Longitudinal Assessment of Bone Mineral Density in Women Living With and Without HIV Across Reproductive Phases.

BACKGROUND: Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states. SETTING: Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites. METHODS: This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables. RESULTS: Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (ß: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (ß: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (ß: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (ß: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (ß: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss. CONCLUSIONS: HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age.

Fracture risk and assessment in adults with cancer.

Individuals with cancer face unique risk factors for osteoporosis and fractures. Clinicians must consider the additive effects of cancer-specific factors, including treatment-induced bone loss, and premorbid fracture risk, utilizing FRAX score and bone mineral densitometry when available. Pharmacologic therapy should be offered as per cancer-specific guidelines, when available, or local general osteoporosis guidelines informed by clinical judgment and patient preferences. Our objective was to review and summarize the epidemiologic burden of osteoporotic fracture risk and fracture risk assessment in adults with cancer, and recommended treatment thresholds for cancer treatment-induced bone loss, with specific focus on breast, prostate, thyroid, gynecological, multiple myeloma, and hematopoietic stem cell transplant. This narrative review was informed by PubMed searches to July 25, 2022, that combined terms for cancer, stem cell transplantation, fracture, bone mineral density (BMD), trabecular bone score, FRAX, Garvan nomogram or fracture risk calculator, QFracture, prediction, and risk factors. The literature informs that cancer can impact bone health in numerous ways, leading to both systemic and localized decreases in BMD. Many cancer treatments can have detrimental effects on bone health. In particular, hormone deprivation therapies for hormone-responsive cancers such as breast cancer and prostate cancer, and hematopoietic stem cell transplant for hematologic malignancies, adversely affect bone turnover, resulting in osteoporosis and fractures. Surgical treatments such as hysterectomy with bilateral salpingo-oophorectomy for gynecological cancers can also lead to deleterious effects on bone health. Radiation therapy is well documented to cause localized bone loss and fractures. Few studies have validated the use of fracture risk prediction tools in the cancer population. Guidelines on cancer-specific treatment thresholds are limited, and major knowledge gaps still exist in fracture risk and fracture risk assessment in patients with cancer. Despite the limitations of current knowledge on fracture risk assessment and treatment thresholds in patients with cancer, clinicians must consider the additive effects of bone damaging factors to which these patients are exposed and their premorbid fracture risk profile. Pharmacologic treatment should be offered as per cancer-specific guidelines when available, or per local general osteoporosis guidelines, in accordance with clinical judgment and patient preferences.

Evaluation of the fracture risk assessment tool for determining bone disease and the impact of secondary causes of osteoporosis in people living with HIV.

BACKGROUND: Among HIV-infected individuals, screening for bone disease is encouraged to assess reversible risk factors and plan therapeutic interventions. OBJECTIVE: We assessed the usefulness of Fracture Risk Assessment (FRAX) tool to identify candidates for dual X-ray absorptiometry (DXA) scan, or individuals with bone loss progression. We further explored how secondary causes of osteoporosis are reflected on FRAX. METHODS: Longitudinal study of 217 consecutive individuals (mean, 45.8 years, 24% females) included after DXA scan. FRAX was calculated without/with femoral neck bone mineral density (BMD), checking the box of "secondary osteoporosis" for all the individuals. RESULTS: Low BMD was observed in 133/217 (61%) individuals, of whom 98.5% had not been selected as candidates for DXA by current FRAX thresholds. Specifically, 23% of individuals aged <50 had low BMD but none was candidate for DXA. Adding BMD data, FRAX results increased by 50-100%, with 2/217 individuals (1%) above the thresholds. Classical and HIV-related secondary causes of osteoporosis (observed in 98% overall) correlated with low BMD, modifying significantly FRAX results (HCV coinfection, +124%; longer time of HIV infection, +93%; longer time on antiretroviral therapy, +147%; tenofovir exposure +36%). Individuals with lower BMD and higher FRAX results at inclusion had less bone decline in a follow-up DXA after a median of 3.5 years. CONCLUSIONS: Currently recommended FRAX thresholds are not useful to select candidates for DXA scan, which could delay its performance in a population with a high prevalence of secondary factors for low BMD. Classical and HIV-related factors alter BMD and fracture risk estimation.

