Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism. OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence). AUTHORS' CONCLUSIONS: Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.

Association between post-stroke disability and 5-year hip-fracture risk: The Women's Health Initiative.

BACKGROUND: Hip fractures are a significant post-stroke complication. We examined predictors of hip fracture risk after stroke using data from the Women's Health Initiative (WHI). In particular, we examined the association between post-stroke disability levels and hip fracture risk. METHODS: The WHI is a prospective study of 161,808 postmenopausal women aged 50-79 years. Trained physicians adjudicated stroke events and hip fractures. Our study included stroke survivors from the observational and clinical trial arms who had a Glasgow Outcome Scale of good recovery, moderately disabled, or severely disabled and survived more than 7 days post-stroke. Hip fracture-free status was compared across disability levels. Secondary analysis examined hip fracture risk while accounting for competing risk of death. RESULTS: Average age at time of stroke was 74.6±7.2 years; 84.3% were white. There were 124 hip fractures among 4,640 stroke survivors over a mean follow-up time of 3.1±1.8 years. Mortality rate was 23.3%. Severe disability at discharge (Hazard Ratio (HR): 2.1 (95% Confidence Interval (CI): 1.4-3.2), but not moderate disability (HR: 1.1 (95%CI: 0.7-1.7), was significantly associated with an increased risk of hip fracture compared to good recovery status. This association was attenuated after accounting for mortality. White race, increasing age and higher Fracture Risk Assessment Tool (FRAX)-predicted hip fracture risk (without bone density information) were associated with an increased hip fracture risk. After accounting for mortality, higher FRAX risk and white race remained significant. CONCLUSION: Severe disability after stroke and a higher FRAX risk score were associated with risk of subsequent hip fracture. After accounting for mortality, only the FRAX risk score remained significant. The FRAX risk score appears to identify stroke survivors at high risk of fractures. Our results suggest that stroke units can consider the incorporation of osteoporosis screening into care pathways.

Racial Disparities Exist in Outcomes After Major Fragility Fractures.

BACKGROUND: Fractures associated with postmenopausal osteoporosis (PMO) are associated with pain, disability, and increased mortality. A recent, nationwide evaluation of racial difference in outcomes after fracture has not been performed. OBJECTIVE: To determine if 1-year death, debility, and destitution rates differ by race. DESIGN: Observational cohort study. SETTING: US Medicare data from 2010 to 2016. PARTICIPANTS: Non-Hispanic black and white women with PMO who have sustained a fragility fracture of interest: hip, pelvis, femur, radius, ulna, humerus, and clinical vertebral. MEASUREMENTS: Outcomes included 1-year: (1) mortality, identified by date of death in Medicare vital status information, (2) debility, identified as new placement in long-term nursing facilities, and (3) destitution, identified as becoming newly eligible for Medicaid. RESULTS: Among black and white women with PMO (n = 4,523,112), we identified 399,000 (8.8%) women who sustained a major fragility fracture. Black women had a higher prevalence of femur (9.0% vs 3.9%; P < .001) and hip (30.7% vs 28.0%; P < .001) fractures and lower prevalence of radius/ulna (14.7% vs 17.0%; P < .001) and clinical vertebral fractures (28.8% vs 33.5%; P < .001) compared with white women. We observed racial differences in the incidence of 1-year outcomes after fracture. After adjusting for age, black women had significantly higher risk of mortality 1 year after femur, hip, humerus, and radius/ulna fractures; significantly higher risk of debility 1 year after femur and hip fractures; and significantly higher risk of destitution for all fractures types. CONCLUSIONS: In a sample of Medicare data from 2010 to 2016, black women with PMO had significantly higher rates of mortality, debility, and destitution after fracture than white women. These findings are a first step toward understanding and reducing disparities in PMO management, fracture prevention, and clinical outcomes after fracture. J Am Geriatr Soc 68:1803-1810, 2020.

Bone Health and Survival in Women With Multiple Myeloma.

