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Total Hip (total + hip)
Terms modified by Total Hip Selected AbstractsLongitudinal Study of Changes in Hip Bone Mineral Density in Caucasian and African-American WomenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2005Jane A. Cauley DrPH Objectives: To determine whether changes in hip bone mineral density (BMD) differ in Caucasian and African American women. Design: Longitudinal study of changes in hip BMD. Setting: Four U.S. clinical centers. Participants: Six thousand seven Caucasian (mean age 73) and 482 African-American (mean age 75) women enrolled in the Study of Osteoporotic Fractures. Measurements: Total hip and femoral neck BMD were measured an average of 3.5 years apart (Caucasian) and 2.0 years apart (African American). Annual absolute and percentage changes in BMD and bone mineral apparent density (BMAD) were calculated. Results: The multivariate adjusted annual percentage change in BMD was greater in Caucasian than African-American women at the total hip (,0.574%/y vs ,0.334%/y) and femoral neck (,0.515%/y vs ,0.203%/y) (both, P<.001). Similar findings were observed for BMAD. The average annualized rate of BMD loss was twice as high in women aged 75 and older as in women younger than 75 in both ethnic groups. The annual percentage loss in femoral neck BMD in nonusers versus hormone therapy users was (,0.57% vs ,0.22%) in Caucasians and (,0.35% vs 0.64%) in African Americans (interaction P=.03). Conclusion: The average rate of hip BMD loss is approximately twice as great in Caucasian as African-American women and increases with age in both groups. The hormonal and biochemical factors that contribute to ethnic differences and the increase in bone loss with advancing age need to be identified. [source] Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide TreatmentJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Richard Prince Abstract A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 ,g) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture. Introduction: Treatment with teriparatide {rhPTH(1-34)} 20 and 40 ,g once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months. Materials and Methods: All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction. Results: Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p < 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p < 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 ,g and combined groups versus placebo but not for the 20 ,g group versus placebo. However, the 20 and 40 ,g groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p = 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment. Conclusions: While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment. [source] Normative data of bone mineral density in an unselected adult Austrian populationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2003S. Kudlacek Abstract Background There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. Methods We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21,76 years, who had been recruited by 17 centres across Austria. Results Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = ,0·23), total hip (r = ,0·07), trochanter (r = ,0·10), femoral neck (r = ,0·30) and Ward's triangle (r = ,0·40) in the women but only at the femoral neck (r = ,0·23) and at Ward's triangle (r = ,0·40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7·6,27·4% of the women and 16,41% of the men in our study group had low bone mass, whereas 0·6,2·7% of the female and 0·2,1·0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4,9-fold more females and 5,15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. Conclusion Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis. [source] Rivaroxaban , an oral, direct Factor Xa inhibitor , lessons from a broad clinical study programmeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Haas Abstract Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside. [source] Physical activity for prevention of osteoporosis in patients with severe haemophilia on long-term prophylaxisHAEMOPHILIA, Issue 3 2010M. KHAWAJI Summary., Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long-term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long-term prophylaxis to prevent bleeding. The bone density (BMD g cm,2) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X-ray absorptiometry. Physical activity was assessed using the self-report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1-L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long-term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis. [source] Bone turnover 18 months after a single intravenous dose of zoledronic acidINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2007V. Z. C. Borba Summary Zoledronic acid inhibits bone resorption for up to 12 months. It is not known whether the duration of this antiresorptive effect extends beyond this period of time. The aim of this study was to evaluate the changes in bone turnover at 12 months (T12) and 18 months (T18) after a single injection of 4 mg of zoledronic acid. It is a prospective, longitudinal study, with a follow-up for 18 months. We studied male and female patients (60.5 ± 11.0 years old), with low bone mineral density (BMD) coming from the outpatient clinic in a metabolic bone unit of a tertiary care hospital. All patients received a single intravenous dose of 4 mg of zoledronic acid, bone turnover markers [serum carboxyterminal telopeptide of type I collagen (CTX-I), bone-specific alkaline phosphatase (BSAP)] and BMD [lumbar spine (LS) and total hip (TH)] were measured at baseline, and after 12 months (T12) and 18 months (T18). Median serum CTX-I and BSAP levels were suppressed at T12 in comparison with baseline values: 0.183 to 0.039 ng/ml for CTX-I (p = 0.0002) and 16.95 to 13.96 U/l for BSAP (p = 0.005). At T18, both CTX-I and BSAP continued to be suppressed below baseline at 0.108 ng/ml and 12.23 U/l (p = 0.009 and p = 0.02, vs. T0). Significant increases in BMD at T18 as compared with T12 were observed in patients (median increase 6.1% for LS and 2.0% for TH). Zoledronic acid inhibits bone turnover effectively for 12 months, with evidence for continued suppression and gains in BMD even after 18 months. [source] Single-Point