Assessment of the effect of estradiol on biochemical bone turnover markers among postmenopausal women.

INTRODUCTION: Estrogen deficiency found in postmenopausal women may lead to disturbances in the balance of bone metabolism. Study of the influence of estradiol on markers of bone turnover may help to understand the mechanisms of bone metabolism and to monitor osteoporosis therapy in postmenopausal women at high risk of fractures. The aim of the study was evaluation of the effect of estradiol on the basic markers of bone turnover in postmenopausal women. MATERIAL AND METHODS: The study was conducted in a group of 92 postmenopausal women, divided into two groups: Gr-1 with low estradiol levels ≤ 10 pg/ml and Gr-2 with reference estradiol levels ≥ 25 pg/ml). Basic markers of bone turnover were examined: Ctx (C-terminal cross-linked telopeptide of type I collagen alpha chain) and OC (osteocalcin); pro-resorptive cytokines: IL-6 and TNF-α; vitamin 25(OH)D3 and lipid profile. Women was also analyzed according to demographic and clinical data. RESULTS: A positive relationship was found between estradiol and the main bone formation marker - OC (p = 0.041, r = 0.213) and IL-6, TNF-α (p = 0.007, r = 0.281 and p = 0.018, r = 0.246, respectivly, but only in the group with a reference hormone level. Moreover, the main markers of bone turnover: Ctx and OC showed a mutual positive correlation (p = 0.013; r = 0.257) in women with reference estradiol levels. Relationships between markers of bone remodeling, pro-resorptive cytokines and vitamin D3 depending on the level of estradiol showed no statistically significant correlation. CONCLUSIONS: The study showed that only in women with the reference estradiol level (≥ 25 pg/ml) were the bone formation and resorption processes balanced.

Assessment of eldecalcitol and alendronate effect on postural balance control in aged women with osteoporosis.

INTRODUCTION: Older people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis. MATERIALS AND METHODS: A randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 µg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated. RESULTS: The Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups. CONCLUSIONS: These results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.

Assessment of safety and efficacy of pine bark extract in normal and ovariectomized mice.

We evaluated the influence of pine bark extract (PBE) on organs, the cytochrome-P450 (CYP) activities in liver and estrogenic effects in normal and ovariectomized (OVX) female mice. The PBE did not affect organ weights and liver-function indexes (activities of alkaline phosphatase, aspartate amino transferase, and alanine amino transferase) at doses; 0.04%, 0.4%, and 2.0% PBE in the diet, in normal and OVX female mice. In the OVX mice, CYP1A1 activity was significantly higher in the 0.4% and 2.0% PBE groups than in the OVX control group, and in the 0.4% and 2.0% PBE groups were significantly higher than in the 0.04% PBE group. CYP1A2 and 3A4 activities were significantly higher in the 2.0% PBE group than in all other groups. The PBE did not affect uterine weight and femoral bone mineral density at all PBE doses. These results showed that the dose of PBE at the recommended human intake, had no toxic and estrogenic effects in normal female and OVX mice, however, it may need attention to use the excess intake of PBE with some drugs in postmenopausal women.

Sensitivity and specificity assessment of DWI and ADC for the diagnosis of osteoporosis in postmenopausal patients.

