osteonecrosis; Prednisolone; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome

Immunosuppressant-related hip pain can greatly affect a patient's mobility and increase the number of total hip arthroplasties. We investigated risk factors and causes of hip pain after orthotopic liver transplant.. The medical records of 175 adult orthotopic liver transplant patients, who were followed-up for more than 2 years, were retrospectively reviewed. Data collected from the records included primary disease, medications, biochemical results, Child-Turcotte-Pugh score, death, rejection, and complications related to liver transplant.. A total of 11 patients (6.3%) complained of hip pain, which was diagnosed as calcineurin-inhibitor-induced pain syndrome in 4 patients (2.3%), osteonecrosis of the femoral head in 3 patients (1.7%), and osteoporosis in 2 patients (1.1%). The incidence of calcineurin-inhibitor-induced pain syndrome was related to the dosage of tacrolimus (P > .05) but independent of methylprednisolone use. The occurrence of osteonecrosis of the femoral head was independent of the dosage and early withdrawal of methylprednisolone (P > .05). Patients with methylprednisolone withdrawal within 6 months had significantly longer survival than those using methylprednisolone for more than 6 months (50 ± 15 vs 41 ± 18 mo; P = .007).. Calcineurin-inhibitor-induced pain syndrome and osteonecrosis of the femoral head are main causes of hip pain in adult orthotopic liver transplant patients. Osteonecrosis of the femoral head was not common, but the incidence of hip pain owing to calcineurin-inhibitor-induced pain syndrome was relatively high in orthotopic liver transplant patients. Early withdrawal of methylprednisolone could benefit the patients' survival.

Topics: Adult; Aged; Arthralgia; Calcineurin Inhibitors; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hip Joint; Humans; Immunosuppressive Agents; Incidence; Liver Cirrhosis; Liver Failure; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Osteonecrosis; Osteoporosis; Retrospective Studies; Risk Factors; Tacrolimus

With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China.. A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported.. The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up.. The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

Topics: Adult; Aged; Cyclosporine; Female; Femur Head Necrosis; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Osteonecrosis; Retrospective Studies; Risk Factors; Sirolimus; Tacrolimus; Young Adult

The aim of this study was to investigate the incidence of osteonecrosis of the hip and knee among renal allograft recipients treated with cyclosporin- or tacrolimus-based immunosuppressive regimens and its predictors focusing on the first 8 weeks after transplantation. The subjects were 232 renal allograft recipients who had MRI for osteonecrosis of the hip and knee 3 months or longer after transplant. The following potential predictors of osteonecrosis were tested using univariate and multivariate logistic regression analyses: age, gender, body weight, body mass index, duration on dialysis before transplant, number of human leukocyte antigen mismatches, ABO mismatches, type of transplanted kidney, immunosuppressive regimen, cumulative steroid dose and steroid pulses, incidence of acute rejection, and delayed graft function, defined as requiring dialyses in the first week. Evidence of osteonecrosis was visible on the MRI of 11 recipients (4.7%, 95% confidence interval 2.4-8.3). Univariate and multivariate logistic regression analyses indicated that delayed graft function was the most important predictor of osteonecrosis. In conclusion, we found a lower incidence of osteonecrosis of the hip and knee in renal allograft recipients treated with cyclosporin or tacrolimus. In the patients treated with improved immunosuppressive regimens, delayed graft function was a significant early predictor of osteonecrosis.

Topics: ABO Blood-Group System; Adolescent; Adult; Body Mass Index; Child; Cyclosporine; Delayed Graft Function; Female; Graft Rejection; Hip; HLA Antigens; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Knee; Male; Middle Aged; Osteonecrosis; Tacrolimus; Treatment Outcome; Young Adult

The present study examined the effects of tacrolimus (FK506) on the development of osteonecrosis in rabbits. In Experiment A, rabbits were given FK506, and also given a single dose of steroid. Control rabbits were given the same dose of steroid only. In Experiment B, rabbits were given FK506 and a reduced dose of steroid. The results showed that addition of FK506 did not change the number of rabbits with osteonecrosis when an identical steroid dose was given. When the steroid dose was reduced, the osteonecrosis incidence significantly decreased (p < 0.01). These results suggest that the clinically reported decrease in the osteonecrosis incidence following the introduction of FK506 is most likely attributable to the lower doses of steroids.

Topics: Animals; Disease Models, Animal; Immunosuppressive Agents; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Osteonecrosis; Rabbits; Steroids; Tacrolimus