Margaret L. Gourlay

Bone-Density Testing Interval and Transition to Osteoporosis in Older Women

BACKGROUND Although bone mineral density (BMD) testing to screen for osteoporosis (BMD T score, -2.50 or lower) is recommended for women 65 years of age or older, there are few data to guide decisions about the interval between BMD tests. METHODS We studied 4957 women, 67 years of age or older, with normal BMD (T score at the femoral neck and total hip, -1.00 or higher) or osteopenia (T score, -1.01 to -2.49) and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis, followed prospectively for up to 15 years. The BMD testing interval was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustment for estrogen use and clinical risk factors. Transitions from normal BMD and from three subgroups of osteopenia (mild, moderate, and advanced) were analyzed with the use of parametric cumulative incidence models. Incident hip and clinical vertebral fractures and initiation of treatment with bisphosphonates, calcitonin, or raloxifene were treated as competing risks. RESULTS The estimated BMD testing interval was 16.8 years (95% confidence interval [CI], 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI, 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia. CONCLUSIONS Our data indicate that osteoporosis would develop in less than 10% of older, postmenopausal women during rescreening intervals of approximately 15 years for women with normal bone density or mild osteopenia, 5 years for women with moderate osteopenia, and 1 year for women with advanced osteopenia. (Funded by the National Institutes of Health.).

Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-α(OH)D and calcitriol 1,25(OH)2D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus placebo studies had an ES of 0.36 (P < 0.0001), whereas native vitamin D versus placebo had an ES of 0.17 (P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 (P = 0.0002) for vitamin D analogs and ES = 0.21 (P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 (P < 0.0001) and ES = 0.33 (P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, −9.5 to 4.3) and RD = 6.4 (95%CI, −2.3 to 10), respectively. In head-to-head studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm studies including an inactive comparator.

The Use of Active Surveillance Cultures in Adult Intensive Care Units to Reduce Methicillin-Resistant Staphylococcus aureus-Related Morbidity, Mortality, and Costs: A Systematic Review

Active surveillance cultures (ASCs) are universal or targeted microbiological screening cultures for patients admitted to a hospital. ASCs have been proposed to control the increasing numbers of infections due to multidrug-resistant organisms, but their efficacy and cost-effectiveness are unproven. We conducted a systematic review of the literature pertaining to the use of ASCs and control of methicillin-resistant Staphylococcus aureus (MRSA). We searched relevant journals and the PubMed Medline, Web of Science, CINAHL, and Cochrane Library databases. No randomized, controlled trials were identified. Sixteen observational studies and 4 economic analyses were reviewed. Only 2 of the observational studies had a control group. None of the studies were of good quality. Thus, we identified important gaps in the literature, including a need for a clear definition of ASCs, a clear implementation protocol, and rigorous economic evaluations. Existing evidence may favor the use of ASCs, but the evidence is of poor quality, and definitive recommendations cannot be made.

Performance of osteoporosis risk assessment tools in postmenopausal women aged 45–64 years

Osteoporosis risk factor assessment is of uncertain utility in women under 65 years of age. Previous comparative studies of osteoporosis risk assessment tools were not stratified by age. We compared the discriminatory ability of three previously validated osteoporosis risk assessment tools in a referral population of postmenopausal women aged 45–64 years (n=2539) and aged 65–96 years (n=1496) seen at a university-based outpatient osteoporosis center in Belgium. Risk scores for the Osteoporosis Self-assessment Tool, Osteoporosis Risk Assessment Instrument, and Simple Calculated Osteoporosis Risk Estimation were calculated for each patient. The reference standard was osteoporosis at the femoral neck, defined as a T-score ≤−2.5 based on bone mineral density measured by dual energy X-ray absorptiometry. Osteoporosis was present in 139 of 2539 (5.5%) women aged 45–64 years and 241 of 1496 (16.1%) women aged 65 years or older. The tools had similar overall discriminatory ability to identify women with osteoporosis [area under the ROC curve 0.750–0.768, P=0.23 for women aged 45–64 years; area under the ROC curve 0.745–0.762, P=0.06 for women aged 65 years or older (P>0.05 indicates no difference among tools)]. The likelihood ratios for the high-risk score categories ranged from 3.60 to 6.73 for the younger women and 3.45 to 6.99 for the older women when different score thresholds were set to maximize the performance of each tool in each age group. We conclude that the diagnostic accuracy of three osteoporosis risk assessment tools was similar in postmenopausal women aged 45–64 years and women aged 65 years or older. Use of structured risk assessment tools to identify women at high risk of osteoporosis in the early postmenopausal period warrants further study. Of the three tools evaluated, the OST is the simplest and has the best potential for use in clinical practice.

Salmon Calcitonin Use and Associated Cancer Risk

Objective: To evaluate the strength of evidence supporting a possible association between salmon calcitonin (SCT) use and cancer incidence. Data Sources: Searches of MEDLINE/PubMed, MEDLINE/OVID, and EMBASE (January 1973 to September 2013) were performed using the key search terms salmon calcitonin, humans, nasal calcitonin, and (for EMBASE only) randomized controlled trial. We also performed a manual review of data reviewed by the US Food and Drug Administration (FDA) committee in 2013. Study Selection and Data Extraction: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. Data Synthesis: Intranasal and injectable SCT are FDA-approved for the treatment of postmenopausal osteoporosis. After a safety signal suggested a possible link between SCT use and prostate cancer, the European Medicines Agency and FDA regulatory agencies conducted analyses of SCT randomized controlled trial data to assess cancer-related adverse events and to readdress the approval status of SCT. Eighteen studies were found that compared nasal or oral SCT and placebo. In 15 of the 18 studies, the percentage of malignancy was greater in the SCT arm. The studies varied in quality, outcomes, and length. Most of the studies had poor-quality methods to assess new cancer cases. Conclusions: Current evidence may suggest an association between SCT use and cancer incidence based on studies with poor-quality cancer assessment methods. However, considering the lack of demonstrated efficacy of SCT to reduce fractures, clinicians should consider discontinuing its use for osteoporosis treatment regardless of the FDA’s final approval decision.