OBJECTIVE: In this study, we prospectively investigated the diagnostic capability of diffusion-weighted magnetic resonance imaging (DWI) in assessing vertebral marrow changes in postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty postmenopausal women (mean age 60.2 ± 6.11 years) underwent both dual-energy X-ray absorptiometry (DEXA) of the spine and MRI. Results were acquired from each patient's L2 to L4, for a total of 180 lumbar vertebrae. Based on bone mineral density (BMD) measurements obtained from DEXA, the vertebrae were divided into three groups as follows: normal (n = 52), osteopenic (n = 92), and osteoporotic (n = 36). DWI of the vertebral body was performed to assess the apparent diffusion coefficient (ADC). The ADC outcomes were compared among the three groups and correlated with BMD. RESULTS: ADC values (× 10-6 mm2/s) were significantly lower in the osteoporotic group (135.67 ± 44.10) in comparison to the normal group (561.85 ± 190.37) (P = 0.0001). The results showed a positive correlation between ADC and BMD values (r = 0.748, P = 0.0001). In receiver operating characteristic (ROC) analysis, the area under the curve for DWI was 0.912 (P = 0.001). A cut-off value of 400 mm2/s for the diagnosis of osteoporosis; had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 90.90%, 83.34%, 88.89%, 93.75%, and 76.93%, respectively. CONCLUSION: ADC values correlated positively with BMD in women. DWI can allow quantitative evaluation of bone marrow changes and osteoporosis in postmenopausal women.

Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study.

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. INTRODUCTION: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. METHODS: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. RESULTS: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. CONCLUSIONS: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.

Prevalent vertebral fractures and minor vertebral deformities analyzed by vertebral fracture assessment (VFA) increases the risk of incident fractures in postmenopausal women: the FRODOS study.

The incidence of vertebral fractures (VF) by vertebral fracture assessment (VFA) was 6.6% in postmenopausal women (FRODOS cohort) after 4 years of follow-up, increasing with prevalent VF and minor vertebral deformities, age, lower bone mass, glucocorticoid use, and rheumatoid arthritis. This study supports the usefulness of VFA to identify VF. PURPOSE: Vertebral fracture assessment (VFA) is increasingly used to identify spine fractures, but few cohort studies have used this method in prevalence and incidence assessment. We previously reported the prevalence of vertebral fractures (VF) and minor vertebral deformities (MVD) by morphometric VFA in a population-based cohort of postmenopausal women (FRODOS study). Therefore, the aim of this study was to analyze the incidence of VF, the associated risk factors, and particularly the role of MVD in this cohort of subjects. METHODS: We performed a longitudinal analysis of 2510 women aged 59-70 years participating in the FRODOS prevalence study (2006-2009) with evaluable VFA 4 years later. VFA at baseline and in the present study was assessed by quantitative vertebral morphometry and by visual semiquantitative measurement. The multivariate Poisson regression model was performed, and relative risks with confidence interval of 95% were calculated for the incidence of VF. Bone mineral density (BMD) and an osteoporosis questionnaire were collected. RESULTS: Overall, the incidence of VF was 6.6%, increasing with prevalent VF (24.5%) and in women with prevalent MVD (17.7%). Age and low BMD were also associated risk factors as were the presence of rheumatoid arthritis and exposure to glucocorticoids and bisphosphonates. CONCLUSIONS: The presence of prevalent VF assessed by VFA is associated with further incident spinal fractures in postmenopausal women. In addition, having MVD confers an increased risk of new VF.

Cost-effectiveness of implementing guidelines for the treatment of glucocorticoid-induced osteoporosis in Japan.

A model-based cost-effectiveness analysis was performed to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO). The treatment indication for GIO in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture. INTRODUCTION: The purpose of this study was to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO) from the perspective of the Japanese healthcare system. METHODS: A patient-level state transition model was developed to predict lifetime costs and quality-adjusted life years (QALYs) in postmenopausal Japanese women with osteopenia or osteoporosis using glucocorticoid (GC). An annual discount rate of 2% for both costs and QALYs was applied. The incremental cost-effectiveness ratio (ICER) of 5-year alendronate therapy compared with no therapy was estimated with different combinations of the risk factors such as starting age (45, 55, or 65), femoral neck BMD (% young adult mean (YAM) of 70%, 75%, or 80%), dose of GC (2.5, 5, or 10 mg per day), and the presence of previous fracture (yes or no). RESULTS: For 55-year-old women using GC with a BMD of 75% of YAM, the ICER ranged from $10,958 to $ 29,727 per QALY. Scenario analyses indicated that the lower age, the lower BMD, the higher dose of GC, and the presence of previous fracture associated with lower ICER. The best-case scenario was 45-year-old women with a BMD of 70% of YAM, GC dose of 10 mg per day, and previous fracture, and resulted in healthcare cost-savings. The worst-case scenario was 65-year-old women with a BMD of 80% of YAM, GC dose of 2.5 mg per day, and no previous fracture, and resulted in the ICER of $66,791 per QALY. Sensitivity analyses in the worst-case scenario showed that the annual discount rate for costs and health benefit had the strong influence on the estimated ICER. Although the ICER was influenced by other parameters such as disutility due to vertebral fracture, efficacy of alendronate, and so on, the ICERs remained more than $50,000 per QALY. CONCLUSIONS: The cost-effectiveness of preventive alendronate therapy for postmenopausal women with osteopenia or osteoporosis using GC is sensitive to age, BMD, GC dose, and the presence of previous fracture. Our analysis suggested that the treatment indication for postmenopausal women with osteopenia or osteoporosis using GC in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture.