The impact of height on low/reduced bone mineral density in Chinese adolescents aged 12-14 years old: gender differences.

Low/reduced bone mineral density (BMD) is an important predictor of childhood fracture. In this article, we presented the prevalence of BMD in Chinese adolescents and, for the first time, demonstrated the gender disparities in the impact of height on BMD. PURPOSE: To analyze the gender disparities in the association of low/reduced BMD with height in Chinese adolescents at the stage of growth spurt. METHODS: A total of 8152 adolescents aged 12-14 years old were included based on a cross-sectional study in Tianjin, China. Height and weight were measured with standard equipment. BMD was measured using the method of quantitative ultrasound. Adolescents with Z ≤ - 2.0 or - 2.0 < Z ≤ - 1.0 were defined as "low BMD" or "reduced BMD". RESULTS: The total low/reduced BMD rate was 22.0% in Chinese adolescents aged 12-14 years old, and boys were more likely to have low/reduced BMD than girls (30.1% vs. 12.9%, P < 0.001). The rate of low/reduced BMD significantly increased with age in boys (Ptrend = 0.019), whereas decreased with age in girls (Ptrend = 0.018). We found significant interaction effect between gender and height standard deviation score (height-Z) in the association with low/reduced BMD (Pinteraction < 0.001). There was a positive association of height-Z among boys (OR = 1.30, 95%CI 1.21-1.39, P < 0.001), meanwhile low/reduced BMD was inversely associated with height-Z among girls (OR = 0.85, 95%CI 0.78-0.94, P < 0.001). CONCLUSIONS: Our study suggested strong gender disparities in the impact of height on BMD in Chinese adolescents aged 12-14 years old, where the association between low/reduced BMD and height was positive among boys but inverse among girls. The study provides evidence on the early prevention and the risk factor identification of low/reduced BMD and childhood fractures.

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.

Risk Assessment Tools for Osteoporosis-Related Fractures.

Osteoporosis is a prevalent and po- tential debilitating disease. Characterized by archi- tectural modifications in bone matrix, osteoporosis ultimatelyincreases the propensity forbones to frac- ture, especially at the hip and spine. Fortunately, osteoporosis can be treated effectively if detected at an early stage. While recognizing an increased risk offracture inwomen with osteoporosis, mostcases of fracture occur in women with osteopenia orlowbone mass. A good fracture risk assessment tool would be more clinically meaningful than an accurate osteo-. porosis screening or diagnostic tool. Here we present a concise review ofthe existing modalities which may be utilized to screen for osteoporosis or predict risk of oteonorotic fractures.

Cost-effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan.

Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of this study was to estimate the cost-effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan. An individual simulation model was developed to predict lifetime costs and quality-adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy. The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan. We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors. For 70-year-old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost-effectiveness ratio (ICER) of alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These results were sensitive to age, BMD, and number of clinical risk factors. Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost-effective in 0.2% to 2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is willing to pay $50,000 per QALY. Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10-year probability for a osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost-effectiveness.

[Assessment of a set of FRAX(®)-based criteria for the indication of bone densitometry in Spanish postmenopausal women]. / Evaluación de una propuesta de criterios de indicación de densitometría ósea en mujeres posmenopáusicas españolas basados en la herramienta FRAX(®)

BACKGROUND AND OBJECTIVE: To assess the effect of the application in routine clinical practice of a proposal of thresholds for the indication of bone densitometry in Spanish postmenopausal women. PATIENTS AND METHODS: We determined the risk of major fracture (RMF) by FRAX(®) of the patients referred to a bone densitometry unit from Primary Care who were untreated. We calculated how many scans would have been avoided if they had been performed only to women ≥ 65 years with a RMF < 10% or women<65 years with a RMF ≥ 3.6%. RESULTS: We included 643 women with a mean age of 61 (9) years. Twenty-three percent had a normal bone mineral density, 56% had osteopenia, and 21% osteoporosis. The RMF was 5.9 (5.5)%. Eighty of 217 (37%) bone scans in women ≥ 65 years and 273 of 426 (64%) in women<65 years would have been avoided. As a whole, 55% of the scans would have been avoided. The sensitivity of the threshold of 3.6% of RMF for the diagnosis of osteoporosis was 51%, specificity 68%, positive predictive value 20%, and negative predictive value 20%. CONCLUSIONS: The application of the proposed thresholds for the indication of bone densitometry in Spanish postmenopausal women, based on age and risk of fracture calculated by FRAX(®) would result in a significant decrease of the activity of the bone densitometry unit.

