Fracture Incidence (fracture + incidence)

Distribution by Scientific Domains


Selected Abstracts


Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women's Health Initiative Randomized Trial

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2006
Rebecca D Jackson MD
Abstract Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture. Introduction: The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented. Materials and Methods: Postmenopausal women 50,79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk. Results: CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45,0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44,0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47,0.72), and total fracture (HR, 0.71; 95% CI, 0.64,0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68,1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62,1.05; mid risk: HR, 1.09; 95% CI, 0.92,1.30; highest risk: HR, 1.04; 95% CI, 0.88,1.23; interaction, p = 0.42). Conclusions: CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit. [source]


Root canal preparation with FlexMaster: asessment of torque and force in relation to canal anatomy

INTERNATIONAL ENDODONTIC JOURNAL, Issue 12 2003
W. Hübscher
Abstract Aim, To investigate physical parameters of FlexMaster nickel-titanium instruments while preparing curved canals in maxillary molars in vitro. Methodology, A torque-testing platform was used to prepare root canals in 11 extracted human maxillary molars with FlexMaster rotary instruments. Peak torque and force was registered along with numbers of rotations required to shape the canals. Canals were divided into ,wide' and ,constricted' groups depending on canal volumes assessed by microcomputed tomography. Resistance to cyclic fatigue was also tested. Mean scores for each instrument type were calculated and statistically compared using anova and Scheffé post hoc tests. Results, Mean torque varied between 0.1 ± 0.1 and 0.8 ± 0.5 N cm while mean force ranged from 4.2 ± 2.0 to 7.3 ± 3.5 N. Mean numbers of rotations totalled up to 18. All three variables registered showed weak correlations to preoperative canal volumes (P < 0.01) and differed significantly between ,wide' and ,constricted' canals (P < 0.001). Numbers of rotations to fracture in a cyclic fatigue test were between 348 and 1362. Conclusion, FlexMaster instruments generated low torque scores and were highly resistant to cyclic fatigue, whilst three instruments fractured in extremely narrow canals. Consequently, more research is required to limit fracture incidence and to optimize instrumentation guidelines. [source]


Treatment of osteopenia and osteoporosis in anorexia nervosa: A systematic review of the literature

INTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2009
Philip S. Mehler MD
Abstract Objective: To systematically review the evidence supporting treatment of osteopenia and osteoporosis in patients with anorexia nervosa (AN). Data sources: We identified controlled clinical studies of interventions for low bone mass in AN via searches of MEDLINE; the Cochrane Library; EMBASE; PsycINFO; and cumulative index to nursing and allied health literature. Outcomes of interest were changes in bone mineral density and fracture incidence. Results: Six randomized controlled trials (RCTs) and two cohort trials examined five classes of medical therapy on bone mineral density outcomes. One RCT of bisphosphonates showed no benefit and a second flawed RCT showed some benefit; one RCT showed a benefit of insulin-like growth factor-I; none of the five trials evaluating estrogen therapy showed benefit. Discussion: Although patients with AN are often losing bone mass when they should be optimizing bone growth, there is no good evidence to guide medicinal interventions. Therefore, early detection and weight restoration are of utmost importance whereas ongoing trials define effective therapies. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [source]


Evaluating the Cost-Effectiveness of Fall Prevention Programs that Reduce Fall-Related Hip Fractures in Older Adults