Health-related quality of life in Romanian postmenopausal women with osteoporosis and fragility fractures.

OBJECTIVES: Osteoporosis is a common skeletal disorder characterized by decreased bone mass and increased susceptibility to fractures, which are associated with pain and decrease in physical function, social function, and well-being, which are all aspects of quality of life (QoL). The purpose of this study was to evaluate the burden of osteoporosis and fragility fractures in Romanian postmenopausal women from Cluj County using the 36-Item Short Form Health Survey (SF-36) and Quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) questionnaires. MATERIALS AND METHODS: An analytical cross-sectional study on 364 postmenopausal women was carried out between June 2016 and August 2017 in the Clinical Rehabilitation Hospital in Cluj-Napoca, Cluj County, Romania. Data were collected by interview and from the medical documents: clinical and demographic data, personal medical history, risk factors for osteoporosis, and bone mineral density at the lumbar spine and femur. The patients included in the study were asked to complete the Romanian versions of the SF-36 and QUALEFFO-41 questionnaires. RESULTS: Women with osteoporosis had significantly lower scores in the SF-36 domains (P<0.001) than healthy controls. In the osteoporosis group, a significant association was found in the SF-36 pain domain, where women with a history of fracture had higher scores (P=0.035). As for QUALEFFO-41, a statistical significance was found in the total score (P<0.05), revealing a significantly lower QoL in osteoporotic women with a history of fracture. CONCLUSION: The SF-36 scores registered a loss of QoL in women with osteoporosis. The QUALEFFO-41 total score was significantly lower in the osteoporosis associated with fracture, revealing a lower health-related QoL in these patients.

A study of the value of trabecular bone score in fracture risk assessment of postmenopausal women.

OBJECTIVE: Trabecular Bone Score (TBS) is an index of bone microarchitecture that provides additional skeletal information to areal Bone Mineral Density (aBMD). Recently TBS data has been used to optimize the Fracture Risk Assessment Tool (FRAX) predictive value. The aim of this study was to evaluate the clinical value of TBS on FRAX algorithm. MATERIALS AND METHODS: Among total of 358 postmenopausal Iranian women (mean age 61.3 ± 9.5 years) tested for aBMD and TBS, 184 osteopenic women were identified. Thoracolumbar spine X-ray done in all participants revealed twenty-one vertebral fractures. For the osteopenic group, FRAX and TBS adjusted FRAX (FRAX-TBS) were calculated and compared. RESULTS: Mean TBS of the patients was 1.31 (±0.11). A significant correlation was found between TBS and spine aBMD (r = 0.50, p < 0.001) and TBS and femoral neck aBMD (r = 0.37, p < 0.0001). A strong positive correlation was observed between aBMD adjusted FRAX and FRAX-TBS in predicting the risk of major osteoporotic fracture (r = 0.90, p < 0.0001), and hip fracture (r = 0.97, p < 0.0001). According to the area under the receiver operating characteristics curve, the predictive value of the three different models using aBMD, TBS, and combination of aBMD and TBS were similar (0.765, 0.776, and 0.781, respectively; p = 0.19). The proportion of the women needed treatment remained unchanged using FRAX or FRAX-TBS. CONCLUSION: This study showed no clinical benefit for TBS in postmenopausal women. Adding TBS data to aBMD or FRAX neither improved aBMD predictive value for vertebral fracture nor changed the decision on treatment based on FRAX.

