tacrolimus and Fractures--Bone

After osteoporotic fracture or low bone mineral density measurements, it is necessary to look for secondary causes of osteoporosis, such as drugs. Corticosteroids are the most common cause of drug-induced metabolic bone disease. Other drugs responsible for bone disease include: aromatase inhibitors, GnRH agonists, anticonvulsants, heparin, and L thyroxin at TSH-suppressive doses. Confirmation is required of data about neuroleptics and antivitamin K.

Topics: Aged; Animals; Anticoagulants; Anticonvulsants; Antipsychotic Agents; Aromatase Inhibitors; Bone Density; Child; Cyclosporins; Densitometry; Disease Progression; Diuretics; Female; Follow-Up Studies; Fractures, Bone; Gonadotropin-Releasing Hormone; Humans; Hypoglycemic Agents; Iatrogenic Disease; Immunosuppressive Agents; Lithium Compounds; Male; Menopause; Methotrexate; Middle Aged; Osteomalacia; Osteoporosis; Osteoporosis, Postmenopausal; Placebos; Prospective Studies; Protease Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Tacrolimus; Thyroid Hormones; Time Factors

Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant in a Taiwanese population.. We identified newly diagnosed liver transplant recipients from the National Health Insurance Research Database in Taiwan between 2003 and 2015. Risk factors of post-transplant fractures were analyzed using a Cox proportional hazards model.. A total of 4821 patients underwent liver transplantation, of whom 419 (8.7%) had post-transplant fractures. Independent predictors of post-transplant fractures were age ≥65 years at transplantation (hazard ratio (HR): 1.566; 95% confidence interval (CI) 1.122-2.186), female sex (HR: 1.648; 95% CI 1.319-2.057), fractures within 1 year prior to transplant (HR: 3.664; 95% CI 2.503-5.364), hepatitis C carriers (HR: 1.594; 95% CI 1.289-1.970), alcoholism (HR: 1.557; 95% CI 1.087-2.230) and daily prednisolone dose >1.61-3.78 mg/day (HR: 1.354; 95% CI 1.005-1.824), >3.78-9.18 mg (HR: 4.182; 95% CI 3.155-5.544) and >9.18 mg (HR: 13.334; 95% CI 9.506-18.703). Post-transplant fractures were inversely correlated with tacrolimus (HR: 0.617; 95% CI 0.417-0.913) and sirolimus/everolimus (HR: 0.504; 95% CI 0.391-0.650) treatment.. The liver transplant recipients, and especially those who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were associated with an increased risk of post-transplant fractures. Conversely, the use of tacrolimus and sirolimus/everolimus was associated with a decreased risk of fractures.. This study identified risk factors for fractures after liver transplant in a population-based study in an area with high prevalence of hepatitis B and hepatitis C.Recipients who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were independent risk factors for post-transplant fractures.Our findings highlight the importance of identifying individuals at high risk of fractures and concomitant tacrolimus and sirolimus/everolimus treatment to avoid the use of high-dose steroids and prevent post-transplant fractures.

Topics: Alcoholism; Cohort Studies; Everolimus; Female; Fractures, Bone; Hepatitis C; Humans; Immunosuppressive Agents; Liver Transplantation; Prednisolone; Proportional Hazards Models; Risk Factors; Sirolimus; Tacrolimus

Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1-/- femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.

Topics: Animals; B-Lymphocytes; Femur; Fracture Healing; Fractures, Bone; Homeodomain Proteins; Male; Mice; Mice, Inbred C57BL; Osteotomy; T-Lymphocytes; Tacrolimus; X-Ray Microtomography

Low bone mineral density (BMD) has been reported in 30.4% of adult patients with atopic dermatitis (AD).. The aim of this study was to determine the prevalence of low BMD in children with moderate to severe AD and to investigate the relation between BMD and corticosteroid and cyclosporine therapy.. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry in 60 children (age 5-16 years) with moderate to severe AD. BMD (in g/cm(2)) was expressed in Z-scores, the number of SD above or below the mean value of an age- and sex-matched reference population. In children, low BMD was defined as a Z-score less than -2. Information on lifestyle parameters and bone fractures were collected by use of a standardized questionnaire. The cumulative dose of corticosteroids and cyclosporine therapy was calculated for the previous 5-year period.. Three patients (5%) had low BMD; one patient (1.7%) had osteoporosis. The observed prevalence of low BMD in this study (6.7%; 95% confidence interval 1.8%-16.2%) does not differ from the expected prevalence of low BMD in the general population (P = .06). Overall, use of topical corticosteroids in the previous 5 years was not associated with a decrease in BMD (Z-score). When children received additional systemic treatment (oral corticosteroids and/or cyclosporine) in the previous 5 years, BMD decreased, although the decrease was not statistically significant. Correction for lifestyle parameters did not change these associations.. The number of patients studied was limited. The cumulative dose of corticosteroids and cyclosporine therapy was only registered for the previous 5 years, and relatively low amounts of topical corticosteroids were used. The definition of low BMD differs between adults (Z-score < -1) and children (Z-score < -2). Because there is no Dutch BMD reference population for children, normative BMD references were obtained from a different population (US children).. Low BMD did not occur more frequently in this population of children with moderate to severe AD compared with the general population. Use of topical corticosteroids in the previous 5 years was not associated with a decrease in BMD.

