Elizabeth M Haney

Screening for Osteoporosis: An Update for the U.S. Preventive Services Task Force

BACKGROUND This review updates evidence since the 2002 U.S. Preventive Services Task Force recommendation on osteoporosis screening. PURPOSE To determine the effectiveness and harms of osteoporosis screening in reducing fractures for men and postmenopausal women without known previous fractures; the performance of risk-assessment instruments and bone measurement tests in identifying persons with osteoporosis; optimal screening intervals; and the efficacy and harms of medications to reduce primary fractures. DATA SOURCES Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2009), MEDLINE (January 2001 to December 2009), reference lists, and Web of Science. STUDY SELECTION Randomized, controlled trials of screening or medications with fracture outcomes published in English; performance studies of validated risk-assessment instruments; and systematic reviews and population-based studies of bone measurement tests or medication harms. DATA EXTRACTION Data on patient populations, study design, analysis, follow-up, and results were abstracted, and study quality was rated by using established criteria. DATA SYNTHESIS Risk-assessment instruments are modest predictors of low bone density (area under the curve, 0.13 to 0.87; 14 instruments) and fractures (area under the curve, 0.48 to 0.89; 11 instruments); simple and complex instruments perform similarly. Dual-energy x-ray absorptiometry predicts fractures similarly for men and women; calcaneal quantitative ultrasonography also predicts fractures, but correlation with dual-energy x-ray absorptiometry is low. For postmenopausal women, bisphosphonates, parathyroid hormone, raloxifene, and estrogen reduce primary vertebral fractures. Trials are lacking for men. Bisphosphonates are not consistently associated with serious adverse events; raloxifene and estrogen increase thromboembolic events; and estrogen causes additional adverse events. LIMITATION Trials of screening with fracture outcomes, screening intervals, and medications to reduce primary fractures, particularly those enrolling men, are lacking. CONCLUSION Although methods to identify risk for osteoporotic fractures are available and medications to reduce fractures are effective, no trials directly evaluate screening effectiveness, harms, and intervals. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening and treatment for lipid disorders in children and adolescents: systematic evidence review for the US Preventive Services Task Force.

OBJECTIVE. This was a systematic evidence review for the US Preventive Services Task Force, intended to synthesize the published evidence regarding the effectiveness of selecting, testing, and managing children and adolescents with dyslipidemia in the course of routine primary care. METHODS. Literature searches were performed to identify published articles that addressed 10 key questions. The review focused on screening relevant to primary care of children without previously identified dyslipidemias, but included treatment trials of children with dyslipidemia because some drugs have only been tested in that population. RESULTS. Normal values for lipids for children and adolescents are defined according to population levels (percentiles). Age, gender, and racial differences and temporal trends may alter these statistical cut points. Approximately 40% to 55% of children with elevated total cholesterol and low-density lipoprotein levels will continue to have elevated lipid levels on follow-up. Current screening recommendations based on family history will fail to detect substantial numbers (30%–60%) of children with elevated lipid levels. Drug treatment for dyslipidemia in children has been studied and shown to be effective only for suspected or proven familial monogenic dyslipidemias. Intensive dietary counseling and follow-up can result in improvements in lipid levels, but these results have not been sustained after the cessation of the intervention. The few trials of exercise are of fair-to-poor quality and show little or no improvements in lipid levels for children without monogenic dyslipidemias. Although reported adverse effects were not serious, studies were generally small and not of sufficient duration to determine long-term effects of either short or extended use. CONCLUSIONS. Several key issues about screening and treatment of dyslipidemia in children and adolescents could not be addressed because of lack of studies, including effectiveness of screening on adult coronary heart disease or lipid outcomes, optimal ages and intervals for screening children, or effects of treatment of childhood lipid levels on adult coronary heart disease outcomes.

The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5)

Novel molecular pathways obligatory for bone health are being rapidly identified. One pathway recently revealed involves gut-derived 5-hydroxytryptamine (5-HT) mediation of the complete skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Mounting evidence supports 5-HT as an important regulatory compound in bone with previous evidence demonstrating that bone cells possess functional pathways for responding to 5-HT. In addition, there is growing evidence that potentiation of 5-HT signaling via inhibition of the 5-HT transporter (5-HTT) has significant skeletal effects. The later is clinically significant as the 5-HTT is a popular target of pharmaceutical agents, such as selective serotonin reuptake inhibitors (SSRIs), used for the management of major depressive disorder and other affective conditions. The observation that 5-HT mediates the complete skeletal effects of LRP5 represents a significant paradigm shift from the traditional view that LRP5 located on the cell surface membrane of osteoblasts exerts direct skeletal effects via Wnt/beta-catenin signaling. This paper discusses the mounting evidence for skeletal effects of 5-HT and the ability of gut-derived 5-HT to satisfactorily explain the skeletal effects of LRP5.

Effects of selective serotonin reuptake inhibitors on bone health in adults: Time for recommendations about screening, prevention and management?

