Estimate Fracture Risk Research Articles

Use of a Decision Aid to Improve Treatment Decisions in Osteoporosis: The Osteoporosis Choice Randomized Trial

Objective Poor adherence to therapy, perhaps related to unaddressed patient preferences, limits the effectiveness of osteoporosis treatment in at-risk women. A parallel patient-level randomized trial in primary care practices was performed. Methods Eligible postmenopausal women with bone mineral density T-scores less than −1.0 and not receiving bisphosphonate therapy were included. In addition to usual primary care, intervention patients received a decision aid (a tailored pictographic 10-year fracture risk estimate, absolute risk reduction with bisphosphonates, side effects, and out-of-pocket cost), and control patients received a standard brochure. Knowledge transfer, patient involvement in decision-making, and rates of bisphosphonate start and adherence were studied. Data came from medical records, post-visit written and 6-month phone surveys, video recordings of clinical encounters, and pharmacy prescription profiles. Results A total of 100 patients (range of 10-year fracture risk, 6%-60%) were allocated randomly to receive the decision aid (n = 52) or usual care (n = 48). Patients receiving the decision aid were 1.8 times more likely to correctly identify their 10-year fracture risk (49% vs 28%; 95% confidence interval [CI], 1.03-3.2) and 2.7 times more likely to identify their estimated risk reduction with bisphosphonates (43% vs 16%; 95% CI, 1.3-5.7). Patient involvement improved with the decision aid by 23% (95% CI, 13.6-31.4). Bisphosphonates were started by 44% of patients receiving the decision aid and 40% of patients receiving usual care. Adherence at 6 months was similarly high across both groups, but the proportion with more than 80% adherence was higher with the decision aid (n = 23 [100%] vs n = 14 [74%]; P = .009). Conclusion A decision aid improved the quality of clinical decisions about bisphosphonate therapy in at-risk postmenopausal women, did not affect start rates, and may have improved adherence.

Periarticular and generalised bone loss in patients with early rheumatoid arthritis (ERA). Influence of alendronate (AL) and glucocorticoid treatment, and disease activity

Periarticular and generalised bone loss in patients with early rheumatoid arthritis (ERA). Influence of alendronate (AL) and glucocorticoid treatment, and disease activity

Fracture risk in men with prostate cancer: A population-based study

Fractures are increased among men with prostate cancer, especially those on androgen-deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population-based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990-1999 (mean age 68.2 ± 8.9 years) were followed for 6821 person-years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time-to-fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person-years). Overall fracture risk was elevated 1.9-fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7-fold among ADT-treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited.

Ethnic difference of clinical vertebral fracture risk

SummaryVertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate.IntroductionVertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups.MethodsFour thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations.ResultsThe mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio.ConclusionsThe incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate.

Quantitative Ultrasound Normative Reference Data for Community-Dwelling White and Black Females in the United States

Quantitative ultrasound (QUS) race-specific normative reference data are not available for accurate calculation of Z-scores. The primary aims of this study were (1) to develop a race-specific QUS reference database for white and black females and to compare estimated fracture risk between these 2 racial groups and (2) to compare stiffness index (SI) values of white females in this study to manufacturer-obtained values. Subjects included 1111 females (31% black), aged 20–85 yr (52 ± 19 yr), with a mean SI score of 93.7 ± 20.1. White females, aged 20–39 yr (n = 213), were used to calculate T-scores, whereas Z-scores were age and race specific. Black females had significantly higher SI scores than white females ( p < 0.001). White females aged 50+ yr in this study had significantly higher SI scores compared with manufacturer-derived values. Results highlight the need for population- and race-specific normative data when using QUS as a screening tool for identifying high fracture risk.

Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: A population-based HR-pQCT study

In this cross-sectional study, we aimed to predict age-related changes in bone microarchitecture and strength at the distal radius (DR) and distal tibia (DT) in 644 Canadian adults (n = 442 women and 202 men) aged 20 to 99 years. We performed a standard morphologic analysis of the DR and DT with high-resolution peripheral quantitative computed tomography (pQCT) and used finite-element analysis (FEA) to estimate bone strength (failure load) and the load distribution. We also calculated a DR load-to-strength ratio as an estimate of forearm fracture risk. Total bone area, which was 33% larger in young men at both sites, changed similarly with age in women and men at the DT but increased 17% more in men than in women at the DR (p < .001). Trabecular number and thickness (Tb.Th) were 7% to 20% higher in young men than in young women at both sites, and with the exception of Tb.Th at the DR, which declined more with age in men (-16%) than in women (-2%, p < .01), the age-related decline in these outcomes was similar in women and in men. In the cortex, porosity (Ct.Po) was 31% to 44% lower in young women than in young men but increased 92% to 176% more with age in women than in men (p < .001). The DR cortex carried 14% more load in young women than in young men, and the percentage of load carried by the DR cortex did not change with age in women but declined by 17% in men (p < .01). FEA-estimated bone strength was 34% to 47% greater in young men, but the predicted change with age was similar in both sexes. In contrast, the load-to-strength ratio increased 27% more in women than in men with age (p < .01). These results highlight important site- and sex-specific differences in patterns of age-related bone loss. In particular, the trends for less periosteal expansion, more porous cortices, and a greater percentage of load carried by the DR cortex in women may underpin sex differences in forearm fracture risk.

Decreased bone density in men on methadone maintenance therapy

Opioid use may impact adversely upon skeletal health. Participants in methadone maintenance programmes commonly have prolonged exposure to opioids. We sought to determine whether participants in a methadone maintenance programme have evidence of altered bone mineral density (BMD) and bone turnover. Cross-sectional study of people taking methadone maintenance therapy (MMT). Clinical research centre. Eighty-three people (48 men, 35 women) who had taken MMT for a median (interquartile range) of 11 (6-16) years. Comparison data were from both a normative database and control subjects recruited and assessed at the same location as the participants taking MMT. BMD at lumbar spine, total hip and total body; biochemical markers of bone turnover. In men taking MMT, BMD was lower than normal at each skeletal site [mean, 95% confidence interval Z-score -1.1 (-1.6 to -0.7) at the lumbar spine, -1.0 (-1.3 to -0.7) at the total hip, and -1.1 (-1.4 to -0.8) at the total body, P < 0.001 at each site]. BMD in the women taking MMT was not different from control values. Bone turnover was within the normal range in both genders. Serum testosterone was lower in the men taking MMT than in controls. BMD is lower than normal throughout the skeleton in men, but not women, taking MMT. Assessment of skeletal health, including estimation of absolute fracture risk, should be undertaken in men participating in methadone maintenance programmes.

Ultrasonic characterization of bone quality based on Bayesian probability theory.

The hypothesis that underlies the approach to be reported is that ultrasonic properties obtained using Bayesian probability theory can produce reliable estimates of bone quality and fracture risk. A key factor in this approach is to provide quantitative estimates of the confidence to be associated with the derived values of speed of sound (SOS) and frequency dependence of attenuation or broadband ultrasonic attenuation (BUA). Our laboratory demonstrated that when overlapping fast and slow compressional wave mode data are processed using phase spectroscopy and spectral subtraction techniques, interference effects may result in artifacts. In previous reports of studies of bone conducted in vitro, Bayesian probability theory was shown to be an effective method for extracting the ultrasonic properties of the individual fast and slow waves, even in the presence of substantial interference, whereas the same signals processed using conventional methods often exhibited anomalous features including non-causal negative dispersion. The focus of the present report is on the distribution of the probability density functions about their maximum values as a means for providing meaningful estimates of the confidence to be associated with the reported values for SOS and BUA for fast and slow wave modes. [Work supported by NIH R01HL40302, R01AR057433, and NSF CBET-0717830.]

