Association of inflammatory markers with muscle and cognitive function in early and late-aging older adults.

OBJECTIVES: Age-related loss in muscle and cognitive function is common in older adults. Numerous studies have suggested that inflammation contributes to the decline in physical performance and increased frailty in older adults. We sought to investigate the relationship of inflammatory markers, including CRP, IL-6, IL-10, TNF-α, TNFR1, and TNFR2, with muscle and cognitive function in frail early-aging and non-frail late-aging older adults. DESIGN: Secondary analysis of a cross-sectional study. SETTINGS AND PARTICIPANTS: Two hundred community-dwelling older men and women were included. They had been recruited in two groups based on age and functional status: 100 early-agers (age 65-75, who had poor functional status, and more co-morbidities) and 100 late-agers (older than 75 years, who were healthier and had better functional status). MEASUREMENTS: We assessed CRP, IL-6, IL-10, TNF-α, TNFR1, TNFR2, grip strength, Short Physical Performance Battery (SPPB) score, and cognitive function. We used correlation coefficients, partial correlations, and regression modeling adjusted for age, BMI, gender, and exercise frequency. RESULTS: The mean age in the two groups were 70.4 and 83.2, respectively. In regression models adjusting for age, BMI, gender and exercise frequency, early-agers demonstrated significant associations between inflammatory markers and outcomes. Each mg/dl of CRP was associated with (regression coefficient ± standard error) -0.6 ± 0.2 kg in grip strength (p = 0.0023). Similarly, each pg/mL of TNF-α was associated with -1.4 ± 0.7 (p = 0.0454), each 500 pg/mL of TNFR1 was associated with -1.9 ± 0.6 (p = 0.0008), and each 500 pg/mL of TNFR2 was associated with -0.5 ± 0.2 (p = 0.0098) in grip strength. Each 500 pg/mL of TNFR1 was associated with -0.4 ± 0.2 point in SPPB (p = 0.0207) and each pg/mL in IL-10 with 0.2 ± 0.1 point in MoCA (p = 0.0475). In late-agers, no significant correlation was found between any of the inflammatory markers and functional outcomes. CONCLUSION: In early-agers with frailty and more co-morbidities, the inflammatory markers CRP, TNF-α, TNFR1, and TNFR2 were associated with grip strength, TNFR1 was correlated with physical performance, and IL-10 was correlated with cognitive function. However, in healthier late-agers, no relationship was found between inflammatory markers and muscle or cognitive function. Our findings suggest presence of a relationship between inflammation and loss of muscle performance and cognitive function in frailer and sicker individuals, regardless of their chronological age.

Abaloparatide followed by alendronate in women ≥80 years with osteoporosis: post hoc analysis of ACTIVExtend.

OBJECTIVE: Fracture risk increases with age, but few studies focus on persons ≥80 years. In the ACTIVE trial, treatment with abaloparatide for 18 months reduced osteoporotic fracture risk and increased bone mineral density. These effects were maintained with 24 months alendronate treatment in ACTIVExtend. We postulated that similar improvements in bone mineral density and safety would be demonstrated in women ≥80 years. METHODS: Post hoc analyses of bone mineral density and fracture incidence in women with osteoporosis at high risk of fracture ≥80 years from ACTIVExtend. RESULTS: In total, 56 women aged ≥80 years at ACTIVE baseline entered the ACTIVExtend study; 46 of these completed the study. Mean age was 83.3 years; other baseline characteristics were similar. At the end of ACTIVE, bone mineral density increased at all sites for abaloparatide versus placebo. Bone mineral density increased in parallel in both groups during alendronate therapy (19 to 43 months) in ACTIVExtend. At month 43, mean percent change in bone mineral density from baseline was 17.2% abaloparatide/alendronate versus 8.6% placebo/alendronate (P < 0.0001) at the lumbar spine, 5.3% abaloparatide/alendronate versus 3.0% placebo/alendronate (P = 0.024) at the total hip, and 4.6% abaloparatide/alendronate versus 3.1% placebo/alendronate (P = 0.044) at the femoral neck. Fracture incidence was low and did not differ significantly between groups. Sequential treatment with abaloparatide followed by alendronate was well tolerated; the proportion of participants reporting adverse events was similar between groups. CONCLUSIONS: Sequential treatment with abaloparatide followed by alendronate (43 months follow-up) in this small subgroup of ACTIVExtend participants suggests abaloparatide is well tolerated and effective in women aged ≥80 years. : Video Summary:http://links.lww.com/MENO/A618.

