tacrolimus and Bone-Diseases

Transient hyperphosphatasemia, characterized by isolated highly elevated alkaline phosphatase (ALP) activity in the absence of liver or bone disease, is typically seen in children but rarely in adults. Here we report highly elevated ALP activity in a complicated multiple-organ transplant patient due to benign transient hyperphosphatasemia.. A 54-year-old male had a complicated past medical history including a bilateral lung transplant for cystic fibrosis in 2006, colonic resection due to colon cancer in December 2011 and subsequent chemotherapy which ended in June 2022. He also had combined liver and kidney transplant in 2022 at our academic medical center. Post-transplant, he was treated with triple drug immunosuppressant therapy (tacrolimus, mycophenolic acid, and prednisone). Although his alkaline phosphatase (ALP) activity was 83 U/L, it continued to increase three months after combined liver and kidney transplant even though other liver enzymes were mildly elevated but total bilirubin remained within their reference ranges. Flecainide was discontinued but his ALP remained high, peaking at 5904 U/L. Finally, lansoprazole, ergocalciferol (vitamin D2) and vitamin E supplement were discontinued as nonessential medications, and coincidently ALP activity started to decline.. After ruling out all possibilities that may cause elevated ALP, we concluded that this is a rare case of benign transient hyperphosphatasemia in an adult transplant recipient.

Topics: Adult; Alkaline Phosphatase; Bone Diseases; Child; Humans; Immunosuppressive Agents; Liver; Male; Middle Aged; Tacrolimus

To identify the value of magnetic resonance imaging (MRI)-proven bone edema in patients with very early rheumatoid arthritis (RA).. All of the 13 patients included in the study were positive at entry for MRI-proven bone edema of the wrist and finger joints and anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. A tight control approach was applied for 12 months. Plain MRI and radiographs of both wrist and finger joints were examined every 6 months. MRI was scored by the RA MRI scoring (RAMRIS) technique and plain radiographs were scored using the Genant-modified Sharp score. Variables that were correlated with plain radiographic changes at 12 months were examined.. Simplified disease activity index (SDAI) remission was achieved in 7 patients, and a significant reduction in the RAMRIS bone edema score, which declined to <33 % as compared with the baseline, was achieved in 8 out of 13 patients. Four patients showed plain radiographic progression while 9 patients did not. Significant reductions in the RAMRIS bone edema score (p = 0.007) and the time-integrated SDAI (p = 0.031) were the variables involved in plain radiographic progression.. Improvement in bone edema may be associated with protection against structural damage in very early RA patients managed using the tight control approach.

Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Bone Diseases; Disease Progression; Edema; Female; Finger Joint; Humans; Magnetic Resonance Imaging; Male; Methotrexate; Middle Aged; Radiography; Sulfasalazine; Tacrolimus; Treatment Outcome; Wrist Joint

The purpose of this study was to demonstrate that living bone allotransplants can incorporate, remodel, and maintain mechanical properties without long-term immunosuppression in a fashion comparable to living autotransplants. For this, viability is maintained by repair of nutrient vessels and neovascularization from implanted host-derived vasculature. Microsurgically revascularized femoral diaphysis allotransplants were transferred from young male New-Zealand-White (NZW) into 4 groups of male Dutch-Belted (DB) rabbits. Short-term immunosuppression by tacrolimus (IS, groups 4 and 5) and host-derived neovascularization (NV) from implanted fascial flaps was used to maintain viability (groups 3 and 5) as independent variables. Group 2 received neither IS nor NV. Vascularized pedicled autotransplants were orthotopically transplanted in group 1. After 16 weeks, transplants were evaluated using radiologic, histologic, biomechanical, and histomorphometric parameters. Vascularized bone allotransplants treated with both short-term IS and host-derived NV (group 5) healed in a fashion similar to pedicled autotransplants (group 1). Their radiographic scores were higher than other groups. Groups with patent fascial flaps (3 and 5) showed significantly greater neoangiogenesis than ligated controls (2 and 4). Tacrolimus administration did not affect neoangiogenesis. Elastic modulus and ultimate stress were significantly greater in autogenous bone than in allotransplanted femora. Biomechanical properties were not significantly different among allotransplants. Bone turnover was decreased with IS, but increased with NV by the implanted fascial flaps. Living allogeneic femoral allotransplants treated with short-term IS and host-derived neoangiogenesis can lead to stable transplant incorporation in this rabbit model. The combination of both factors optimizes bone healing. Transplant mineralization is improved with neoangiogenesis but diminished with IS.