Response to questions regarding conclusions reached in “Age dependence of femoral strength in white women and men”

We thank the Editors for the opportunity to assess Dr. Kaufman's analysis of our data and to further expound on the clinical relevance of our findings. Dr. Kaufman is concerned that our analysis implicitly assumes that “femoral strength as estimated by BCT is a much better quantity to estimate fracture risk than is aBMD.” He also concludes that “the implication that BCT provides superior information on bone strength and fracture risk at the proximal femur to that provided by aBMD is questionable at least based on the data provided in the article by Keaveny and colleagues.” In fact, our analysis does not address assessment of fracture risk, nor does it assume that our BCT-derived estimates of femoral strength are better at fracture risk assessment than aBMD. We were careful in our conclusions not to broach comparatives of fracture risk assessment because we had no fracture outcome data available for this cohort at the time of our analysis. Instead, the focus of this article was on the more general issue of age-related trends for the population, highlighting differences in trends for aBMD and femoral strength, and not addressing superiority of one over the other. As such, Dr. Kaufman mischaracterized our study. In reaching his conclusions, Dr. Kaufman made several unsubstantiated statements. For example, he concluded from analysis of our data that aBMD of the femoral neck is “an excellent proxy for femoral strength.” Dr. Kaufman's argument was based on the relation between age-specific mean values between the two variables. His reported correlation was so high because, after midlife, we found that mean strength and mean aBMD both declined in an approximately linear fashion with age. By Dr. Kaufman's logic, age also would be an excellent proxy for aBMD. However, none of this speaks to the correlation for individuals, which is the relevant issue for fracture risk assessment. In a study of clinically defined postmenopausal osteoporotic women, for example, the correlation between BCT-derived strength and dual-energy X-ray absorptiometry (DXA)–derived aBMD was quite low (R2 ≈ 0.50).1 Dr. Kaufman mischaracterized our second conclusion by extrapolating his paraphrasing to comparisons of fracture risk assessment—but, in fact, we made no conclusions about fracture risk assessment or the superiority of BCT-derived femoral strength over aBMD in this regard. Dr. Kaufman's also dismissed our 3000 N cut point for femoral strength as “largely arbitrary.” Since this empirical cut point was based on prospective, fracture outcome clinical data (albeit for men),2 clearly it was not chosen arbitrarily. Mathematically, of course, one can increase the T-score cut point to match the prevalence for the strength cut point. But this has little relevance in a clinical context because increasing the T-score will compromise specificity, which is not desirable clinically, and changing the World Health Organization aBMD criteria for the definition of osteoporosis is not feasible. Dr. Kaufman also questioned the relevance of our results, stating that our observation of greater changes in strength than aBMD “is of little consequence.” While this viewpoint may be reasonable from a purely mathematical perspective, the clinical implications are more nuanced. aBMD is used widely as an implicit surrogate for bone strength. In this clinical context, our results raise the issue of whether such widespread reliance on aBMD as a surrogate for bone strength may provide a misleading clinical impression that annual percent reductions in femoral strength are on the same order as in aBMD—about 0.5% to 0.7% per year (see Fig. 4 of our paper). Such a rate of loss does not appear too alarming, does not change much with aging, and probably would justify the current approach of waiting until individuals are at very high risk before commencing treatment. However, our results suggest instead that the rate of loss in strength is much greater, particularly in elderly women. This raises the possibility that too few women are being treated and too late. Thus, while our results are indeed consistent with current efforts to improve clinical fracture risk assessment, we believe that they additionally provide unique insight into effects of age on femoral strength and highlight issues central to the debate of how one might improve management of osteoporosis from a public health perspective.

Evaluation of the FRAX and Garvan fracture risk calculators in older women

Fracture risk calculators estimate the absolute risk of osteoporotic fractures. We investigated the performance of the FRAX and Garvan Institute fracture risk calculators in healthy, older, New Zealand, postmenopausal women with normal bone mineral density (BMD) for their age. Fractures were ascertained in women initially enrolled in a 5-year trial of calcium supplements and followed on average for 8.8 years. Baseline data (1422 women, mean age 74 years, mean femoral neck BMD T-score -1.3) were used to estimate fracture risk during follow-up using the FRAX and Garvan calculators. The FRAX-New Zealand tool was used both with and without baseline BMD. The discrimination of the calculators was assessed using the area under the curve (AUC) of receiver operating characteristic curves. The calibration was assessed by comparing estimated risk of fracture with fracture incidence across a range of estimated fracture risks and clinical factors. For each fracture subtype, the calculators had comparable moderate predictive discriminative ability (AUC range: hip fracture 0.67-0.70; osteoporotic fracture 0.62-0.64; any fracture 0.60-0.63) that was similar to that of models using only age and BMD. The Garvan calculator was well calibrated for osteoporotic fractures but overestimated hip fractures. FRAX with BMD underestimated osteoporotic and hip fractures. FRAX without BMD underestimated osteoporotic and overestimated hip fractures. In summary, none of the calculators provided better discrimination than models based on age and BMD, and their discriminative ability was only moderate, which may limit their clinical utility. The calibration varied, suggesting that the calculators should be validated in local cohorts before clinical use.