Video Summary:http://links.lww.com/MENO/A618.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.

Proceedings of the 2018 Santa Fe Bone Symposium: Advances in the Management of Osteoporosis.

The Santa Fe Bone Symposium is an annual meeting devoted to clinical applications of recent advances in skeletal research. The 19th Santa Fe Bone Symposium convened August 3-4, 2018, in Santa Fe, New Mexico, USA. Attendees included physicians of many specialties, fellows in training, advanced practice providers, clinical researchers, and bone density technologists. The format consisted of lectures, case presentations by endocrinology fellows, and panel discussions, with all involving extensive interactive discussions. Topics were diverse, including an evolutionary history of calcium homeostasis, osteoporosis treatment in the very old, optimizing outcomes with orthopedic surgery, microbiome and bone, new strategies for combination and sequential therapy of osteoporosis, exercise as medicine, manifestations of parathyroid hormone excess and deficiency, parathyroid hormone as a therapeutic agent, cell senescence and bone health, and managing patients outside clinical practice guidelines. The National Bone Health Alliance conducted a premeeting on development of fracture liaison services. A workshop was devoted to Bone Health TeleECHO (Bone Health Extension for Community Healthcare Outcomes), a strategy of ongoing medical education for healthcare professions to expand capacity to deliver best practice skeletal healthcare in underserved communities and reduce the osteoporosis treatment gap.

Radiographic Emphysema, Circulating Bone Biomarkers, and Progressive Bone Mineral Density Loss in Smokers.

RATIONALE: Osteoporosis is common in individuals with chronic obstructive pulmonary disease. Lung-specific factors, including radiographic emphysema, independently associate with low bone mineral density in cross-sectional smoking cohorts. However, factors associated with progressive bone loss in smokers are understudied and largely unknown. OBJECTIVES: To determine the relationship between radiographic emphysema, circulating bone metabolism markers, and pulmonary function and accelerated bone mineral density loss in smokers. METHODS: Two hundred and forty male and female current and former smokers, 40 years of age or older, underwent baseline and 2-year assessments of pulmonary function, computed tomography-assessed emphysema, dual X-ray absorptiometry-measured bone mineral density, and circulating bone metabolism biomarker levels (type I collagen C-telopeptide [CTX], amino-terminal propeptide of type I procollagen [P1NP]). The association of radiographic emphysema, bone metabolism biomarker levels, and pulmonary function with accelerated hip bone mineral density loss, defined by the 75th percentile of annual hip bone mineral density decline, was determined by logistic regression modeling with adjustment for age, sex, inhaled and intermittent steroid use, active smoking, body mass index, and the presence of baseline low hip bone mineral density. RESULTS: Of those participants with accelerated hip bone mineral density loss, 22% had moderate or severe visually assessed emphysema compared with 7.2% of smokers without accelerated bone mineral density decline. Moderate to severe visually assessed emphysema (odds ratio, 2.84; 95% confidence interval, 1.01-7.98 compared with trace/mild or no visually assessed emphysema) and the 75th percentile of CTX levels (odds ratio, 2.38; 95% confidence interval, 1.20-4.72 compared with CTX levels below the 75th percentile), a marker of bone resorption, were associated with accelerated hip bone mineral density decline after adjustment for covariates and the presence of baseline low hip bone mineral density. FEV1% predicted was not associated with accelerated bone mineral density decline after adjustment for covariates. Multivariate modeling showed moderate to severe visually assessed emphysema, and the 75th percentiles of CTX were independently associated with accelerated hip bone mineral density decline after adjustment for covariates. CONCLUSIONS: Emphysema and elevated markers of bone resorption are independently associated with progressive bone mineral density loss in smokers. These clinical markers may guide targeted bone mineral density screening and monitoring in smokers at highest risk.

