Nonspine Fractures Research Articles

Pain and falls and fractures in community-dwelling older men.

Pain may reduce stability and increase falls and subsequent fractures in older men. To examine the association between joint pain and any pain with falls, hip and non-spine fractures in older community-dwelling men. A cohort study. Analyses included 5,993 community-dwelling men aged ≥65 years from the MrOS cohort. Pain at hip, knee and elsewhere (any) was assessed by self-report. Men reported falls via questionnaires mailed 3× per year during the year following the baseline visit. Fractures were verified centrally. Mean follow-up time for fractures was 9.7 (SD 3.1) years. Logistic regression models estimated likelihood of falls and proportional hazards models estimated risk of fractures. Models were adjusted for age, BMI, race, smoking, alcohol use, medications use, co-morbidities and arthritis; fracture models additionally adjusted for bone mineral density. One quarter (25%, n = 1,519) reported ≥1 fall; 710 reported ≥2 falls in the year after baseline. In multivariate models, baseline pain at hip, knee or any pain increased likelihood of ≥1 fall and ≥2 falls over the following year. For example, knee pain increased likelihood of ≥1 fall (odds ratio, OR 1.44; 95% confidence interval, CI 1.25-1.65) and ≥2 falls (OR 1.75; 95% CI 1.46-2.10). During follow-up, 936 (15.6%) men suffered a non-spine fracture (n = 217, 3.6% hip). In multivariate models, baseline pain was not associated with incident hip or non-spine fractures. Any pain, knee pain and hip pain were each strong independent risk factors for falls in older men. Increased risk of falls did not translate into an increased risk of fractures.

Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD Bone Study.

In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown. The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men. This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed every 2-4 months at clinic visits, were modeled as time-varying covariates in proportional hazards models for occurrence of first non-spine fracture. We studied a total of 6865 participants in ACCORD BONE. Main outcome measures were centrally adjudicated non-spine fracture. Average age was 62.4 (SD, 6.6) years; average duration of diabetes was 11.1 (SD, 7.8) years. Rosiglitazone was used by 74% and pioglitazone by 13% of participants. During a mean follow-up of 4.8 (SD, 1.5) years, 262 men and 287 women experienced at least one non-spine fracture. The fracture rate was higher in women with 1-2 years of TZD use (hazard ratio [HR] = 2.32; 95% confidence interval [CI], 1.49, 3.62) or >2 years of TZD use (HR = 2.01; 95% CI, 1.35, 2.98), compared with no use. The fracture rate was reduced in women who had discontinued TZD use for 1-2 years (HR = 0.57; 95% CI, 0.35, 0.92) or > 2 years (HR = 0.42; 95% CI, 0.24, 0.74) compared with current users. TZD use and discontinuation were not associated with non-spine fractures in men. TZD use was associated with increased non-spine fractures in women, but not men, with type 2 diabetes. When women discontinued TZD use, the fracture effects were attenuated.

Subclinical Hyperthyroidism Is Associated with Increased Risks of Hip Fractures, Fractures at Any Site, Nonspine Fractures, and Clinical Spine Fractures in the Largest Meta-analysis to Date

Subclinical Hyperthyroidism Is Associated with Increased Risks of Hip Fractures, Fractures at Any Site, Nonspine Fractures, and Clinical Spine Fractures in the Largest Meta-analysis to Date

Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Efficacy, effectiveness and side effects of medications used to prevent fractures.

There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long-term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit-risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and 'drug holidays' should be considered at this time. Further studies are needed to guide clinical practice in this area.