Fracture Risk Assessment in Chronic Kidney Disease, Prospective Testing Under Real World Environments (FRACTURE): a prospective study.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of fracture. Decreased bone mass and disruption of microarchitecture occur early in the course of CKD and worsens with the progressive decline in renal function so that at the time of initiation of dialysis at least 50% of patients have had a fracture. Despite the excess fracture risk, and the associated increases in morbidity and mortality, little is known about the factors that are associated with an increase in fracture risk. Our study aims to identify prognostic factors for bone loss and fractures in patients with stages 3 to 5 CKD. METHODS: This prospective study aims to enroll two hundred and sixty men and women with stages 3 to 5 CKD. Subjects will be followed for 24 months and we will examine the ability of: 1) bone mineral density by dual x-ray absorptiometry at the spine, hip, and radius; 2) volumetric bone density by high resolution peripheral quantitated computed tomography at the radius and tibia; 3) serum markers of bone turnover; 4) bone formation rate by bone biopsy; and 5) muscle strength and balance to predict spine and non-spine fractures, identified by self-report and/or vertebral morphometry. All measurements will be obtained at baseline, at 12 and at 24 months with the exception of bone biopsy, which will be measured once at 12 months. Subjects will be contacted every 4 months to determine if there have been incident fractures or falls. DISCUSSION: This study is one of the first that aims to identify risk factors for fracture in early stage CKD patients. Ultimately, by identifying risk factors for fracture and targeting treatments in this group-before the initiation of renal replacement therapy--we will reduce the burden of disease due to fractures among patients with CKD.

Primary care use of FRAX: absolute fracture risk assessment in postmenopausal women and older men.

Osteoporosis-related fractures (low-trauma or fragility fractures) cause substantial disability, health care costs, and mortality among postmenopausal women and older men. Epidemiologic studies indicate that at least half the population burden of osteoporosis-related fractures affects persons with osteopenia (low bone density), who comprise a larger segment of the population than those with osteoporosis. The public health burden of fractures will fail to decrease unless the subset of patients with low bone density who are at increased risk for fracture are identified and treated. Risk stratification for medically appropriate and cost-effective treatment is facilitated by the World Health Organization (WHO) FRAX algorithm, which uses clinical risk factors, bone mineral density, and country-specific fracture and mortality data to quantify a patient's 10-year probability of a hip or major osteoporotic fracture. Included risk factors comprise femoral neck bone mineral density, prior fractures, parental hip fracture history, age, gender, body mass index, ethnicity, smoking, alcohol use, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis. FRAX was developed by the WHO to be applicable to both postmenopausal women and men aged 40 to 90 years; the National Osteoporosis Foundation Clinician's Guide focuses on its utility in postmenopausal women and men aged >50 years. It is validated to be used in untreated patients only. The current National Osteoporosis Foundation Guide recommends treating patients with FRAX 10-year risk scores of > or = 3% for hip fracture or > or = 20% for major osteoporotic fracture, to reduce their fracture risk. Additional risk factors such as frequent falls, not represented in FRAX, warrant individual clinical judgment. FRAX has the potential to demystify fracture risk assessment in primary care for patients with low bone density, directing clinical fracture prevention strategies to those who can benefit most.

The health and economic consequences of osteopenia- and osteoporosis-attributable hip fractures in Germany: estimation for 2002 and projection until 2050.