BACKGROUND: Multiple myeloma (MM) is a disease of aging adults resulting in osteolytic and/or osteoporotic bone disease. Primary osteoporosis is also highly prevalent in aging adults and is associated with increased mortality. It is unknown how concurrent osteoporosis is associated with outcomes in patients who develop MM. PATIENTS AND METHODS: We identified 362 women with MM of the 161,808 enrolled in the Women's Health Initiative (WHI) dataset and evaluated bone health using the Fracture Risk Assessment Tool (FRAX) to identify clinical factors that affect overall MM survival in post-menopausal women, as measured from the time of diagnosis. RESULTS: Of the 362 participants who developed incident MM, with an average 10.5 years of follow-up, 226 died, including 71 with high FRAX scores and 155 with low FRAX scores. On average, women with high FRAX scores were 8.3 years older at enrollment (95% confidence interval [CI], 7.2-9.3 years) and 8.0 years older at time of MM diagnosis (95% CI, 7.0-9.2 years) compared with those with low FRAX scores. MM mortality for women with high FRAX scores was greater (covariate-adjusted hazard ratio scores [aHR] 1.51; 95% CI, 1.01-2.25; P = .044) compared with those with low FRAX scores. CONCLUSION: Higher fracture risk, measured by FRAX, was associated with higher MM mortality in post-menopausal women, independent of many other clinical factors.

Risk factors for 5-year prospective height loss among postmenopausal women.

OBJECTIVE: Height loss is common in older women and has been associated with increased morbidity and mortality. In this study, we identified factors that could predict prospective height loss in postmenopausal women. METHODS: Height was measured in 1,024 postmenopausal women, enrolled in the Buffalo Osteoporosis and Periodontal Disease Study, at baseline and 5 years later using a fixed stadiometer. Demographics, lifestyle, medical history, and medication use were assessed at baseline. Stepwise logistic regression was used to identify factors that are associated with marked height loss of ≥1 inch. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each predictor. Receiver-operating characteristic (ROC) curve was performed to determine the discriminatory ability of the prediction model. RESULTS: The mean loss of height was 0.4 (SD 0.7) inches. Age (OR 1.11, 95% CI 1.06-1.16), weight (OR 1.05, 95% CI 1.03-1.07), use of oral corticosteroids (OR 4.96, 95% CI 1.25-19.72), and strenuous exercise at age 18 ≥ three times per week (OR 0.55, 95% CI 0.31-0.98) were significantly associated with marked height loss in the multivariable-adjusted model. The area under the ROC curve is 72.1%. Addition of bone mineral density measures did not improve the discriminatory ability of the prediction model. CONCLUSIONS: This set of available variables may be useful in predicting the 5-year risk of height loss of 1 inch or more in postmenopausal women. These findings may help to target older women at risk of height loss who may benefit most from prevention strategies for fracture and mortality.

The mortality and direct medical costs of osteoporotic fractures among postmenopausal women in Taiwan.

UNLABELLED: This study estimated the fracture-related mortality and direct medical costs among postmenopausal women in Taiwan by fracture types and age groups by utilizing a nationwide population-based database. Results demonstrated that hip fractures constituted the most severe and expensive complication of osteoporosis across fracture sites. INTRODUCTION: The aims of the study were to evaluate the risk of death and direct medical costs associated with osteoporotic fractures by fracture types and age groups among postmenopausal women in Taiwan. METHODS: This nationwide, population-based study was based on data from the National Health Insurance Research Database in Taiwan. Female patients aged 50 years and older in the fracture case cohort were matched in 1:1 ratio with randomly selected subjects in the reference control cohort by age, income-related insurance amount, urbanization level, and the Charlson comorbidity index. There were two main outcome measures of the study: age-differentiated mortality and direct medical costs in the first and subsequent years after osteoporotic fracture events among postmenopausal women. The bootstrap method by resampling with replacement was conducted to generate descriptive statistics of mortality and direct medical costs of the case and control cohorts. Student's t tests were then performed to compare mortality and costs between the two cohorts. RESULTS: A total of 155,466 postmenopausal women in the database met the inclusion criteria for the fracture case cohort, including 22,791 hip fractures, 72,292 vertebral fractures, 15,621 upper end humerus (closed) fractures, 36,774 wrist fractures, and 7,988 multiple fractures. Analytical results demonstrated that patients experiencing osteoporotic fractures were at considerable excess risk of death and incurred substantially higher treatment costs, notably for hip fractures. Furthermore, results also revealed that the risk of mortality increased with advancing age across the spectrum of fracture sites. CONCLUSIONS: The present study confirmed an excess mortality and higher direct medical costs associated with osteoporotic fractures. Moreover, hip fractures constituted the most severe and expensive complication of osteoporosis among fracture types.