MP71-17 LOWER URINARY TRACT SYMPTOMS AND RISK OF INCIDENT NON-SPINE FRACTURE AMONG OLDER US MEN

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Evaluation and Symptoms1 Apr 2015MP71-17 LOWER URINARY TRACT SYMPTOMS AND RISK OF INCIDENT NON-SPINE FRACTURE AMONG OLDER US MEN Lynn Marshall, Jodi Lapidus, Jack Wiedrick, Kathleen Holton, Elizabeth Barrett Connor, and J. Kellogg Parsons Lynn MarshallLynn Marshall More articles by this author , Jodi LapidusJodi Lapidus More articles by this author , Jack WiedrickJack Wiedrick More articles by this author , Kathleen HoltonKathleen Holton More articles by this author , Elizabeth Barrett ConnorElizabeth Barrett Connor More articles by this author , and J. Kellogg ParsonsJ. Kellogg Parsons More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2630AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lower urinary tract symptoms (LUTS) are associated with an increased risk of falls in older men. Falls are a strong risk factor for fractures. Therefore, we assessed associations of LUTS severity with fracture risk in community dwelling U.S. men ages 65 years or older METHODS We conducted a prospective study in the Osteoporotic Fractures in Men (MrOS) cohort. The American Urological Association Symptom Index (AUA-SI), prescription medications for LUTS, hip bone mineral density (BMD), and other traditional fracture risk factors were recorded at baseline (2000-02) and every two years thereafter for a total of three assessments. LUTS severity was categorized from the AUA-SI as mild (0-7 points), moderate (8-19 points), or severe (>19 points). Men were followed from the date of their baseline visit to date of first non-spine fracture, death, voluntary withdrawal, or third study visit (2007-09), whichever occurred first. Associations of LUTS severity with fracture rate were estimated with hazard ratios (HR) and 95% confidence intervals (CI) from extended proportional hazards regression with age as the timescale. Models accounted for competing risks from death. RESULTS Among 5,989 men with baseline AUA-SI score and hip BMD measures, 576 incident non-spine fractures occurred during 35,947 person-years of follow-up. Crude fracture rates per 1000 person-years in each LUTS severity category did not differ statistically among men who used prescription LUTS medications and non-users (Figure 1). Adjusted for age and compared to mild LUTS, HR (95% CI) were 1.0 (0.9, 1.2) for moderate LUTS and 1.3 (1.0, 1.7) for severe LUTS, respectively. Further adjustment for hip BMD, falls in the past year, and prevalent fracture before baseline attenuated the HR to 0.9 (0.8, 1.1) for moderate and 1.1 (0.8, 1.4) for severe LUTS. CONCLUSIONS In this cohort of older US men, the association of severe LUTS with higher rate of incident non-spine fracture was explained by traditional fracture risk factors. Older men with LUTS may benefit from screening and counseling about their fracture risk factors. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e918-e919 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lynn Marshall More articles by this author Jodi Lapidus More articles by this author Jack Wiedrick More articles by this author Kathleen Holton More articles by this author Elizabeth Barrett Connor More articles by this author J. Kellogg Parsons More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The effect of osteoporotic treatment on the functional outcome, re-fracture rate, quality of life and mortality in patients with hip fractures: A prospective functional and clinical outcome study on 520 patients

Numerous high quality studies have shown the positive effects of various osteoporotic medical treatment regimens on bone mass and on the reduction of risk for new spinal, hip and non-spinal fractures in osteoporotic patients. However, the effect of osteoporotic treatment on the functional and clinical outcome of patients who have sustained hip fractures and been treated surgically has not yet been addressed.Five hundred and twenty patients out of 611 who were admitted (2009–2011), operated on due to a hip fracture and completed their follow-up evaluations were included in this study. Data related to functional outcome scores, re-fracture rate, quality of life and mortality rate were prospectively recorded, analysed and correlated to osteoporotic medical treatment. There were 151 (25%) men and 369 (71%) women with a mean age of 80.7 years (range, 60 to 90 years). At a mean follow-up of 27.5 months (range, 24 to 36 months) a mortality rate of 23.6% at 2 years was recorded. Mean values of functional and quality of life scores were found to have progressively improved within two years after surgery. Seventy-eight (15%) patients were taking osteoporotic treatment before their hip fracture and 89 (17.1%) started afterwards. Osteoporotic treatment proved to be an important predictor of functional recovery (all p values<0.05), re-fracture rate (p=0.028) and quality of life (EQ-5D, all dimensions, p values<0.05). Osteoporotic treatment did not affect post-fracture mortality rates.Osteoporotic treatment taken before or initiated after fracture is a strong predictor of functional and clinical outcome in patients with hip fractures treated surgically.