Impact of UK National Guidelines based on FRAX®– comparison with current clinical practice

To assess whether clinician-determined treatment intervention thresholds are in line with the assessment of fracture risk provided by FRAX® and treatment recommendations provided by UK guidelines produced by the National Osteoporosis Guidelines Group (NOGG). This was a retrospective cohort analysis of 288 patients consecutively referred for dual-energy X-ray absorptiometry (DXA) scanning from primary care immediately prior to the introduction of the FRAX® algorithm. In addition to DXA assessment, patients completed a clinical risk factor questionnaire which included risk factors used in the FRAX® algorithm. Initial risk assessment and treatment decisions were performed after DXA. FRAX® was used, retrospectively, with femoral neck T-score, to estimate fracture risk which was applied to NOGG to generate guidance on treatment intervention. Clinician- and NOGG-determined outcomes were audited for concordance. There was concordance between clinician and NOGG treatment decisions in 215 (74.6%) subjects. Discordance was observed in 73 (25.3%) subjects. In the discordant group, seven subjects were given lifestyle advice when NOGG recommended treatment, 42 given treatment when NOGG recommended lifestyle advice only, and 24 were referred to a metabolic bone clinic for further evaluation. The reasons for treatment differences in subjects recommended treatment by clinician but not NOGG were largely (90.2%) attributed to the use of lumbar spine bone mineral density (BMD). There is high concordance between clinician-determined and FRAX®-NOGG intervention. The absence of spine BMD from FRAX® is the primary source of discrepancy. This study provides some assurance of the validity of the treatment thresholds generated from FRAX®-NOGG in 'real-world' usage.

A poisson process model for hip fracture risk

The primary method for assessing fracture risk in osteoporosis relies primarily on measurement of bone mass. Estimation of fracture risk is most often evaluated using logistic or proportional hazards models. Notwithstanding the success of these models, there is still much uncertainty as to who will or will not suffer a fracture. This has led to a search for other components besides mass that affect bone strength. The purpose of this paper is to introduce a new mechanistic stochastic model that characterizes the risk of hip fracture in an individual. A Poisson process is used to model the occurrence of falls, which are assumed to occur at a rate, lambda. The load induced by a fall is assumed to be a random variable that has a Weibull probability distribution. The combination of falls together with loads leads to a compound Poisson process. By retaining only those occurrences of the compound Poisson process that result in a hip fracture, a thinned Poisson process is defined that itself is a Poisson process. The fall rate is modeled as an affine function of age, and hip strength is modeled as a power law function of bone mineral density (BMD). The risk of hip fracture can then be computed as a function of age and BMD. By extending the analysis to a Bayesian framework, the conditional densities of BMD given a prior fracture and no prior fracture can be computed and shown to be consistent with clinical observations. In addition, the conditional probabilities of fracture given a prior fracture and no prior fracture can also be computed, and also demonstrate results similar to clinical data. The model elucidates the fact that the hip fracture process is inherently random and improvements in hip strength estimation over and above that provided by BMD operate in a highly "noisy" environment and may therefore have little ability to impact clinical practice.