Assessment of Warfarin Use and Risk of Osteoporosis in Elderly MenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2008Claudine Woo PhD OBJECTIVES: To determine whether warfarin use, assessed at a single point in time, is associated with bone mineral density (BMD), rates of bone loss, and fracture risk in older men. DESIGN: Secondary analysis of data from a prospective cohort study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Five thousand five hundred thirty-three community-dwelling, ambulatory men aged 65 and older with baseline warfarin use data. MEASUREMENTS: Warfarin use was assessed as current use of warfarin at baseline using an electronic medication coding dictionary. BMD was measured at the hip and spine at baseline, and hip BMD was repeated at a follow-up visit 3.4 years later. Self-reported nonspine fractures were centrally adjudicated. RESULTS: At baseline, the average age of the participants was 73.6 ± 5.9, and 321 (5.8%) were taking warfarin. Warfarin users had similar baseline BMD as nonusers (n=5,212) at the hip and spine (total hip 0.966 ± 0.008 vs 0.959 ± 0.002 g/cm2, P=.37; total spine 1.079 ± 0.010 vs 1.074 ± 0.003 g/cm2, P=.64). Of subjects with BMD at both visits, warfarin users (n=150) also had similar annualized bone loss at the total hip as nonusers (n=2,683) (,0.509 ± 0.082 vs ,0.421 ± 0.019%/year, P=.29). During a mean follow-up of 5.1 years, the risk of nonspine fracture was similar in warfarin users and nonusers (adjusted hazard ratio=1.06, 95% confidence interval=0.68,1.65). CONCLUSION: In this cohort of elderly men, current warfarin use was not associated with lower BMD, accelerated bone loss, or higher nonspine fracture risk. [source] Longitudinal Study of Changes in Hip Bone Mineral Density in Caucasian and African-American WomenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2005Jane A. Cauley DrPH Objectives: To determine whether changes in hip bone mineral density (BMD) differ in Caucasian and African American women. Design: Longitudinal study of changes in hip BMD. Setting: Four U.S. clinical centers. Participants: Six thousand seven Caucasian (mean age 73) and 482 African-American (mean age 75) women enrolled in the Study of Osteoporotic Fractures. Measurements: Total hip and femoral neck BMD were measured an average of 3.5 years apart (Caucasian) and 2.0 years apart (African American). Annual absolute and percentage changes in BMD and bone mineral apparent density (BMAD) were calculated. Results: The multivariate adjusted annual percentage change in BMD was greater in Caucasian than African-American women at the total hip (,0.574%/y vs ,0.334%/y) and femoral neck (,0.515%/y vs ,0.203%/y) (both, P<.001). Similar findings were observed for BMAD. The average annualized rate of BMD loss was twice as high in women aged 75 and older as in women younger than 75 in both ethnic groups. The annual percentage loss in femoral neck BMD in nonusers versus hormone therapy users was (,0.57% vs ,0.22%) in Caucasians and (,0.35% vs 0.64%) in African Americans (interaction P=.03). Conclusion: The average rate of hip BMD loss is approximately twice as great in Caucasian as African-American women and increases with age in both groups. The hormonal and biochemical factors that contribute to ethnic differences and the increase in bone loss with advancing age need to be identified. [source] Human monocyte response to retrieved polymethylmethacrylate particlesJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 3 2002Masatsugu Miyaguchi Abstract The purpose of this study was to compare retrieved polymethylmethacrylate (PMMA) particles from failed total hip arthroplasties in terms of size, shape, and the response of human monocytes with commercially available particles. PMMA particles were isolated from peri-implant tissues of five failed cemented total hip arthroplasties using tissue digestion and a sucrose density gradient technique. Prepolymerized cement powder and those from which barium sulfate had been removed were examined for comparison. After exposure of peripheral human monocytes to PMMA particles, tumor necrosis factor-, and interleukin-6 in medium were measured by using enzyme-linked immunosorbent assays. Image analysis revealed that retrieved particles were larger (retrieved: 1.24 ,m; prepolymerized cement powder: 0.83 ,m; barium sulfate-free powder: 0.87 ,m) and were more irregular in shape and rougher than commercially available particles. Cytokine release was increased by all PMMA particle species. However, commercially available PMMA particles stimulated the release of necrosis factor-, and interleukin-6 more strongly than did retrieved particles at very high doses. The observed difference in monocyte response might be due to the volume of the challenged particles. Another possible reason for the difference might be alteration of the surface chemistry of particles in situ and the difference in surface morphology between them. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 331,337, 2002 [source] Sequential Treatment of Severe Postmenopausal Osteoporosis After Teriparatide: Final Results of the Randomized, Controlled European Study of Forsteo (EUROFORS),,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Richard Eastell Abstract It is unclear which treatment should be given after stopping teriparatide therapy for severe osteoporosis. In a prospective, randomized, controlled, 2-yr study, we compared BMD effects and clinical safety of three follow-up treatments (anabolic with teriparatide, antiresorptive with raloxifene, or no active treatment) after 1 yr of teriparatide. Postmenopausal women with osteoporosis and a recent fragility fracture received open-label teriparatide (20 ,g/d) for 12 mo before they were randomized (3:1:1) to continue teriparatide (n = 305), switch to raloxifene 60 mg/d (n = 100), or receive no active treatment for the second year (n = 102). All patients received calcium and vitamin D supplementation. Changes in areal BMD from baseline to 24 mo were analyzed using mixed-model repeated measures. Daily teriparatide treatment for 2 yr significantly increased spine BMD by 10.7%. Patients receiving raloxifene in year 2 had no further change in spine BMD from year 1 (change from baseline, 7.9%), whereas patients receiving no