Identifying Sarcopenia in Female Long-Term Care Residents: A Comparison of Current Guidelines.

OBJECTIVES: To establish the prevalence of sarcopenia in a long-term care population, assess agreement among different consensus sarcopenia diagnostic criteria, and examine agreement of a self-reported questionnaire with consensus guidelines. DESIGN: Cross-sectional secondary analysis. SETTING: Long-term care communities in the greater Pittsburgh, Pennsylvania, area. PARTICIPANTS: Women aged 65 and older (mean 83.6) undergoing eligibility screening for a fracture reduction trial (N = 141). MEASUREMENTS: We measured appendicular lean muscle mass using dual-energy X-ray absorptiometry. Hand grip strength and usual gait speed were also evaluated. Sarcopenia status was determined according to European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project criteria and the SARC-F questionnaire. RESULTS: Eleven participants were sarcopenic (7.8%) according to the EWGSOP criteria, six (4.3%) according to FNIH conservative cut-point guidelines, and 32.6% (n = 46) according to FNIH intermediate cut-points. Only 2 of 141 participants met criteria for sarcopenia according to all three guidelines. Sarcopenia was identified in 30 (21.3%) participants according to the SARC-F questionnaire. Sensitivity of the SARC-F with consensus panel definitions ranged from 18.2% to 33.3%. Specificity ranged from 78.7% to 81.1%. CONCLUSION: Current consensus criteria from the EWGSOP and FNIH Sarcopenia Project do not agree and have little overlap in older female long-term care residents. The SARC-F questionnaire is a simple tool that could be implemented in long-term care, but it has low sensitivity compared with current consensus guidelines in the identification of sarcopenic individuals.

Inflammatory Markers and Frailty in Long-Term Care Residents.

OBJECTIVES: To determine whether proinflammatory biomarkers are associated with frailty assessed according to functional status, mobility, mental health, and falls over 24 months. DESIGN: Secondary analysis of a 2-year double-blind clinical trial for osteoporosis. SETTING: Nursing homes and assisted living facilities. PARTICIPANTS: Women aged 65 and older with osteoporosis in long-term care (LTC) (N = 178). MEASUREMENTS: Baseline serum concentrations of proinflammatory cytokines and soluble receptors (high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNFα) and its two receptors (TNFα-R1 and TNFα-R2), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), IL-10), functional status assessed according to activities of daily living, the Nursing Home Physical Performance Test, gait speed, cognitive status, mental health, and falls. RESULTS: At baseline, older age was moderately associated with higher serum concentrations of hs-CRP (correlation coefficient (r) = 0.22), TNFα-R1 (r = 0.36), TNFα-R2 (r = 0.34), and IL-10 (r = 0.16) (all P < .05). Frail participants had significantly higher hs-CRP, TNFα-R1, TNFα-R2, IL-6, and IL-6-sR levels (all P < .05) than those nonfrail participants. Higher baseline hs-CRP and IL-6 levels were associated with worse physical performance and gait speed at 12 months independent of age, zoledronic acid use, and comorbidity (|r| = 0.25-0.30; all P < .05). Inflammatory markers were not significantly associated with incident falls. CONCLUSIONS: Higher proinflammatory biomarker levels are associated with frailty and poorer function and mobility in older women residing in LTC facilities.

Non-tricyclic and Non-selective Serotonin Reuptake Inhibitor Antidepressants and Recurrent Falls in Frail Older Women.

OBJECTIVE: To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. METHODS: This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. RESULTS: At least 15% of women experienced recurrent falls between 0-6 and 6-12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01-4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24-6.01). CONCLUSIONS: Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women.

Risedronate may preserve bone microarchitecture in breast cancer survivors on aromatase inhibitors: A randomized, controlled clinical trial.

