Volume 8 · Number 1 · March 2016
- Study of miRNAs expression patterns in osteoporotic bone [5-14]
- Medical professionals’ perceptions regarding therapeutic adherence in patients with osteoporosis [15-23]
- Serum dickkopf1 (DKK1), bone metabolism and atherosclerotic disease in patients with type 2 diabetes [24-29]
- Changes induced by DKK1 in rheumatoid arthritis patients who commence biologic therapy treatment [30-35]
- Classic non-deforming osteogenesis imperfecta. Report of a new mutation in the COL1A1 gene in two cases in the same family [36-39]
Osteoporosis is a common disease, its main clinical complication being bone fragility 1. This chronic, generally assymptomatic process deteriorates the bone, exposing it to fracture risk. Current treatment techniques aim to minimize the possibility of new fractures 1-4 but there is no medication to eliminate such risk. Most drugs currently available for treating osteoporosis achieve reductions of between 40 and 65% 2-4, if the medication is taken continuously over a period ranging from 3 to 5 years. This would be mere utopian, as, in fact, the patients frequently abandon their osteoporosis treatment, once they have begun.
Numerous studies have shown that adherence to osteoporosis treatment is generally low, and that in the first year the dropout rate is between 30-50% in most cases 5. One reason may be their asymptomatic condition, which does not provide the patient with a sense of improvement. Perhaps, if all goes well, the patient does not suffer fracture, but subjectively does not perceive anything. In this respect, osteoporosis differs from other chronic diseases in which symptoms return as soon as the patient discontinues treatment, such as migraines, ischemic heart disease or diabetes mellitus.
Objectives: To identify microRNAs (miRNAs) differentially expressed in bone samples with osteoporotic fracture compared with healthy bones.
Methods: Total RNA was extracted from fresh trabecular bone of the femoral neck of women undergoing hip replacement surgery, either because to osteoporotic fracture (n=6) or in the absence of osteoarthritis osteoporosis (based on BMD) (n=6). The samples were hybridized on an array of miRNAs and PCA diagrams and heat map were made. To compare expression levels >1.5 times and a value <0.05 Student's T test (corrected for multiple testing) was set as a threshold of significant change. Results: Both PCA analysis and the heat map showed a samples grouping whether there was fracture or not. 790 were detected miRNAs in bone samples, 82 of which were altered in the osteoporotic samples. After validation in another panel of 6 samples 6 osteoporotic and non-osteoporotic by PCR real time of the most significant miRNAs, and for which there was a test available, the miRNAs, miR-320a and miR-22-3p were confirmed. These two miRNAs were detected in cultures of primary osteoblasts, although they did not maintain the same pattern of expression in total bone samples. Conclusions: We have shown that there are differences in the expression of miRNAs in samples with osteoporotic fracture. This opens prospects for research and design of new therapies.
Introduction: Adherence to oral treatment of patients with osteoporosis is low, with a high dropout rate in the first year. The most noteworthy result is the lack of therapeutic response.
Objective: To ascertain the perception of physicians working with osteoporotic patients regarding adherence of these patients.
Methods: Cross-sectional study conducted by opinion survey aimed at primary care physicians and specialists involved in osteoporosis treatment. Participants were selected by purposive sampling.
Results: The questionnaire was answered by 235 specialists encompassing rheumatology (54.5%), orthopedics (10.6%) and primary care (18.7%). In 43.8% of participants, more than 25% of patients sometimes forget to take their treatment. According to 34.9%, more than 75% of patients are aware of treatment. Side effects and management complexity are the majority reasons that lead to a change in medication, mean value of 7.94±2.06 6±2.01 points respectively on a 0-10 scale.
Conclusions: Overall, medical specialists attributed low adherence to side effects, polypharmacy and lack of communication between professionals. Dosage and space use of soluble dosage forms may be options to facilitate patient adherence to treatment with oral bisphosphonates. Improved education concerning the importance of the disease or increased patient monitoring could foster adherence.
Serum dickkopf1 (DKK1), bone metabolism and atherosclerotic disease in patients with type 2 diabetes
Background and objectives: Type 2 diabetes (T2DM) is a risk factor for osteoporotic fractures and cardiovascular disease. The aims of our study were to evaluate serum Dickkopf-1(DKK1) levels in a cohort of T2DM patients and to analyze its relationships with bone metabolism and atheroesclerotic disease (AD).