active treatment had a BMD decrease of 2.5% in year 2 (change from baseline, +3.8%). At the total hip, BMD increases from baseline at 2 yr were 2.5% with teriparatide, 2.3% with raloxifene, and 0.5% with no active treatment; the respective changes at the femoral neck were 3.5%, 3.1%, and 1.3%. The study had insufficient power to assess antifracture efficacy. In conclusion, BMD increases progressively over 2 yr of teriparatide therapy in women with severe osteoporosis. After discontinuation of teriparatide, raloxifene maintains spine BMD and increases hip BMD. [source] Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2009William D Leslie Abstract Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs),prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ,50 yr of age at the time of baseline BMD (1998,2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10,20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1,6.4], moderate 11.5 [95% CI, 10.1,13.0], high 25.4 [95% CI, 23.2,27.9] per 1000 person-years; p -for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3,16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1,18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates. [source] Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2009Jacques P Brown Abstract Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score , ,2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p , 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments. [source] Skeletal Fluorosis From Instant Tea,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael P Whyte MD Abstract Introduction: Skeletal fluorosis (SF) can result from prolonged consumption of well water with >4 ppm fluoride ion (F,; i.e., >4 mg/liter). Black and green teas can contain significant amounts of F,. In 2005, SF caused by drinking 1,2 gallons of double-strength instant tea daily throughout adult life was reported in a 52-yr-old woman. Materials and Methods: A 49-yr-old woman developed widespread musculoskeletal pains, considered fibromyalgia, in her mid-30s. Additionally, she had unexplained, increasing, axial osteosclerosis. She reported drinking 2 gallons of instant tea each day since 12 yr of age. Fluoxetine had been taken intermittently for 5 yr. Ion-selective electrode methodology quantitated F, in her blood, urine, fingernail and toenail clippings, tap water, and beverage. Results: Radiographs showed marked uniform osteosclerosis involving the axial skeleton without calcification of the paraspinal, intraspinal, sacrotuberous, or iliolumbar ligaments. Minimal bone excrescences affected ligamentous attachments in her forearms and tibias. DXA Z-scores were +10.3 in the lumbar spine and +2.8 in the total hip. Her serum F, level was 120 ,g/liter (reference range, 20,80 ,g/liter), and a 24-h urine collection contained 18 mg F,/g creatinine (reference value, <3). Fingernail and toenail clippings showed 3.50 and 5.58 mg F,/kg (control means, 1.61 and 2.02, respectively; ps < 0.001). The instant tea beverage, prepared as usual extra strength using tap water with ,1.2 ppm F,, contained 5.8 ppm F,. Therefore, the tea powder contributed ,35 mg of the 44 mg daily F, exposure from her beverage. Fluoxetine provided at most 3.3 mg of F, daily. Conclusions: SF from habitual consumption of large volumes of extra strength instant tea calls for recognition and better understanding of a skeletal safety limit for this modern preparation of the world's most popular beverage. [source] Endogenous Estrogen Levels and the Effects of Ultra-Low-Dose Transdermal Estradiol Therapy on Bone Turnover and BMD in Postmenopausal Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2007Alison J Huang Abstract In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra-low-dose estrogen therapy on the postmenopausal skeletal health may depend critically on women's endogenous estrogen levels before treatment. Introduction: Postmenopausal women with very low or undetectable estradiol levels have lower BMD, increased bone turnover, and increased risk of hip and vertebral fracture. We assessed whether the effects of ultra-low-dose 0.014 mg/d transdermal estradiol (Menostar; Berlex, Montvale, NJ, USA) on bone turnover and BMD are influenced by endogenous estradiol levels. Materials and Methods: We analyzed data from postmenopausal women (mean age, 66 yr) randomized to an 0.014-mg/d transdermal estradiol patch or placebo in the ultra-low-dose transdermal estrogen (ULTRA) trial. The free estradiol index (FEI), calculated as the ratio of total estradiol (by mass spectometry) to sex hormone-binding globulin (SHBG; by immunoradiometric assay) × 100, was used to estimate bioavailable estradiol at baseline. Among the 382 women who adhered to ,80% of study medication, we examined change in serum osteocalcin and bone-specific alkaline phosphatase levels at 12 mo and total hip and lumbar spine BMD at 24 mo in each quintile of FEI. Results: Compared with women in the highest quintile of FEI, those in the lowest quintile of FEI had a 26% greater reduction in bone-specific alkaline phosphatase and 15% greater reduction in osteocalcin in response to ultra-low estradiol treatment (p for trend across quintiles < 0.05). There was a trend toward greater improvement in total hip BMD (p = 0.06) but not spine BMD (p = 0.90) in those with lower versus higher FEI levels. Conclusions: The beneficial effects of ultra-low-dose 0.014-mg/d transdermal estrogen therapy on skeletal health may depend critically on women's endogenous estrogen levels before treatment. [source] Large-Scale Genome-Wide Linkage Analysis for Loci Linked to BMD at Different Skeletal Sites in Extreme Selected Sibships,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007Yi-Hsiang Hsu Abstract Few genome-wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome-wide scan involving 3093 adult siblings with at least one sib-pair extremely concordant or discordant for hip BMD. Our results indicated four genome-wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance. Introduction: The genetic basis for osteoporosis has been firmly established, but efforts to identify genes associated with this complex trait have been incomplete, especially in Asian populations. The purpose of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese population. Materials and Methods: We performed a genome-wide scan involving 3093 siblings 25,64 years of age from 941 families, with at least one sib-pair extreme concordant or discordant for total hip BMD from a large community-based cohort (n = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals adjusted for age, height, weight, occupation, cigarette smoking, physical activity, and alcohol consumption using the revised Haseman-Elston regression-based linkage model. Results: Our results revealed significant QTLs on chromosome 7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage analysis further revealed a significant QTL for lumbar spine BMD on chromosome 13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral neck, and lumbar spine BMD), an additional significant QTL was found at chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study overlapped with major QTLs reported by other studies. Conclusions: This study reveals four novel QTLs in a Chinese population and suggests that BMD at different skeletal sites may also share common genetic determinants. [source] Ghrelin and Bone: Is There an Association in Older Adults?: The Rancho Bernardo Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2006Lauren A Weiss Abstract Laboratory studies suggest that ghrelin is involved in bone metabolism, but studies of ghrelin and bone in humans are limited. We studied sex-specific associations of ghrelin with BMD, NTX, and bone loss. Ghrelin was not associated with BMD or bone loss in either sex. There was a significant inverse association with NTX in men but not in women. Introduction: Ghrelin is a gastric hormone recently shown to be associated with bone metabolism in animal and in vitro studies. Studies in humans are limited. We investigated the association of ghrelin with BMD, the bone resorption marker N-telopeptide (NTX), and bone loss in older men and women. Materials and Methods: Participants were 977 community-dwelling men and non,estrogen-using postmenopausal women, 50,91 years of age. Plasma ghrelin was measured by radioimmunoassay from blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. Axial BMD measurements were repeated an average of 4 years later in 544 participants. Bone turnover was assessed by NTX in urine obtained at the same time as the initial BMD. Multiple regression analyses were used to test sex-specific associations of ghrelin with BMD, NTX, and bone loss in both sexes. Results: No significant ghrelin,BMD or ghrelin,bone loss associations were observed in either sex, after adjusting for age and body mass index (BMI). Ghrelin was inversely associated with NTX in men and positively associated with NTX in women, independent of age. After adjusting for both age and BMI, this association reached statistical significance in men and was weakened in women. Conclusions: Ghrelin may be associated with bone turnover, but there is no evidence for an association with BMD or short-term change in BMD in older adults. [source] Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006Louis G Ste-Marie Abstract The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Introduction: Teriparatide {rhPTH(1-34)}, given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 ,g/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400,1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar. [source] Identification of Osteopenic Women at High Risk of Fracture: The OFELY Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2005Elisabeth Sornay-Rendu MD Abstract About one-half of women with incident fractures have BMD above the WHO diagnostic threshold of osteoporosis. In the OFELY study, low BMD, increased markers of bone turnover, and prior fracture could be used to identify, within osteopenic women, those at high risk of fracture. Introduction: Recent data suggest that about one-half of women with incident fractures have BMD above the World Health Organization (WHO) diagnostic threshold of osteoporosis (T score , ,2.5). We aimed to identify, within osteopenic women, those at high risk of fracture. Materials and Methods: In the 671 postmenopausal women (mean age: 62 years) belonging to the Os des Femmes de Lyon (OFELY) population-based prospective cohort, we measured at baseline BMD by DXA at the spine and total hip, bone turnover markers (BTM) and clinical risk factors for osteoporosis. All fragility vertebral or nonvertebral fractures, confirmed by radiographs, were assessed during a median follow-up of 9.1 years (IQ: 2.3). Results: 158 incident fractures were recorded in 116 women: 8% in normal, 48% in osteopenic, and 44% in osteoporotic women. Among osteopenic women, low BMD (,2.5 < T score , ,2.0) was associated with an increased fracture risk with an age-adjusted hazard ratio (HR) of 2.5 (1.3-4.6). In addition, age, prior fracture, and high BTM,but not other risk factors,were independently associated with an increased fracture risk with an age-adjusted HR of 2.2 (1.2-4.3) for prior fractures and 2.2 (1.4-3.8) for bone alkaline phosphatase (BALP) in the highest quartile. In the whole group of osteopenic women, a large majority of incident fractures occurred in those with a low BMD, prior fractures, or BALP in the highest quartile, with an age-adjusted HR of 5.3 (2.3-11.8). The 10-year probability of fracture in osteopenic women was 26% if at least one predictor was present, contrasting with 6% in those without any of the three risk factors. Conclusions: In postmenopausal women with osteopenia, low BMD, increased BTM, and prior fracture are associated with an increased risk of fracture in the subsequent 10 years. Their assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone and who may benefit from a therapeutic intervention. [source] Oropharyngeal Skeletal Disease Accompanying High Bone Mass and Novel LRP5 Mutation,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005Michael R Rickels Abstract Gain-of-function mutation in the gene encoding LRP5 causes high bone mass. A 59-year-old woman carrying a novel LRP5 missense mutation, Arg154Met, manifested skeletal disease affecting her oropharynx as well as dense bones, showing that exuberant LRP5 effects are not always benign. Introduction: Gain-of-function mutation (Gly171Val) of LDL receptor-related protein 5 (LRP5) was discovered in 2002 in two American