Topics: Animals; Biomechanical Phenomena; Bone Diseases; Bone Remodeling; Bone Transplantation; Diaphyses; Femur; Fracture Healing; Immunosuppression Therapy; Immunosuppressive Agents; Male; Neovascularization, Physiologic; Rabbits; Surgical Flaps; Tacrolimus; Tomography, X-Ray Computed; Transplantation, Homologous

Since the advent of transplantation as a life-saving procedure for patients with end-stage liver disease, more than 15,000 children and adolescents have received liver transplants. With the improvements in long-term posttransplant survival offered by advances in medical and surgical therapy, the concept of transplantation outcome has expanded beyond simple patient and graft survival rates. The quality of the life years restored, the long-term complications of transplant immunosuppression, and the overall cost of care have been increasingly recognized as important components of liver transplantation outcome. This review focuses on the efforts of a single pediatric transplant center to examine the incidence of, and risk factors for, common posttransplantation complications, to characterize posttransplantation health-related quality of life, to describe the cost of posttransplant care, and to implement novel programs to improve health care delivery. Together, these projects set the future course for research and care improvement initiatives in this population and encourage us to "keep the end in mind" when considering pediatric liver transplantation.

Topics: Adolescent; Biliary Atresia; Bone Density; Bone Diseases; Calcineurin Inhibitors; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Cyclosporine; Enzyme Inhibitors; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Humans; Immunosuppressive Agents; Information Services; Kidney Failure, Chronic; Length of Stay; Liver Failure, Acute; Liver Transplantation; Male; Ohio; Postoperative Complications; Quality of Life; Risk Factors; Tacrolimus; Treatment Outcome

To investigate the relationship between polyunsaturated fatty acid (PUFA) and bone metabolism in renal transplant patients, plasma phospholipid (PP) PUFA levels, biochemical markers of bone turnover and bone mineral density (BMD) were determined in 22 recipients of a first renal allograft at baseline and after a mean 24.4 month follow-up. A significant increase in PP n-3 PUFA content, in the [n-3 PUFA/ arachidonic acid] ratio and in BMD values was observed, as well as a close correlation between the increase in PP n-3 PUFA content and femoral neck BMD. Multivariate regression analysis showed that BMD improvement was positively related to PP n-3 PUFA variation and baseline PP eicosapentaenoic acid levels, and negatively to PP arachidonic acid modification. Tacrolimus- versus cyclosporine-treated patients demonstrated a significant increase in femoral neck BMD and PP n-3 PUFA content. This is the first longitudinal study showing a link between PP-PUFA composition and bone disease in renal transplantation.

Topics: Adult; Arachidonic Acid; Biomarkers; Bone Density; Bone Diseases; Bone Remodeling; Cyclosporine; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Femur Neck; Humans; Immunosuppressive Agents; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Phospholipids; Tacrolimus

Bone marrow derived mesenchymal stem cells (MSC) have been shown to be progenitor cells for mesenchymal tissues. These cells may also provide a potential therapy for bone repair. Our previous studies showed that MSC engineered with the gene for bone morphogenetic protein 2 (BMP-2), a growth factor for bone cells, were capable of differentiating into osteoblast lineage and inducing autologous bone formation in several animal models. Culturing individual MSC for autologous implantation, however, remains problematic. The number of human MSC with osteogenic potential decreases with age, and, in certain diseases, the patient's marrow may be damaged or the healthy cells reduced in number. In this study, we used rats with a femoral segmental defect to investigate whether allogeneic BMP-2 engineered MSC would facilitate bone healing. We show that BMP-2 engineered allogeneic MSC can repair critical bone defects to the same degree as rats treated with BMP-2 engineered autologous MSC, if the allogeneic group receives short-term treatment with immunosuppressant FK506. We also show that allogeneic gene transferred MSC are directly involved in bone repair, in addition to acting as gene deliverers.

Topics: Animals; Bone Density; Bone Diseases; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Cell Differentiation; Female; Femur; Genetic Therapy; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Male; Mesoderm; Osteoblasts; Radiography; Rats; Rats, Inbred BN; Rats, Inbred F344; Stem Cell Transplantation; Tacrolimus; Transforming Growth Factor beta; Transplantation, Homologous

Topics: Bone Diseases; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Leg Bones; Middle Aged; Pain; Syndrome; Tacrolimus