Quantitative ultrasound and dual-energy X-ray absorptiometry in the prediction of fragility fracture in men

Fragility fractures in men represent a major health problem, and this prompts a necessity for reliable tools for the identification of men at risk of fracture. In order to assess the ability of dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) in the prediction of fracture risk in men and whether their combination might be useful in a clinical setting, we studied 401 men (age range 45–82 years, mean 60.3±12.5), of whom 133 had osteoporotic fractures and 268 did not. In all subjects we measured bone mineral density at the lumbar spine (BMD-LS) and at the femur, calculating thereafter the standard femoral subregions: neck (BMD-FN), total hip (BMD-T), trochanter (BMD-TR), intertrochanter (BMD-ITR), and Wards triangle (BMD-W), by DXA. We also performed ultrasound parameters at the calcaneus: speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness, by Achilles plus, and at the phalanxes: amplitude dependent speed of sound (AD-SoS) and the parameters of the graphic trace: bone transmission time (BTT), fast wave amplitude (FWA), signal dynamic (SDy) and ultrasound bone profile index (UBPI), by Bone Profiler. All DXA and QUS parameters, apart from FWA, were significantly (P<0.001) lower in patients with a history of fracture. BMD at the proximal femur showed the best ability in discriminating men with or without fractures. QUS at the heel showed discriminatory ability significantly better than QUS at the fingers. By logistic regression analysis, adjusted for age and BMI, BMD-T showed the best association with fragility fracture [odds ratio (OR)=3.43, 95% confidence interval (CI)=2.47–4.77]. Among QUS parameters, the highest value of the OR was shown by stiffness (OR=3.18, CI=2.27–4.48). FWA and SDy were not associated with fragility fractures in men. If DXA and QUS were combined, the prediction of the OR of fragility fracture events in men increases; in fact Stiffness was able to increase the OR when added to BMD-LS (OR=5.44, CI=3.16–10.13) and BMD-T (OR=6.08, CI=2.63–14.27). SOS and BUA showed a similar pattern. AD-SoS improved the prediction of fracture only when combined with BMD-LS (OR=4.36, CI=1.99–9.57). If BMD-LS and BMD-FN or BMD-T were combined, the value of the OR increases (OR=4.59, CI=2.27–9.25 and OR=4.68, CI=2.24–9.76), respectively. Our study supports the effectiveness of QUS in the identification of osteoporotic fractures in men. QUS seems to play an independent and complementary role, with respect to DXA, in order to enhance the power for predicting osteoporotic fractures in men.     

Osteoporotic Fractures in the Brazilian Community-Dwelling Elderly: Prevalence and Risk Factors

The risk of osteoporotic fractures is known to vary among populations. There are no studies analyzing concomitantly clinical, densitometric, and lab risk factors in miscigenated community-dwelling population of Brazil. A total of 1007 elderly subjects (600 women and 407 men) from São Paulo, were evaluated using a questionnaire that included risk factors for osteoporotic fractures. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the hip and lumbar spine. Laboratory blood tests were also obtained. The prevalence of osteoporotic fractures was 13.2% (133 subjects), and the main fracture sites were distal forearm (6.0%), humerus (2.3%), femur (1.3%), and ribs (1.1%). Women had a higher prevalence (17.5%; 95% confidence interval [CI]: 14.6–20.6) than men (6.9%; 95% CI: 4.4–9.3) (p < 0.001). After adjusting for significant variables, logistic regression revealed that female gender (odds ratio [OR] = 2.7; 95% CI; 1.6–4.5; p < 0.001), current smoking (OR = 1.9; 95% CI: 1.2–3.3; p = 0.013), and the femoral neck T-score (OR = 0.7; 95% CI: 0.5–0.9; p = 0.001) remain significant risk factors for osteoporotic fractures in the community-dwelling elderly. Our findings identified that female gender, current smoking, and low hip BMD are independent risk factors for osteoporotic fractures.     

