A clinical decision rule to enhance targeted bone mineral density testing in healthy mid-life women.

SUMMARY: The rates of bone mineral density testing for osteoporosis among healthy mid-life women are high, although their osteoporosis or fracture risk is low. To reduce unnecessary testing, we created and evaluated a tool to guide bone density testing based on the woman's age, weight, fracture history, and menopausal status. INTRODUCTION: This study aims to improve case finding of mid-life women with low bone mass on bone mineral density (BMD) assessment. METHODS: Among healthy women aged 40-60 years having their first BMD test, osteoporosis risk factors were assessed by questionnaire and BMD by dual-energy X-ray absorptiometry. The combination of risk factors that best discriminated women with/without low bone mass (T-score ≤ -2.0) was determined from the logistic regression model area under the curve (AUC) and internally validated using bootstrapping. Using the model odds ratios, a clinical prediction rule was created and its discriminative properties assessed and compared with that of the osteoporosis self-assessment tool (OST). Sensitivity analyses examined results for pre-/peri- and post-menopausal women, separately. RESULTS: Of 1,664 women referred for baseline BMD testing, 433 with conditions known to be associated with bone loss were excluded. Of 1,231 eligible women, 944 (77%) participated and 87 (9.2%) had low bone mass (35 pre-/peri- and 52 post-menopausal). Four risk factors for low bone mass were identified and incorporated into a clinical prediction rule. Selecting women for BMD testing with weight of ≤70 kg or any two of age >51, years' post-menopause of ≥1, and history of fragility fracture after age 40 was associated with 93% sensitivity to identify women with low bone mass, compared with 47% sensitivity for an OST score of ≤1 (AUC 0.75 versus OST AUC 0.69, p = 0.04). Results restricted to post-menopausal women were similar. CONCLUSIONS: Among healthy mid-life women receiving a baseline BMD test, few had low bone mass, supporting the need for guidance about testing. A prediction rule with four risk factors had improved sensitivity over the OST. Further validation is warranted.

Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature.

UNLABELLED: Based on a systematic review of the literature, only low body weight and menopausal status can be considered with confidence, as important risk factors for low BMD in healthy 40-60 year old women. The use of body weight to identify high risk women may reduce unnecessary BMD testing in this age group. INTRODUCTION: BMD testing of perimenopausal women is increasing but may be unnecessary as fracture risk is low. Appropriate assessment among younger women requires identification of risk factors for low BMD specific to this population. METHODS: We conducted a systematic literature review of risk factors for low BMD in healthy women aged 40-60 years. Articles were retrieved from six databases and reviewed for eligibility and methodological quality. A grade for overall strength of evidence for each risk factor was assigned. RESULTS: There was good evidence that low body weight and post-menopausal status are risk factors for low BMD. There was good or fair evidence that alcohol and caffeine intake, and reproductive history are not risk factors. There was inconsistent or insufficient evidence for the effect of calcium intake, physical activity, smoking, age at menarche, history of amenorrhea, family history of OP, race and current age on BMD. CONCLUSIONS: Based on current evidence in Caucasians, we suggest that, in healthy women aged 40-60 years, only those with a low body weight (< 70 kg) be selected for BMD testing. Further research is necessary to determine optimal race-specific discriminatory weight cut-offs and to evaluate the risk factors for which there was inconclusive evidence.

Comparative evaluation of three semi-quantitative radiographic grading techniques for hip osteoarthritis in terms of validity and reproducibility in 1404 radiographs: report of the OARSI-OMERACT Task Force.

OBJECTIVE: The objective of this work was to compare the measurement properties of three categorical X-ray scoring methods for hip osteoarthritis (OA). METHODS: In data obtained from trials and cohorts, radiographs were evaluated using the Kellgren and Lawrence (KL) grading system, the Osteoarthritis Research Society International (OARSI) joint space narrowing score, and quantitative measurement of joint space width (JSW), analysed as a categorical variable according to Croft and Lane's cutoffs (1.5, 2.5 and 3mm). Predictive validity was assessed through logistic regression to predict joint replacement in one database. Construct validity was assessed through logistic regression between pain and function and X-ray stages. Inter-observer and intra-observer reliability were assessed in 50 subjects by weighted kappa. Sensitivity to change was assessed in 50 patients over a 24-month interval, by standardized response mean (SRM). RESULTS: Radiographs were available from one trial and two cohorts (1404 X-rays). All three methods predicted joint replacement in the trial. Correlation with clinical parameters was low for the three scoring methods, except for the single community-based cohort. Interrater reliability was higher for categorical JSW (kappa, 0.71 vs 0.44 and 0.47 for KL and OARSI, respectively). Intrarater reliability was similar for the three methods (0.79 vs 0.69 and 0.81). Sensitivity to change was higher for categorical JSW than KL and OARSI (SRM, 0.77 vs 0.28 and 0.35). CONCLUSION: Categorical JSW has similar validity and higher sensitivity to change than the other categorical scoring techniques in hip OA. These results indicate categorical JSW may be the preferred method to evaluate structural severity in hip OA clinical trials.