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2010
Kevin D. Frick PhD
OBJECTIVES: To model the incremental cost-utility of seven interventions reported as effective for preventing falls in older adults. DESIGN: Mathematical epidemiological model populated by data based on direct clinical experience and a critical review of the literature. SETTING: Model represents population level interventions. PARTICIPANTS: No human subjects were involved in the study. MEASUREMENS: The last Cochrane database review and meta-analyses of randomized controlled trials categorized effective fall-prevention interventions into seven groups: medical management (withdrawal) of psychotropics, group tai chi, vitamin D supplementation, muscle and balance exercises, home modifications, multifactorial individualized programs for all elderly people, and multifactorial individualized treatments for high-risk frail elderly people. Fall-related hip fracture incidence was obtained from the literature. Salary figures for health professionals were based on Bureau of Labor Statistics data. Using an integrated healthcare system perspective, healthcare costs were estimated based on practice and studies on falls in older adults. Base case incremental cost utility ratios were calculated, and probabilistic sensitivity analyses were conducted. RESULTS: Medical management of psychotropics and group tai chi were the least-costly, most-effective options, but they were also the least studied. Excluding these interventions, the least-expensive, most-effective options are vitamin D supplementation and home modifications. Vitamin D supplementation costs less than home modifications, but home modifications cost only $14,794/quality-adjusted life year (QALY) gained more than vitamin D. In probabilistic sensitivity analyses excluding management of psychotropics and tai chi, home modification is most likely to have the highest economic benefit when QALYs are valued at $50,000 or $100,000. CONCLUSION: Of single interventions studied, management of psychotropics and tai chi reduces costs the most. Of more-studied interventions, home modifications provide the best value. These results must be interpreted in the context of the multifactorial nature of falls. [source]


Association Between Changes in Habitual Physical Activity and Changes in Bone Density, Muscle Strength, and Functional Performance in Elderly Men and Women

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2008
Robin M. Daly PhD
OBJECTIVES: To investigate the long-term effects of habitual physical activity on changes in musculoskeletal health, functional performance, and fracture risk in elderly men and women. DESIGN: Ten-year prospective population-based study. SETTING: Malmö-Sjöbo Prospective Study, Sweden. PARTICIPANTS: Participants were 152 men and 206 women aged 50, 60, 70, and 80 who were followed for 10 years. MEASUREMENTS: Distal radius bone mineral density (BMD) (single photon absorptiometry), upper limb muscle (grip) strength, balance, gait velocity, occupational and leisure-time activity, and fractures (interview-administered questionnaire) were reassessed after 10 years. Annual changes for all measures were compared between participants with varying habitual physical activity histories at baseline and follow-up: inactive,inactive (n=202), active,inactive (n=47), inactive,active (n=49), and active,active (n=60). Data for men and women were pooled, because there were no sex-by-activity group interactions. To detect possible differences in fracture incidence between the varying habitual activity groups, participants were classified into two activity groups based on their activity classification at baseline and follow-up: inactive:less active versus active:more active. RESULTS: The annual rate of bone loss was 0.6% per year less in individuals classified as active at both time points than in those classified as inactive at both time points (P<.01). Similar results were observed for balance, but there was no effect of varying habitual activity on changes in muscle strength or gait velocity. There were also no differences in fracture incidence between individuals categorized as active:more active and those categorized as inactive:less active during the follow-up (adjusted hazard ratio=0.90, 95% confidence interval (CI)=0.42,1.90). CONCLUSION: This study showed that elderly men and women who maintained a habitually active lifestyle over 10 years had lower bone loss and retained better balance than those who remained habitually inactive. [source]


Prevalence and trends in low femur bone density among older US adults: NHANES 2005,2006 compared with NHANES III

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010
Anne C Looker
Abstract Hip fracture incidence appears to be declining in the United States, but changes in bone mineral density (BMD) of the population have not been evaluated. We used femur BMD data from the National Health and Nutrition Examination Survey (NHANES) 2005,2006 to estimate the prevalence of low femoral BMD in adults age 50 years and older and compared it with estimates from NHANES III (1988,1994). Dual-energy X-ray absorptiometry systems (pencil-beam geometry in NHANES III, fan-beam geometry in NHANES 2005,2006) were used to measure femur BMD, and World Health Organization (WHO) definitions of low BMD were used to categorize skeletal status. In 2005,2006, 49% of older US women had osteopenia and 10% had osteoporosis at the femur neck. In men, 30% had femur neck osteopenia and 2% had femur neck osteoporosis. An estimated 5.3 million older men and women had osteoporosis at the femur neck, and 34.5 million more had osteopenia in 2005,2006. When compared with NHANES III, the age-adjusted prevalence of femur neck osteoporosis in NHANES 2005,2006 was lower in men (by 3 percentage units) and women (by 7 percentage units) overall and among non-Hispanic whites. Changes in body mass index or osteoporosis medication use between surveys did not fully explain the decline in osteoporosis. Owing to the increase in the number of older adults in the US population, however, more older adults had low femur neck BMD (osteoporosis + osteopenia) in 2005,2006 than in 1988,1994. Thus, despite the decline in prevalence, the estimated number of affected older adults in 2005,2006 remained high. Copyright © 2010 American Society for Bone and Mineral Research [source]


Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005
Richard 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]


Low Skeletal Muscle Mass Is Associated With Poor Structural Parameters of Bone and Impaired Balance in Elderly Men,The MINOS Study,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005
Pawel Szulc MD
Abstract In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls. Introduction: In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men. Materials and Methods: This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)2.3. Results: After adjustment for age, body size, tobacco smoking, professional physical activity, and 17,-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p < 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p < 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L3), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p < 0.05-0.001). Conclusions: In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence. [source]


Incidence of Hip and Other Osteoporotic Fractures in Elderly Men and Women: Dubbo Osteoporosis Epidemiology Study,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004
Kevin P Chang
Abstract In this prospective 12-year study in men and women 60 years of age and older, there was a 4,6% per year reduction in the incidence rate of overall osteoporotic fractures, but the study was unable to exclude any change in the hip fracture incidence rate. Approximately one-half of hip fractures occurred before 80 years in men and two-thirds before 85 years in women. The age distribution of hip fractures underlines the need for earlier intervention in osteoporosis. Introduction: Although hip fracture is the major osteoporotic fracture in terms of health outcomes, quality of life, and costs, there is a paucity of long-term data on secular changes in men and women within a defined community. This long-term prospective population-based study over 12 years from 1989 to 2000 specifically examined the age distribution and secular changes in the incidence rates of hip and other osteoporotic fractures in men and women 60 years of age and older in a predominantly white population in Dubbo, Australia. Materials and Methods: Hip and all other clinical fractures were ascertained by reviewing all radiography reports from the two area radiology services, ensuring complete ascertainment of all clinical osteoporotic fractures. Results and Conclusion: Among the 1055 symptomatic atraumatic fractures (after excluding pathological fractures), there was a significant reduction in the overall fracture incidence rate in women (4% per year; p = 0.0003) and men (6% per year; p = 0.0004) over the 12 years. There were 229 hip fractures (175 in women and 54 in men) within 39,357 person-years of observation. The overall rate ± SE of hip fracture was 759 ± 57 per 100,000 person-years in women and 329 ± 45 per 100,000 person-years in men, with an exponential increase with age. With advancing age, the incidence rate of hip fractures in men approached that in women; the female:male ratio fell from 4.5 (95% CI: 1.3,15.7) to 1.5 (0.9,2.5) and 1.9 (1.2,2.8) in the 60,69, 70,79, and 80+ year age groups, respectively. In women, the absolute number of fractures and incidence rate continuously increased with age; however, in men, the absolute number of hip fractures peaked at 80,84 years of age and then decreased. Most importantly, despite the continuing increase with age, almost one-half (48%) of the hip fractures occurred before the age of 80 years in men, and 66% of hip fractures occurred before the age of 85 years in women. The overall hip fracture incidence is comparable with other white (except Sweden) and Asian groups as well as two other Australian studies. This study could not exclude a change in hip fracture incidence rate, even in those 80 years of age and over among whom the incidence of hip fractures was the highest. The incidence data highlight the fact that a large proportion of hip fractures occurs in those under 80 years of age, particularly in men. This age distribution underlines the need for earlier intervention in osteoporosis in women and particularly in men to achieve the most cost-effective outcomes. [source]


Preventing osteoporotic fractures with antiresorptive therapy: implications of microarchitectural changes

JOURNAL OF INTERNAL MEDICINE, Issue 1 2004
S. Boonen
Abstract. Prospective studies have demonstrated that low bone mass correlates well with increased risk of osteoporotic fractures at various skeletal sites. Trials have likewise confirmed that enhancing bone mass with antiresorptive therapy reduces fracture incidence in individuals at risk. However, correlation of bone mineral density (BMD) increases with therapeutic risk reduction has proved less consistent than correlation of BMD decreases with greater fracture risk in the untreated. Indeed, various analyses have indicated that , even during treatment with potent bisphosphonates like alendronate and risedronate , BMD changes from baseline account for <30% of the reduction in vertebral fractures in treated women. It is clearly, therefore, that factors other than BMD are involved in the reduction of fracture risk achieved by antiresorptive therapies. According to recent micro-computed tomography imaging and other studies, antiresorptive therapy can help rebuild the microarchitecture of bone as well as strengthen the materials that go into it. When treating individuals with osteoporosis, these microarchitectural changes contribute to the reduction of fracture risk achieved by antiresorptive therapies. [source]


Latest news and product developments

PRESCRIBER, Issue 6 2007
Article first published online: 8 JUN 200
Initial macrolide better for pneumonia? An observational study has suggested that initial treatment with a macrolide antibiotic (such as erythromycin) may be more effective than a fluoroquinolone (like ciprofloxacin) or tetracycline as initial treatment for community acquired pneumonia and bacteraemia (Chest 2007;131:466-73). The US review of 2209 hospital episodes found that macrolide therapy was associated with a 40 per cent lower risk of death during hospital stay or within 30 days and of hospital readmission within 30 days of discharge. By contrast, no such benefit was apparent with fluoroquinolones or tetracycline. Two-year safety data for inhaled insulin Compared with sc insulin, inhaled insulin (Exubera) is associated with a small early decrease in lung function in the first three months of therapy but no further difference for up to two years (Diabetes Care 2007;30: 579-85). The comparative trial found that FEV1 declined at a mean rate of 0.051 litres per year with inhaled insulin and 0.034 litres per year with sc insulin, but there was no significant difference in the rates of decline after three months. Inhaled insulin was associated with a higher incidence of cough (37.6 vs 13.1 per cent) but a lower incidence of severe hypoglycaemic events (2.8 vs 4.1 events per 100 subject- months) and mean weight gain was 1.25kg less. Fracture risk warning with rosiglitazone GlaxoSmithKline has warned US prescribers that rosiglitazone may be associated with an increased risk of fractures. The company says information for prescribers in Europe will follow shortly. The warning comes from the ADOPT study (N Engl J Med 2006;355:2427-43), which found a significantly higher incidence of fractures of the humerus, hand and foot among women taking rosiglitazone (9.3 per cent) than with metformin (5.1 per cent) or glibenclamide (3.5 per cent). There was no difference in fracture incidence among men. The company recommends that fracture risk should be considered for women taking or about to take rosiglitazone. Oral treatment for grass pollen allergy A new treatment for allergic rhinitis due to grass pollen allergy has been introduced by ALK-Abelló. Grazax is a sublingual tablet containing a stan-dardised dose of allergen from the pollen of timothy grass. Treatment should be initiated by a specialist four months before the onset of the allergy season and continued throughout the season. Adverse effects include oral and ear pruritus, nasopharyngitis and mouth oedema. A month's treatment at the recommended dose of one tablet daily costs £67.50. Frequent analgesics linked with hypertension Men who take analgesics regularly have an increased frequency of hypertension, a US study has shown (Arch Intern Med 2007;167:394-9). The US Health Professionals Follow-Up study evaluated the use of NSAIDs, paracetamol and aspirin in 16 031 men with normal blood pressure and followed them up for four years. Compared with those who did not report analgesic use, the risk of hypertension was increased by 38 per cent for NSAID use, 34 per cent for paracetamol and 26 per cent for aspirin, all for for six or seven days a week. Similar risks were found when anal- gesic use was determined according to the number of tablets taken. The authors acknowledge the increased risk is modest, but point out that the implications may nonetheless be important because analgesics are widely used. Multiples do most pharmacist MURs Uptake of medicines use reviews (MURs) by pharmacists was modest in 2005 and most reviews were carried out by pharmacy chains