Is raloxifene associated with lower risk of mortality in postmenopausal women with vertebral fractures after vertebroplasty?: a hospital-based analysis.

BACKGROUND: Osteoporotic fractures are associated with mortality in postmenopausal woman. Whether raloxifen treatment after vertebroplasty can reduce mortality is unclear in this group. To compare the effect of raloxifene and no osteoporosis treatment on the risk of mortality after vertebroplasty, we designed this study. METHODS: This was a retrospective study (January 2001 to December 2007). Follow-up for each participant was calculated as the time from inclusion in the study to the time of death, or to December 31(st), 2013, whichever occurred first. All of the patients underwent baseline bone density studies, and age and body mass index (kg/m(2)) were recorded. All associated medical diseases such as diabetes, hypertension, and liver and renal disease were recorded. RESULTS: One hundred and forty-nine patients with vertebral fractures were enrolled, of whom 51 used raloxifene and 98 patients did not receive any anti-osteoporotic therapy. At the end of the follow-up period, 62 patients had died and 87 were still alive. The treated patients had a lower mortality rate than those who did not receive treatment (P = 0.001, HR = 3.845, 95% CI 1.884-7.845). The most common cause of mortality was sepsis, and those who received raloxifene had a lower rate of sepsis compared to those who did not receive treatment (P < 0.001). CONCLUSIONS: Effective treatment with raloxifene may had a lower mortality rate in patients with postmenopausal osteoporosis-related vertebral fractures after vertebroplasty.

A survey of outcomes and management of patients post fragility fractures in China.

UNLABELLED: We found that the fragility hip and vertebral fractures caused excess mortality rates in this Chinese female population, which was unexpectedly lower than those in western countries and other Asian countries. This was the first nationwide survey relating to post-fracture outcomes conducted among Chinese population in Mainland China. INTRODUCTION: This study aimed to investigate the mortality, self-care ability, diagnosis, and medication treatment of osteoporosis following fragility hip and vertebral fractures through a nationwide survey among female patients aged over 50 in Mainland China. METHODS: This was a multicenter, retrospective cohort study based on medical chart review and patient questionnaire. Female patients aged 50 or older admitted for low-trauma hip or vertebral fractures and discharged from Jan 1, 2008 to Dec 31, 2012 were followed. RESULTS: Total of 1151 subjects of hip fracture and 842 subjects of vertebral fracture were included. The mean age was 73.4 ± 10.0, and the median of duration from index fracture to interview was 2.6 years. The overall 1-year, 2-year, 3-year, 4-year, and 5-year cumulative mortality rates were 3.5, 7.0, 11.2, 13.1, and 16.9 %, respectively. The first year mortality rates in hip (3.8 %, 95% CI 3.3-4.4 %) and vertebral fracture (3.1 %, 95% CI 2.5-3.7 %) were significantly higher than that in the general population (1.6 %). Impaired self-care ability was observed in 33.2, 40.6, and 23.8 % of overall, hip fracture, and vertebral fracture group, respectively. The overall diagnosis rate of osteoporosis was 56.8 %, and bone mineral density (BMD) measurement had never been conducted in 42.0 % among these women. After the index fracture, 69.6 % of them received supplements and/or anti-osteoporotic medications, among which 39.6 % only received calcium with/without vitamin D supplementation. CONCLUSIONS: The osteoporotic hip and vertebral fractures caused excess mortality rates in this population of Mainland China. The current diagnosis and medical treatment following the fragility fractures is still insufficient in Mainland China.

Accelerated bone loss and increased post-fracture mortality in elderly women and men.

