mycophenolic-acid and Osteonecrosis

The treatment of SLE remains complex, and management is constrained by a lack of safe, effective, targeted therapies. Physicians, also, are constrained by a lack of evidence-based approaches with existing agents, including glucocorticoids, utilized in the majority of patients. While Cushingoid side effects of glucocorticoids are widely recognized, emerging literature now suggests that glucocorticoid use actually contributes to harmful outcomes in SLE, over and above these effects. These studies provide a compelling case for a re-evaluation of the long-term use of glucocorticoids in SLE, focusing on minimizing glucocorticoid exposure as part of the strategy to improve long-term outcomes. In this article, we review the evidence for the harmful effects of glucocorticoids in SLE, and propose therapeutic options that reduce reliance on glucocorticoids. We propose that it is time for the lupus community to have a louder conversation about glucocorticoid use, and for any residual complacency about their risk-benefit ratio to be banished.

Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Azathioprine; Cardiovascular Diseases; Cataract; Cushing Syndrome; Diabetes Mellitus; Disease Progression; Evidence-Based Medicine; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Osteonecrosis; Osteoporotic Fractures

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

Systemic lupus erythematosus is a multi-organ inflammatory autoimmune disease; immune complexes are part of the pathogenesis, but not entirely responsible. Trisomy X is the most common female chromosomal abnormality and the role of an additional X chromosome in the development of systemic lupus erythematosus is well recognized. However, the potential complications and optimal management of childhood lupus with trisomy X remain unclear. Herein, we describe a case of childhood-onset systemic lupus erythematosus associated with severe bone complications presumably secondary to trisomy X.. A 16-year-old Japanese girl was diagnosed with childhood-onset systemic lupus erythematosus and trisomy X. A chromosomal abnormality (47, XXX) was incidentally identified on bone marrow examination initially done to determine the cause of pancytopenia. She had a persistent headache, fever　for six days, diffuse hair loss, mucosal ulcers, butterfly eruptions, and palmar erythema. Furthermore, thrombocytopenia, anemia, and erythrocyte fragmentation were detected, suggesting secondary thrombotic microangiopathy. She was initially treated with intravenous methylprednisolone pulse therapy and prescribed monthly cyclophosphamide for severe disease activity, prednisolone, mycophenolate mofetil, and hydroxychloroquine as remission maintenance drugs. She developed generalized extremity pain that had been worsening throughout the disease. Extremity magnetic resonance imaging performed 12 months after the treatment onset revealed multifocal avascular necrosis, and dual-energy X-ray absorptiometry revealed further decreased bone mineral density. High plasma levels of factor VIII were detected by additional tests for coagulation functions, and we suspected the possibility that factor VIII might cause avascular necrosis due to thrombosis. Currently, she is being treated with prednisolone and MMF for SLE. However, her extremity pain has not been managed effectively even under the administration of non-steroidal anti-inflammatory drugs and pregabalin.. An additional X chromosome has been reported to be associated with factor VIII and osteoporosis. Additionally, elevated plasma levels of FVIII is the risk factors for thrombosis, which leads to the risk of avascular necrosis. Patients with systemic lupus erythematosus complicated by trisomy X might be at a higher risk of avascular necrosis and osteoporosis that can also manifest in childhood systemic lupus erythematosus.

Topics: Adolescent; Antirheumatic Agents; Bone Marrow Examination; Chromosomes, Human, X; Cyclophosphamide; Factor VIII; Female; Humans; Lupus Erythematosus, Systemic; Medication Therapy Management; Methylprednisolone; Mycophenolic Acid; Osteonecrosis; Osteoporosis; Pancytopenia; Severity of Illness Index; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development; Thrombosis; Trisomy

Topics: Aged, 80 and over; Bone Density Conservation Agents; Denosumab; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Jaw Diseases; Mycophenolic Acid; Osteonecrosis; Osteoporosis; Pemphigus; Prednisolone

Osteoporosis, osteopenia, and osteonecrosis are common in renal transplant recipients. In this study, we evaluated relationship between bone mineral density (BMD) and posttransplant duration; creatinine clearance; serum levels of glucose, calcium, phosphorus, alkaline phosphatase, vitamin D (vitD), parathormone, magnesium, C telopeptide, osteocalcin, lipids, and vit D therapy. Eighty five subjects included in this study had a mean age of 36.25 ± 10.5 years. At least at 6-month intervals we measured femoral neck (FN) and lumbar vertebra (LV) by DEXA and biochemical parameters. VitD was prescribed in 57 patients (vitDG). The mean duration of posttransplantation follow-up was 9.82 ± 2.72 months. T scores (TS) of FN and LV were normal in 29.4% and 21.2%; osteopenia in 56.5% and 49.4%; and osteoporosis in 12.1% and 29.4% of patients, respectively. Upon follow-up, TS improved significantly from -1.58 to -1.46 in FN and from -1.88 to -1.70 in LV (P < .05 for both). In patients receiving vitDG, TS improved significantly from -1.74 to -1.61 on FN and from -2.16 to -1.97 on LV (P < .05 for both). Osteocalcin and vitDG levels decreased in all patients (P < .05 for all). Blood urea nitrogen and serum creatinine increased (P < .05). In VitDG cohort, triglyceride levels decreased (P < .05) with unchanged blood glucose values; but among the other patients, triglycerides were unchanged but glucose levels had increased (P < .05). Bone disease including osteopenia or osteoporosis was observed among 70%. During the follow-up period, BMD increased significantly from baseline at 9.82 ± 2.72 months. VitD therapy caused more prominent improvements in BMD and decreases in serum triglycerides as well as mutigated the increase in blood glucose.

Topics: Azathioprine; Bone Density; Bone Diseases; Bone Diseases, Metabolic; Creatinine; Female; Humans; Kidney Transplantation; Lipids; Male; Methylprednisolone; Mycophenolic Acid; Osteonecrosis; Osteoporosis; Sirolimus; Vitamin D