Fracture Risk Assessment Tool (FRAX®) Results Calculated With and Without Bone Mineral Density Values for the Evaluation of Fracture Risk in Postmenopausal Women With Osteopenia.

The aim of this study was to evaluate the agreement between fracture risk predictions based on calculations made with and without bone mineral density (BMD) values using the Fracture Risk Assessment Tool (FRAX®) in Turkish postmenopausal women with osteopenia and to compare the treatment recommendations. This descriptive, cross-sectional study included postmenopausal women aged 50-79 yr with a diagnosis of osteoporosis who were not receiving any treatment. A questionnaire was administered to the participants face-to-face to obtain sociodemographic characteristics, medical history, and fracture history. Fracture risk was calculated with FRAX® separately with and without BMD. The study included 230 postmenopausal patients with osteopenia. The mean age of the patients was determined as 63.16 ± 7.59 yr, and the mean body mass index was 30.61 ± 5.02. The intraclass correlation coefficient values of the 10-yr major osteoporotic (MO) fracture and hip fracture score agreement with FRAX® with and without BMD were mean 0.486 and 0.462, respectively. The risk of MO fracture with an intervention threshold of ≥20 was determined in 227/230 patients (98.7%), and the risk of hip fracture with treatment recommendations of ≥3 was determined in 204/230 patients (88.7%). Treatment recommendations in patients with no fracture history and secondary osteoporosis were 100% for MO fracture and 94.7% (123/130) for hip fracture risk. The treatment recommendation rates of FRAX® with and without BMD were similar for the majority of postmenopausal women with osteopenia. The agreement between the values was of a moderate level. When patients with a fracture history and secondary osteoporosis were excluded, the agreement increased. Even though values with BMD are of basic importance for medical treatment in postmenopausal women, the use of measurements evaluating fracture risk, such as FRAX® without BMD, could be useful in postmenopausal women with osteopenia.

A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. METHODS: A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. RESULTS: The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. CONCLUSIONS: In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for postmenopausal Japanese women over 60 years. In terms of cost-effectiveness, the individual need for osteoporosis screening should be determined by age and clinical risk factors.

Comorbidity indices for clinical trials: adaptation of two existing indices for use with the FREEDOM trial in women with postmenopausal osteoporosis.

UNLABELLED: Two comorbidity indices were adapted for use in the FREEDOM trial and significantly correlated with the number of medications and impaired health status at baseline. The indices have applications for the analysis of clinical trial data and would allow for the appropriate adjustment of comorbidities when evaluating clinical trial outcomes. INTRODUCTION: The purpose of this study is to adapt two published comorbidity indices for use with the FREEDOM clinical trial evaluating postmenopausal women with osteoporosis. METHODS: FREEDOM enrolled women aged 60-90 years with a bone mineral density T-score <-2.5 at the lumbar spine or total hip and ≥-4.0 at both sites. Comorbidity indices were calculated using methods described by Sangha (Arthritis Rheum 49:156-163, 2003) and Wolfe (J Rheumatol 37:305-315, 2010) following modification. The adapted Sangha index included 12 conditions with a summary score of 0-12; the adapted Wolfe index included 7 conditions with a weighted summary score of 0-8. Higher scores indicated greater comorbidity. A panel of clinicians independently reviewed subjects' medical histories using a systematic process based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to map specified comorbid conditions. Spearman correlations between the adapted indices and baseline subject characteristics expected to be associated with comorbidities were examined. RESULTS: Of the 7808 subjects in this study, 74 % had ≥1 comorbidities based on the adapted Sangha or Wolfe comorbidity indices. The mean (SD) adapted Sangha and Wolfe comorbidity indices were 1.4 (1.2) and 1.4 (1.3), respectively. Both indices correlated positively with age, body mass index, and the number of medications (r = 0.54 to 0.55) at baseline and inversely correlated with health-related quality of life (r = -0.22 to -0.30) (all P < 0.0001). Further, when either the adapted Sangha or Wolfe index was included as a covariate for assessing mortality over 36 months in the FREEDOM population, the hazard ratio of the comorbidity index indicated that the mortality risk increased by 27 or 28 %, respectively, for each unit increase in the adapted index (both P < 0.0001). CONCLUSIONS: Our work suggests these comorbidity indices may be adapted for use with clinical trial data, thereby allowing for the appropriate adjustment and reporting of covariates in the evaluation of clinical trial outcomes in an osteoporotic population.