Evidence regarding a functional serotonin (5-hydroxytryptamine) signaling system in bone has generated considerable recent interest. The specific biochemical nature of serotoninergic pathways and their direct and/or indirect effects on bone metabolism are still unclear. Clinical evidence supports an effect of serotonin and altered serotonin signaling on bone metabolism. Serotonin is involved in the pathophysiology of depression, and therefore studies of depression and antidepressant treatments (as modulators of the serotonin system) are relevant with regard to bone outcomes. Studies on the effect of depression on bone mineral density (BMD) and fractures have been mixed. Studies on the associations between antidepressant use and BMD and/or fractures are more consistent. SSRIs have been associated with lower BMD and increased rates of bone loss, as well as increased rates of fracture after accounting for falls. These studies are limited by confounding because depression is potentially associated with both the outcome of interest (BMD and fracture) and the exposure (SSRIs). With mounting evidence for an effect on bone, this review considers the question of causality and whether selective serotonin reuptake inhibitors should be considered among those medications that contribute to bone loss, and therefore prompt clinicians to evaluate BMD proactively. Future research will be required to confirm the serotoninergic effects on bone and the biochemical pathways involved, and to identify clinical implications for treatment based on this novel pathway.

Depressive Symptoms and Bone Mineral Density in Older Men

Most studies examining the relation between depression and bone mineral density (BMD) have been limited to psychiatric patients or to community-dwelling, older women. We conducted a cross-sectional and prospective cohort study to determine whether depressive symptoms are associated with low BMD in community-dwelling, older men. We recruited 515 men 50 years of age or older from population-based listings of age-eligible men. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they scored 6 or more out of 15 possible points. BMD was measured in the spine and hip using dual energy x-ray absorptiometry in all participants, and again an average of 3.6 years later in a random subset of 100 participants. The prevalence of depressive symptoms (GDS = 6) was 3.1% (16 of 515). We found no difference in mean BMD or mean percent change in BMD per year of the hip and lumbar spine in men who had 6 or more depressive symptoms compared with men who reported 5 or fewer symptoms of depression. These findings suggest that depressive symptoms are not associated with BMD in community-dwelling, older men.

Influence of menopause on mood: a systematic review of cohort studies

Objective This systematic evidence review evaluates the independent influence of the menopausal transition on mood including depression, anxiety, and other psychological symptoms. Methods Community-based, prospective cohort studies of mid-life women transitioning through menopause that assessed at least one mood symptom on two or more occasions were identified by searches of MEDLINE (1966–2007) and PsycINFO (1974–2007) databases. Articles were selected based on predetermined inclusion and exclusion criteria. Each study was quality-rated by three authors; poor quality studies were excluded. Results Nine studies met inclusion criteria. They varied broadly in design, outcome measures, statistical methodology, and in consideration of and adjustment for important confounders. Five found no association between the menopausal transition and depression, negative mood, major depressive disorder, other psychological symptoms, and general mental health. Three found that women entering or completing the menopausal transition were more likely than premenopausal women to be depressed. One found that well-being increased from the early to late menopausal transition. Conclusion There is no demonstrated pattern of an adverse independent influence of the menopausal transition on mood symptoms in mid-life women. However, the available studies are too methodologically diverse to be definitive.

Normocalcemic Hyperparathyroidism and Hypoparathyroidism in Two Community-Based Nonreferral Populations

CONTEXT Normocalcemic primary hyperparathyroidism is typically identified after referral to a specialty clinic. At diagnosis, patients demonstrate features seen in hypercalcemic primary hyperparathyroidism. Normocalcemic hypoparathyroidism has been discovered after hypocalcemia unmasked after bisphosphonate administration. OBJECTIVE We hypothesized that screening unselected, nonreferral populations, such as The Osteoporotic Fractures in Men (MrOS) study and Dallas Heart Study (DHS), would identify asymptomatic subjects with normocalcemic hyperparathyroidism and hypoparathyroidism. METHODS Normocalcemic hyperparathyroidism was defined as serum PTH greater than the upper reference range with normal albumin-adjusted serum calcium, excluding common secondary causes (renal failure [estimated glomerular filtration rate <60 mL/min], 25-hydroxyvitamin D <20 ng/mL, and thiazide use), and normocalcemic hypoparathyroidism as PTH below the reference range with normocalcemia. Cross-sectional data were obtained from MrOS, and longitudinal data (baseline and 8 years) from DHS. RESULTS In 2364 men from MrOS, we identified 9 with normocalcemic hyperparathyroidism (prevalence 0.4%) and 26 with normocalcemic hypoparathyroidism (1.1%). In 3450 men and women from DHS, we identified 108 with normocalcemic hyperparathyroidism (3.1%) and 68 with normocalcemic hypoparathyroidism (1.9%). Of the 108 normocalcemic hyperparathyroid subjects, 64 had follow-up data. Hypercalcemic primary hyperparathyroidism developed in 1 subject whereas 13 (0.6% of the follow-up cohort) showed persistently elevated PTH levels with normocalcemia. Of the 26 normocalcemic hypoparathyroid subjects with follow-up data, none developed overt hypoparathyroidism and 2 (0.09%) had persistent evidence of normocalcemic hypoparathyroidism. CONCLUSIONS This study documents normocalcemic primary hyperparathyroidism and hypoparathyroidism identified among community-dwelling individuals. Larger studies are needed to determine the true prevalence and natural history of these parathyroid disorders.