Topics: Absorptiometry, Photon; Adolescent; Adrenal Cortex Hormones; Bone Density; Child; Child, Preschool; Cyclosporine; Dermatitis, Atopic; Female; Fractures, Bone; Humans; Immunosuppressive Agents; Lumbar Vertebrae; Male; Osteoporosis; Prevalence; Risk Factors; Severity of Illness Index; Tacrolimus

Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation.. A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A--chronic cholestatic liver disease (n = 28), and group B--chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-1-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals.. BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving cyclosporin A.. Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.

Topics: Adult; Aged; Alkaline Phosphatase; Biomarkers; Bone Density; Bone Resorption; Cholestasis; Collagen; Collagen Type I; Cyclosporine; Female; Femur Neck; Follow-Up Studies; Forearm; Fractures, Bone; Glucocorticoids; Humans; Immunosuppressive Agents; Liver Diseases; Liver Transplantation; Longitudinal Studies; Lumbar Vertebrae; Male; Middle Aged; Norway; Osteocalcin; Osteoporosis; Peptide Fragments; Peptides; Postoperative Complications; Survival Analysis; Tacrolimus; Treatment Outcome; Waiting Lists

We report a 20-year-old-male with severe aplastic anaemia who was treated with nonmyeloablative haematopoietic stem cell transplantation (NSCT) from a sibling donor. As the patient presented with complications consisting of mental retardation, severe obesity, a bone fracture, and recurrent infections, we selected NSCT instead of a myeloablative regimen, to reduce regimen-related toxicity (RRT). Conditioning therapy consisting of busulfan, fludarabine, antithymocyte globulin and FK506 was used to obtain immune suppression. RRT was limited and he is now in complete remission 19 months after NSCT. On day 91, he developed chronic graft-vs.-host disease; it was resolved by the combination of FK506, corticosteroids, and mycophenolate mofetil. Our experience contributes to the growing interest in NSCT as a modality for treating not only malignant haematological disorders associated with complications, but also nonmalignant haematological diseases.

Topics: Adult; Anemia, Aplastic; Antilymphocyte Serum; Busulfan; Female; Fractures, Bone; Graft Rejection; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Intellectual Disability; Male; Methylprednisolone; Mycophenolic Acid; Obesity; Peripheral Blood Stem Cell Transplantation; Prednisolone; Remission Induction; Siblings; T-Lymphocytes; Tacrolimus; Tissue Donors; Transplantation Chimera; Transplantation Conditioning; Vidarabine

Osteoporosis is known to occur in patients with kidney transplants, but limited information is available about the prevalence and causes of this complication. We asked all 330 patients with kidney transplants in our unit to participate in this study of whom 165 (50%) agreed to do so. The characteristics of the participating patients were similar to the remaining 165 nonparticipants. Seventy of 165 (42%) of the participants were women of whom 40 were postmenopausal in contrast to the men of whom only one was hypogonadal. Bone mineral density (BMD) was significantly reduced at the radius (Z score, -1.5) and femoral neck (Z score, -0.7), but the lumbar spine was normal. BMD was lower in women than men at all skeletal sites. Osteoporosis was found in 10-44% and osteopenia was found in 35-50% of women depending on the site. BMD was related inversely to time since transplantation and cumulative prednisolone dose. Twenty-seven of the 165 (16%) patients had either vertebral deformities or a history of a low trauma fracture after transplantation. This fracture group consisted of 10/27 (37%) men and 17/27 (63%) women, of whom 14 were postmenopausal. Fracture patients tended to be older and have a longer duration of renal failure, dialysis, transplantation, greater cumulative steroid dose, and higher bone resorption markers than the nonfracture group. No differences were found for cumulative doses of cyclosporin or tacrolimus. Logistic regression showed that only duration of dialysis and time since transplantation significantly increased fracture risk, with odds ratio (OR) for each year of dialysis or transplantation being 1.21 (CI, 1.00-1.48) and 1.14 (CI, 1.05-1.23), respectively. These data show that low bone density and fractures are common in patients with kidney transplant and are determined by both pre- and posttransplant variables. Fracture risk was greatest in women, particularly if they were postmenopausal and we recommend that this subgroup is targeted for assessment and treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Back Pain; Biomarkers; Bone Density; Cyclosporine; Female; Fractures, Bone; Humans; Kidney Transplantation; Male; Middle Aged; Prednisolone; Prevalence; Tacrolimus; United Kingdom

Topics: Bone Density; Bone Resorption; Female; Follow-Up Studies; Fractures, Bone; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Tacrolimus; Time Factors