Measuring metacarpal cortical bone by digital x-ray radiogrammetry: a step forward?

Changes in metacarpal cortical bone mineral density (BMD) using digital x-ray radiogrammetry were studied in patients with early rheumatoid arthritis. After 1, 2, and 5 years, large BMD losses were found: -1.7%, -2.8%, and -5.6%, respectively. Elevated erythrocyte sedimentation rate and anti-cyclic citrullinated peptide levels were independent predictors of bone loss, indicating that the largest amount of bone loss was found in patients with severe inflammation and high production of auto-antibodies, who are known to be at the highest risk of developing radiological bone damage. Studies are needed about the spatial and time relationship between erosions and juxta-articular and metacarpal bone los

Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver

Progress in osteoporosis and fracture prevention: focus on postmenopausal women

In the past decade, we have witnessed a revolution in osteoporosis diagnosis and therapeutics. This includes enhanced understanding of basic bone biology, recognizing the severe consequences of fractures in terms of morbidity and short-term re-fracture and mortality risk and case finding based on clinical risks, bone mineral density, new imaging approaches, and contributors to secondary osteoporosis. Medical interventions that reduce fracture risk include sufficient calcium and vitamin D together with a wide spectrum of drug therapies (with antiresorptive, anabolic, or mixed effects). Emerging therapeutic options that target molecules of bone metabolism indicate that the next decade should offer even greater promise for further improving our diagnostic and treatment approaches

Osteoimmunology and osteoporosis

The concept of osteoimmunology is based on growing insight into the links between the immune system and bone at the anatomical, vascular, cellular, and molecular levels. In both rheumatoid arthritis (RA) and ankylosing spondylitis (AS), bone is a target of inflammation. Activated immune cells at sites of inflammation produce a wide spectrum of cytokines in favor of increased bone resorption in RA and AS, resulting in bone erosions, osteitis, and peri-inflammatory and systemic bone loss. Peri-inflammatory bone formation is impaired in RA, resulting in non-healing of erosions, and this allows a local vicious circle of inflammation between synovitis, osteitis, and local bone loss. In contrast, peri-inflammatory bone formation is increased in AS, resulting in healing of erosions, ossifying enthesitis, and potential ankylosis of sacroiliac joints and intervertebral connections, and this changes the biomechanical competence of the spine. These changes in bone remodeling and structure contribute to the increased risk of vertebral fractures (in RA and AS) and non-vertebral fractures (in RA), and this risk is related to severity of disease and is independent of and superimposed on background fracture risk. Identifying patients who have RA and AS and are at high fracture risk and considering fracture prevention are, therefore, advocated in guidelines. Local peri-inflammatory bone loss and osteitis occur early and precede and predict erosive bone destruction in RA and AS and syndesmophytes in AS, which can occur despite clinically detectable inflammation (the so-called 'disconnection'). With the availability of new techniques to evaluate peri-inflammatory bone loss, osteitis, and erosions, peri-inflammatory bone changes are an exciting field for further research in the context of osteoimmunology

Osteoporosis therapy: an example of putting evidence-based medicine into clinical practice

A major aim of evidence-based medicine is to assist clinical decision-making by providing the most current and reliable medical information. Systematic reviews and meta-analyses are important tools in this process. Systematic reviews identify and compile relevant evidence, while meta-analyses summarize and quantify the results of such reviews. Results from meta-analyses are, at present, the main source of summary evidence for the efficacy of treatments for a specific condition. They are important tools for helping to choose among treatment options, although they cannot be used to directly compare the magnitude of the effect of various therapies. However, the methods used and the consequent clinical value of the results, may be poorly understood by clinicians, who may therefore not take full advantage of the evidence. Recently, a panel of experts in osteoporosis and evidence-based medicine applied rigorous, validated, scientific standards to produce a systematic review and meta-analysis of randomized controlled trials of anti-resorptive agents used to treat osteoporosis. They found that, although several agents reduced the risk of vertebral fracture, only two, alendronate and risedronate, demonstrated convincing evidence for both non-vertebral and vertebral fracture risk reductions. The clinical implication of these results is that there are important differences in anti-fracture efficacy among currently available agents. In the absence of evidence from head-to-head clinical trials and because of the systematic nature and methodological rigor of the analyses, these data provide important information for clinical decision-makin

Reducing hip fracture risk with risedronate in elderly women with established osteoporosis

Tahir Masud1, Michael McClung2, Piet Geusens31Nottingham University Hospitals NHS Trust, Nottingham, UK; 2Oregon Osteoporosis Center, Portland, Oregon, USA; 3Department of Internal Medicine, Subdivision of Rheumatology, Maastricht University Medical Center, BelgiumBackground: There is limited evidence to support the efficacy of current pharmaceutical agents in reducing the risk of hip fracture in older postmenopausal women with established osteoporosis.Objective: To clarify the efficacy of risedronate in reducing the risk of hip fracture in elderly postmenopausal women aged ≥70 years with established osteoporosis, i.e., those with bone mineral density-defined osteoporosis and a prevalent vertebral fracture.Methods: Post hoc analysis of the Hip Intervention Program (HIP) study, a randomized controlled trial comparing risedronate with placebo for reducing the risk of hip fracture in elderly women. Women aged 70 to 100 years with established osteoporosis (baseline femoral neck T-score ≤ −2.5 and ≥ 1 prior vertebral fracture) were included. The main outcome measure was 3-year hip fracture incidence in the risedronate and placebo groups.Results: A total of 1656 women met the inclusion criteria. After 3 years, hip fracture had occurred in 3.8% of risedronate-treated patients and 7.4% of placebo-treated patients (relative risk 0.54; 95% confidence interval 0.32–0.91; P = 0.019).Conclusion: Risedronate significantly reduced the risk of hip fracture in women aged up to 100 years with established osteoporosis.Keywords: osteoporosis, postmenopausal, hip fracture, risedronat

Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms