Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

Cost-effectiveness model of using zoledronic acid once a year versus current treatment strategies in postmenopausal osteoporosis.

OBJECTIVES: To compare effectiveness, associated cost of outcomes and cost-effectiveness of a single annual infusion of zoledronic acid versus current treatment strategies plans for postmenopausal osteoporosis in France. METHODS: Twelve simulation-based models were built to investigate three types of fractures: vertebral (VF), non-vertebral excluding hip (NVF) and hip (HF), comparing two groups: zoledronic acid and current postmenopausal antiosteoporotic treatment strategies. Two effectiveness comparability assumptions have been tested: specific agent efficacy values, and same standard efficacy values for all active agents. Direct medical costs included drug costs, medical visits, monitoring and fracture management. Adherence levels were integrated into the model under the assumption that non-adherent patients had treatment effects similar to the levels of placebo effectiveness. RESULTS: Using the most conservative assumption (same standard efficacy values for all active agents), zoledronic acid strategy results in less vertebral, non-vertebral and hip fractures than other current antiosteoporotic treatment options over 3 years: 12.04% vs. 14.18%, 10.61% vs. 11.28% and 2.82% vs. 4.64% respectively, (p<0.001). In addition, zoledronic acid is more cost-effective than the current treatment strategies in all types of fractures (p<0.001): 1497 euros vs. 1685 euros per VF avoided, 1337 euros vs. 1404 euros per NVF avoided and 1216 euros vs. 1323 euros per HF avoided. CONCLUSION: Zoledronic acid is a cost-effective treatment strategy regardless of fracture type or effectiveness comparability assumptions.

Epidemiology, impact, management, and cost of Paget's disease of bone in France.

OBJECTIVES: To evaluate the epidemiology, quality-of-life (QoL) impact, management, and cost of Paget's disease of bone. METHODS: Retrospective and prospective data were collected in a representative cross-section of office-based and hospital-based rheumatologists in France, in early 2005. Each rheumatologist included consecutive outpatients with Paget's disease seen over a 2-month period. For each patient, a medical questionnaire and the 36-item Short-Form self-questionnaire (SF-36) evaluating health-related quality of life were completed. A descriptive analysis of the patient population was conducted. Medical costs over the last 12 months were estimated. RESULTS: Four hundred and forty-six medical questionnaires and 387 SF-36 questionnaires were available. Mean age was 74 years, and 58.3% of patients were male. The diagnosis was fortuitous (usually radiological) in 39.2% of cases. Complications occurred in 40% of cases; 97.8% of complications involved the joints. Bisphosphonate therapy was used in nearly 84% of patients. The SF-36 scores were significantly decreased compared to the general population, in both males and females. Total cost of management was less than one-third the cost of managing type 2 diabetes mellitus. CONCLUSION: The results confirm the well-established characteristics of Paget's disease. Bisphosphonate therapy was widely used. Quality of life was significantly altered. The cost of management was moderate.