FRAX-based assessment and intervention thresholds--an exploration of thresholds in women aged 50 years and older in the UK.

UNLABELLED: Under current guidelines, based on prior fracture probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold (a fixed threshold from the age of 70 years) reduces this disparity, increases treatment access and decreases the need for bone densitometry. INTRODUCTION: Several international guidelines set age-specific intervention thresholds at the 10-year probability of fracture equivalent to a woman of average BMI with a prior fracture. At older ages (≥70 years), women with prior fracture selected for treatment are at lower average absolute risk than those selected for treatment in the absence of prior fracture, prompting consideration of alternative thresholds in this age group. METHODS: Using a simulated population of 50,633 women aged 50-90 years in the UK, with a distribution of risk factors similar to that in the European FRAX derivation cohorts and a UK-matched age distribution, the current NOGG intervention and assessment thresholds were compared to one where the thresholds remained constant from 70 years upwards. RESULTS: Under current thresholds, 45.1% of women aged ≥70 years would be eligible for therapy, comprising 37.5% with prior fracture, 2.2% with high risk but no prior fracture and 5.4% selected for treatment after bone mineral density (BMD) measurement. Mean hip fracture probability was 11.3, 23.3 and 17.6%, respectively, in these groups. Under the alternative thresholds, the overall proportion of women treated increased from 45.1 to 52.9%, with 8.4% at high risk but no prior fracture and 7.0% selected for treatment after BMD measurement. In the latter group, the mean probability of hip fracture was identical to that observed in women with prior fracture (11.3%). The alternative threshold also reduced the need for BMD measurement, particularly at older ages (>80 years). CONCLUSIONS: The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages.

Targeted assessment of fracture risk in women at midlife.

UNLABELLED: This study establishes a profile for women at midlife, referred for a dual energy X-ray absorptiometry (DXA), most likely to have osteoporosis, and from this, a pre-DXA screening tool has been developed. These findings inform much needed evidence-based guidelines for targeted and effective screening for osteoporosis and osteoporotic fracture prevention in women at midlife. INTRODUCTION: There is no consensus as to whether women at midlife should undergo screening dual energy X-ray absorptiometry (DXA) to identify osteoporosis (T-score < -2.5). METHODS: We investigated the prevalence of osteoporosis in women, aged 40-65 years, referred to 42 community-based Australian radiology centres, and identified the characteristics that best predict osteoporosis in women having a screening DXA. RESULTS: One thousand four hundred and two women completed the study questionnaire and had DXA reports available. After excluding women with an established indication for a DXA (58 %), users of bone-specific medication (10.5 %) and cancer (7.6 %), 466 women were classified as having a screening DXA. Forty of these women had osteoporosis at the lumbar spine (n = 32, 6.9 %) or femoral neck (n = 17, 3.6 %). Three predictors of osteoporosis (postmenopausal, nonuse of hormonal therapy and body mass index) were identified and incorporated into the Monash Osteoporosis Risk Score for women at midlife (MORS). In the screened study population, the MORS had a sensitivity of 70 % and specificity of 66 %, with a positive predictive value of 16.2 % and negative predictive value of 95.9 % for osteoporosis. CONCLUSIONS: Very few women referred for a screening DXA scan will be found to have osteoporosis. The MORS, a simple decision tool, would have identified 70 % of the women in our screening DXA study population and would have eliminated over 60 % of the screening DXA studies. Hence, use of the MORS may reduce unnecessary DXA scans and facilitate identification of the majority of cases of osteoporosis in women aged 40 to 65 years.