kindreds with high bone mass and benign phenotypes. In 2003, however, skeletal disease was reported for individuals from the Americas and Europe carrying any of six novel LRP5 missense mutations affecting the same LRP5 protein domain. Furthermore, in 2004, we described a patient with neurologic complications from dense bones and extensive oropharyngeal exostoses caused by the Gly171Val defect. Materials and Methods: A 59-year-old woman was referred for dense bones. Three years before, mandibular buccal and lingual exostoses (osseous "tori") were removed because of infections from food trapping between the teeth and exostoses. Maxillary buccal and palatal exostoses were asymptomatic. Radiographic skeletal survey showed marked thickening of the skull base and diaphyses of long bones (endosteal hyperostosis). BMD Z scores assessed by DXA were +8.5 and +8.7 in the total hip and L1 -L4 spine (both ,195% average control), respectively. LRP5 mutation analysis was carried out for the LRP5 domain known to cause high bone mass. Results: Biochemical evaluation excluded most secondary causes of dense bones, and male-to-male transmission in her family indicated autosomal dominant inheritance. PCR amplification and sequencing of LRP5 exons 2-4 and adjacent splice sites revealed heterozygosity for a new LRP5 missense mutation, Arg154Met. Conclusions: LRP5 Arg154Met is a novel defect that changes the same first ",-propeller" module as the eight previously reported LRP5 gain-of-function missense mutations. Arg154Met alters a region important for LRP5 antagonism by dickkopf (Dkk). Therefore, our patient's extensive oropharyngeal exostoses and endosteal hyperostosis likely reflect increased Wnt signaling and show that exuberant LRP5 effects are not always benign. [source] Two-Year Results of Once-Weekly Administration of Alendronate 70 mg for the Treatment of Postmenopausal OsteoporosisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002R Rizzoli Abstract The aim of this study was to provide confirmation that once-weekly dosing with 70 mg of alendronate (seven times the daily oral dose) and twice-weekly dosing with 35 mg is equivalent to the 10-mg once-daily regimen and to gain more extensive safety experience with this new dosing regimen. Twelve hundred fifty-eight postmenopausal women (aged 42,95 years) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak young adult mean or prior vertebral or hip fracture) were assigned to receive oral once-weekly alendronate, 70 mg (n = 519); twice-weekly alendronate, 35 mg (n = 369); or daily alendronate 10 mg (n = 370) for a total of 2 years of double-blind experience. Mean BMD increases from baseline (95% CI) at 24 months in the once-weekly, twice-weekly, and daily treatment groups, respectively, were 6.8% (6.4, 7.3), 7.0% (6.6, 7.5), and 7.4% (6.9, 7.8) at the lumbar spine and 4.1% (3.8, 4.5), 4.3% (3.9, 4.7), and 4.3% (3.9, 4.7) at the total hip. These increases in BMD as well as the BMD increases at the femoral neck, trochanter, and total body and the reductions of biochemical markers of bone resorption (urinary cross-linked N-telopeptides of type I collagen [NTx]) and bone formation (serum bone-specific alkaline phosphatase [BSAP]) were similar for the three dosing regimens. All treatment regimens were well tolerated with a similar incidence of upper gastrointestinal (GI) adverse experiences. The incidence rates of clinical fractures, captured as adverse experiences, were similar among the groups. The 2-year results confirm the conclusion reached after 1 year that once-weekly alendronate is therapeutically equivalent to daily dosing, providing patients with a more convenient dosing option that may potentially enhance adherence to therapy. [source] Ibandronate: A Comparison of Oral Daily Dosing Versus Intermittent Dosing in Postmenopausal OsteoporosisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001B. J. Riis Abstract The objective of this study was to compare efficacy and safety of continuous versus intermittent oral dosing of ibandronate. Two hundred forty women aged 55,75 years with postmenopausal osteoporosis were randomized to active treatment or placebo. Similar total doses of ibandronate were provided by treatment regimens with either continuous 2.5 mg of ibandronate daily (n = 81) or intermittent 20 mg of ibandronate every other day for the first 24 days, followed by 9 weeks without active drug (n = 78). The placebo group (total, n = 81) was crossed over after 12 months to receive either continuous (n = 37) or intermittent ibandronate (n = 35). By 24 months, bone mineral density (BMD) had increased significantly relative to baseline in both active treatment groups. The continuous and intermittent groups showed statistically equivalent increases in lumbar spine BMD of +5.64% (±0.53) and +5.54% (±0.53) and in total hip of +3.35% (±0.40) and +3.41% (±0.40), respectively (per protocol population). Biochemical markers of bone turnover decreased significantly in both treatment groups. The level of marker suppression was similar, although the intermittent group displayed, as expected, more fluctuation over the treatment period. The frequency of adverse events was similar in the treatment groups. In conclusion, the intermittent and continuous regimens showed equivalent changes in BMD and bone turnover. These results confirm previous preclinical findings indicating that the efficacy of ibandronate depends on the total oral dose given rather than on the dosing schedule. This supports development of new flexible dosing regimens targeted to minimize the frequency of dosing, which are expected to improve convenience and lead to enhanced long-term patient compliance. [source] Tooth loss and osteoporosis: the osteodent studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2009Kety Nicopoulou-Karayianni Abstract Aim: To determine the cross-sectional association of the osteoporotic status of patients with the number of their teeth, with and without taking into account age and/or smoking. Material & Methods: At four centres, the study recruited 665 females aged 45,70 years and the number of teeth was counted for 651 subjects. Bone density was measured at the total hip, femoral neck and lumbar spine. Results: The mean number of teeth in the osteoporotic subjects was 3.3 fewer than