UNLABELLED: This study provides preliminary evidence that risedronate not only preserves BMD but may also attenuate the loss of bone microarchitecture over 2years during a time of accelerated bone loss in post-menopausal breast cancer survivors on aromatase inhibitors. INTRODUCTION: Accelerated bone loss and elevated fracture risk are associated with the use of aromatase inhibitors (AIs) in women with breast cancer. We previously reported that the oral bisphosphonate, risedronate, can maintain bone mineral density (BMD) in the hip and spine over 2-years in post-menopausal breast cancer survivors on AIs. In this study, we examined whether oral bisphosphonates can also preserve bone microarchitecture as measured by the trabecular bone score (TBS) in this population. METHODS: This 2-year randomized, double-blind, placebo-controlled trial included postmenopausal women over age 55 with breast cancer on an AI who had low bone mass. Participants provided informed consent and were randomized to risedronate 35mg once weekly or placebo. We examined 12- and 24-month changes in spine TBS, analyzed using linear mixed models. RESULTS: One-hundred and nine women with a mean age of 70.5years were included in the analysis. In the placebo group, BMD declined at the spine and hip over the 24-month period but was preserved in the active treatment group (data previously reported). TBS declined in the placebo group by -2.1% and -2.3% at 12- and 24-months, respectively (p<0.005). The TBS percent change in bisphosphonate-treated patients was -0.9% and -1.3% at 12 and 24-months but did not reach statistical significance (p=0.24 and 0.14). The 12- and 24-month between-group differences were 0.9 (p=0.38) and 0.8 (p=0.44) percentage points. TBS change correlated with spine BMD changes in the placebo group at 12- and 24-months (r=0.33 and 0.34, p<0.01) but not in the active treatment group. CONCLUSION: The oral bisphosphonate risedronate preserves BMD and may attenuate loss of bone microarchitecture over 2years during a time of accelerated bone loss in breast cancer survivors on AIs, but more definitive evidence is needed.

Cost-Effectiveness of Osteoporosis Screening Strategies for Men.

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual-level state-transition cost-effectiveness model with a lifetime time horizon to identify the cost-effectiveness of different osteoporosis screening strategies for US men involving various screening tests (dual-energy X-ray absorptiometry [DXA]; the Osteoporosis Self-Assessment Tool [OST]; or a fracture risk assessment strategy using age, femoral neck bone mineral density [BMD], and Vertebral Fracture Assessment [VFA]); screening initiation ages (50, 60, 70, or 80 years); and repeat screening intervals (5 years or 10 years). In base-case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was "dominated" by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost-effective in base-case analyses and one-way sensitivity analyses when assuming willingness-to-pay of $50,000/quality-adjusted life-year (QALY) or $100,000/QALY included screening initiation at age 50 years with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 years with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 years with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for US men to initiate routine screening at age 50 or 60 years would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost-effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. © 2016 American Society for Bone and Mineral Research.

Assessing the Effects of Teriparatide Treatment on Bone Mineral Density, Bone Microarchitecture, and Bone Strength.

BACKGROUND: To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans. METHODS: In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 µg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety. RESULTS: Thirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed. CONCLUSIONS: High-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Vertebral fractures and trabecular microstructure in men with prostate cancer on androgen deprivation therapy.