SUMMARY: The health and economic burden of osteopenia- and osteoporosis-attributable hip fractures (OHF) in Germany was estimated for 2002 and projected until 2050. We found 108,341 OHF resulting in 2,998 million Euros cost, which will more than double by the year 2050, calling for improvement and development of prevention strategies for OHF. INTRODUCTION: This study aimed to estimate the health impact and the societal costs of OHF in Germany in the year 2002 and to extrapolate these estimates to the years 2020 and 2050. METHODS: We estimated OHF-attributable deaths, years of potential life lost (YPLL) and quality-adjusted life years lost (QALYs) using attributable fractions. Direct costs for acute treatment, rehabilitation, nursing care, non-medical costs and indirect costs for sickness absence, early retirement and mortality were estimated. All estimates were extrapolated to 2020 and 2050 using an estimation of future population composition and life expectancy. RESULTS: We found 108,341 OHF resulting in 3,485 deaths, 22,724 YPLL, 114,058 QALYs, 2,736 millions of Euros direct cost and 262 millions of Euros indirect costs. Projection to 2020 showed corresponding increases of 44%, 62%, 56%, 49%, 47% and 33%, whereas the projection to 2050 resulted in changes of 128%, 215%, 196%, 152%, 138% and 90%, respectively. CONCLUSIONS: OHF have considerable impact on health and direct costs in the elderly. Both may strongly increase in future decades due to demographic changes, calling for improvement and development of effective strategies for preventing and dealing with OHF.

Routine versus targeted vertebral fracture assessment for the detection of vertebral fractures.

UNLABELLED: Fracture risk is underestimated in women with unknown vertebral fractures. Using VFA, we compared two screening methods: targeted (6,388 women) and routine (2,176 women). Routine screening detected fractures in 20%. Targeted screening only required 5% attending for DXA to undergo VFA but only detected 9.6% of women with fractures. INTRODUCTION: BMD alone underestimates fracture risk in women with unknown vertebral fractures. We report the results of routine vertebral fracture assessment (VFA) screening and compare with targeted screening. METHOD: Our centre initially targeted VFA at women with reasons to suspect a vertebral fracture. Later we changed to routine VFA screening for all women over 65. We retrospectively compare each screening method's ability to detect vertebral fractures. RESULTS: Six thousand three hundred and eighty-eight women over 65 underwent DXA during the period of targeted VFA and 2,176 during routine VFA. Routine VFA detected 420 (20.0%) women with fracture. Most vertebral fractures (56.2%) occurred in women with osteopenia. Routine VFA would be expected to alter the management of 1 in 6 osteopenic women. Targeted VFA was performed in 332 (5.2%) women detecting 122 (1.9%) women with fractures. It was estimated that targeted VFA only detected 9.6% of women with a vertebral fracture. Targeted VFA failed to detect fractures in 18.1% of the population attending for DXA and in 29% of those with osteoporosis. CONCLUSION: Routine VFA detects vertebral fractures in 20% of women over 65. Targeted VFA greatly reduces the number of VFAs performed but only detects a minority of the women with vertebral fractures.

The cost effectiveness of bisphosphonates for the prevention and treatment of osteoporosis: a structured review of the literature.