Osteoporosis screening in postmenopausal women 50 to 64 years old: Comparison of US preventive services task force strategy and two traditional strategies in the Women's Health Initiative

The US Preventive Services Task Force (USPSTF) recommends osteoporosis screening for women younger than 65 years whose 10‐year predicted risk of major osteoporotic fracture is ≥9.3%. For identifying screening candidates among women aged 50 to 64 years, it is uncertain how the USPSTF strategy compares with the Osteoporosis Self‐Assessment Tool (OST) and the Simple Calculated Osteoporosis Risk Estimate (SCORE). We examined data (1994 to 2012) from 5165 Womens Health Initiative participants aged 50 to 64 years. For the USPSTF (Fracture Risk Assessment Tool [FRAX] major fracture risk ≥9.3% calculated without bone mineral density [BMD]), OST (score <2), and SCORE (score >7) strategies, we assessed sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to discriminate between those with and without femoral neck (FN) T‐score ≤−2.5. Sensitivity, specificity, and AUC for identifying FN T‐score ≤−2.5 were 34.1%, 85.8%, and 0.60 for USPSTF (FRAX); 74.0%, 70.8%, and 0.72 for SCORE; and 79.8%, 66.3%, and 0.73 for OST. The USPSTF strategy identified about one‐third of women aged 50 to 64 years with FN T‐scores ≤−2.5. Among women aged 50 to 64 years, the USPSTF strategy was modestly better than chance alone and inferior to conventional SCORE and OST strategies in discriminating between women with and without FN T‐score ≤−2.5.

Strategies for the prevention of hip fracture

Hip fractures are associated with 10% to 20% excess mortality in the first year and cause functional disability in most survivors. An estimated 17% of white women in the United States will sustain a hip fracture after the age of 50 years. Despite the availability of evidence-based guidelines for hip fracture prevention, routine screening and preventive measures have not been incorporated into standard primary care practice. Many physicians lack adequate knowledge to initiate bone mineral density testing and treatment with preventive medications to decrease the incidence of osteoporosis and fractures. Furthermore, patients are less likely to request information about bone health than about diseases for which systematic screening and prevention protocols have been established. This review describes preventive measures to decrease hip fracture in postmenopausal women, including screening by bone mineral density testing, risk factor assessment, and chemoprevention. Existing guidelines are summarized, and dilemmas regarding their implementation are discussed.

Comparison of fracture risk prediction by the US Preventive Services Task Force strategy and two alternative strategies in women 50-64 years old in the Women's Health Initiative.

CONTEXT The United States Preventive Services Task Force (USPSTF) recommends osteoporosis screening for women younger than 65 years whose 10-year predicted risk of major osteoporotic fracture (MOF) is at least 9.3% using the Fracture Risk Assessment Tool. In postmenopausal women age 50-64 years old, it is uncertain how the USPSTF screening strategy compares with the Osteoporosis Self-Assessment Tool and the Simple Calculated Osteoporosis Risk Estimate (SCORE) in discriminating women who will and will not experience MOF. OBJECTIVE This study aimed to assess the sensitivity, specificity, and area under the receiver operating characteristic curve of the three strategies for discrimination of incident MOF over 10 years of follow-up among postmenopausal women age 50-64 years. SETTING AND DESIGN This was a prospective study conducted between 1993-2008 at 40 US Centers. PARTICIPANTS We analyzed data from participants of the Womens Health Initiative Observational Study and Clinical Trials, age 50-64 years, not taking osteoporosis medication (n = 62 492). MAIN OUTCOME MEASURES The main outcome was 10-year (observed) incidence of MOF. RESULTS For identifying women with incident MOF, sensitivity of the strategies ranged from 25.8-39.8%, specificity ranged from 60.7-65.8%, and AUC values ranged from 0.52-0.56. The sensitivity of the USPSTF strategy for identifying incident MOF ranged from 4.7% (3.3-6.0) among women age 50-54 years to 37.3% (35.4-39.1) for women age 60-64 years. Adjusting the thresholds to improve sensitivity resulted in decreased specificity. CONCLUSIONS Our findings do not support use of the USPSTF strategy, Osteoporosis Self-Assessment Tool, or SCORE to identify younger postmenopausal women who are at higher risk of fracture. Our findings suggest that fracture prediction in younger postmenopausal women requires assessment of risk factors not included in currently available strategies.

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

PURPOSE Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. METHODS We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). RESULTS FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. CONCLUSIONS After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight.

United States Adults Meeting 2010 American College of Rheumatology Criteria for Treatment and Prevention of Glucocorticoid‐Induced Osteoporosis

The American College of Rheumatology (ACR) updated its guidelines on the prevention and treatment of glucocorticoid‐induced osteoporosis (GIO) in 2010. An unknown proportion of US adults at risk of fracture due to glucocorticoid use would be recommended antiosteoporosis pharmaceutical (AOP) therapies based on the ACR guidelines.