Androgen deprivation therapy (ADT), a treatment for prostate cancer, is associated with bone loss and fractures. Dual-energy X-ray absorptiometry (DXA)-measured bone mineral density does not assess vertebral fractures (VF). High-resolution micro-magnetic resonance imaging (HR-MRI) assesses bone microarchitecture and provides structural information. To determine if VF identification increased the diagnosis of osteoporosis beyond DXA and if HR-MRI demonstrated skeletal deterioration in men with VF, we cross-sectionally studied 137 men aged ≥ 60 years with nonmetastatic prostate cancer on ADT for ≥ 6 months. Vertebral fracture assessment (VFA) by DXA was confirmed with X-rays. HR-MRI of the wrist included bone volume to total volume (BV/TV), surface density (trabecular plates), surface/curve ratio (plates/rods), and erosion index (higher depicts deterioration). VF were found in 37% of men; the majority were unknown. Seven percent of participants were classified as osteoporotic by hip or spine DXA. Thirty-seven percent of men without osteoporosis by DXA had VF identified, suggesting that 90% of patients with clinical osteoporosis would have been misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV, surface density, and spine, hip, and wrist DXA were lower, and erosion index was higher in men with moderate-severe VF compared with lesser grades (all p < 0.05). By unadjusted ROC analysis, the addition of HR-MRI to DXA at the spine, hip, and femoral neck added substantially (AUC increased 0.831 to 0.902, p < 0.05) to prediction of moderate-severe vertebral fracture. HR-MRI indices were associated with spine, hip, and wrist DXA measures (p < 0.01). Longer duration of ADT was associated with lower BV/TV, surface density, and surface/curve ratio (p < 0.05). ADT for men with prostate cancer is associated with silent VF. DXA alone leads to misclassifications of osteoporosis, which can be avoided by VF assessment. HR-MRI provides a novel technique to assess deterioration of structural integrity in men with VF and adds micro-structural information.

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment.

INTRODUCTION: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. METHODS: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. RESULTS: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated. CONCLUSIONS: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less.

Heel ultrasound can assess maintenance of bone mass in women with breast cancer.

Postmenopausal women with early stage breast cancer are at increased risk for bone loss and fractures. Bisphosphonates can prevent bone loss, but little data are available on changes in bone mass assessed by heel quantitative ultrasound (QUS). Our objectives were to determine if (1) heel QUS would provide a reliable and accessible method for evaluation of changes in bone mass in women with breast cancer when compared with the current standard of bone mass measurement, dual-energy X-ray absorptiometry (DXA) and (2) oral risedronate could affect these changes. Eighty-six newly postmenopausal (up to 8 yr) women with nonmetastatic breast cancer were randomized to risedronate, 35 mg once weekly or placebo. Outcomes were changes in heel QUS bone mass measurements and conventional DXA-derived bone mineral density (BMD). Over 2 yr, bone mass assessed by heel QUS remained stable in women on risedronate, whereas women on placebo had a 5.2% decrease (p ≤ 0.05) in heel QUS bone mass. Both total hip BMD and femoral neck BMD assessed by DXA decreased by 1.6% (p ≤ 0.05) in the placebo group and remained stable with risedronate. Spine BMD remained stable in both groups. Heel QUS was moderately associated with BMD measured by DXA at the total hip (r=0.50), femoral neck (r=0.40), and spine (r=0.46) at baseline (all p ≤ 0.001). In conclusion, risedronate helps to maintain skeletal integrity as assessed by heel QUS for women with early stage breast cancer. Heel QUS is associated with DXA-derived BMD at other major axial sites and may be used to follow skeletal health and bone mass changes in these women.

Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW).

INTRODUCTION: Greater awareness of the relationship between co-morbidities and fracture risk may improve fracture-prediction algorithms such as FRAX. MATERIALS AND METHODS: We used a large, multinational cohort study (GLOW) to investigate the effect of co-morbidities on fracture risk. Women completed a baseline questionnaire detailing past medical history, including co-morbidity history and fracture. They were re-contacted annually to determine incident clinical fractures. A co-morbidity index, defined as number of baseline co-morbidities, was derived. The effect of adding the co-morbidity index to FRAX risk factors on fracture prevention was examined using chi-squared tests, the May-Hosmer test, c index and comparison of predicted versus observed fracture rates. RESULTS: Of 52,960 women with follow-up data, enrolled between October 2006 and February 2008, 3224 (6.1%) sustained an incident fracture over 2 years. All recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson's disease (age-adjusted hazard ratio [HR]: 2.2; 95% CI: 1.6-3.1; P<0.001). Co-morbidities that contributed most to fracture prediction in a Cox regression model with FRAX risk factors as additional predictors were: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, osteoarthritis, and heart disease. CONCLUSION: Co-morbidities, as captured in a co-morbidity index, contributed significantly to fracture risk in this study population. Parkinson's disease carried a particularly high risk of fracture; and increasing co-morbidity index was associated with increasing fracture risk. Addition of co-morbidity index to FRAX risk factors improved fracture prediction.