Vitamin D Insufficiency in Internal Medicine Residents

Medical residents may be vulnerable to low vitamin D status because of long work hours and lack of sun exposure. We conducted a prospective cohort study to measure serum 25-hydroxyvitamin D concentrations among internal medicine residents, document seasonal variation in vitamin D status, and assess risk factors for inadequate vitamin D stores. Dietary intake of calcium and vitamin D, lifestyle characteristics, and serum concentrations of 25(OH)-vitamin D and intact parathyroid hormone (iPTH) were measured in 35 resident volunteers before and after the winter season. A total of 63–69% of medical residents consumed <400 IU/day of vitamin D; 61–67% consumed <1000 mg/day of calcium. Twenty-five (74%) had lower serum 25(OH)-vitamin D concentrations and 23 (68%) had higher serum iPTH in the spring than in the fall. Nine (26%) residents had serum concentrations of 25(OH)-vitamin D of <20 ng/mL in the fall; and sixteen (47%) in the spring. Seven residents (20%) had serum concentrations of 25(OH)-vitamin D of <20 ng/mL at both time-periods; Eighteen residents (51.4%) had 25(OH)-vitamin D levels of <20 ng/mL for at least one of the time-periods. Medical residents are at risk for hypovitaminosis D, particularly during the winter months and should be aware of the need to supplement their vitamin D stores. Insufficient vitamin D status and inadequate vitamin D intake may have long-term implications for bone health in these individuals. Increased educational efforts to promote healthy dietary and lifestyle choices that allow attainment and maintenance of skeletal health are appropriate in this population.

Male osteoporosis : new insights in an understudied disease

Purpose of reviewOsteoporosis in men is increasingly recognized as an important health problem. New research contributes to our knowledge of gender differences in osteoporosis risk, diagnosis and management. We undertook this review to summarize recent developments in the field of male osteoporosis. Recent findingsThe paper reviews recently published studies that reveal new insights into male osteoporosis. It addresses epidemiology, risk factors, use of clinical risk assessment tools, diagnosis and treatment. New data continue to suggest that men have higher mortality rates than women after hip fracture, and that men may experience fractures at higher bone mineral density values than women. Treatments for osteoporosis have been studied mostly in women, but trials including both men and women are now being conducted. Likewise, there are several newer cohorts with bone and fracture outcomes that include men and women. The Osteoporotic Fractures in Men (MrOS) study is the first United States-based cohort to include only men; this study is contributing importantly to our understanding of epidemiology and risk factors for osteoporosis in men. SummaryMen and their physicians should be aware of the risk for osteoporosis and the gender differences that exist within this disease. Further research is needed to continue to understand differences in pathophysiology, epidemiology and risk factors, and to promote appropriate therapies among men.

Association of Intact Parathyroid Hormone Levels with Subsequent Hip BMD Loss: The Osteoporotic Fractures in Men (MrOS) Study

INTRODUCTION There is little information on the association between intact PTH (iPTH) and longitudinal changes in bone mineral density (BMD) in older men. This association was evaluated in relation to conditions related to higher iPTH [e.g. decreased renal function, low serum 25-hydroxyvitamin D (25[OH]D)]. METHODS Eligible men were part of a random sample of 1593 community-dwelling individuals aged 65 yr or older participating in the Osteoporotic Fractures in Men study with baseline iPTH data. Of these, 1227 had at least two BMD measurements at the total hip and femoral neck over a mean follow-up of 4.5 yr. Annualized BMD change across iPTH quartiles was estimated using mixed-effects regression models, adjusting for age, serum calcium, serum 25(OH)D, estimated glomerular filtration rate, and other factors. Splines were used to identify more optimal iPTH thresholds associated with less BMD loss. RESULTS Among the cohort of 1138 eligible men, men in the highest quartile of iPTH (≥38 pg/ml) lost 0.46% per year at the total hip compared with men in the lowest iPTH quartile who lost 0.22% per year (P = 0.0004). Results were similar at the femoral neck. The association between iPTH and BMD loss was not modified by baseline estimated glomerular filtration rate or 25(OH)D status. Spline results suggested that iPTH levels below 30 pg/ml were more physiologically optimal than higher iPTH values in reducing BMD loss, although an exact threshold for optimal iPTH was not identified. CONCLUSION Older men with higher iPTH levels had approximately a 2-fold greater rate of BMD loss compared with men with lower iPTH levels, irrespective of estimated glomerular filtration rate and 25(OH)D.