Different risk profiles for hip fractures and distal forearm fractures: A prospective study

In a prospective cohort of elderly persons, aged 70 years and over, we examined risk indicators for which data could be easily obtained, to construct risk profiles for hip fractures and distal forearm fractures. Participants lived independently, in apartment houses for the elderly or in homes for the elderly. At baseline, information was obtained in 2578 subjects on age, gender, residence, mobility and the frequency of going outdoors. Mobility was measured using a walking score ranging from 1 (not able to walk independently) to 3 (able to walk independently for a fair distance). During the study period (median duration 3.5 years, maximum 4 years) 106 participants sustained a hip fracture and 60 participants suffered a distal forearm fracture. Women compared with men, adjusted for age, had a higher risk of hip fracture (adjusted relative risk (RR)=2.4, 95% confidence interval (CI) 1.3–4.3) and distal forearm fracture (RR=3.7, 95% CI 1.5–9.2). Age, adjusted for gender, was related to hip fractures only: the relative risk of fracture for those in the highest age category (>85 years) was 9.5 (95% CI 4.3–21.2) compared with those in the lowest age category (70–75 years). Moderately impaired walking ability compared with normal walking ability, adjusted for age and gender, was associated with a higher risk of hip fracture (RR=1.8, 95% CI 1.2–2.7) but with a lower risk of distal forearm fracture (RR=0.4, 95% CI 0.2–0.8). The outdoor score, adjusted for age and gender, was associated with distal forearm fractures only: going outdoors less than once a week, compared with three times or more, was associated with a lower risk of fractures (RR=0.3, 95% CI 0.1–0.9). In those living in homes for the elderly the risk of hip fracture was higher compared with those living independently (RR=2.4, 95% CI 1.4–4.2), adjusted for age and gender. Risk profiles were constructed using stepwise Cox's proportional-hazards regression. The risk profile predicted probabilites of sustaining a hip fracture in a 4-year period ranging from 0.4% to 25.9%, and of distal forearm fractures ranging from 0.2% to 4.5%, depending on the subject's characteristics as defined by the risk indicators. We conclude that easily obtainable risk indicators can be used in the prediction of fractures and can discriminate among fracture types.     

Left-handedness as a risk factor for fractures

Left-handedness has been associated with increased fracture risk in a small number of previous studies. This study reports risks for fractures at the proximal humerus, distal forearm, pelvis, foot, and shaft of the tibia/fibula according to handedness in a case-control study conducted from October 1996 to May 2001 among members of Northern California Kaiser Permanente. Handedness was assessed by questionnaire for 2,841 cases and 2,192 controls, and subjects were categorized as left-handed, right-handed, ambidextrous, or forced to switch from the left to the right hand. Compared to right-handedness, left-handedness was most strongly associated with an increased risk for proximal humerus fractures (adjusted odds ratio (OR)=2.00, 95% confidence interval (CI) 1.33 to 3.01) and less definitively with fractures of the distal forearm (adjusted OR=1.28, 95% CI 0.92 to 1.80), foot (adjusted OR=1.17, 95% CI 0.82 to 1.65), and pelvis (adjusted OR=1.40, 95% CI 0.71 to 2.74). Ambidextrous individuals had elevated risks for fractures of the distal forearm (adjusted OR=2.99, 95% CI 1.42 to 6.30), foot (adjusted OR=2.59, 95% CI 1.13 to 5.97), shaft of the tibia/fibula (adjusted OR=3.91, 95% CI 1.01 to 15.17), and proximal humerus (adjusted OR=2.37, 95% CI 0.85 to 6.65) when compared with right-handed individuals. Those individuals forced to use the right hand demonstrated no increased risk for fractures at any site. These results suggest that handedness does influence fracture risk, but the reasons for this increased risk are unclear.     

