Alendroninezuur effectiever dan alfacalcidol voor preventie van osteoporose bij patiënten met een reumatische ziekte die starten met glucocorticoïdtherapie

OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www. clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with rheumatic disease who were starting glucocorticoid treatment at a daily dose that was equivalent to at least 7.5 mg of prednisone were randomised to alendronate (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1 microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary outcome was change in lumbar spine bone mineral density at 18 months. The main secondary outcome was the incidence of morphometrically confirmed vertebral deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol group. At 18 months the mean difference in change in bone mineral density between the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate group had a new vertebral deformity, compared with 8 patients in the alfacalcidol group, including 5 symptomatic vertebral fractures in 3 patients; the hazard ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month trial in patients with rheumatic diseases who were starting glucocorticoid treatment

Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture.

Background: Previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB) are frequently found in patients with osteoporosis, but the prevalence in patients at the time they present with a clinical fracture is unknown. Methods: All consecutive patients with a recent clinical vertebral or nonvertebral fracture, who were able and willing to be investigated (n = 626: 482 women, 144 men, age range 50-97 yr) had bone mineral density and laboratory investigations (serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, TSH, free T-4, serum and urine protein electrophoresis, and in men also serum testosterone). Results: Known SECOB contributors were present in 23.0% of patients and newly diagnosed SECOB contributors in 26.5%: monoclonal proteinemia (14 of 626), renal insufficiency grade III or greater (54 of 626), primary (17 of 626) and secondary (64 of 626) hyperparathyroidism, hyperthyroidism (39 of 626), and hypogonadism in men (12 of 144). Newly diagnosed SECOBs, serum 25-hydroxyvitamin D less than 50 nmol/liter (in 63.9%), and dietary calcium intake less than 1200 mg/d (in 90.6%) were found at any age, in both sexes, after any fracture (except SECOB in men with finger and toe fractures) and at any level of bone mineral density. Conclusion: At presentation with a fracture, 26.5% of patients have previously unknown contributors to SECOB, which are treatable or need follow-up, and more than 90% of patients have an inadequate vitamin D status and/or calcium intake. Systematic screening of patients with a recent fracture identifies those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present. (J Clin Endocrinol Metab 96: 1360-1367, 2011

Bij alle fractuurpatienten vitamine D bepalen?

Vitamin D deficiency is endemic worldwide. The Health Council of the Netherlands advises a colecalciferol intake of 800 IU/day and an intended serum level of calcidiol of at least 50 nmol/l for people aged 50 years and older and for osteoporosis patients. In 64% of 626 fracture patients, we found a reduced serum calcidiol level according to this definition. According to calculations based on meta-analyses, a substantial proportion of fracture patients would not achieve the target calcidiol level of 50 nmol/l with a vitamin D supplement of 800 IU/day. For example, this would be the case in 37% of elderly patients with osteoporosis. Until the results of a prospective study on this are published, we propose that fracture patients are either systematically given doses of vitamin D supplements higher than 800 IU/day, or that their serum calcidiol is measured and the dose of vitamin D supplements is adjusted according to this initial value and the desired serum concentrations, and that the measurement is repeated after 3 months so that the dosage can be adjusted if necessary

NSAIDs and fracture healing

Purpose of review Published data raise concerns about the use of nonselective NSAIDs and selective cyclo-oxygenase (COX)-2 inhibitors as anti-inflammatory or analgesic drugs in patients after a recent fracture or who are undergoing (uncemented) arthroplasty or osteotomy. However, clinical reports on the effect of COX-2 inhibition on fracture healing in humans have been variable and inconclusive. This review gives an overview of the published data and an advice when to avoid NSAIDs. Recent findings Prostaglandins play an important role as mediators of inflammation and COX are required for their production. Inflammation is an essential step in the fracture healing process in which prostaglandin production by COX-2 is involved. Data from animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway. Animal data suggest that the effects of COX-2 inhibitors are dependent on the timing, duration, and dose, and that these effects are reversible. Summary These animal data, together with the view of limited scientifically robust clinical evidence in humans, indicate that physicians consider only short-term administration of COX-2 inhibitors or other drugs in the pain management of patients who are in the phase of fracture or other bone defect healing. COX-2-inhibitors should be considered a potential risk factor for fracture healing, and therefore to be avoided in patients at risk for delayed fracture healing

Endothelial influences on monocyte maturation

The aims of this project were to determine the phenotype of migrating monocytes and examine the influence transmigration has on their differentiation to macrophages or DC. To determine stages of differentiation and activation of monocytes cultured in the presence of autologous serum without endothelium nine cell surface receptors were used.  These cells matured over time with an increase in CD16⁺ cells and increased major histocompatibility complex II and macrophage mannose receptor (MMR) expression suggesting alternative activation over time compared to cells cultured in foetal calf serum.  Monocyte contact with unstimulated endothelium and a gradient of CCL2 also results in cells with an alternatively activated phenotype with a proportion having a tendency to form dendritic cells (DC). Migration of monocytes is markedly enhanced and endothelium is activated by chemokines and cytokines in the context of inflammation.  Contact with endothelium activated with interferon gamma (IFN<span style='font-family:Symbol'>g) prevents monocytes development into alternatively activated macrophages and may bias them towards classical activation.  However contact with endothelium activated with an interleukin 10 (IL-10) results in cells with an alternatively activated phenotype with a subpopulation of cells, which remain on the apical surface, showing a tendency to become DC. These results show that IFN<span style='font-family:Symbol'>g and IL-10 confer different effects on endothelium and  monocytes.  Manipulation or activation of the endothelium to program the transmigrating cells to become alternatively activated may provide a novel option to alter macrophage function for therapeutic gain.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Individualizing fracture risk prediction

Low bone mineral density (BMD) and clinical factors (CRF) have been identified as factors associated with an increased relative risk of fractures. From this observation and for clinical decision making, the concept of prediction of the individual absolute risk of fractures has emerged. It refers to the individual's risk for fractures over a certain time period, e.g. the next 5 and 10 years. Two individualized fracture risk calculation tools that are increasingly used and are available on the web are the FRAX algorithm and the Garvan fracture risk calculator. These tools integrate BMD and CRFs for fracture risk calculation in the individual patient in daily practice. Although both tools include straightforward risk factors, such as age, sex, previous fractures, body weight and BMD, they differ in several aspects, such as the inclusion of other CRFs, fall risks and number of previous fractures. Both models still need to be validated in different populations before they can be generalized to other populations, since the background risk for fractures is population specific. Further studies will be needed to validate their contribution in selecting patients who will achieve fracture risk reduction with anti-osteoporosis therapy

Assessment of individual fracture risk: FRAX and beyond

The World Health Organization fracture risk assessment tool (FRAX) and the Garvan fracture risk calculator are both widely available tools for individualized fracture risk prediction in daily practice. The FRAX model is implemented in several guidelines and most widely used at present. However, clinicians should take into account the differences between the models, especially with regard to the effect of the number of falls, number and clustering of previous fractures, and the number of clinical risk factors on the outcome of predicted fracture risk. Further development will be needed for optimal integration of bone- and fall-related risks, clustering of fractures, and dosing of risk factors to validate the models in different populations and to validate the ability to select patients who will achieve fracture risk reduction with anti-osteoporosis therapy. FRAX may be used as the primary model, and in patients with recurrent fractures and falls the use of the Garvan model may be of additional value