Caudal lumbar vertebral fractures in California Quarter Horse and Thoroughbred racehorses.

To gain insight into the pathophysiology of equine lumbar vertebral fractures in racehorses. To characterise equine lumbar vertebral fractures in California racehorses. Retrospective case series and prospective case-control study. Racehorse post mortem reports and jockey injury reports were retrospectively reviewed. Vertebral specimens from 6 racehorses affected with lumbar vertebral fractures and 4 control racehorses subjected to euthanasia for nonspinal fracture were assessed using visual, radiographic, computed tomography and histological examinations. Lumbar vertebral fractures occurred in 38 Quarter Horse and 29 Thoroughbred racehorses over a 22 year period, primarily involving the 5th and/or 6th lumbar vertebrae (L5-L6; 87% of Quarter Horses and 48% of Thoroughbreds). Lumbar vertebral fractures were the third most common musculoskeletal cause of death in Quarter Horses and frequently involved a jockey injury. Lumbar vertebral specimens contained anatomical variations in the number of vertebrae, dorsal spinous processes and intertransverse articulations. Lumbar vertebral fractures examined in 6 racehorse specimens (5 Quarter Horses and one Thoroughbred) coursed obliquely in a cranioventral to caudodorsal direction across the adjacent L5-L6 vertebral endplates and intervertebral disc, although one case involved only one endplate. All cases had evidence of abnormalities on the ventral aspect of the vertebral bodies consistent with pre-existing, maladaptive pathology. Lumbar vertebral fractures occur in racehorses with pre-existing pathology at the L5-L6 vertebral junction that is likely predisposes horses to catastrophic fracture. Knowledge of these findings should encourage assessment of the lumbar vertebrae, therefore increasing detection of mild vertebral injuries and preventing catastrophic racehorse and associated jockey injuries.

Hypoxia during sleep and the risk of falls and fractures in older men: the Osteoporotic Fractures in Men Sleep Study.

To test the hypothesis that low arterial oxygen saturation during sleep is associated with a greater risk of falls and fractures. Prospective cohort study. Six U.S. clinical centers. Men aged 67 and older (N = 2,911). The primary exposure measure was percentage of sleep time with arterial oxygen saturation less than 90% measured using polysomnography. The main outcome measures were incident falls within 1 year and incident nonspine fractures over an average follow-up of 6.8 years. Men with 10% or more of sleep time at an arterial oxygen saturation of less than 90% were older, reported more comorbidities, had poorer physical function, and were more likely to have sleep disordered breathing than men with less than 10% sleep time at an arterial oxygen saturation of less than 90%. After multivariate adjustment, men with 10% or more of sleep time with arterial oxygen saturation of less than 90% had a greater risk of having one or more falls (relative risk (RR) = 1.25, 95% confidence interval (CI) = 1.04-1.51) and two or more falls (RR = 1.43, 95% CI = 1.06-1.92) than those with less than 10% of sleep time with less than 90% arterial oxygen saturation. Men with greater percentage of sleep time with arterial oxygen saturation less than 90% had a 30% to 40% greater risk of nonspine fracture than those with normal nocturnal oxygen saturation in models adjusting for sleep disordered breathing. Hypoxia during sleep may be a risk factor for falls and fractures in older men. Interventions aimed at decreasing nocturnal hypoxia may decrease falls and fractures.

Intensive blood pressure control, falls, and fractures in patients with type 2 diabetes: the ACCORD trial.