Long-term mental distress, bone mineral density and non-vertebral fractures. The Tromsø Study

The purpose of this study was to examine, prospectively, the risk of non-vertebral fractures and low bone mineral density in a population-based cohort with respect to indicators of subjective mental distress. In 1979–1980 all males born 1925–1959 and all females born 1930–1959 living in Tromsø were invited (21,441; response rate, 78%). The same individuals were invited to the subsequent studies in 1986–1987 and 1994–1995 (74% attended the first two, and 71% attended all three surveys). Non-vertebral fractures were registered by linkage to the hospital X-ray register for the period 1988–1995, and forearm bone mineral density (BMD) was available in a subsample of 4,690 who had attended three times. Questions about mental distress (depression, insomnia and coping problems) were repeated three times and analyzed as cumulated exposure. Women who reported being depressed at two time points had an adjusted odds ratio (OR) =2.5 (95% confidence interval [CI] 1.3–4.9) for sustaining a non-vertebral fracture and OR=3.1 (95% CI 1.3–7.2) for sustaining an osteoporotic fracture, compared with those without depression on any occasion. The corresponding odds ratios for those with coping problems at two time points were slightly higher, whereas sleeping problems seem only to be weakly associated with non-vertebral fractures. The pattern of associations and the magnitude of OR estimates were mainly the same in women younger than 50 years and those 50 years and older. Women using nerve medicine and reporting depression twice had an odds ratio of 4.4 (95% CI 1.1–17.7) for sustaining a non-vertebral fracture, and those using nerve medicine and reporting coping problems twice had a corresponding OR 4.7 (95% CI 1.2–18.4). Among men no significant associations were found for either fracture type. No association was found between mean BMD and number of times reporting depression, insomnia or coping problems, in women or men. Long-term mental distress is associated with risk of all non-vertebral fractures and osteoporotic fractures in middle-aged women, but not in men. Mental distress itself seems to be more important than the use of nerve medicine.     

Prevalent Vertebral Fractures in Black Women and White Women

Vertebral fractures are the most common osteoporotic fracture. Hip and clinical fractures are less common in black women, but there is little information on vertebral fractures. We studied 7860 white and 472 black women ≥65 yr of age enrolled in the Study of Osteoporotic Fractures. Prevalent vertebral fractures were identified from lateral spine radiographs using vertebral morphometry and defined if any vertebral height ratio was >3 SD below race‐specific means for each vertebral level. Information on risk factors was obtained by questionnaire or examination. Lumbar spine, total hip, and femoral neck BMD and BMC were measured by DXA. The prevalence of vertebral fractures was 10.6% in black and 19.1% in white women. In age‐adjusted logistic regression models, a 1 SD decrease in femoral neck BMD was associated with 47% increased odds of fracture in black women (OR = 1.47; 95% CI, 1.12–1.94) and 80% increased odds in white women (OR = 1.80; 95% CI, 1.68–1.94; interaction p = 0.14). The overall lower odds of fracture among black women compared with white women was independent of femoral neck BMD and other risk factors (OR = 0.51; 95% CI, 0.37–0.72). However, the prevalence of vertebral fractures increased with increasing number of risk factors in both groups. The prevalence of vertebral fractures is lower in black compared with white women but increases with age, low BMD, and number of risk factors.     

Smoking and fracture risk: a meta-analysis

Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted -coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15–1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13–1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52–2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27–2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.     

Determinants of incidence of osteoporotic fractures in the female Spanish population older than 50

It is well known that the adoption of preventive measures for osteoporosis may contribute to minimizing its impact as a result of bone fractures. However, there are well-recognized risk factors involved in the onset of osteoporosis that are not possible to modify. Better knowledge of these non-modifiable factors could aid prevention in subjects at high risk of fractures. The aim of this study was to evaluate the likely association between gynecological, reproductive and family history of hip fracture with the incidence of vertebral and nonvertebral osteoporotic fractures in women older than 50. We studied 255 women aged 50 and over, randomly selected from a Spanish population that had participated in a study of prevalence of vertebral fractures (EVOS study). This cohort was prospectively followed for 8 years by means of four postal questionnaires, in order to find out the incidence of nonvertebral fractures. Concerning the incidence of vertebral fractures, participants were invited to repeat the lumbar spine X-rays 4 years after the initial study. A total of 31 women had incident osteoporotic fractures. The analysis of gynecological variables showed that an increase in the age at menarche was a risk factor for all incident osteoporotic fractures [OR=1.57 (1.04–2.37)]. The presence of amenorrhea at any age during the fertile period was associated with higher incidence of all osteoporotic fractures [OR=6.30 (1.61–24.70]. Among all the reproductive variables analyzed (pregnancy, number of live births and breast-feeding) only pregnancy was an important protective factor in preventing incident Colles fracture [OR=0.15 (0.03–0.62)]. A family history of hip fracture was associated with a higher incidence of all osteoporotic fractures [OR=3.59 (1.01–12.79)]. In summary, a late age at menarche, the presence of amenorrhea and having close relatives with hip fracture were all risk factors which, independently of bone mineral density (BMD) and age, were associated with higher incidence of all osteoporotic fractures. Pregnancy was an important protective factor for the incidence of Colles fractures.     