rather than independent contractors, a new study has shown (Pharm J 2007;278:218-23). The survey of PCTs and SHAs in England and Wales found that, although 38 per cent of community pharmacies claimed payments for the service, 84 per cent of MURs were carried out by pharmacy chains. Uptake was low, amounting to only 7 per cent of the maximum possible number of MURs. Patients see information needs differently There is a mismatch in the perceptions of patients and health professionals about the purpose of written information about medicines, a systematic review has concluded (Health Technol Assess 2007;11:1-178). Some health professionals believe the main purpose of information is to promote compliance, whereas patients want information to help them make decisions about their treatment, including not taking it. In particular, patients want information on adverse effects, but health professionals have reservations about providing it. Aspirin for all women over 65? All women over 65 should take low-dose aspirin if the benefits are likely to outweigh the risk of adverse effects, according to new guidelines from the American Heart Association on preventing cardiovascular disease in women (published online 19 Feb 2007;doi: 10.1161/circulationaha.107.181546). The guidelines have moved away from the long-established Framingham model of risk assessment to categorising three levels of risk: high (heart disease or other relevant disease present), at risk (at least one risk factor) and optimal (healthy lifestyle, no risk factors). Low-dose aspirin is recommended for all women at high risk, for women aged 65 or over when reducing the risk of MI or ischaemic stroke outweighs the risk of adverse effects, and for younger women when reducing the risk of ischaemic stroke outweighs that of toxicity. Combination inhaler therapy Combining an inhaled long-acting bronchodilator with a steroid reduces COPD exacerbations but not all-cause mortality, a three-year trial has shown (N Engl J Med 2007;356:775-89). However, inhaled steroids appear to increase the risk of pneumonia. The TORCH trial randomised 6112 patients (FEV1<60 per cent predicted) to treatment with salmeterol 50µg plus fluticasone 500µg (Seretide) twice daily, salmeterol (Serevent) or fluticasone (Flixotide) as monotherapy, or placebo. All-cause mortality rates were 12.6, 13.5, 16.0 and 15.2 per cent respectively; the risk of death was 17 per cent lower with combined therapy, but the difference did not reach statistical significance. The combination reduced the incidence of exacerbations by 25 per cent and improved health status and FEV1. Use of fluticasone was not associated with more ocular or bone disorders, but there was an increased incidence of pneumonia among users (19.6 per cent with combined therapy and 18.3 per cent with fluticasone vs 12.3 per cent with placebo). Seretide is currently licensed in the UK for use in patients with FEV1 <50 per cent predicted. Tamoxifen long- term benefits Women with breast cancer who take tamoxifen for five to eight years continue to have a lower risk of recurrence for 10-20 years, long-term follow-up of two blinded trials has shown (J Nat Cancer Inst 2007; 99:258-60, 272-90). The frequency of adverse effects was markedly reduced when treatment ended, changing the balance of risk and benefit. Copyright © 2007 Wiley Interface Ltd [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 2009
Kenneth 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]


Water fluoridation, osteoporosis, fractures,recent developments

AUSTRALIAN DENTAL JOURNAL, Issue 2 2001
Lisa L. Demos
Abstract Background: Optimal (1 ppm) water fluoridation is seen as the most socially equitable way to prevent dental caries, however concerns about the safety of fluoridation are periodically raised. Methods: Research on effects on bone published since the 1991 National Health and MedicalResearch Council report on water fluoridation was reviewed. Results: Thirty-three studies were identified. Adverse effects in animal feeding studies were only seen at doses much greater than those currently used in artificial water fluoridation. The majority of animal studies showed no effect or a beneficial effect of lowfluoride doses. The results of ecological studies were conflicting. One of the two cohort studies showed an increase in fracture incidence at fluoride levels four times greater than optimal water fluoridation and the other showed no effect after 20 years' optimal fluoridation. The cross-sectional studies showed a favourable effect on bone mineral density. The clinical trials predominantly showed increased bone density in several sites associated with fluoride treatment of 9,22.6mg fluoride per day for one-four years. Conclusion: These studies provide a substantial body of evidence that fluoride at up to 1ppm does not have an adverse effect on bone strength, bone mineral density or fracture incidence. [source]