normal subjects and 2.1 fewer if those with no teeth were excluded. The association between osteoporosis and having <6 or having <28 teeth remained significant after adjusting for age, smoking and centre with p -values of 0.016 and 0.011, respectively. A single regression model for tooth count with normal errors would not fit all the data. By fitting mixture regression models to subjects with tooth count >0, three clusters were identified corresponding to different degrees of tooth loss. The overall effect of osteoporosis was as follows: ,1.8 teeth before and after adjusting for smoking, ,1.2 teeth after adjusting for age, and ,1.1 teeth after adjusting for both age and smoking. Conclusions: We have established a significant association between osteoporosis and tooth loss after adjusting the effect for age and smoking. [source] Major elective joint replacement surgery: socioeconomic variations in surgical risk, postoperative morbidity and length of stayJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 3 2010Jennifer Hollowell PhD Abstract Background, Patient deprivation is associated with greater need for total hip and knee replacement surgery (THR/TKR) and a higher prevalence of risk factors for surgical complications. Our aim was to examine associations between deprivation and aspects of the inpatient episode for patients undergoing these procedures. Methods, We analysed socioeconomic variations in preoperative surgical risk, postoperative morbidity and length of stay for 655 patients undergoing elective THR/TKR at a large metropolitan hospital. Surgical risk was assessed using the orthopaedic version of the POSSUM scoring system, postoperative morbidity was assessed using the postoperative morbidity survey, and socioeconomic status was measured using the Index of Multiple Deprivation. We adjusted for age, sex, surgical site and primary vs. revision surgery. Results, We found only a modest, clinically insignificant socioeconomic gradient in preoperative surgical risk and no socioeconomic gradient in postoperative morbidity. There was a strong socioeconomic gradient in length of stay, but only for patients undergoing TKR. This was due to deprived patients being more likely to remain in hospital without morbidity following TKR. Conclusions, Our findings suggest differential selection of healthier patients for surgery. Hospitals serving deprived communities may have excess, unfunded costs because of the increased length of stay of socioeconomically disadvantaged patients. [source] Fitness, fatness and activity as predictors of bone mineral density in older personsJOURNAL OF INTERNAL MEDICINE, Issue 5 2002K. J. Stewart Abstract. Stewart KJ, DeRegis JR, Turner KL, Bacher AC, Sung J, Hees PS, Tayback M, Ouyang P (Johns Hopkins Bayview Medical Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA). Fitness, fatness, and activity as predictors of bone mineral density in older persons. J Intern Med 2002; 252: 381,388. Objectives. To determine relationships of bone mineral density (BMD) with fitness, physical activity, and body composition and fat distribution. Design. Cross-sectional. Setting. General Clinical Research Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. Subjects. Men (n = 38) and women (n = 46), aged 55,75 years with high normal blood pressure or mild hypertension but otherwise healthy. Methods. Aerobic fitness (oxygen uptake) on a treadmill, muscle strength by one-repetition maximum, activity by questionnaire, abdominal obesity by magnetic resonance imaging; anthropometrics, and body composition by dual energy X-ray absorptiometry (DXA) which measured total fat and lean mass, and BMD for the total skeleton, lumbar spine (L1,L4) and total hip. Results. Aerobic fitness did not correlate with BMD. Using multivariate analysis to ascertain independent contributions to the variance in BMD, in women, with adjustment for hormone replacement therapy (HRT), total skeleton BMD was independently related to muscle strength and abdominal total fat; total hip BMD to body weight; lumbar spine BMD to abdominal total fat. HRT also influenced BMD in the lumbar spine. In men, lumbar spine BMD was independently related to abdominal total fat physical activity and total hip BMD related to lower body strength. P < 0.05 for all of these correlations. Conclusions. Abdominal obesity and muscle strength emerge as predominant correlates of BMD in older persons with stronger relationships seen in women. Body weight and HRT also explained portions of the variance in BMD in women. Whether abdominal obesity is simply a marker for general obesity or has independent protective effects on bone is yet to be determined. [source] Low Bone Mineral Density and Impaired Bone Metabolism in Young Alcoholic Patients Without Liver Cirrhosis: A Cross-Sectional StudyALCOHOLISM, Issue 2 2009Peter Malik Background:, Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol,s direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. Methods:, In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1,L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. Results:, In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z -score , ,2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D < 30 ng/ml). Conclusions:, Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism. [source] Latest news and product developmentsPRESCRIBER, Issue 9 2008Article first published online: 21 MAY 200 Dabigatran launched Dabigatran (Pradaxa), an orally active direct thrombin inhibitor, has been introduced for the prophylaxis of venous thromboembolism in patients undergoing elective total hip or knee replacement. Treatment is initiated within four hours of surgery and continued for 10 days after knee replacement and 28-35 days after hip replacement. Dabigatran has been shown to be as effective and well tolerated as enoxaparin (Clexane). The launch was widely publicised in the lay media; the charity Lifeblood claimed it could help prevent tens of thousands of deaths. NICE is preparing a technology appraisal of the new agent but it has not announced a publication date. Loop diuretics may increase bone loss Continuous use of a loop diuretic appears to double the rate of bone loss in men compared with nonusers, an observational study suggests (Ann Intern Med 2008;168: 