Hand-held dynamometry fixated with a tripod is reliable for assessment of back extensor strength in women with osteoporosis.

UNLABELLED: An appropriate method to assess back extensor strength in clinical practice has not yet been described. Our results showed that a hand-held dynamometry fixated with a tripod is reliable for assessing back extensor strength in women with osteoporosis. INTRODUCTION: Back strengthening exercises play an important role in the rehabilitation of patients with osteoporotic vertebral fractures. Evaluation of the effect of back strengthening exercises requires a method suitable for use in clinical practice to measure back extensor strength. A hand-held dynamometer (HHD) is quick and easy to handle in clinical practice. Currently, there is a lack of evidence whether a HHD is reliable for assessment of back extensor strength in people with osteoporosis. When using a HHD, it may be difficult for the tester to provide a counter pressure corresponding to the effort of the patient. In order to accommodate this, we have developed a tripod and a belt system, which was used to fixate the HHD. This study examined the intra-tester reliability of back extensor strength assessment in women with osteoporosis using a HHD. METHODS: Back extensor strength of the participants was measured on two events with 7-day intervals. Test procedures were standardized, and all tests were performed by the same tester. RESULTS: Forty-eight women with osteoporosis and vertebral fractures were included in the analysis. The coefficient of variation was 22% using a HHD fixated by the tester and 17% using a HHD fixated with the tripod. ICC was 0.75 (95% confidence interval (CI), 0.63 and 0.88) when using a HHD with fixated by the tester and 0.90 (95% CI, 0.84 and 0.95) when using a HHD fixated with the tripod. CONCLUSION: A HHD fixated with a tripod is reliable for the assessment of back extensor strength in women with osteoporosis and vertebral fractures.

Osteoporosis Assessment Questionnaire-Physical Function (OPAQ-PF): a psychometrically validated osteoporosis-targeted patient reported outcome measure of daily activities of physical function.

UNLABELLED: The purpose of this study was to evaluate the measurement properties of the Osteoporosis Assessment Questionnaire-Physical Functioning (OPAQ-PF). Based on this study, the OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample. METHODS: Dimensionality was established through exploratory and confirmatory factor analysis. Patients completed three patient reported outcome (PRO) measures and four performance-based measures (PBMs) at baseline to enable an evaluation of construct validity. Patients without a recent fracture completed the OPAQ-PF 2 weeks after baseline to enable an evaluation of test-retest reliability. Ability to detect change and interpretation of change were investigated following completion of the OPAQ-PF 12 and 24 weeks postbaseline by patients with a recent fracture. RESULTS: A prospective psychometric validation study in 144 postmenopausal women, with moderate to severe osteoporosis, 37 of whom had experienced a recent fragility fracture (<6 weeks). Unidimensionality was established for the OPAQ-PF by factor analysis. The OPAQ-PF had good internal consistency (α = 0.974) and test-retest reliability (mean intraclass correlation coefficient (ICC) 0.993. The OPAQ-PF differentiated between patients with/without recent fracture, and by severity of osteoarthritis; it correlated strongly with hypothesized-related scales and PBMs (r > 0.3, p < 0.001). Ability to detect change was established with high correlations between changes in OPAQ-PF score and changes in global concept scores in recent fracture patients (r ≥ 0.6, 24-week change). Effect size of change on OPAQ-PF score increased by level of global change (p < 0.001). Anchor-based methods identified an OPAQ-PF change of 10 at an individual patient level and 20 at a group level as meaningful to patients. CONCLUSIONS: The OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample.