The Effect of Aromatase Inhibitors on Bone Metabolism

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2009
Lars Folkestad
Aromatase is a cytochrome P450 enzyme complex catalysing the conversion of androgens to oestrogens. These properties cause a significant increase in bone loss. In this MiniReview, we present data from the aromatase inhibitor studies and the studies designed to investigate aromatase inhibitor effect on bone metabolism. At the cellular level, oestrogen has profound effects on both osteoblasts and osteoclasts. Oestrogen decreases the osteoblastic production of resorptive cytokines and simultaneously increases the production of antireceptive cytokines, which leads to increased osteoclastic apoptosis and increased osteoblastic activity. Aromatase inhibitors inhibit the endogenous production of oestrogen by 50,90%. Studies designed to look at the effect of aromatase inhibitors on bone mineral density have shown a significant decrease in bone mineral density of the femoral neck in the aromatase inhibitor groups compared to placebo groups. Placebo-controlled studies lack statistical power to detect changes in fracture incidence; however, aromatase inhibitors increase the incidence of fractures in comparison with tamoxifen. We conclude that treatment with aromatase inhibitors leads to an increased bone loss and thus an increase in the risk of fractures in women with breast cancer. [source]


REVIEW ARTICLE: Reducing fracture risk with calcium and vitamin D

CLINICAL ENDOCRINOLOGY, Issue 3 2010
Paul Lips
Summary Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50,75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in succesfull fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits. [source]


How Well Are Bones Designed to Resist Fracture?,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2003
John D Currey
Abstract Because bone is obviously in some way adapted to the loads falling on it and because fracture is usually the failure of mechanical competence of main clinical importance, it is often thought that bones are adapted to resist fracture. In this perspective, I consider that this may not be the case. Bones may be designed to be very stiff, and therefore highly mineralized, and therefore brittle; they may be adapted to normal loads, but not to the characteristic loads occurring in falls, or may be very poorly designed to stop cracks traveling once they have started. Bones may also potentially fail in completely contrasting modes, and therefore their design has to be a compromise that does not resist either mode completely successfully. The greatly differing fracture incidences in different bones seen in pre-senile adults suggest that safety factors have been adapted, over evolutionary time, to produce the best compromise for a host of different design constraints. [source]


Does Hormone-Replacement Therapy Prevent Fractures in Early Postmenopausal Women?,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2002
Kaisa M. Randell M.D.
Abstract The purpose of this population-based prospective cohort study was to examine the effect of hormone-replacement therapy (HRT) on the risk of fractures. The study population consisted of 7217 postmenopausal women aged 47-56 years (mean, 53.3 years) at baseline from data taken from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) in Finland. We compared fracture incidences between HRT users and nonusers. A total of 679 (9.4%) women recorded validated fractures during the 5-year follow-up. Of these, 268 (39%) women had a distal forearm fracture. Two thousand six hundred seventy women (37%) had used HRT >6 months during the follow-up,one-half of them continuously. The relative risk, estimated as hazard ratio with Cox regression, was 0.69 (95% CI, 0.58-0.82) for any fracture and 0.49 (0.36-0.66) for distal forearm fracture among HRT users as compared with never-users. After adjusting for age, body mass index (BMI), number of chronic health disorders, fracture history, and time since menopause (independent risk factors) the corresponding risks were 0.67 (0.55-0.81) and 0.53 (0.37-0.74), respectively. The respective adjusted risks for continuous HRT users were 0.62 (0.48-0.79) and 0.41 (0.26-0.67). The adjusted risk of other than distal forearm fracture was 0.74 (0.55-0.98). The results suggest that HRT has a beneficial effect on prevention of fractures in general and on that of distal forearm fracture in particular in early postmenopausal women. [source]