Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3–20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L) <1 g/kg body weight (BW) and high (H) ≥1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01–1.36) versus 0.15 (0–1.42) pmol/l (p < 0.05), respectively, and 3.76 (1.01–7.25) versus 3.92 (2.39–10.23) pmol/l (p < 0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p < 0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02–1.36 ) versus 0.19 (0.01–1.25) (p < 0.01) and 0.14 (0.01–0.71) versus 0.05 (0.002–0.37) (p < 0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r = 0.33, p < 0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG

Excess mortality following hip fracture: a systematic epidemiological review

This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlighting the need for interventions to reduce this risk.Patients experiencing hip fracture after low-impact trauma are at considerable risk for subsequent osteoporotic fractures and premature death. We conducted a systematic review of the literature to identify all studies that reported unadjusted and excess mortality rates for hip fracture. Although a lack of consistent study design precluded any formal meta-analysis or pooled analysis of the data, we have shown that hip fracture is associated with excess mortality (over and above mortality rates in nonhip fracture/community control populations) during the first year after fracture ranging from 8.4% to 36%. In the identified studies, individuals experienced an increased relative risk for mortality following hip fracture that was at least double that for the age-matched control population, became less pronounced with advancing age, was higher among men than women regardless of age, was highest in the days and weeks following the index fracture, and remained elevated for months and perhaps even years following the index fracture. These observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their ris

Alendronate pivotal trial fit and real world patients: one trial does not fit all

Objective: To compare clinical characteristics of real-life users of alendronate with inclusion criteria in the pivotal alendronate trial FIT. Material and methods: Multinational cross-sectional study using data obtained from the SIDIAP database (Sistema d’Informació per al Desenvolupament de l’Investigació en Atenció Primària) and the Danish Health Registries (DHR), which contain prescriptions, diagnosis codes, and treatments of 5.2 and 5.6 million subjects from Catalonia (Spain) and Denmark respectively. Inclusion criteria: incident user of alendronate (1 year wash-out), ≥40 years old. Exclusion criteria: Paget disease, use of any antiosteoporosis drug in the previous year. Results: 14,316 (SIDIAP) and 21,221 (DHR) subjects were analyzed. The population of SIDIAP and DHR had 2,347 (16.4 %) and 5,275 (24.9 %) subjects >80 years old, reported 9 (0.1 %) and 91 (0.4 %) diagnoses of myocardial infarction, 423 (3 %) and 368 (1.7 %) of erosive gastrointestinal disease, 200 (1.4 %) and 1,109 (5.2 %) of dyspepsia and 349 (2.4 %) and 149 (0.7 %) of metabolic bone disease, all of which were FIT exclusion criteria. Men and glucocorticoid consumption were excluded from the FIT trial (included in subsequent RCT), representing 3,818 (26.7 %) and 3,885 (18.3 %) men and 1,229 (8.6 %) and 4,716 (22.2 %) glucocorticoid users in the SIDIAP and DHR database respectively. A total of 5,172 (36.1 %) and 8646 (40.7 %) subjects in the SIDIAP and DHR respectively, had at least one of the previously mentioned exclusion criteria (except sex/glucocorticoid consumption) and would have been excluded from the FIT trial. Conclusion: Patient characteristics used as exclusion criteria in FIT were commonly found among real- life users of alendronate. This severely limits the external validity of this trial. While subsequent RCTs have established the efficacy of alendronate in men and glucocorticoid users, efficacy data is S300 Osteoporos Int (2015) 26 (Suppl 1):S71–S380 needed for octogenarians, as well as for patients with other common comorbidities

Alendronate pivotal trial fit and real world patients: one trial does not fit all

Objective: To compare clinical characteristics of real-life users of alendronate with inclusion criteria in the pivotal alendronate trial FIT. Material and methods: Multinational cross-sectional study using data obtained from the SIDIAP database (Sistema d’Informació per al Desenvolupament de l’Investigació en Atenció Primària) and the Danish Health Registries (DHR), which contain prescriptions, diagnosis codes, and treatments of 5.2 and 5.6 million subjects from Catalonia (Spain) and Denmark respectively. Inclusion criteria: incident user of alendronate (1 year wash-out), ≥40 years old. Exclusion criteria: Paget disease, use of any antiosteoporosis drug in the previous year. Results: 14,316 (SIDIAP) and 21,221 (DHR) subjects were analyzed. The population of SIDIAP and DHR had 2,347 (16.4 %) and 5,275 (24.9 %) subjects &gt;80 years old, reported 9 (0.1 %) and 91 (0.4 %) diagnoses of myocardial infarction, 423 (3 %) and 368 (1.7 %) of erosive gastrointestinal disease, 200 (1.4 %) and 1,109 (5.2 %) of dyspepsia and 349 (2.4 %) and 149 (0.7 %) of metabolic bone disease, all of which were FIT exclusion criteria. Men and glucocorticoid consumption were excluded from the FIT trial (included in subsequent RCT), representing 3,818 (26.7 %) and 3,885 (18.3 %) men and 1,229 (8.6 %) and 4,716 (22.2 %) glucocorticoid users in the SIDIAP and DHR database respectively. A total of 5,172 (36.1 %) and 8646 (40.7 %) subjects in the SIDIAP and DHR respectively, had at least one of the previously mentioned exclusion criteria (except sex/glucocorticoid consumption) and would have been excluded from the FIT trial. Conclusion: Patient characteristics used as exclusion criteria in FIT were commonly found among real- life users of alendronate. This severely limits the external validity of this trial. While subsequent RCTs have established the efficacy of alendronate in men and glucocorticoid users, efficacy data is S300 Osteoporos Int (2015) 26 (Suppl 1):S71–S380 needed for octogenarians, as well as for patients with other common comorbidities

The Relationship of Perceived Risk and Biases in Perceived Risk to Fracture Prevention Behavior in Older Women

BACKGROUND: A bias in perceived risk for health outcomes, including fracture, exists. PURPOSE: We compared perceived risk and biases in perceived risk for fracture to fracture preventive behavior. METHODS: Women over age 55 (n=2874) completed a survey five times over five years and data was pulled from the medical record. Perceived risk was measured by asking women to rate their risk of fracture compared to similar women. Actual risk was measured using FRAX score. Bias was measured using an interaction between perceived and actual risk. RESULTS: Higher perceived risk was related to lower quality of life and self-reported health, more medication and calcium use, increased bone density scan use and less walking. Bias was only associated with less medication use. Neither perceived risk nor bias predicted medication adherence. CONCLUSIONS: Perceived risk, but not bias, may predict different fracture prevention behaviors. Clinicians may need to base interventions on risk perceptions