Patients and methods: We studied 126 subjects: T2DM patients (n: 72, mean age 58,2±6 years) and non-diabetic subjects (n: 54, mean age 55,4±7 years). DKK-1 was measured by enzyme-linked immunosorbent assay (ELISA, Biomedica Gruppe). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The presence of AD (cerebrovascular disease, peripheral arterial disease, ischemic heart disease) was recorded. Intima-media thickness (IMT) was determined by doppler ultra- sonography and aortic calcification by evaluation of lateral view conventional X-rays.
Results: We did not find significant differences in DKK1 between groups. Serum DKK1 concentrations were significantly higher in females in total sample (24,3±15,2 vs 19,6±10,2 pmol/L, p=0,046) and in T2DM group (27,5±17,2 vs 19,8±8,9 pmol/L, p=0,025). There was a positive correlation between serum DKK1 and LS BMD in total sample (r=0,183, p=0,048). However, we did not find a significant relationship with osteoporosis diagnosis or morphometric vertebral fractures. Serum DKK1 was significantly higher in T2DM patients with AD (26,4±14,5 pmol/L vs 19,1±11,6 pmol/L, p=0,026) and also in patients with abnormal IMT (26,4±;15,1 pmol/L vs 19,8±11,3 pmol/L, p=0,038). In the ROC curve analysis to evaluate the usefulness of DKK-1 as a marker for high risk of AD, the area under the curve was 0,667 (95% confidence interval: 0,538-0,795; p=0,016). A concentration of 17,3 pmol/L or higher showed a sensitivity of 71,4% and a specificity of 60% to identify an increased risk of AD.
Conclusions: Circulating DKK1 levels are higher in T2DM with AD and are associated with an abnormal IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients.
Introduction: The aim of this study is to assess the relationship among inflammatory charge, cardiovascular risk and bone metabolism in patients with rheumatoid arthritis initiating biological therapy treatment.
Patients and methods: This is a prospective cohort study conducted in patients diagnosed with active rheumatoid arthritis (RA) assessed in the Rheumatology Unit and initiating biological therapy.
Patients will be selected consecutively, with preliminary data on 14 patients. We present preliminary data from 14 patients.
Results: Reduced Dickkopf-1 (DKK1) concentrations after commencing biological therapy were detected (baseline: 53.12±60.43 pg/ml vs 6 months 13.5±23.2 pg/ml, p=0.307) but without statistical significance. Changes were found in markers for bone remodeling with increased osteocalcin levels and CTX which were not statistically significant either.
Conclusions: We observed a nonsignificant decrease in DKK1 serum in patients with active RA treated with biologic therapy. Expanding the scope of study subjects and pending biochemical determinations will allow us, in the near future, to establish more precisely this link and the relationship of DKK1, bone remodeling, biological therapy and cardiovascular disease in RA patients.
Classic non-deforming osteogenesis imperfecta. Report of a new mutation in the COL1A1 gene in two cases in the same family
Osteogenesis imperfecta (OI), is a rare condition which is heterogeneous in clinical and genetic terms. Several types have been described and its main feature is bone fragility. It is generally caused by gene mutations in those genes which codify for the α1 and α2 of the type 1 collagen (COL1A1 and COL1A2) with dominant autosomal heredity.
We report the case of two relatives (father and daughter) with OI whose genetic study shows a mutation in COL1A1 previously undetected: the deletion of a Guanine, G(c.3524delG). Clinical aspects, heredity and reproductive options of the patients affected are considered.
Micro-RNAs (miRs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level. Generally, they act on gene expression by silencing or degrading mRNAs, and are involved in regulating various biological processes, such as cell differentiation, proliferation, apoptosis and in embryonic and tissue development. They are currently a major focus of interest in the study of various diseases such as cancer or type 2 diabetes mellitus. At level of bone metabolism, various miRs are emerging that are involved in their regulation, opening an important research field to identify new biomarkers for diagnosis of osteoporosis and its development, and to design new drug therapies.read more