There are few rigorous studies to confirm or refute the commonly cited concern that control of blood pressure to lower thresholds may result in an increased risk of falls and fractures. To compare falls and fractures in participants with type 2 diabetes in the intensive (targeting a systolic blood pressure of < 120 mmHg) and standard (targeting a systolic blood pressure of < 140 mmHg) blood pressure control arms of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial (N = 4,733). A subset of 3,099 participants self-reported annually on the occurrence of falls and non-spine fractures. Fractures were centrally adjudicated. The incidence of falls in the two treatment groups was compared using a random-effects negative binomial model, and fracture risk was compared using Cox proportional hazards models. At enrollment in both groups, the mean age was 62 years, 44% were women, 25% were Black, and mean blood pressure was 138/75 mmHg. During follow-up, all classes of medications, particularly thiazide diuretics, were more commonly prescribed in the intensive group. After 1 year of follow-up, the mean systolic blood pressure was 133 ± 15 mmHg in the standard group and 119 ± 14 mmHg in the intensive group. The adjusted rate of falls did not differ in the intensive and standard groups (62.2/100 person-years vs. 74.1/100 person-years, RR = 0.84, 95% CI 0.54-1.29, p = 0.43). The risk of non-spine fractures was nonsignificantly lower in the intensive than in the standard blood pressure group (HR 0.79, 95% CI 0.62-1.01, p = 0.06). We conclude that intensive antihypertensive treatment that lowered mean systolic blood pressure to below 120 mmHg was not associated with an increased risk of falls or non-spine fractures in patients age 40 to 79 years with type 2 diabetes.

Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis.

Data on the association between subclinical thyroid dysfunction and fractures conflict. To assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts. Search of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction. Two physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes. One reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies. The 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%). Selective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies. Subclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed. Swiss National Science Foundation.

Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study.

Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established. To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years. The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years. Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover. During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]). Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended. clinicaltrials.gov Identifier: NCT00398931.

Hyperkyphosis, Kyphosis Progression, and Risk of Non-Spine Fractures in Older Community Dwelling Women: The Study of Osteoporotic Fractures (SOF)

While accentuated kyphosis is associated with osteoporosis, it is unknown whether it increases risk of future fractures, independent of bone mineral density (BMD) and vertebral fractures. We examined the associations of baseline Cobb angle kyphosis and 15 year change in kyphosis with incident non-spine fractures using data from the Study of Osteoporotic Fractures. A total of 994 predominantly white women, aged 65 or older, were randomly sampled from 9704 original participants to have repeated Cobb angle measurements of kyphosis measured from lateral spine radiographs at baseline and an average of 15 years later. Non-spine fractures, confirmed by radiographic report, were assessed every 4 months for up to 21.3 years. Compared with women in the lower three quartiles of kyphosis, women with kyphosis greater than 53° (top quartile) had a 50% increased risk of non-spine fracture (95% CI, 1.10-2.06 after adjusting for BMD, prevalent vertebral fractures, prior history of fractures, and other fracture risk factors. Cobb angle kyphosis progressed an average of 7° (SD = 6.8) over 15 years. Per 1 SD increase in kyphosis change, there was a multivariable adjusted 28% increased risk of fracture (95% CI, 1.06-1.55) that was attenuated by further adjustment for baseline BMD (HR per SD increase in kyphosis change, 1.19; 95% CI 0.99-1.44). Greater kyphosis is associated with an elevated non-spine fracture risk independent of traditional fracture risk factors in older women. Furthermore, worsening kyphosis is also associated with increased fracture risk that is partially mediated by low baseline BMD that itself is a risk factor for kyphosis progression. These results suggest that randomized controlled fracture intervention trials should consider implementing kyphosis measures to the following: (1) further study kyphosis and kyphosis change as an additional fracture risk factor; and (2) test whether therapies may improve or delay its progression.