Osteoporotic fragility fractures constitute a significant public health concern. The lifetime risk of any osteoporotic fracture is very high (40-50% in women and 13-22% in men). Fractures are associated with significant mortality and morbidity and represent a substantial economic burden to society. Bisphosphonates (alendronate, etidronate, risedronate and ibandronate) are indicated for the treatment and prevention of osteoporosis but are costly compared with other treatments, such as vitamin D and calcium. Our search identified 23 studies evaluating the cost effectiveness of bisphosphonate therapy for the treatment and prevention of fragility fractures; these studies were from five geographical areas and employed a variety of comparators and assumptions. We identified 11 studies investigating bisphosphonates in women with low bone mineral density (BMD) [T-score >2.5 standard deviations {SDs} below normal {mean} peak values for young adults] and previous fractures, five studies investigating bisphosphonates in women with low BMD and no previous fracture, one study of bisphosphonates in women with osteopenia, five studies involving screening and two studies of bisphosphonates in special populations (women initiating corticosteroid treatment and men). In women with low BMD and previous fractures, bisphosphonate therapy was most cost effective in populations aged > or =70 years and was unlikely to be cost effective in populations aged < or =50 years. There was uncertainty concerning the cost effectiveness of bisphosphonates in such populations aged 60-69 years. In women with low BMD without previous fractures, treatment with alendronate or risedronate appeared to be cost effective across countries (UK, US, Denmark), but there was some uncertainty about the cost effectiveness of etidronate in patients in the highest age groups. Identifying risk factors for fractures through means such as spine radiographs to detect vertebral deformities improves the cost effectiveness of treatment. In women with osteopenia, alendronate therapy may be cost effective in women with a T-score of -2.4SD in the US. Screening for low BMD and treatment with alendronate or etidronate appears to be cost effective in postmenopausal women in general and in women with rheumatoid arthritis initiating corticosteroid therapy. Alendronate therapy without screening was also shown to be potentially cost effective in certain at-risk male populations, as well as in women initiating corticosteroid therapy after the age of 40 years. Decision makers in the US, UK and Sweden should consider funding the use of bisphosphonates for the prevention and treatment of osteoporosis in women aged >70 years, particularly if they have other risk factors for fracture. Further studies are required to make more definitive conclusions in other countries and patient populations. Screening strategies for low BMD followed by bisphosphonate treatment should also be considered in the general female population aged >65 years in the UK and US and in patients with rheumatoid arthritis initiating corticosteroid therapy.

Vertebral Fracture Assessment by dual-energy X-ray absorptiometry: insurance coverage issues in the United States. A White Paper of the International Society for Clinical Densitometry.

Clinical trial data and fracture risk prediction models unequivocally demonstrate the utility of identifying prevalent vertebral fractures to predict future fractures of all types. Knowledge of prevalent vertebral fractures can alter patient management decisions and result in initiation of therapy to reduce fracture risk in some patients who would not otherwise be treated. Cost-benefit analysis demonstrates that identifying and treating patients with vertebral fractures, even those with a densitometric classification of osteopenia, is cost effective. Vertebral fractures can be readily identified in the office setting using standard radiography or Vertebral Fracture Assessment (VFA), a software addition to a central dual-energy X-ray absorptiometry (DXA) machine. In the United States, VFA was assigned a Current Procedural Terminology (CPT) code in January 2005. Nevertheless, coverage of VFA has not been uniformly embraced by Medicare carriers, companies that contract with the federal government to administer Medicare coverage and process claims for a region of the United States. Unlike DXA, for which uniform national coverage of qualified Medicare beneficiaries is mandated by the Balanced Budget Act of 1997, VFA coverage policies are determined by the local Medicare carriers. Third-party insurers are also variable in their coverage of VFA. This International Society for Clinical Densitometry (ISCD) White Paper documents the role of VFA in the evaluation and treatment of women with postmenopausal osteoporosis and compares it with standard spine radiography. Arguments used by some Medicare carriers and insurers to deny coverage of VFA in the United States are analyzed and critiqued. For health care providers within the United States, this White Paper may serve as a resource to respond to insurers who deny coverage of VFA. For health care providers regardless of their country, this article underscores the value of VFA as an alternative to spine radiography in the evaluation and management of postmenopausal women with suspected osteoporosis.

Discriminatory ability of calcaneal quantitative ultrasound in the assessment of bone status in patients with inflammatory bowel disease.

A high incidence of bone disease in patients with inflammatory bowel disease (IBD) requires frequent monitoring of skeletal status and, for that reason, evaluation of radiation-free technology is an issue of interest. Our objective was to appraise the parameters of calcaneal quantitative ultrasound (QUS): broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI), and establish their t-score values to investigate discriminatory ability of QUS in IBD patients with metabolic bone disease. The study included 126 patients (Crohn's disease [n = 94] and ulcerative colitis [n = 32]), and 228 age- and sex-matched healthy volunteers. Bone status was evaluated on the same day by calcaneal QUS and dual-energy x-ray absorptiometry (DXA) at spine (L1-L4) and total hip. All QUS measurements were lower in patients compared with healthy controls (BUA p < 0.001; SOS p < 0.001; QUI p < 0.001) and correlated significantly but inversely with disease duration (r = -0.3, p = 0.002). There was no difference with respect to type of disease (Crohn's disease or ulcerative colitis) or corticosteroid therapy. All three QUS t-scores were significantly lower in patients who had previously sustained fragile fractures (n = 28) than in those without fracture in their history (n = 98) (t-scores: BUA -2.0 vs. -1.3, p = 0.008; SOS -2.1 vs. -1.4, p = 0.02: QUI -2.3 vs. -1.5, p = 0.009). Axial DXA was not significantly different between the fracture and nonfracture patients (-1.7 vs. -1.2, p = 0.1), whereas total hip DXA showed a discriminatory power between the two (-1.6 vs. -0.7, p = 0.001). Patients with t-score < -1.0 scanned by DXA were classified as bone disease. The sensitivity of QUS to identify bone disease was 93% and specificity 63%. The sensitivity of QUS to detect osteopenia was 84% and 72% for osteoporosis. Alternatively, lower negative QUS t-score cutoff

Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy.

INTRODUCTION AND HYPOTHESIS: Over half of all fractures among post-menopausal women occur in those who do not have osteoporosis by bone density criteria. Measurement of bone turnover may cost-effectively identify a subset of women with T-score >-2.5 for whom anti-resorptive drug therapy is cost-effective. METHODS: Using a Markov model, we estimated the cost per quality adjusted life year (QALY) for five years of oral bisphosphonate compared to no drug therapy for osteopenic post-menopausal women aged 60 to 80 years with a high (top quartile) or low (bottom 3 quartiles) level of a bone turnover marker. RESULTS: For women with high bone turnover, the cost per QALY gained with alendronate compared to no drug therapy among women aged 70 years with T-scores of -2.0 or -1.5 were $58,000 and $80,000 (U.S. 2004 dollars), respectively. If bisphosphonates therapy also reduced the risk of non-vertebral fractures by 20% among osteopenic women with high bone turnover, then the costs per QALY gained were $34,000 and $50,000 for women age 70 with high bone turnover and T-scores of -2.0 and -1.5, respectively. CONCLUSION: Measurement of bone turnover markers has the potential to identify a subset of post-menopausal women without osteoporosis by bone density criteria for whom bisphosphonate therapy to prevent fracture is cost-effective. The size of that subset highly depends on the assumed efficacy of bisphosphonates for fracture risk reduction among women with both a T-score >-2.5 and high bone turnover and the cost of bisphosphonate treatment.

In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography.

CONTEXT: Assessment of trabecular microarchitecture may enhance the prediction of fracture risk and improve monitoring of treatment response. A new high-resolution peripheral quantitative computed tomography (HR-pQCT) system permits in vivo assessment of trabecular architecture and volumetric bone mineral density (BMD) at the distal radius and tibia with a voxel size of 82 microm3. OBJECTIVE AND PATIENTS: We determined the short-term reproducibility of this device by measuring 15 healthy volunteers three times each. We compared HR-pQCT measurements in 108 healthy premenopausal, 113 postmenopausal osteopenic, and 35 postmenopausal osteoporotic women. Furthermore, we compared values in postmenopausal osteopenic women with (n = 35) and without previous fracture history (n = 78). DESIGN AND SETTING: We conducted a cross-sectional study in a private clinical research center. INTERVENTION AND MAIN OUTCOME MEASURE: We took HR-pQCT measurements of the radius and tibia. Femoral neck and spine BMD were measured in postmenopausal women by dual-energy x-ray absorptiometry. RESULTS: Precision of HR-pQCT measurements was 0.7-1.5% for total, trabecular, and cortical densities and 2.5-4.4% for trabecular architecture. Postmenopausal women had lower density, trabecular number, and cortical thickness than premenopausal women (P < 0.001) at both radius and tibia. Osteoporotic women had lower density, cortical thickness, and increased trabecular separation than osteopenic women (P < 0.01) at both sites. Furthermore, although spine and hip BMD were similar, fractured osteopenic women had lower trabecular density and more heterogeneous trabecular distribution (P < 0.02) at the radius compared with unfractured osteopenic women. CONCLUSION: HR-pQCT appears promising to assess bone density and microarchitecture at peripheral sites in terms of reproducibility and ability to detect age- and disease-related changes.