Physical Activity and Risk Factors for Hip Fractures in Thai Women

Hip fractures are among the most important causes of ill health and death among elderly people. Several potentially modifiable risk factors have been reported. Most claimed physical activity as a promising, inexpensive preventive measure for hip fracture. However, knowledge about risk factors for hip fracture in Asian populations is very limited. We therefore conducted a case–control study to assess the relationships between physical activity and risk of hip fractures in Thai women. From 14 hospitals in Thailand, 229 cases with a radiologically confirmed first hip fracture were enrolled. Two hundred and twenty-four controls were randomly recruited from the same neighborhood and were matched to the cases by age within a 5 year range. Information on physical activity as well as other potential confounders was obtained through personal interviews. Multivariate logistic regression revealed that past physical activity was protective in both very active and active women (OR = 0.67, 95% CI = 0.40–1.12 for moderately active women and OR = 0.20, 95% CI = 0.10–0.38 for very active women; p value for trend <0.01). Recent physical activity reduced the risk to about two-thirds (OR = 0.33, 95% CI = 0.19–0.60 and OR = 0.35, 95% CI = 0.18–0.69 for moderately and very active women respectively). In addition, breastfeeding was identified to be a protective factor (OR = 0.87, 95% CI = 0.80–0.94). In contrast, the following risk factors were identified: current use of antihistamine (OR = 13.96, 95% CI = 1.38–141.13) or traditional medicine (OR = 7.66, 95% CI = 2.71–21.63), underlying cerebrovascular diseases (OR = 6.53, 95% CI = 2.10–20.34), history of fracture (OR = 4.04, 95% CI = 1.26–12.99), parental Chinese racial background (OR = 2.52, 95% CI = 1.49–4.23), alcohol consumption (OR = 2.30, 95% CI = 1.04–5.09). Received: 14 April 2000 / Accepted: 17 October 2000     

Association of quantitative heel ultrasound with history of osteoporotic fractures in elderly men: The ESOPO study

In order to evaluate the usefulness of calcaneal quantitative ultrasound (QUS) in the assessment of male osteoporosis, a cross-sectional, population-based study was performed. A cohort of 4,832 men, randomly selected, community-dwelling, aged 60–80 years and representative of the general older male Italian population was recruited. QUS measurements were assessed in 83 centers distributed all over Italy and equipped with an Achilles device (GE-Lunar, Madison, Wisconsin, USA). All participants were administered a questionnaire covering lifestyle variables and medical history. Low-energy fractures that had occurred since age 50 were recorded. Overall, 43 subjects reported a previous hip fracture and 455 subjects reported other non-spinal fractures. Univariate analysis showed that fractured subjects were older, with a lower level of outdoor physical activity and a more frequent history of prolonged bedridden periods in comparison with unfractured subjects. Men reporting non-spinal fractures showed a higher prevalence of smoking, while no difference was found among groups in anthropometric measures and calcium intake. QUS measurements showed that all QUS parameters were significantly lower in both fracture groups ( p <0.001). Multiple logistic regression analysis demonstrated that each SD reduction in QUS measures was associated with an approximate doubling of the risk for hip fracture, independent of age and other clinical variables (broadband ultrasound attenuation [BUA]: odds ratio [OR]=2.24; 95% confidence interval [CI] 1.61–3.08; stiffness index: OR=2.19; CI 1.56–3.11; speed of sound [SOS]: OR=1.71; CI 1.18–3.24) and with an increase of the risk of other non-spinal fractures (BUA: 1.38; CI 1.22–1.59; stiffness index: OR=1.27; CI 1.17–1.38; SOS: OR=1.14; CI 0.96–1.40). It can be concluded that calcaneal QUS measurement is associated with the risk for hip fracture and any non-spinal fractures among a community-dwelling cohort of elderly men. The strength of the association between QUS measurement and fracture is similar to that observed in elderly women.     

