Osteomalacia in a patient with Paget's bone disease treated with long-term etidronate

SummaryA 93 year-old woman with Paget\u27s disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5 mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget\u27s disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated

Treatment of endometriosis by aromatase inhibitors: efficacy and side effects

The recent demonstration that aromatase is expressed at higher levels in endometriosis implants than in normal endometrium has led to pilot studies using inhibitor aromatasis in patients with endometriosis. We conducted a systematic review of the literature and studied the efficacy of aromatase inhibitors on endometriosis. There were seventeen studies (case reports/series) evaluating outcomes of aromatase inhibitors. Studies suggest that aromatase inhibitors alone or co-administered with progestins, oral contraceptives or gonadotrophin releasing hormone (GnRH) agonist could reduce pain and endometriosis. There is only one randomized controlled trial comparing aromatase inhibitor+GnRH agonist and GnRH agonist and one study with eighty patients. Side-effects profiles of aromatase inhibitor regimens are favorable; it does not appear a significant bone loss. Aromatase inhibitors seem to have a promising effect on endometriosis but randomized controlled trials are needed to prove their effects and their safety

Whipple's disease diagnosed during biological treatment for joint disease

Objectives Increased susceptibility to infections is among the main safety concerns raised by biological agents. We describe five cases of Whipple\u27s disease diagnosed during treatment with biological agents. Methods We retrospectively identified five cases of Whipple\u27s disease diagnosed between 2003 and 2009 in patients treated with TNFα antagonists in five French hospitals. Results Five patients (four male; mean age: 50.4 years; range: 38–67) underwent biological therapy according to prior diagnoses of rheumatoid arthritis (n = 2), ankylosing spondylitis (n = 2), or spondyloarthropathy (n = 1). Biological therapy failed to control the disease, which responded to appropriate antibiotics for Whipple\u27s disease. Retrospectively, clinical symptoms before biological therapy were consistent with Whipple\u27s disease. All five patients had favorable outcomes (mean follow-up, 29 months [13–71]). Conclusions Biological therapy probably worsened preexisting Whipple\u27s disease, triggering the visceral disorders. Whipple\u27s disease must be ruled out in patients with joint disease, as patients with this spontaneously fatal condition should not receive immunosuppressive agents

The random case of Conley's theorem: III. Random semiflow case and Morse decomposition

In the first part of this paper, we generalize the results of the author \cite{Liu,Liu2} from the random flow case to the random semiflow case, i.e. we obtain Conley decomposition theorem for infinite dimensional random dynamical systems. In the second part, by introducing the backward orbit for random semiflow, we are able to decompose invariant random compact set (e.g. global random attractor) into random Morse sets and connecting orbits between them, which generalizes the Morse decomposition of invariant sets originated from Conley \cite{Con} to the random semiflow setting and gives the positive answer to an open problem put forward by Caraballo and Langa \cite{CL}.Comment: 21 pages, no figur

Fracture incidence after 3 years of aromatase inhibitor therapy

BACKGROUND: The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. RESULTS: Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. CONCLUSION: This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women

Management of male osteoporosis: lessons for clinical practice

International audienc

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants