A rare side effect of methotrexate therapy: drug-induced osteopathy with multiple fractures of the lower limb.

Methotrexate is associated with bone lesions that are rare and, although presenting with a typical localisation to the lower extremities and appearing with a characteristic radiologic morphology, largely unknown and often misdiagnosed as osteoporotic insufficiency fractures. The correct and early diagnosis, however, is key for treatment and prevention of further osteopathology. Here, we present a patient with rheumatoid arthritis who developed multiple painful insufficiency fractures in the left foot (processus anterior calcanei, tuber calcanei) and in the right lower leg and foot (anterior and dorsal calcaneus and at the cuboid and distal tibia) during therapy with methotrexate, which were all misdiagnosed as osteoporotic. The fractures occurred between 8 months and 35 months after starting methotrexate. Discontinuation of methotrexate resulted in rapid pain relief and no further fractures have occurred. This case powerfully demonstrates the importance of raising awareness of methotrexate osteopathy in order to take appropriate therapeutic measures, including and perniciously discontinuing methotrexate.

Fibrinolysis in trauma patients: wide variability demonstrated by the Lysis Timer.

Hyperfibrinolysis contributes to the pathophysiology of trauma-induced coagulopathy. At present, systematic administration of tranexamic acid (TXA) is recommended in all patients in the early phase of trauma. However, there is some debate regarding whether TXA is beneficial in all trauma patients. A rapid and accurate tool to diagnose hyperfibrinolysis may be useful for tailoring TXA treatment. We conducted a proof-of-concept study of consecutive adult trauma patients. A first blood sample was obtained at the time of pre-hospital care (T1). Patients received 1 g of TXA after T1. A second sample was obtained on arrival at the emergency unit (T2). We examined coagulation, fibrin and fibrinogen formation and degradation. Fibrinolysis was assessed by determining tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor 1 (PAI-1) activity and global fibrinolysis capacity assay using a device developed by Hyphen BioMed: the Lysis Timer (GFC/LT). The study population consisted of 20 patients (42 ± 21 years, index of severity score 32 ± 21). Both coagulation and fibrinolysis were altered at T1. GFC/LT values exhibited hyperfibrinolysis only in five patients. Principal component analysis carried out at T1 showed two main axes of alteration. The major axis was related to coagulation, altered in all patients, while the second axis was related to fibrinolysis. GFC/LT was mainly influenced by PAI-1 activity while fibrin monomers were related to the severity of trauma. At T2, GFC/LT exhibited the marked effect of TXA on clot lysis time. In conclusion, GFC/LT demonstrated huge variation in the fibrinolytic response to trauma.

Multiple pseudofractures due to Fanconi's syndrome associated with Wilson's disease.

We report a 40-year-old man who presented with multiple bone pseudofractures after about 20 years from the onset of Wilson's disease (WD). At age 36, he first noticed pain in his left shoulder. At age 39, he had multiple chest pain. On neurologic examinations, dysarthria and dysphagia due to pseudobulbar palsy, rigidity and tremor on right upper lim were observed. WD was confirmed because of low levels of plasma cupper and ceruloplasmin in addition to ATP7B gene mutation. The chest X-ray revealed multiple fractures of the several ribs. We diagnosed osteomalacia due to Fanconi's syndrome because of hypophosphatemia and the impairment of renal tubules for WD. After administration of vitamin D, there happened no new bone pseudofractures. Although bone pseudofractures accompanied by Wilson's disease generally happen in childhood, we should be aware of this symptom even in adulthood.

Osteogenesis imperfecta type III and hypogonadotropic hypogonadism result in severe bone loss: a case report.

We present the case of a 33-year-old male patient with multiple fractures and typical radiographical and clinical characteristics of osteogenesis imperfecta (OI) type III. Furthermore, the patient has suffered from hypogonadotropic hypogonadism since childhood. On the basis of antiresorptive therapy, no further fractures occurred within several years. Recently, recurrent nontraumatic fractures without bone healing were observed. Decreased bone mineral density was assessed by dual X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) showed impaired trabecular bone structure. Due to recurrent fragility fractures and severe deterioration of bone structure, an osteoanabolic treatment with teriparatide was initiated to potentially stimulate fracture healing and to increase bone formation.