735-40). Up to five years' follow-up of 3269 men aged over 65 revealed that the mean rate of bone loss in the hip among those who did not use a loop diuretic was 0.33 per cent compared with 0.78 per cent among users and 0.58 per cent in those who had intermittently used a loop diuretic. Use of these agents should be included as a risk factor for fractures, the authors suggest. Rosuvastatin not for heart failure patients? Prescribers should pause before using rosuvastatin (Crestor). in patients with heart failure and ischaemic heart disease, the National Prescribing Centre (NPC). says. Commenting on the CORONA trial (N Engl J Med 2008; published online 5 Nov 2007; 10.1056/NEJMoa 0706201)., which found no reduction in cardiovascular events or mortality in older patients with systolic heart failure despite a reduction in LDL-C, the NPC says GPs should still consider evidence-based statins such as simvastatin in this patient group. The reason for the outcome of CORONA is unclear but the NPC points out that not all statins affect mortality equally. Rimonabant CV benefits sustained Two-year follow-up of the RIO-Europe trial has shown that the benefits of rimonabant (Acomplia). on weight loss and cardiovascular risk factors are sustained with continuing treatment (Eur Heart J 2008; published online doi: 10.1093/ eurheartj/ehn076). In addition to a dietary deficit of 600kcal per day, rimonabant 20mg per day achieved greater mean weight loss (5.5 vs 1.2kg). and improvements in waist circumference, HDL-cholesterol, triglycerides, fasting glucose and insulin levels, insulin resistance, and metabolic syndrome prevalence compared with placebo. Many patients discontinued treatment (placebo 42 per cent, rimonabant 45 per cent). but, although psychiatric events were more common with rimonabant during the first year, there was little difference in patients remaining in the second year. Early glatiramer cuts MS progression risk Early treatment with glatiramer acetate (Copaxone). appears to reduce the risk of progression to multiple sclerosis (MS), according to a study presented at the 60th Annual Meeting of the American Academy of Neurology in Chicago. Interim analysis of the PreCISE trial showed that, in patients with a single episode and MRI suggestive of MS, glatiramer was associated with a lower incidence of progression to a second episode of MS compared with placebo (25 vs 43 per cent). The placebo arm of the trial has now been stopped. NRT before quitting Beginning nicotine replacement therapy (NRT) before stopping smoking may double the six-month success rate compared with beginning treatment on the scheduled quit day, a meta-analysis suggests (Addiction 2008;103: 557-63). The analysis of four trials involving 755 participants found that starting NRT two to four weeks before the agreed quit date was twice as likely as the conventional strategy to achieve abstinence after six weeks and six months. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 6 2008Article first published online: 24 APR 200 Government responds to NICE report The Government has published its response to the Health Select Committee's report into NICE, broadly arguing that the Committee's recommendations are either already being dealt with or are not appropriate. The Committee recommended appraisals for all new drugs, shorter, rapid appraisals to coincide with their launch, and improved mechanisms for setting drug prices. The Government says its negotiations on the PPRS preclude a detailed response but suggests a rapid system may not be transparent or legally robust. It is exploring how high-cost drugs can be brought within the payment-by-results tariff. While defending NICE's reliance on QALYs, the Government accepts the need to explore how wider economic factors can be considered. As for the threshold cost per QALY by which NICE defines cost effectiveness, it says this is being validated scientifically and NICE will continue to determine the threshold. More topically, the Committee criticised the quality of clinical trial data available to NICE. The Government sees no need to compel pharmaceutical companies to disclose information and says NICE is already becoming more involved with research programmes. All clinical trials must be registered (confidentially) with the EU and the Government believes mandatory registration in the UK would be ineffective and illegal. Prescription charge up again from April The Government has raised the prescription charge by 25p to £7.10 per item with effect from 1 April. Prescription prepayment certificates will cost £27.85 for three months and £102.50 for 12 months. The increase, below the annual rate of inflation for the 10th successive year, will be levied on the 12 per cent of prescriptions that are liable for the charge: 5 per cent via prepayment certificates and 7 per cent from other prescriptions. The charge will generate £435 million in England in 2008/09; this excludes money from prescriptions written by dispensing doctors, which is retained by the PCT. Following criticism of the charge by the Health Select Committee, the Government says it has reviewed the charge and is now consulting on ,cost-neutral' options. MHRA safety update The MHRA warns of possible dose errors associated with Boots Medisure Domiciliary Dosage System in its latest issue of Drug Safety Update (2008;1:issue 8). One case has been reported in which incomplete sealing allowed tablets to mix between compartments. No other cases are known and the MHRA says no harm was reported but the risk is serious. The system should be carefully sealed and inspected visually and physically. The MHRA reaffirms its plans to reclassify all pseudoephedrine and ephedrine products to prescription-only status in 2009 if the new restrictions on sales do not reduce misuse. Other topics in this month's Update include revised indications for oral ketoconazole (Nizoral), restricting its use to selected conditions unresponsive to topical therapy; reformulation of the injectable antibiotic Tazocin (piperacillin plus tazobactum); the risk of peripheral neuropathy associated with pegylated interferon and telbivudine (Sebivo) in the treatment of hepatitis B; and serious adverse events associated with modafinil (Provigil). First oral anticoagulant since warfarin In January