UNLABELLED: Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We found accelerated bone loss (≥1.31 % bone loss/year for women and ≥1.35 % bone loss/year for men) associated with 44-77 % increased mortality. It remains unclear whether bone loss is a marker or plays a role in mortality. INTRODUCTION: Osteoporotic fractures are associated with increased mortality although the cause is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated with increased mortality, but its role in mortality risk post-fracture is unclear. This study aimed to examine post-fracture mortality risk according to levels of bone loss. METHODS: Community-dwelling participants aged 60+ from Dubbo Osteoporosis Epidemiology Study with incident fractures were followed from 1989 to 2011. Kaplan-Meier survival curves were constructed according to bone loss quartiles. Cox proportional hazard models were used to determine the effect of bone loss on mortality. RESULTS: There were 341 women and 106 men with ≥2 BMD measurements. The rate of bone loss was similar for women and men (women mean -0.79 %/year, highest bone loss quartile -1.31 %/year; men mean -0.74 %/year, highest quartile -1.35 %/year). Survival was lowest for the highest quartile of bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture type, the association of bone loss with mortality was observed for vertebral (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an additional role in mortality risk following hip fractures. Importantly, overall, rapid bone loss was associated with 44-77 % increased mortality risk after multiple variable adjustment. CONCLUSION: Rapid bone loss was an independent predictor of post-fracture mortality risk in both women and men. The association of bone loss and post-fracture mortality was predominantly observed following vertebral fracture in both women and men and non-hip non-vertebral fracture in women. It remains to be determined whether bone loss is a marker or plays a role in the mortality associated with fractures.

C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort.

SUMMARY: This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indicator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased. INTRODUCTION: Inflammation may contribute to the pathophysiology underlying impaired bone metabolism. This study investigates the association between CRP, BMD, bone loss, fracture risk, and mortality in women aged 75 and above. METHODS: This longitudinal study is based on 1044 women, all age 75 at inclusion, reassessed at ages 80 and 85, with a mean follow-up time of 11.6 years (maximum 16.9 years). RESULTS: Women in the lowest CRP quartile (mean 0.63 mg/L) had lower BMD compared to those in the highest CRP quartile (mean 5.74 mg/L) at total hip (TH) (0.809 vs. 0.871 g/cm2, p<0.001) and femoral neck (FN) (0.737 vs. 0.778 g/cm2, p=0.007). A single measurement of CRP was not associated with bone loss; however, women with persistently elevated CRP, i.e., ≥3 mg/L at ages 75 and 80 had significantly higher bone loss compared to women with CRP<3 mg/L (TH -0.125 vs. -0.085 g/cm2, p=0.018 and FN -0.127 vs. -0.078 g/cm2, p=0.005) during 10 years of follow-up. Women in the highest CRP quartile had a lower risk of osteoporotic fractures (hazard ratios (HR) 0.76 (95% confidence intervals (CI) 0.52-0.98)) compared to those in the lowest, even after adjusting for weight and BMD. Mortality risk was only increased among women with the highest CRP levels. CONCLUSION: CRP was not an indicator for low BMD, bone loss, or fracture in elderly women in this study. Persistently elevated CRP however seemed to be detrimental to bone health and may be associated with a higher rate of bone loss. Only the highest CRP levels were associated with mortality.

MiR-503 regulates osteoclastogenesis via targeting RANK.

MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR-503 was markedly reduced in circulating progenitors of osteoclasts-CD14(+) peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR-503 in CD14(+) PBMCs inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Conversely, silencing of miR-503 in CD14(+) PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR-503. In vivo, silencing of miR-503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR-503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR-503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis.

Is diabetes mellitus a heart disease equivalent in women? Results from an international study of postmenopausal women in the Raloxifene Use for the Heart (RUTH) Trial.