Predictors of treatment with osteoporosis medications after recent fragility fractures in a multinational cohort of postmenopausal women.

OBJECTIVES: To determine the proportion of untreated women who reported receiving treatment after incident fracture and to identify factors that predict treatment across an international spectrum of individuals. DESIGN: Prospective observational study. Self-administered questionnaires were mailed at baseline and 1 year. SETTING: Multinational cohort of noninstitutionalized women recruited from 723 primary physician practices in 10 countries. PARTICIPANTS: Sixty thousand three hundred ninety-three postmenopausal women aged 55 and older were recruited with a 2:1 oversampling of women aged 65 and older. MEASUREMENTS: Data collected included participant demographics, medical history, fracture occurrence, medications, and risk factors for fracture. Anti-osteoporosis medications (AOMs) included estrogen, selective estrogen receptor modulators, bisphosphonates, calcitonin, parathyroid hormone, and strontium. RESULTS: After the first year of follow-up, 1,075 women reported an incident fracture. Of these, 17% had started AOM, including 15% of those with a single fracture and 35% with multiple fractures. Predictors of treatment included baseline calcium use (P = .01), baseline diagnosis of osteoporosis (P < .001), and fracture type (P < .001). In multivariable analysis, women taking calcium supplements at baseline (odds ratio (OR) = 1.67) and with a baseline diagnosis of osteoporosis (OR = 2.55) were more likely to be taking AOM. Hip fracture (OR = 2.61), spine fracture (OR = 6.61), and multiple fractures (OR = 3.79) were associated with AOM treatment. Age, global region, and use of high-risk medications were not associated with treatment. CONCLUSION: More than 80% of older women with new fractures were not treated, despite the availability of AOM. Important factors associated with treatment in this international cohort included diagnosis of osteoporosis before the incident fracture, spine fracture, and to a lesser degree, hip fracture.

FRAX or fiction: determining optimal screening strategies for treatment of osteoporosis in residents in long-term care facilities.

OBJECTIVES: To examine screening strategies for osteoporosis and fractures for treatment of long-term care residents. DESIGN: Cross-sectional analysis to examine screening strategies for treatment. SETTING: Assisted living and skilled care facilities. PARTICIPANTS: Two hundred two frail women aged 65 and older (mean 85), excluding those receiving bisphosphonates. MEASUREMENTS: Clinical fractures of the hip or spine (Clin Fx); Clin Fx or bone mineral density (BMD); Clin Fx, BMD, or vertebral fractures (VF) assessed according to dual-energy X-ray absorptiometry-based vertebral fracture assessments; fracture risk algorithm using femoral neck BMD (FRAX-FN); fracture risk algorithm using body mass index (FRAX-BMI); or Clin Fx or heel ultrasound (heel US). RESULTS: Treatment eligibility ranged from 17% (Clin Fx) to 98% (FRAX-BMI). VFs were found in 47%, 74% of which were silent. Criteria with Clin Fx, BMD, or VF identified 73% of study participants for treatment. FRAX-FN suggested treatment in 81% but would have missed approximately 10% of individuals with silent VFs. Clin Fx or heel US suggested that 39% of participants were eligible for treatment. CONCLUSION: Long-term care residents eligible for osteoporosis treatment ranged from fewer than 20% to roughly all residents depending on screening criteria. VFs are common and identify a subset of residents missed by conventional BMD scans or FRAX-FN. A reasonable clinical approach could consider treatment for those with Clin Fx of the hip or spine, radiological evidence of a VF, or osteoporosis according to BMD classification. Prospective studies are needed to determine optimal screening strategies for treatment in this cohort.

Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women.