Risk Factors for Perimenopausal Fractures: A Prospective Study

This prospective study was aimed at determining the risk factors for the development of fractures in perimenopausal women. The study group (n= 3068) was comprised of a stratified population sample of women aged between 47 and 56 years. During the follow-up period of 3.6 years, 257 (8.4%) of the women sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 [95% confidence interval (CI) 1.2–1.6] for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). Women with a previous fracture history were found to have an increased risk of fracture [RR 1.7 (95% CI 1.3–2.2)] and those reporting three or more chronic illnesses exhibited a RR of 1.4 (95% CI 1.0–1.9). Women not using hormone replacement therapy (HRT) had a RR of 1.5 (95% CI 1.1–2.2) for all fracture types. When osteoporotic fractures (vertebral, hip, proximal humerus and wrist fractures; n= 98) were used as an endpoint, the independent risk factors were found to be a low BMD (RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6, 95% CI 1.3–2.0), a previous fracture history (RR 1.9, 95% CI 1.3–2.9) and nonuse of HRT (RR 2.2, 95% CI 1.3–4.0). The independent risk factors for all other fractures (n = 158) were a low BMD (RR for a 1 SD decrease in the spinal BMD was 1.4, 95% CI 1.2–1.6 and in the femoral neck BMD was 1.3, 95% CI 1.1–1.5), a previous fracture history (RR 1.6, 95% CI 1.1–2.2), smoking (RR 1.8, 95% CI 1.1–2.7) and having had three or more chronic illnesses (RR 1.6, 95% CI 1.1–2.2). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture. We conclude that the independent risk factors for perimenopausal fractures are a low bone density, previous fracture history, nonuse of HRT, having had three or more chronic illnesses and smoking, the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population. The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures. Received: 6 April 1999 / Accepted: 18 August 1999     

Contributions of bone density and structure to fracture risk assessment in men and women

Although bone mineral density (BMD) is a strong predictor of fractures, it is only a surrogate for bone strength. Bone structural parameters can now be measured on BMD scans, but it is unclear whether they would be more useful for risk assessment. We measured structural parameters using the Hip Structural Analysis Program and evaluated their association, compared with standard hip BMD, with fracture risk in a population-based sample of 213 postmenopausal women and 200 men 50 years of age. Altogether, 38% of the women and 27% of the men had experienced a fracture due to moderate trauma (half involved hip, spine or distal forearm), while 23% and 36%, respectively, had a previous fracture due to severe trauma. In logistic regression analyses adjusted for age, the hip BMD and structural parameters were all associated with moderate trauma fractures generally, and osteoporotic fractures specifically, in women, but the best predictor in a multivariate model was femoral neck BMD (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.9–4.0). BMD and the structural parameters were strongly correlated, however, and could be interchanged with little reduction in predictive power. These variables were less predictive of moderate trauma fractures in men. The best model included age (OR per 10 years, 1.5; 95% CI, 1.1–2.1), femoral neck section modulus (OR, 1.6; 95% CI, 1.1–2.5) and intertrochanteric buckling ratio (OR, 1.6; 95% CI, 1.3–2.0). Correction for body size did not alter these relationships. Fractures due to severe trauma were best predicted by structural parameters: in women, femoral neck buckling ratio (OR, 1.2; 95% CI, 1.04–1.5) and, in men, intertrochanteric buckling ratio (OR, 1.4; 95% CI, 1.2–1.6). These data suggest that selected structural variables as assessed by dual-energy X-ray absorptiometry would be as good as standard BMD measurements for predicting fracture risk. Because of the strong correlations, however, some judgment can be used in selecting the variables easiest to measure.     

Relationships Between Risk Factors and Fractures Differ by Type of Fracture: A Population-Based Study of 12192 Perimenopausal Women

Relationship between selected factors and fractures according to type of fracture were retrospectively examined in 12192 women aged 47–56 years responding to the baseline postal enquiry of the Kuopio Osteoporosis Study, Finland, in 1989. A total of 1358 women reported fractures sustained during the previous 9.4 years, i.e. at ages 38–57 years. The incidence of fractures per 1000 person-years was 17.2 after menopause and 9.5 before (p < 0.0001). The adjusted fracture risk was elevated in smokers versus non-smokers (OR: 1.5; (95%CI = 1.3–1.9) and in those with chronic health disorders versus the healthy (OR = 1.3; 95% CI 1.1–1.5). Long-term work disability was associated with fractures independently of health disorders (OR = 1.3; 95% CI 1.1–1.6). Anthropometric measures were not associated with the overall fracture risk. Menopause was strongly and linearly related to wrist fracture but not to ankle fracture. A 1 SD increase in body mass index decreased the risk of wrist fracture by 21% (p = 0.0001) but increased that of ankle fracture by 24% (p = 0.002). Smoking was related to ankle fracture (OR = 2.2; 95% CI 1.6–3.2) but not to wrist fracture (OR = 0.9; 95% CI 0.6–1.4). Health disorders were more markedly associated with fractures other than those of the wrist or ankle. Relationships between several risk factors and pre- and perimenopausal fractures vary by type of fracture. This may affect, for example, the comparability of studies with varying fracture profiles.     

The Effect of a Screening and Treatment Program for the Prevention of Fractures in Older Women: A Randomized Pragmatic Trial

Population screening for fracture risk may reduce the fracture incidence. In this randomized pragmatic trial, the SALT Osteoporosis Study (SOS), we studied whether screening for fracture risk and subsequent treatment in primary care can reduce fractures compared with usual care. A total of 11,032 women aged 65 to 90 years with ≥1 clinical risk factor for fractures were individually randomized to screening (n = 5575) or usual care (n = 5457). Participants in the screening group underwent a screening program, including bone densitometry and vertebral fracture assessment. Participants with a high 10-year fracture probability (FRAX) or a vertebral fracture were offered treatment with anti-osteoporosis medication by their general practitioner. Incident fractures as reported by questionnaires were verified with medical records. Follow-up was completed by 94% of the participants (mean follow-up = 3.7 years). Of the 5575 participants in the screening group, 1417 (25.4%) had an indication for anti-osteoporosis medication. Screening and subsequent treatment had no statistically significant effect on the primary outcome fracture (hazard ratio [HR] = 0.97; 95% confidence interval [CI] 0.87–1.08), nor on the secondary outcomes osteoporotic fractures (HR = 0.91; 95% CI 0.81–1.03), major osteoporotic fractures (HR = 0.91; 95% CI 0.80–1.04), hip fractures (HR = 0.91; 95% CI 0.71–1.15), falls (odds ratio [OR] = 0.91; 95% CI 0.72–1.15), or mortality (HR = 1.03; 95% CI 0.91–1.17). Post hoc explorative finding suggested that screening might be most effective after a recent fracture (HR = 0.65; 95% CI 0.44–0.96 for major osteoporotic fractures and HR = 0.38; 95% CI 0.18–0.79 for hip fractures). The results of this study might have been compromised by nonparticipation and medication nonadherence in the screening group. Overall, this study does not provide sufficient indications to consider screening for fracture prevention. However, we cannot exclude its clinical relevance to reduce (major) osteoporotic fractures and hip fractures because of the relatively small number of women with a treatment indication in the intervention group. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.     

Hepatitis C Co‐infection and Severity of Liver Disease as Risk Factors for Osteoporotic Fractures Among HIV‐Infected Patients

Osteoporosis is increasingly reported in the aging HIV‐positive population, and co‐infection with hepatitis C virus (HCV) may further increase the risk of osteoporosis. However, it remains unclear whether HCV‐related increased fracture risk is a function of the severity of liver disease. We calculated the time‐updated alanine aminotransferase to platelet ratio index (APRI) score (an indirect marker of hepatic fibrosis) in all HIV‐infected patients enrolled in the Veterans Affairs' Clinical Case Registry between 1984 and 2009. The association between HCV co‐infection and incident osteoporotic fracture (defined as closed wrist, vertebral, or hip fracture) was assessed in univariate and multivariate Cox survival models adjusting for traditional risk factors for osteoporosis and APRI score or the presence of cirrhosis. A total of 772 osteoporotic fractures were identified among 56,660 HIV‐infected patients (98.1% male; 31.3% HCV co‐infected; median age 44.0 years) contributing 305,237 patient‐years of follow‐up. Fracture rates were significantly higher among HIV/HCV patients than HIV‐only patients (2.57 versus 2.07/1000 patient‐years, relative risk = 1.24, p < 0.0001). In a Cox multivariable model including age, race, smoking, drug use, body mass index, and antiretroviral therapy, HCV co‐infection remained an independent predictor of osteoporotic fractures after controlling for presence of cirrhosis (hazard ratio [HR] = 1.32; p < 0.001) or APRI score (HR = 1.30; p = 0.003). Among HIV/HCV co‐infected patients, cirrhosis strongly predicted osteoporotic fractures (HR = 1.65; 95% confidence interval [CI] 1.11–2.44; p = 0.012), but APRI score was a weaker predictor (HR = 1.008; 95% CI 1.002–1.014; p = 0.015). In conclusion, among HIV‐infected patients, severity of liver disease partly explains the HCV‐associated increased risk of osteoporotic fractures. Other determinants of this increased risk remain to be defined. © 2013 American Society for Bone and Mineral Research.     

Risk-taking,coordination and upper limb fractures in children: a population based case-control study

The aim of this population based case-control study was to examine the association between risk-taking behaviour, motor coordination and upper limb fractures in children aged 9–16 years. A total of 321 fracture cases and 321 randomly selected individually matched controls were studied. The number for different types of upper limb fractures was 91 for hand, 190 for wrist and forearm and 40 for upper arm. Risk-taking behaviour was determined by a 5-item interview-administered questionnaire. Motor coordination was assessed by the 8-point movement ABC that tests manual dexterity, ball skills as well as static and dynamic balance. Bone mass was assessed by dual energy X-ray absorptiometry (DXA) and metacarpal morphometry. In general, there was heterogeneity by fracture site with regard to associations. Risk-taking behaviour was associated with hand fracture risk but not other fracture sites for downhill cycling behaviour (OR: 2.0/category, 95% CI: 1.1–3.7), dare behaviour (OR: 3.3/category, 95% CI: 1.1–10.0) and total risk-taking score (OR: 2.6/category, 95% CI: 1.3–5.7). Conversely, coordination measures were associated with wrist and forearm fractures only: cutting/threading (OR: 1.2/unit, 95% CI: 1.0–1.4); flower trail (OR: 1.2/unit, 95% CI: 1.0–1.4) and dynamic balance score (OR: 1.1/unit, 95% CI: 1.0–1.2). Backward stepwise analysis selected total risk taking score for hand fracture, and dynamic balance score for wrist and forearm fracture. None of the risk-taking or coordination scores were associated with upper arm fractures. These associations were unchanged following adjustment for bone mass. In conclusion, the propensity to take risks is most strongly associated with hand fracture risk while dynamic balance is most strongly associated with wrist and forearm fracture risk in children. These results inform the development of fracture prevention strategies in children.     

Risk factors for fracture of the shafts of the tibia and fibula in older individuals

A case-control study to identify risk factors for fracture of the shafts of the tibia and fibula among persons 45 years of age and older was undertaken in five Northern California Kaiser Permanente Medical Centers during 1996–2001. One hundred seventy-nine cases of newly diagnosed fracture of the tibia/fibula shaft and 2,399 controls sampled from the membership lists of the same five medical centers were included. Information on potential risk factors was obtained by a standardized questionnaire administered by trained interviewers. The number of previous fractures was associated with an increased risk [adjusted odds ratio (OR) (95% confidence interval) =1.49 (1.09–2.03) per previous fracture]. Attributes known or thought to be associated with protection against loss of bone mass, including high body mass index [adjusted OR =0.82 (0.69–0.97) per 5 kg/m² increase], having ever used thiazide diuretics or water pills for at least 1 year [adjusted OR =0.62 (0.38–1.02)], and current use of menopausal hormone therapy among females [adjusted OR =0.84 (0.53–1.32)] tended to show decreased risks. Factors generally associated with lower bone mass, such as current cigarette smoking [OR =1.55 (1.01–2.39)] and, to some extent, lack of physical activity [OR =1.31 (0.87–1.96) for the lowest quartile compared to the upper three quartiles], tended to demonstrate increased risks. The number of falls in the past year and risk factors for falls were not associated with tibia/fibula shaft fractures, and indicators of health status were weakly and inconsistently associated with risk. Thus, this study suggests that risk factors for low bone mass, but not health status or risk factors for falls, may be important in the etiology of fracture of the shaft of the tibia/fibula in older individuals.     

