Bone loss associated with use of antiepileptic drugs

Importance of the field: Epilepsy is a neurological disorder associated with several comorbidities, one of them being reduced bone health. As the bone loss most often is insidious and asymptomatic, they are usually not recognized, and thus untreated. The key message of this paper is to make clinicians aware of the problem.

Areas covered in this review: This article reviews data from basic and clinical studies of bone loss associated with usage of antiepileptic drugs (AEDs) within the last 4 decades.

What the reader will gain: The reader will learn that there is accumulating evidence of biochemical abnormalities indicating a disturbed bone metabolism, a decreased bone density and a 2 – 6 times increased risk of fractures among those with epilepsy compared to the general population. These findings most likely have many causes, both internal and external, but long-term use of AEDs seems to play an important role. Enzyme-inducing drugs, such as phenytoin, phenobarbital and carbamazepine, but also the enzyme inhibitor valproate, appear to have bone-depleting properties. Reduced bone density may be detected during the first 1 – 5 years of treatment. Although many theories have been launched, the exact mechanisms by which the the drugs affect bone architecture are not fully understood.

Take home message: We recommend clinicians to promote osteoprotective behavior among their epilepsy patients; that is, sunlight exposure and weight-bearing exercise as well as avoidance of risk factors such as bone-depleting drugs other than AEDs, smoking and heavy alcohol consumption. Enzyme inducing drugs should be avoided, if possible. Bone mineral density screening should be assessed on an individual basis, taking risk factors for bone loss into account. All patients taking AEDs on long-term basis ought to have adequate amounts of dietary calcium and vitamin D, and those who have developed bone loss should in addition be given specific antiosteoporotic treatment.     

Initial Implant Stability Predicts Migration But Not Failure in Cementless Acetabular Revision with Bone Grafting

Host bone contact of less than 50% is perceived but not proven to cause migration and loosening after actetabular revision. A prospective analysis of cementless acetabular revision cases with impaction grafting was performed to determine if this was an independent risk factor for these events. Sixty-two hips in 54 patients were assessed at a mean follow-up of 84.5 months (range 61–112) yielding a probability of 94.6% of retaining the acetabular component using revision for aseptic loosening as the end point. No single factor was independently causative for loosening, although Type III fixation was associated with migration (p = 0.0159); subanalysis suggested that achieving host–bone contact in at least part of the dome and posterior column is important.     

Nephrotoxicity in isoxazolylpenicillin prophylaxis in hip surgery

In 789 courses of antibiotic prophylaxis in hip arthroplasty surgery, either dicloxacillin (Diclocil®) or cloxacillin (Ekvacillin®) was used during two different time periods. The surgical methods, anesthesia, preoperative and postoperative care of the patients, and laboratory procedures were the same all the time. Changes in creatinine values were used as a method for evaluating the impact on renal function. When using dicloxacillin, a pathologic increase of creatinine was noted in 12 and 13 percent by two different calculation methods. Sixteen patients (4.2 percent) had a severe creatinine increase during the first postoperative week after dicloxacillin prophylaxis, requiring dialysis in 2 patients. Cloxacillin had only a marginal impact on renal function. Patients above aged 70 years were more vulnerable as regards renal function than younger persons, and the impairment was slightly dose related in all ages. In the dicloxacillin group, preoperative use of antiphlogistic drugs was correlated with reduced postoperative renal function.     

G protein-coupled receptors in haematopoietic disruption

Haematopoiesis is the process by which blood and immune cells are replenished from a finite number of resident bone marrow (BM) haematopoietic stem cells (HSCs). Regulatory molecules within the BM microenvironment contribute developmental signals to an interactive network capable of ensuring ordered biological processes. Many bioactive molecules contribute to the network through G protein-coupled receptors (GPCRs). GPCRs are seven-transmembrane receptors that, following ligand binding, signal by activating coupled heterotrimeric G proteins. This review focuses on those bioactive molecules that regulate haematopoietic development through GPCRs. Chemokines (SDF-1α, MIP-1), opioids and tachykinins (SP, NK-A) are important G protein-coupled haematopoietic regulators. Their biology in normal and diseased haematopoiesis is discussed below, as well as their potential as therapeutic targets.     

Animal Model for Evaluating Bone Repair with and without Adjunctive Hyperbaric Oxygen Therapy (HBO): Comparing Dose Schedules

The effect of hyperbaric oxygen (HBO) on the healing of standardized metaphyseal defects in the cortices of rat femurs was studied. The question was whether a known total amount of HBO given twice a day (BID) would have a different effect than once a day (QD) treatments. A microvascular casting technique was developed whereby vessel ingrowth at the repair site could be monitored using scanning electron microscopy (SEM). Bone repair morphology was evaluated by light microscopy (LM) and various tissue components were quantified by histomorphometry (HM). Animals were sacrificed I, 2, 3, or 5 weeks postoperatively. SEM revealed that endosteal bone ingrowth was totally responsible for the repair of the cortical defects. Moreover, endosteal vessel ingrowth did not differ between controls and either group of HBO treated animals. LM displayed enchondral ossification in controls and BID treated animals and a pronounced osteoclastic activity in the latter group throughout the repair process. By contrast the QD treated group healed by primary ossification. Judged by the HM data, QD treatment appeared to accelerate bone repair and vessel ingrowth compared to controls, while BID treatment seemed to retard these processes.     

Infected Non-Union of the Tibial Shaft Treated by Küntscher Intramedullary Reaming and Nail Fixation: A Report of Four Cases

Four cases of infected non-union of the tibial shaft treated by Küntscher intramedullary reaming and nailing are presented, and on the basis of these cases the indications and prerequisites for the method are discussed.     

How does transfusion-associated graft-versus-host disease compare to hematopoietic cell transplantation-associated graft-versus-host disease?

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare life-threatening complication of blood transfusion caused by donor T cells that escape rejection by the recipient immune system. These donor T cells drive recipient tissue damage in response to host antigens. On the other hand, GVHD occurring after allogeneic hematopoietic cell transplantation (HCT-GVHD) is also caused by donor T cells, but its pathophysiology is more complex and differs due to the effects of tissue damage caused by pre?HCT conditioning and profound immunosuppression. Both TA-GVHD and HCT-GVHD can be fatal; however, mortality is higher with TA-GVHD due to the paucity of treatment options. Here, we compare and summarize the presentation, diagnosis, pathophysiology, prevention, and treatment of TA-GVHD and HCT-GVHD.     

Review of Foot Tumors Seen in a University Tumor Institute

Most tumors of the foot and ankle will be benign, and it has been easy for clinicians to underestimate the malignant potential of a given tumor. The purpose of our study was to gain insight into the incidence of different tumor types diagnosed in patients with tumors of the foot and/or ankle treated at the Rizzoli Institute from September 1990 to December 2007. Our series included 1170 patients and 1170 lesions, with an overall mean age at diagnosis of 43 (range 5 to 81) years. Overall, 870 lesions (74.36%) were nonmalignant and 300 (25.65%) were malignant. Soft tissue lesions were diagnosed in 189 patients (16.15%), of which 91 (48.15%) were nonmalignant (pseudotumors or benign). Bone lesions were diagnosed in 981 patients (83.85%), of which 779 (79.41%) were nonmalignant. Epidemiologic knowledge of foot abnormalities and clinical suspicion, an organized diagnostic method, and evidence-based treatment of musculoskeletal tumors are essential elements to obtaining optimal results in the treatment of malignant foot tumors.