Prediction Models of Prevalent Radiographic Vertebral Fractures Among Older Women

It is unknown how well prediction models incorporating multiple risk factors identify women with radiographic prevalent vertebral fracture (PVFx) compared with simpler models and what their value might be in clinical practice to select older women for lateral spine imaging. We compared 4 regression models for predicting PVFx in women aged 68 y and older enrolled in the Study of Osteoporotic Fractures with a femoral neck T-score ≤ −1.0, using area under receiving operator characteristic curves (AUROC) and a net reclassification index. The AUROC for a model with age, femoral neck bone mineral density, historical height loss (HHL), prior nonspine fracture, body mass index, back pain, and grip strength was only minimally better than that of a more parsimonious model with age, femoral neck bone mineral density, and historical height loss (AUROC 0.689 vs 0.679, p values for difference in 5 bootstrapped samples <0.001–0.35). The prevalence of PVFx among this older population of Caucasian women remained more than 20% even when women with low probability of PVFx, as estimated by the prediction models, were included in the screened population. These results suggest that lateral spine imaging is appropriate to consider for all Caucasian women aged 70 y and older with low bone mass to identify those with PVFx.

Impact of androgen suppression and zoledronic acid on bone mineral density and fractures in the Trans‐Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR) randomized controlled trial for locally advanced prostate cancer

To study the influence of adjuvant androgen suppression and bisphosphonates on incident vertebral and non-spinal fracture rates and bone mineral density (BMD) in men with locally advanced prostate cancer. Between 2003 and 2007, 1071 men with locally advanced prostate cancer were randomly allocated, using a 2 × 2 trial design, to 6 months i.m. leuprorelin (androgen suppression [AS]) before radiotherapy alone ± 12 months additional leuprorelin ± 18 months zoledronic acid (ZdA), commencing at randomization. The main endpoint was incident thoraco-lumbar vertebral fractures, which were assessed radiographically at randomization and at 3 years, then reassessed by centralized review. Subsidiary endpoints included incident non-spinal fractures, which were documented throughout follow-up, and BMD, which was measured in 222 subjects at baseline, 2 years and 4 years. Incident vertebral fractures at 3 years were observed in 132 subjects. Their occurrence was not increased by 18 months' AS, nor reduced by ZdA. Incident non-spinal fractures occurred in 72 subjects and were significantly related to AS duration but not to ZdA. Osteopenia and osteoporosis prevalence rates at baseline were 23.4 and 1.4%, respectively, at the hip. Treatment for 6 and 18 months with AS caused significant reductions in hip BMD at 2 and 4 years (P < 0.01) and ZdA prevented these losses at both time points. In an AS-naïve population, 18 months of ZdA treatment prevented the sustained BMD losses caused by 18 months of AS treatment; however, the study power was insufficient to show that AS duration or ZdA influenced vertebral fracture rates.

Association of Serum Uric Acid and Incident Nonspine Fractures in Elderly Men: The Osteoporotic Fractures in Men (MrOS) Study

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD.

Imaging of Osteoporotic Fractures on XR, CT, and MR

The evaluation of skeletal health has progressed from diagnostic labeling (normal-low bone mass-osteoporosis) to quantifying future fracture risk. Thus, the recognition of prevalent and incident fractures has increased in importance because they influence risk assessment. Non-spinal osteoporotic fractures rarely pose diagnostic problems, although those of the proximal femur and pelvis may require computed tomography (CT) and/or magnetic resonance imaging for diagnosis. Spinal fractures remain a paradox. Whereas radiological diagnosis in general benefits increasingly from powerful diagnostic tools to examine disease, many osteoporotic spinal fractures are asymptomatic, and their recognition is often incidental to chest radiography or body CT. Moreover, there are no uniformly agreed criteria by which to decide if a vertebra is fractured. Lastly, it has become apparent that some osteoporosis treatments may themselves contribute to so-called atypical femoral fractures.