Prevalence of vertebral fractures and minor vertebral deformities evaluated by DXA-assisted vertebral fracture assessment (VFA) in a population-based study of postmenopausal women: the FRODOS study.

UNLABELLED: Population-based studies performed with vertebral fracture assessment (VFA) morphometric technology are lacking in postmenopausal osteoporosis. In this study, we show a lower than expected prevalence of vertebral fractures, a high prevalence of minor vertebral deformities, and a clear association with clinical and densitometric parameters indicating the usefulness of this approach. INTRODUCTION: Adequate epidemiological data on the prevalence of vertebral fractures (VF) is essential in studies of postmenopausal osteoporosis. Routine DXA-assisted VFA may be useful to determine the presence of VF. However, population-based studies performed with this technology are lacking. We aimed to assess the prevalence of VF and minor deformities in 2,968 postmenopausal women aged 59-70 years from a population-based cohort. METHODS: VFA and bone mineral density (BMD) measurements were conducted, and McCloskey criteria (vertebral heights under 3 SD from reference values) confirmed with the Genant method were used to define VF. Additionally, minor vertebral deformities (vertebral heights between -2 and -2.99 SD) were evaluated. RESULTS: The prevalence of VF was 4.3%, and 17% of the participants had minor vertebral deformities. Low BMD was frequently observed in women with VF, with 4%, and 42% of participants showing osteoporosis and osteopenia. Minor vertebral deformities were observed in nearly 40% of women with VF. Multivariate logistic regression analysis showed that age, history of previous fracture, osteoporotic BMD, receiving anti-osteoporotic treatment, and current use of glucocorticoids were significantly associated with VF. CONCLUSIONS: Although the VFA approach showed a lower than expected prevalence of VF in our cohort, its association with clinical and densitometric parameters may be useful to identify women at risk for developing fragility fractures and may therefore justify its use in longitudinal studies. The high prevalence of minor vertebral deformities detected in patients with VF indicates the need to evaluate this type of deformity as a risk factor for further skeletal fractures.

Is lower income associated with an increased likelihood of qualification for treatment for osteoporosis in Canadian women?

UNLABELLED: We examined whether low income was associated with an increased likelihood of treatment qualification for osteoporotic fracture probability determined by Canada FRAX in women aged ≥50 years. A significant negative linear association was observed between income and treatment qualification when FRAX included bone mineral density (BMD), which may have implications for clinical practice. INTRODUCTION: Lower income has been associated with increased fracture risk. We examined whether lower income in women was associated with an increased likelihood of treatment qualification determined by Canada FRAX®. METHODS: We calculated 10-year FRAX probabilities in 51,327 Canadian women aged ≥50 years undergoing baseline BMD measured by dual energy x-ray absorptiometry 1996-2001. FRAX probabilities for hip fracture ≥3% or major osteoporotic fracture (MOF) ≥20 % were used to define treatment qualification. Mean household income from Canada Census 2006 public use files was used to categorize the population into quintiles. Logistic regression analyses were used to model the association between income and treatment qualification. RESULTS: Percentages of women who qualified for treatment based upon high hip fracture probability increased linearly with declining income quintile (all p trend <0.001), but this was partially explained by older age among lower income quintiles (p trend <0.001). Compared to the highest income quintile, women in the lowest income quintile had a greater likelihood of treatment qualification based upon high hip fracture probability determined with BMD (age-adjusted odds ratio [OR], 1.34; 95% confidence intervals (CI), 1.23-1.47) or high MOF fracture probability determined with BMD (age-adjusted OR, 1.31; 95% CI, 1.18-1.46). Differences were nonsignificant when FRAX was determined without BMD, implying that BMD differences may be the primary explanatory factor. CONCLUSIONS: FRAX determined with BMD identifies a larger proportion of lower income women as qualifying for treatment than higher income women.

Adherence to raloxifene therapy: assessment methods and relationship with efficacy.

