Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases

STUDY DESIGN: Retrospective, observational study in five consecutive cases. OBJECTIVES: The management of heterotopic ossification (HO), a frequent complication after spinal cord injury (SCI) and after orthopaedic surgery, is a therapeutic challenge with high recurrence rates of over 50%. Conflicting data were reported for Etidronate. The use of the more potent new generation of amino-bisphosphonates has been put forward in different inflammatory, dysmorphogenic bone disease. In order to try and halt the underlying dysfunctional bone metabolism we have studied the action of pamidronate in five consecutive high-risk patients with established HO of different etiology undergoing surgical removal. SETTING: University Hospital of Basel, Switzerland, Division of Endocrinology, Diabetology and Clinical Nutrition and the Department of Orthopedic Surgery. METHODS: In all five patients, ranging from 47 to 68 years of age, we used continuous pamidronate infusions perioperatively at a dosage of 120 mg in the first 12 h and subsequent reduction to 75-60-30-15 mg/12 h over a period of 10-14 days. RESULTS: None of these patients showed clinical, radiographical and laboratory signs of HO recurrence or new forming HO in the follow-up 5-54 month after surgery. Potential side effects of high-dose bisphosphonate therapy such as osteoporosis and osteomalacia were not reported in any case. CONCLUSION: We postulate that pamidronate might have pronounced beneficial effects in high-risk patients with established HO undergoing excision surgery. Since the therapeutic window of amino-bisphosphonates has not yet been defined and the minimal necessary doses for preventing new HO are unknown, further studies are encouraged to confirm our findings and to identify the necessary dosage and duration of treatment and to pinpoint, which patients will benefit most from this treatment

Amyotrophic lateral sclerosis: Genotypes and phenotypes

Mendelian forms of amyotrophic lateral sclerosis (ALS) account for nearly 10 % of all cases. To date, 19 disease genes, usually but not exclusively inherited with an autosomal dominant pattern, have been reported to be associated with ALS or with atypical motor neuron diseases with or without associated frontotemporal dementia (ALS-FTD). Often, it is possible to draw correlations between distinct ALS-associated mutations and specifi c clinical phenotypes. This information is essential for biologists and clinicians alike, providing at the same time an unparalleled insight into the pathogenesis of the disease and invaluable tools for genetic counseling, diagnosis, and development of preventive strategies and treatments for ALS

Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders.

In recent years, research has identified the molecular and neural substrates underlying the transition of moderate "social" consumption of alcohol to the characteristic alcohol use disorder (AUD) phenotypes including excessive and compulsive alcohol use which we define in the review as the GO signaling pathways. In addition, growing evidence points to the existence of molecular mechanisms that keep alcohol consumption in check and that confer resilience for the development of AUD which we define herein as the STOP signaling pathways. In this review, we focus on examples of the GO and the STOP intracellular signaling pathways and discuss our current knowledge of how manipulations of these pathways may be used for the treatment of AUD