BACKGROUND: Several studies have concluded that diabetes mellitus and heart disease carry similar risk for future cardiovascular disease (CVD). Most of these studies were too small to quantify independent risks specific to women. The purpose of this study was to determine whether diabetes mellitus is a coronary heart disease (CHD) risk equivalent for prediction of future CHD and CVD events in women. METHODS AND RESULTS: The Raloxifene Use for the Heart (RUTH) trial was an international, multicenter, double-blind, randomized, placebo-controlled trial of raloxifene and CVD outcomes in 10 101 postmenopausal women selected for high CHD risk. Of these, 3672 had a history of diabetes mellitus without known CHD, and 3265 had a history of CHD without known diabetes mellitus. Cox proportional hazard models were used to compare cardiovascular outcomes in these 2 groups. Mean age at baseline was 67.5 years; median follow-up was 5.6 years. There were 725 deaths, including 450 cardiovascular deaths. In age-adjusted analyses, diabetic women had an increased risk of all-cause mortality compared with women with CHD. Although the overall risk of CHD and CVD was lower in diabetic women compared with women with CHD, the risk of fatal CHD, fatal CVD, and all-cause mortality was similar (hazard ratio [95% confidence interval]: 0.85 [0.65-1.12], 0.99 [0.78-1.25], and 1.18 [0.98-1.42], respectively, after adjusting for age, lifestyle factors, CHD risk factors, statin use, and treatment assignment). CONCLUSIONS: In the RUTH trial, diabetes mellitus was a CHD risk equivalent in women for fatal, but not nonfatal, CHD and CVD.

Burden of postmenopausal osteoporosis in Germany: estimations from a disease model.

UNLABELLED: This article describes the adaptation of a model assessing the incidence of osteoporotic fractures and prevalence of postmenopausal osteoporosis (PMO) in Germany. PURPOSE: The purpose of this paper is to estimate the epidemiological burden of PMO in Germany from 2010 to 2020. METHODS: For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures (1, 2 or ≥3) and deaths. Although the fracture site was not explicitly accounted for in the model structure, the site (hip, vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected the site-specific risk of death and of subsequent fractures. Model inputs included population size and life tables from 1970 to 2020, incidence of fracture and BMD by age in the general population (mean and standard deviation). RESULTS: In 2010, the number of osteoporotic fractures was estimated at 349,560 in women aged 50 years or more, including 80,177 hip and 48,550 vertebral fractures. By 2020, the population is expected to grow by 13.1 %. As a result, the number of fractures is predicted to increase by 15.2 %. The improvement in life expectancy is predicted to lead to a relatively smaller increase in the number of deaths attributable to fractures (+12.8 %), but also to an increase in the prevalence of women with multiple prior fractures (+25.5 %). CONCLUSION: The PMO disease model, first developed for Sweden, was adapted to Germany. Due to the ageing of the population, the number of osteoporotic fractures is expected to increase markedly by +15.2 % by 2020.

The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden.

BACKGROUND: This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIOP). The study's objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. METHODS: A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of -3.0. The GIOP cohorts simulated had an initial BMD T-Score of -2.5. RESULTS: The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. CONCLUSIONS: The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

Changes in vitamin D supplement use and baseline plasma 25-hydroxyvitamin D concentration predict 5-y change in concentration in postmenopausal women.

Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L).

Established osteoporosis associated with high mortality after adjustment for age and co-mobidities in postmenopausal Japanese women.

OBJECTIVE: Osteoporosis has been reported to increase the risk of mortality. However, these reports did not evaluate the effects of co-mobidities and the severity of osteoporosis on mortality. The aim of our study was to determine whether or not major osteoporotic fractures contribute to the increased mortality risk in Japanese women. METHOD: We conducted a prospective observational study. Risk factors contributing to mortality were assessed by Cox's proportional hazard model. SUBJECTS: A total of 1,429 ambulatory postmenopausal female volunteers aged over 50 years old were enrolled in the study. Information was obtained from the subjects on baseline biochemical indices, bone mineral density (BMD), prevalent fractures, and co-morbidities. Mortality was assessed and confirmed by the certificates or hospital records. The subjects were classified into three categories in accordance with or without osteoporosis. The osteoporotic group was further categorized by the basis of the presence or absence of major osteoporotic fractures. RESULTS: Mean age and SD of the participants were 66.5±9.3 (50-90) years old. The participants were followed for a total of 4.5±3.5 years (mean ± SD) and a total of 141 participants (9.9%) died during the observation. In addition to the traditional risks for mortality, such as age (Hazard ratio, 2.817, 95% CI, 2.237-3.560, p<0.0001), BMI (HR 0.504, 0.304-0.824, p=0.0061), prevalent malignancies (HR 2.885, 1.929-4.214, p<0.0001), dementia (HR 1.602, 1.027-2.450, p=0.038) and cardio-vascular disease (HR 1.878, 1.228-2.787, p=0.0043), the serum level of creatinine (HR 2.451, 1.107-5.284, p=0.027) and severity of osteoporosis (HR 1.390, 1.129-1.719, P=0.0018) were found to be significant independent risk factors for all-cause mortality. CONCLUSION: These results emphasize the importance of osteoporotic fracture in terms of survival.