FRAX ® and its applications in health economics—Cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example

Background An important aspect of cost-effectiveness analysis of osteoporosis is to accurately model the fracture risk and mortality related to the patient groups in the analysis. The estimation of fracture risk is based on a number of factors, such as the level of general risk of the normal population, the effect of treatment and the prevalence of clinical risk factors (CRFs) for fracture. Fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior vertebral fracture. The treatment effect has been derived from clinical trials and, in the absence of subgroup analyses, the same efficacy has been assumed irrespective of the fracture risk of the population. The FRAX ® tool enables the estimation of risk based on a wider range of risk factors, and treatment efficacy that is dependent on the level of risk in the analyzed population. The objective was to describe the implementation of the FRAX ® algorithms into health economic osteoporosis models and to highlight how it differs from traditional risk assessment. Methods The selective estrogen receptor modulator, bazedoxifene, was evaluated in a Swedish setting with traditional and FRAX ®-based risk assessment in a previously developed Markov model that included fractures and thromboembolic events, and also was adapted to accommodate risk-dependent efficacy, which is available for bazedoxifene. Results The traditional approach gave lower ICERs at ages up to 60 years compared to the FRAX ® method when only considering age, BMD and prior fracture. At 70 years and older and when adding more CRFs with the FRAX ® approach, the FRAX ® ICER decreased and fell below the traditional approach. The risk dependant efficacy was the main reason for lower ICERs with FRAX ® in women at higher risk of fracture. Discussion FRAX ® applied in cost-effectiveness analyses is a more granular method for the estimation of fracture risk, mortality and efficacy compared to previous approaches that can also improve case finding. Furthermore, it facilitates the estimation of cost-effectiveness for various types of patients with different combinations of CRFs, which more closely matches patients in clinical practice.

Independent clinical validation of a Canadian FRAX tool: Fracture prediction and model calibration

A FRAX model for Canada was constructed for prediction of osteoporotic and hip fracture risk using national hip fracture data with and without the use of femoral neck bone mineral density (BMD). Performance of this system was assessed independently in a large clinical cohort of 36,730 women and 2873 men from the Manitoba Bone Density Program database that tracks all clinical dual-energy X-ray absorptiometry (DXA) test results for the Province of Manitoba, Canada. Linkage with other provincial health databases allowed for the direct comparison of fracture risk estimates from the Canadian FRAX model with observed fracture rates to 10 years (549 individuals with incident hip fractures and 2543 with incident osteoporotic fractures). The 10-year Kaplan-Meier estimate for hip fractures in women was 2.7% [95% confidence interval (CI) 2.1-3.4%] with a predicted value of 2.8% for FRAX with BMD, and in men the observed risk was 3.5% (95% CI 0.8-6.2%) with predicted value of 2.9%. The 10-year estimate of osteoporotic fracture risk for all women was 12.0% (95% CI 10.8-13.4%) with a predicted value of 11.1% for FRAX with BMD, and in men, the observed risk was 10.7% (95% CI 6.6-14.9%) with a predicted value of 8.4%. Discrepancies were observed within some subgroups but generally were small. Fracture discrimination based on receiver operating characteristic curve analysis was comparable with published meta-analyses with area under the curve for osteoporotic fracture prediction of 0.694 (95% CI 0.684-0.705) for FRAX with BMD and for hip fractures 0.830 (95% CI 0.815-0.846), both of which were better than FRAX without BMD or BMD alone. Individual risk factors considered by FRAX made significant independent contributions to fracture prediction in one or more of the models. In conclusion, a Canadian FRAX tool calibrated on national hip fracture data generates fracture risk predictions that generally are consistent with observed fracture rates across a wide range of risk categories.

Using the same bone density reference database for men and women provides a simpler estimation of fracture risk

Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture "threshold." Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50+ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) = 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR = 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex.

Clinical relevance of changes in bone metabolism in inflammatory bowel disease

Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous risk factors have to be considered, and these factors should be weighed properly to help in the identification of the appropriate patients for screening. In this editorial, the authors aim to highlight the most important clinical aspects of the epidemiology, prevention, diagnosis and treatment of IBD-related bone loss.