Comparative evaluation of three semi-quantitative radiographic grading techniques for knee osteoarthritis in terms of validity and reproducibility in 1759 X-rays: report of the OARSI-OMERACT task force.

OBJECTIVE: The objective of this work was to compare the measurement properties of three categorical X-ray scoring methods of knee osteoarthritis (OA), both on semiflexed and extended views. METHODS: In data obtained from trials and cohorts, X-rays were graded using Kellgren and Lawrence (KL), the OA Research Society International (OARSI) joint space narrowing score, and measurement of joint space width (JSW). JSW was analyzed as a categorical variable. Construct validity was assessed through logistic regression between X-ray stages and Western Ontario and McMaster Universities OA Index. Inter-observer reliability was assessed in 50 subjects for extended views by weighted kappa. Intra-observer reliability and sensitivity to change were assessed separately for extended and semiflexed views in 50 patients who had both views performed, over a 30-month interval, by weighted kappa and standardized response mean (SRM). RESULTS: Extended views were available from three trials and two cohorts (1759 X-rays), including one trial in which both extended and semiflexed views (antero-posterior) were obtained. Correlation with clinical parameters was low for the three scoring methods, except for the single community-based cohort. Inter-rater reliability was higher for categorical JSW in extended views (kappa, 0.86 vs 0.56 and 0.48 for KL and OARSI, respectively). Intra-rater reliability was higher for categorical JSW, both in extended views (0.83 vs 0.61 and 0.71) and in semiflexed views (0.89 vs 0.50 and 0.67). Sensitivity to change was also higher for categorical JSW, particularly in semiflexed views (SRM, 0.49 vs 0.22 and 0.34). CONCLUSION: These results indicate categorical JSW, in particular on semiflexed views, may be the preferred method to evaluate structural severity in knee OA clinical trials.

NPS 1506: a novel NMDA receptor antagonist: neuroprotective effects in a model of closed head trauma in rats.

We examined whether NPS 1506, a novel uncompetitive N-methyl-D-aspartate receptor antagonist, influences neurological outcome following closed head trauma (CHT) in rats. One hundred ten rats were divided into 11 groups: CHT (yes/no), treatment with NPS 1506 (yes/no), and time of euthanization (24 h/48 h). The dose of NPS 1506 was 1 mg/kg IV at 1 and 4 hours following CHT or sham operation. Closed head trauma induced the following changes in the injured hemisphere: Decreased specific gravity (sg) (1.036 +/- 0.006) and magnesium (Mg) (0.042 +/- 0.005 microg/mg) at 24 hours, and potassium (K) at 24 (1.145 +/- 0.376 microg/mg) and 48 hours, and increased water content (W) (84.9 +/- 2.5%) and sodium (Na) (2.135 +/- 0.699 microg/mg) at 24 hours, and calcium (Ca) at 24 (0.543 +/- 0.157 microg/mg) and 48 hours. These were reversed by NPS 1506; sg of 1.043 +/- 0.004, Mg of 0.077 +/- 0.009 microg/mg, K of 1.930 +/- 0.238 microg/mg, W of 81.5 +/- 1.9%, Ca of 0.043 +/- 0.023 microg/mg, and Na of 0.688 +/- 0.110 microg/mg. In groups not given NPS 1506, a nonsignificant decrease in neurological severity score (NSS) occurred at 24 and 48 hours as compared to NSS at 1 hour after CHT. In groups given NPS 1506, NSS at 24 and 48 hours decreased significantly (improved) compared to NSS at 1 hour, but not compared to NSS at 24 and 48 hours in groups not given NPS 1506. NPS 1506 caused no significant change in ischemic tissue volume or hemorrhagic necrosis volume in the injured hemisphere at 24 hours or 48 hours. These findings indicate that NPS 1506 improved measures of brain tissue edema (at 24 hours but not at 48 hours) and ion homeostasis, and this improvement was not related to other measures of outcome.