Low bone mineral density at femoral neck is a predictor of increased mortality in elderly Japanese women.

UNLABELLED: This study aimed to determine whether low bone mineral density (BMD) at the femoral neck independently predicts all-cause mortality in elderly Japanese women. A prospective cohort study of 271 women aged 67-89 years was conducted. A Cox proportional hazard model was used to examine independent associations between BMD and total mortality. During a 12-year follow-up period, the mortality risk (as measured by hazard ratio [HR]) was significantly increased in the three categories of baseline BMD (diagnostic criteria of osteoporosis, tertile of BMD, and quartile of BMD). After adjusting for major potential confounding variables for mortality, significantly increased mortality risks were found in subjects with osteoporosis (HR = 2.17, p = 0.032), in subjects in the lowest tertile (HR = 2.57, p = 0.007), and in subjects in the lowest quartile (HR = 3.13, p = 0.014], respectively. Our findings suggest that preventive strategies should be considered to increase and maintain high BMD at the femoral neck in the elderly women not only to prevent hip fractures but also probably to reduce mortality risk. INTRODUCTION: Several longitudinal studies with Caucasian subjects have suggested that osteoporosis is associated with increased mortality. This study aimed to determine whether low bone mineral density (BMD) at the femoral neck independently predicts all-cause mortality in elderly Japanese community-dwelling women. METHOD: A prospective cohort study of 271 women aged 67-89 years was conducted. A Cox proportional hazard model was used to examine independent associations between BMD at both the femoral neck and the trochanter and total mortality. RESULTS: During a 12-year follow-up period, 81 of 271 women (29.9%) died. An independent and significant relationship was found between baseline BMD at the femoral neck and mortality risk. The mortality risk (as measured by HR) was increased by 2.80-fold (95% confidence interval [CI] 1.55-5.06; p < 0.01) in the subjects with osteoporosis or by 2.94-fold (95% CI 1.64-5.26; p < 0.001) in subjects in the lowest tertile or by 3.61-fold (95% CI 1.77-7.41; p < 0.001) in subjects in the lowest quartile of BMD, respectively. After adjusting for major potential confounding factors for mortality such as age, body mass index, blood pressure, blood variables, medical history, alcohol drinking, and smoking status, those in the subjects with osteoporosis (HR = 2.17 [95% CI 1.07-4.41], p = 0.032), in the lowest tertile (HR = 2.57 [95% CI 1.29-5.15], p = 0.007), or in the lowest quartile (HR = 3.13 [95% CI 1.26-7.73], p = 0.014] had a significantly increased risk of mortality. BMD measurement at the trochanter showed similar but weaker results. CONCLUSIONS: Our findings suggest that preventive strategies should be considered to increase and maintain high BMD at the femoral neck in elderly subjects not only to prevent osteoporosis and its associated fractures but also probably to reduce mortality risk.

Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture.

Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062 on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow-up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was approximately 6 wk. Posthoc analyses were performed by dividing the study population into 2-wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2-wk intervals showed a significant total hip BMD response and a consistent reduction of overall clinical fractures and mortality in patients receiving the first dose 2-wk or later after surgical repair. Clinical fracture subgroups (vertebral, nonvertebral, and hip) were also reduced, albeit with more variation and 95% CIs crossing 1 at most time points. We concluded that administration of zoledronic acid to patients suffering a low-trauma hip fracture 2 wk or later after surgical repair increases hip BMD, induces significant reductions in the risk of subsequent clinical vertebral, nonvertebral, and hip fractures, and reduces mortality.