mycophenolic-acid and Osteoporosis

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Bone Density; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Osteoporosis; Protein Kinase Inhibitors; Treatment Outcome

Corticosteroid treatment may have an important effect on body composition and bone mineral density (BMD) in renal transplantation (RTx) patients. We investigated the effect of early steroid withdrawal on body composition and BMD of RTx patients in a prospective design. Post-transplant immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisolone. Three months after RTx, 27 patients participating in a multi-center trial were randomized either to continue steroids (at a dose of 10 mg/day, n=17; steroid+) or be withdrawn from steroids within 2 weeks (n=10; steroid-). Body composition and BMD (lumbar spine (L2-L4) and femoral neck) were measured by dual-energy X-ray absorptiometry (DEXA) just before and 3 months after randomization. With regard to body composition, fat mass tended to increase in the steroid+ group (1.1+/-2.3 kg; P=0.084), but did not change in the steroid- group. Increase in body fat percentage tended to be higher (P=0.08) in the steroid+ group (0.6+/-2.7%) than in the steroid- group (-0.7+/-2.1%). The change in lean body mass was not significantly different between the two groups. BMD of the lumbar spine and femoral neck decreased significantly in the steroid+ group (-1.4+/-3.2% and -2.3+/-2.9%, respectively, P<0.05) while no changes were observed in the steroid- group. The change in BMD of the lumbar spine was significantly different between the steroid+ and the steroid- group, whereas the change in BMD of the femoral neck was not significantly different. Thus, the increase in fat mass tended to be higher in the group continuing on steroids, though not significant, due to large inter-individual variation. In general, the effect of early steroid withdrawal on body composition after RTx appears to be modest. In addition, early steroid withdrawal seems to have beneficial effects on BMD in RTx patients, especially in the lumbar region.

Topics: Adult; Aged; Body Composition; Bone Density; Female; Femur Neck; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney Transplantation; Lumbar Vertebrae; Male; Middle Aged; Mycophenolic Acid; Osteoporosis; Prednisolone; Tacrolimus

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

Post-transplantation bone disease is associated with a high degree of morbidity including pain and fractures. Glucocorticoid-induced osteoporosis on top of pre-existing renal osteodystrophy is considered the major pathogenic factor, while the role of non-glucocorticoid immunosuppressants is less well defined.. In this study, we investigated the influence of sirolimus (SRL) versus calcineurin inhibitor (CI)-based immunosuppressive regimens on biomarkers of bone resorption in renal transplant patients. In addition, the impact of SRL, tacrolimus and mycophenolate mofetil (MMF) on osteoclast activation and function was assessed in cell culture systems.. Using this approach, we demonstrated reduced serum levels of bone resorption markers in patients treated with SRL after kidney transplantation compared to a CI-based regimen. In line with this observation, we detected profoundly reduced osteoclast differentiation and subsequently diminished hydroxyapatite resorption in the presence of SRL compared to MMF and tacrolimus in vitro. Moreover, SRL significantly reduced osteoclast precursor proliferation in vitro compared to tacrolimus and led to augmented apoptosis in osteoclast precursors.. Taken together, SRL was shown to inhibit osteoclast formation in vivo and in vitro. SRL thus may have the potential to balance osteoclast promoting effects of glucocorticoids and CI, thereby counteracting the development of accelerated osteoporosis in renal transplant recipients.

Topics: Adult; Aged; Bone Resorption; Cell Differentiation; Cross-Sectional Studies; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Osteoclasts; Osteoporosis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Sirolimus; Tacrolimus; Young Adult

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

Decreased bone mineral density is a common problem after kidney transplantation. Osteoporosis has a major role in morbidity in these patients. We evaluated the incidence of osteoporosis and determined risk factors in 77 patients aged 17 to 50 years who had undergone renal transplantation 6 months to 2 years previously. Bone mineral densitometry was performed using dual-energy x-ray absorptiometry. The incidence of osteoporosis was 26% (20 of 77 patients). Mean (SD) age of affected patients was 34.6 (8.7) years. The most common sites of osteoporosis were the hip (osteoporotic in 19 patients [24.7%] and osteopenic in 42 [54.5%]) and the spine (osteoporotic in 6 patients [7.8%] and osteopenic in 52 [67.5%]). There was a significant relationship between posttransplantation creatinine concentration and hip osteoporosis (P = .01). No relationship was observed between osteoporosis and age, sex, body mass index, duration of hemodialysis therapy, cumulative dosage of any drugs, or use of pulsed methylprednisolone therapy. A hip or spine z score of 1 or less had no relationship to the number of steroid pulse sessions but was significantly related to the total dosage of cyclosporine (P < .001), prednisolone (P < .001), and mycophenolate mofetil (P < .05). A hip z score of less than 1 was related to the posttransplantation period (P = .02). In conclusion, osteoporosis is a frequent complication that requires detection and treatment to reduce morbidity.

Topics: Absorptiometry, Photon; Adolescent; Adult; Bone Density; Bone Diseases, Metabolic; Creatinine; Cyclosporine; Hip Joint; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lumbar Vertebrae; Middle Aged; Mycophenolic Acid; Osteoporosis; Prednisolone; Risk Factors; Spine; Young Adult

Post-transplantation bone disease is a frequent problem after successful cardiac transplantation. We performed a cross-sectional analysis of male heart transplant recipients in the late post-transplantation period. Nine patients (group A) had received immunosuppressive therapy with cyclosporin A and mycophenolate mofetil (steroid-free treatment), and 12 patients (group B) remained on triple-drug therapy, which included glucocorticosteroids. Bone mineral density status was analyzed by osteodensitometry and by markers of bone turnover. Osteopenia was common in both groups (44.4% in group A and 50% in group B) as was osteoporosis (30% and 33.3% in groups A and B, respectively). beta-CrossLaps were significantly lower in sera of cardiac transplant recipients on double immunosuppressive (i.e., glucocorticosteroid-free) regimen than in sera of patients on triple-drug therapy (428.3+/-109.4 vs 661.7+/-337.0 pg/ml, P<0.05). Lower serum beta-CrossLaps levels in patients undergoing glucocorticosteroid-free treatment may indicate a lower risk of bone deterioration in the long term.

Topics: Bone Density; Bone Diseases, Metabolic; Collagen; Cross-Sectional Studies; Cyclosporine; Drug Therapy, Combination; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Osteoporosis; Peptide Fragments; Prednisolone; Retrospective Studies

Topics: Adrenal Cortex Hormones; Bone Density; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Mass Screening; Mycophenolic Acid; Osteoporosis; Outpatient Clinics, Hospital