BACKGROUND: The best strategies to screen postmenopausal women for osteoporosis are not clear. OBJECTIVE: To identify the cost-effectiveness of various screening strategies. DESIGN: Individual-level state-transition cost-effectiveness model. DATA SOURCES: Published literature. TARGET POPULATION: U.S. women aged 55 years or older. TIME HORIZON: Lifetime. PERSPECTIVE: Payer. INTERVENTION: Screening strategies composed of alternative tests (central dual-energy x-ray absorptiometry [DXA], calcaneal quantitative ultrasonography [QUS], and the Simple Calculated Osteoporosis Risk Estimation [SCORE] tool) initiation ages, treatment thresholds, and rescreening intervals. Oral bisphosphonate treatment was assumed, with a base-case adherence rate of 50% and a 5-year on/off treatment pattern. OUTCOME MEASURES: Incremental cost-effectiveness ratios (2010 U.S. dollars per quality-adjusted life-year [QALY] gained). RESULTS OF BASE-CASE ANALYSIS: At all evaluated ages, screening was superior to not screening. In general, quality-adjusted life-days gained with screening tended to increase with age. At all initiation ages, the best strategy with an incremental cost-effectiveness ratio (ICER) of less than $50,000 per QALY was DXA screening with a T-score threshold of -2.5 or less for treatment and with follow-up screening every 5 years. Across screening initiation ages, the best strategy with an ICER less than $50,000 per QALY was initiation of screening at age 55 years by using DXA -2.5 with rescreening every 5 years. The best strategy with an ICER less than $100,000 per QALY was initiation of screening at age 55 years by using DXA with a T-score threshold of -2.0 or less for treatment and then rescreening every 10 years. No other strategy that involved treatment of women with osteopenia had an ICER less than $100,000 per QALY. Many other strategies, including strategies with SCORE or QUS prescreening, were also cost-effective, and in general the differences in effectiveness and costs between evaluated strategies was small. RESULTS OF SENSITIVITY ANALYSIS: Probabilistic sensitivity analysis did not reveal a consistently superior strategy. LIMITATIONS: Data were primarily from white women. Screening initiation at ages younger than 55 years were not examined. Only osteoporotic fractures of the hip, vertebrae, and wrist were modeled. CONCLUSION: Many strategies for postmenopausal osteoporosis screening are effective and cost-effective, including strategies involving screening initiation at age 55 years. No strategy substantially outperforms another. PRIMARY FUNDING SOURCE: National Center for Research Resources.

Vertebral fractures and the misclassification of osteoporosis in men with prostate cancer.

Androgen deprivation therapy (ADT) has become the cornerstone of treatment for both advanced and nonmetastatic prostate cancer. The presence of a nontraumatic vertebral fracture (VF) identifies a patient who has clinical osteoporosis. Vertebral fracture analysis (VFA), a dual-energy X-ray absorptiometry (DXA)-based technology identifies VFs in conjunction with a standard bone mineral density (BMD) examination. The objective of this study was to determine if VFA would increase the diagnosis of osteoporosis in men with prostate cancer on ADT. One hundred sixteen men aged ≥ 60yrs with nonmetastatic prostate cancer receiving ADT for ≥ 6mos underwent DXA of the spine, hip, and 1/3 distal radius, VFA, and conventional vertebral X-rays. Approximately 40% of the men had clinically defined osteoporosis. The use of conventional DXA criteria (spine and hip) alone resulted in the misdiagnosis of approx 75% of patients. VFA and addition of the 1/3 distal radius site performed by DXA both increased the rate of diagnosis and reduced the misclassification of osteoporosis in men with prostate cancer, compared with conventional DXA criteria alone. Analysis indicated that VFA assessment of mild, moderate, and severe fractures from all readable vertebrae (T5-L4) had a kappa statistic, sensitivity, and specificity of 0.92, 100%, and 95%, respectively, with semiquantitative radiography. Men with prostate cancer on ADT should be screened for osteoporosis at the initiation of therapy, and evaluation should include DXA of the 1/3 distal radius in addition to the spine and hip, as well as evaluation for VFs.