this year the EMEA issued a positive opinion to recommend marketing authorisation of the oral, fixed-dose, direct thrombin inhibitor dabigatran etexilate (Pradaxa) for the primary prevention of venous thromboembolism (VTE) in adult patients that have undergone elective knee or hip replacement surgery. Marketing authorisation for the EU (including the UK) is expected from the European Commission in the next few weeks, making dabigatran the first oral anticoagulant since warfarin was introduced in 1954. Dabigatran etexilate has been shown to be as safe and effective as enoxaparin (Clexane) with a similar adverse event profile in the noninferiority phase III RENOVATE (Lancet 2007;370: 949-56) and RE-MODEL (J Throm Haemost 2007;5:217885) trials, which investigated the efficacy and safety of dabigatran compared to enoxaparin in reducing the risk of VTE after total hip and knee surgery respectively. Dabigatran has the practical advantage over low-molecular-weight heparin of oral postoperative administration and no risk of heparin-induced thrombocytopenia and, unlike warfarin, does not require monitoring or dose titration. Risk scale predicts anticholinergic effects US investigators have developed a scale for predicting the risk of anticholinergic side-effects from older patients' medicines (Arch Intern Med 2008;168: 508-13). The scale assigns a score from 1 (low) to 3 (high) for the risk of anticholinergic effects such as dry mouth, constipation and dizziness associated with commonly prescribed medicines. Checking the scale retrospectively in older patients in residential care, a higher score was associated with a 30 per cent increased risk of side-effects after adjustment for age and number of medicines. When this was repeated prospectively in a primary-care cohort, the increased risk was 90 per cent. HRT cancer risk persists The latest analysis of the Women's Health Initiative (WHI) trial of HRT shows that the small increase in the risk of cancer persists for up to three years after stopping treatment (J Am Med Assoc 2008;299:1036-45). WHI was stopped after 5.6 years' follow-up when it became clear the risks of HRT outweighed its benefits. This follow-up after a further three years (mean 2.4) involved 15 730 women. The annual risk of cardiovascular events was similar for HRT (1.97 per cent) and placebo (1.91 per cent). Cancers were more common among women who had taken HRT (1.56 vs 1.26 per cent), in particular breast cancer (0.42 vs 0.33 per cent). All-cause mortality was higher, but not statistically significantly so, with HRT (1.20 vs 1.06 per cent). Tight glycaemic control may increase falls Maintaining HbA1C at or below 6 per cent with insulin is associated with an increased risk of falls, a US study suggests (Diabetes Care 2008;31:391-6). The Health, Aging and Composition study involved 446 older people with type 2 diabetes (mean age 74) followed up for approximately five years. The incidence of falls ranged from 22 to 30 per cent annually. Comparing subgroups with HbA1C of ,6 per cent and >8 per cent, an increased risk of falls was associated with insulin use (odds ratio 4.4) but not oral hypoglycaemic drugs. Copyright © 2008 Wiley Interface Ltd [source] Subacute pain and function after fast-track hip and knee arthroplastyANAESTHESIA, Issue 5 2009L. Ø. Andersen Summary In a well-defined fast-track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra-operative local anaesthetic infiltration and oral celecoxib, gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1,10 and 30 days postoperatively. Fast-track total hip and knee arthroplasty with early discharge (< 3 days) resulted in acceptable levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30,59 mm), and 16% severe pain (VAS , 60 mm) when walking 1 month after surgery with a concomitant increase in the use of strong opioids. These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty, to facilitate rehabilitation. [source] Trends of spinal fusion surgery in Australia: 1997 to 2006ANZ JOURNAL OF SURGERY, Issue 11 2009Ian Andrew Harris Abstract Background:, This study aims to explore the trend in spine fusion surgery in Australia over the past 10 years, and to explore the possible influence of health insurance status (private versus public) on the rate of surgery. Methods:, Data pertaining to the rate of lumbar spine fusion from 1997 to 2006 were collected from Inpatient Statistics Collection of NSW Health, Medicare Australia Statistics and the Australian Bureau of Statistics. Data on total hip and total knee arthroplasties were collected to provide a comparator. Results:, The number of publicly performed spinal fusion procedures increased by 2% from 1997 to 2006. In comparison, privately performed spinal fusion procedures increased by 167% over the same 10-year period. In 2006, spine fusion surgery was 10.8 times more likely to be done in the private sector than in the public sector, compared with corresponding figures of 4.2 times and 3.0 times for knee replacement and hip replacement, respectively. Waiting list data showed no increase in demand for spine fusion surgery in the public sector. Conclusion:, There is a disproportionately high rate of lumbar spine fusion surgery performed in the private sector, given the rate of private insurance. The rate of increase was found to be higher than that for hip or knee arthroplasty procedures. Possible explanations for this difference include: over-servicing in the private sector, under-servicing in the public sector, differences in medical referral patterns, surgeon and patient preferences and financial incentives. [source] Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: Thirty-six,month results of a randomized, double-blind, controlled trial,ARTHRITIS & RHEUMATISM, Issue 11 2009Kenneth G. Saag Objective To compare the bone anabolic drug teriparatide (20 ,g/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid-induced osteoporosis (OP). Methods This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22,89 years) who had received ,5 mg/day of prednisone equivalent for ,3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety. Results Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001). Conclusion Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate. [source] | ||||||||||||||||||||||