Prediction Models of Prevalent Radiographic Vertebral Fractures Among Older Men

No studies have compared how well different prediction models discriminate older men who have a radiographic prevalent vertebral fracture (PVFx) from those who do not. We used area under receiver operating characteristic curves and a net reclassification index to compare how well regression-derived prediction models and nonregression prediction tools identify PVFx among men age ≥65 yr with femoral neck T-score of −1.0 or less enrolled in the Osteoporotic Fractures in Men Study. The area under receiver operating characteristic for a model with age, bone mineral density, and historical height loss (HHL) was 0.682 compared with 0.692 for a complex model with age, bone mineral density, HHL, prior non-spine fracture, body mass index, back pain, grip strength, smoking, and glucocorticoid use (p values for difference in 5 bootstrapped samples 0.14–0.92). This complex model, using a cutpoint prevalence of 5%, correctly reclassified only a net 5.7% (p = 0.13) of men as having or not having a PVFx compared with a simple criteria list (age ≥ 80 yr, HHL >4 cm, or glucocorticoid use). In conclusion, simple criteria identify older men with PVFx and regression-based models. Future research to identify additional risk factors that more accurately identify older men with PVFx is needed.

The clinical utility of FRAX to discriminate fracture status in men and women with chronic kidney disease

We assessed the ability of the World Health Organization's fracture risk assessment tool (FRAX), bone mineral density (BMD), and age to discriminate fracture status in adults with pre-dialysis chronic kidney disease (CKD). In adults with CKD, FRAX was able to discriminate fracture status but performed no better than BMD alone. Patients with CKD are at increased risk for fracture but the best method to assess fracture risk is not known. We assessed the ability of the World Health Organization's FRAX, compared with BMD at the femoral neck (FN), and age to discriminate fracture status (prevalent clinical nonspine and/or morphometric vertebral) in men and women, 18 years and older with pre-dialysis CKD. Results are presented as area under receiver operator characteristic curves (AUC) with 95% confidence intervals (CI). We enrolled 353 subjects; mean age was 65 ± 14 years; weight was 79 ± 18 kg, and estimated glomerular filtration rate was 28 ml/min/1.73 m(2). About one third of the subjects had a prevalent clinical nonspine and/or morphometric vertebral fracture. FRAX was able to discriminate among those with prevalent clinical nonspine fractures (AUC, 0.72; 95% CI, 0.65-0.78), morphometric vertebral fractures (AUC, 0.66; 95% CI, 0.59-0.73), and any fracture (AUC, 0.71; 95% CI, 0.65-0.77). The discriminative ability of BMD at the FN alone was similar to FRAX for morphometric vertebral and any fractures; FRAX performed better than BMD for prevalent clinical nonspine fractures (AUC for BMD alone, 0.66; 95% CI, 0.60-0.73). Compared to FRAX, the AUC for age alone was lower for all fracture types. Among men and women with CKD, FRAX is able to discriminate fracture status but performs no better than BMD alone.

High hip fracture risk in men with severe aortic calcification: MrOS study

A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged ≥ 65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score. Total hip bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Incident nonspine fractures were centrally adjudicated. After adjustment for age, body mass index (BMI), total hip BMD, fall history, prior fracture, smoking status, comorbidities, race, and clinical center, the risk of nonspine fracture (n=805) was increased among men with higher AAC (hazard ratio [HR] quartile 4 [Q4] [AAC score ≥ 9] versus quartile 1 [Q1] [0-1], 1.36; 96% confidence interval [CI], 1.10-1.68). This association was due to an increased risk of hip fracture (n=178) among men with higher AAC (HR Q4 versus Q1, 2.33; 95% CI, 1.41-3.87). By contrast, the association between AAC and the risk of nonspine, nonhip fracture was weaker and not significant (HR Q4 versus Q1, 1.22; 95% CI, 0.96-1.55). The findings regarding higher AAC and increased risk of fracture were not altered in additional analyses accounting for degree of trauma, estimated glomerular filtration rate, presence of lumbar vertebral fractures (which may bias AAC assessment), preexisting cardiovascular disease, ankle brachial index, or competing risk of death. Thus, in this large cohort of elderly men, greater AAC was independently associated with an increased risk of hip fracture, but not with other nonspine fractures. These findings suggest that AAC assessment may be a useful method for identification of older men at high risk of hip fracture.