UNLABELLED: Response to therapy depends on patient compliance but accurate assessment is difficult and adequate levels of adherence are uncertain. Adherence to raloxifene treatment may be assessed more accurately by electronic monitoring than by counting returned tablets. The level of adherence is positively associated with the degree of bone response. INTRODUCTION: Adherence to study medication is usually estimated by counting returned tablets. This method relies on subjects' honesty and may be inaccurate. We aimed to assess adherence more accurately, and examine its effect on measures of bone response, by using electronic monitoring. METHODS: Osteopenic women, ages 50 to 80, were prescribed daily raloxifene for 2 years. Electronic bottle caps (Medication Event Monitoring System (MEMS), Aardex) recorded the date and time on opening. Returned tablets were also counted. We measured bone mineral density (BMD) in duplicate at the spine and hip at baseline and 2 years. We also measured urinary N-terminal cross-linked telopeptide of type I collagen (NTX) at baseline, 1 and 2 years. We calculated the percentage changes in BMD and NTX from mean baseline to mean follow up measurements. Percentage adherence was assessed by both methods for 71 subjects that completed the study. RESULTS: The two methods correlated significantly (p <0.001, Spearman's rho = 0.73) but the tablet count showed a higher median adherence than the MEMS caps (95.7 vs. 85.0%, p <0.001), with greater divergence at lower adherence levels. MEMS adherence in 65 subjects with complete data correlated with NTX response (p <0.01, rho = -0.33) but with BMD response only at the femoral neck. However, adherence in the lowest quartile was associated with poorer BMD response at all sites (p <0.05). CONCLUSION: Tablet counts may give similar results overall but conceal substantial individual non-adherence. Monitoring caps may assess adherence more accurately than tablet counts and would be the preferred method in clinical trials. The degree of adherence is associated with both bone turnover and BMD responses to anti-resorptive therapy.

An evaluation of the Fracture Risk Assessment Tool (FRAX®) as an indicator of treatment efficacy: the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX®.

SUMMARY: The relationship between baseline Fracture Risk Assessment Tool (FRAX®) and treatment efficacy was evaluated using data from a pivotal phase 3 study. Relative risk of vertebral, nonvertebral, and all clinical fractures decreased with increasing probability of fracture for bazedoxifene (BZA) versus placebo but remained generally constant for raloxifene (RLX). INTRODUCTION: To determine whether the FRAX® predicts osteoporosis treatment efficacy, we evaluated reductions in fracture incidence associated with BZA and RLX according to baseline fracture risk determined by FRAX® using data from a phase 3 osteoporosis treatment study. METHODS: Hazard ratios (HRs) for effects of BZA and RLX versus placebo on incidence of vertebral, nonvertebral, and all clinical fractures were calculated using a Cox regression model. Cox regression analyses were performed in subgroups at or above 10-year fracture probability thresholds determined by FRAX®. RESULTS: HRs for the risk of vertebral, nonvertebral, and all clinical fractures versus placebo decreased with increasing 10-year fracture probability for BZA, while those for RLX remained stable. In all 10-year fracture probability subgroups, all BZA doses significantly reduced vertebral fracture risk versus placebo (HR = 0.22-0.66). BZA at 20, 40, and 20/40 mg significantly reduced risk of nonvertebral fractures (HR = 0.45, 0.44, and 0.45, respectively) and all clinical fractures (HR = 0.38, 0.41, and 0.40, respectively) for ≥20.0 % fracture probability. Vertebral fracture risk reductions for RLX 60 mg versus placebo were significant in subgroups at lower fracture probabilities (≥2.5- ≥ 10.0 %), but not higher (≥12.5 %), and in no subgroups for nonvertebral or all clinical fractures. CONCLUSION: The antifracture efficacy of BZA increased with increasing baseline FRAX® score, but there was no clear relationship between RLX and baseline FRAX®. These findings provide independent confirmation of current literature, suggesting that the relationship between FRAX® and treatment efficacy varies for different agents.