Low Bone Mineral Density, Renal Dysfunction, and Fracture Risk in HIV Infection: A Cross‐Sectional Study

Reduced bone mineral density (BMD) is common in adults infected with human immunodeficiency virus (HIV). The role of proximal renal tubular dysfunction (PRTD) and alterations in bone metabolism in HIV-related low BMD are incompletely understood. We quantified BMD (dual-energy x-ray absorptiometry), blood and urinary markers of bone metabolism and renal function, and risk factors for low BMD (hip or spine T score, -1 or less) in an ambulatory care setting. We determined factors associated with low BMD and calculated 10-year fracture risks using the World Health Organization FRAX equation. We studied 153 adults (98% men; median age, 48 years; median body mass index, 24.5; 67 [44%] were receiving tenofovir, 81 [53%] were receiving a boosted protease inhibitor [PI]). Sixty-five participants (42%) had low BMD, and 11 (7%) had PRTD. PI therapy was associated with low BMD in multivariable analysis (odds ratio, 2.69; 95% confidence interval, 1.09-6.63). Tenofovir use was associated with increased osteoblast and osteoclast activity (P< or = .002). The mean estimated 10-year risks were 1.2% for hip fracture and 5.4% for any major osteoporotic fracture. In this mostly male population, low BMD was significantly associated with PI therapy. Tenofovir recipients showed evidence of increased bone turnover. Measurement of BMD and estimation of fracture risk may be warranted in treated HIV-infected adults.

A perspective on male osteoporosis

Osteoporosis and fragility fracture become common with advancing age in men. The incidence of osteoporosis-related fracture is similar to myocardial infarction and exceeds that of lung and prostate carcinoma combined. These fractures cause substantial morbidity, and the mortality following hip fracture is greater in men than in women. A decline in sex steroids and glucocorticoid and alcohol use, among other factors, contribute to bone loss and fracture risk. Approaches to reduce fracture risk in men are very similar to that in women - recognising and addressing muscle weakness/falls risk and optimising nutrition, with emphasis on calcium and vitamin D and medications when appropriate. Despite the high prevalence, osteoporosis remains largely undiagnosed and undertreated. Hopefully, increased recognition of male osteoporosis by health-care providers and the men themselves, in combination with recent consensus recommendations for treatment based on fracture-risk estimation, will reduce the burden of fragility fracture in men.

Cost-Effectiveness of Using Clinical Risk Factors with and without DXA for Osteoporosis Screening in Postmenopausal Women

According to several guidelines, the assessment of postmenopausal fracture risk should be based on clinical risk factors (CRFs) and bone density. Because measurement of bone density by dual x-ray absorptiometry (DXA) is quite expensive, there has been increasing interest to estimate fracture risk by CRFs. The aim of this study was to determine the cost-effectiveness of osteoporosis screening of CRFs with and without DXA compared with no screening in postmenopausal women in Germany. A cost-utility analysis and a budget-impact analysis were performed from the perspective of the statutory health insurance. A Markov model simulated costs and benefits discounted at 3% over lifetime. Cost-effectiveness of CRFs compared with no screening is euro4607, euro21,181, and euro10,171 per quality-adjusted life-year (QALY) for 60-, 70-, and 80-year-old women, respectively. Cost-effectiveness of DXA plus CRFs compared with CRFs alone is euro20,235 for 60-year-old women. In women above the age of 70, DXA plus CRFs dominates CRFs alone. DXA plus CRFs results in annual costs of euro175 million, or 0.4% of the statutory health insurance's annual budget. Funders should be careful in adopting a strategy based on CRFs alone instead of DXA plus CRFs. Only if DXA is not available, assessing CRFs only is an acceptable option in predicting a woman's risk of fracture.

Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management

Bisphosphonates are widely prescribed and highly effective at limiting the bone loss that occurs in many disorders characterized by increased osteoclast-mediated bone resorption, including senile osteoporosis in both men and women, glucocorticoid-associated osteoporosis, and malignancies metastatic to bone. Although they are generally well tolerated, potential adverse effects may limit bisphosphonate use in some patients. Optimal use of bisphosphonates for osteoporosis requires adequate calcium and vitamin D intake before and during therapy. The World Health Organization fracture risk assessment algorithm is currently available to determine absolute fracture risk in patients with low bone mass and is a useful tool for clinicians in identifying patients most likely to benefit from pharmacological intervention to limit fracture risk. This fracture risk estimate may facilitate shared decision making, especially when patients are wary of the rare but serious adverse effects that have recently been described for this class of drugs.