Fractures Before Menopause: A Red Flag for Physicians

There is substantial interest in the early identification of women at risk for osteoporotic fractures, so that preventive measures may be instituted early. We examined whether women with a history of fractures before menopause were at an increased risk of fractures after menopause. We obtained information about any lifetime fractures of the hip, arm, spine, wrist, leg, ankle, foot and finger from 9086 ambulatory white women ages 65 years and older participating in the Study of Osteoporotic Fractures. We also measured bone mineral density and recorded history of falls, maternal fracture history, drug use, diet, functional status, and other characteristics commonly associated with osteoporotic fractures. We used proportional hazards models to estimate the effects of fractures that occurred before menopause on the risk of fractures after menopause, in particular those that occurred during the 12 years of study follow-up. The risk of fractures of all types during the study period was greater among women with a premenopausal fracture of any type compared with women without a premenopausal fracture (hazard ratio (HR), 1.33; 95% confidence interval (CI), 1.14–1.56; p<0.001). Adjustment for possible confounders, including bone mineral density, had only a modest effect (HR, 1.25; 95% CI, 1.03–1.50; p<0.02). An increased risk of fracture among women with a premenopausal fracture was also seen after stratification by estrogen use, propensity to fall and maternal fracture history. Premenopausal fractures are therefore a risk factor for subsequent fractures independent of other risk factors for osteoporotic fractures, such as bone mineral density. A fracture history, including fractures before menopause, should be obtained when making decisions about preventive treatments. Received: 17 April 2000 / Accepted: 14 June 2000     

The Importance of Previous Fracture Site on Osteoporosis Diagnosis and Incident Fractures in Women

Previous fracture increases the risk of subsequent fractures regardless of the site of the initial fracture. Fracture risk assessment tools have been developed to guide clinical management; however, no discrimination is made as to the site of the prior fracture. Our objective was to determine which sites of previous nontraumatic fractures are most strongly associated with a diagnosis of osteoporosis, defined by a bone mineral density (BMD) T‐score of ≤ ?2.5 at the femoral neck, and an incident major osteoporotic fracture. Using administrative health databases, we conducted a retrospective historical cohort study of 39,991women age 45 years and older who had BMD testing with dual‐energy X‐ray absorptiometry (DXA). Logistic regression and Cox proportional multivariate models were used to test the association of previous fracture site with risk of osteoporosis and incident fractures. Clinical fractures at the following sites were strongly and independently associated with higher risk of an osteoporotic femoral neck T‐score after adjustment for age: hip (odds ratio [OR], 3.58; 95% confidence interval [CI], 3.04–4.21), pelvis (OR, 2.23; 95% CI, 1.66–3.0), spine (OR, 2.16; 95% CI, 1.77–2.62), and humerus (OR, 1.74; 95% CI, 1.49–2.02). Cox proportional hazards models, with adjustment for age and femoral neck BMD, showed the greatest increase in risk for a major osteoporotic fracture for women who had sustained previous fractures of the spine (hazard ratio [HR], 2.08; 95% CI, 1.72–2.53), humerus (HR, 1.70; 95% CI, 1.44–2.01), patella (HR, 1.54; 95% CI, 1.10–2.18), and pelvis (HR, 1.45; 95% CI, 1.04–2.02). In summary, our results confirm that nontraumatic fractures in women are associated with osteoporosis at the femoral neck and that the site of previous fracture impacts on future osteoporotic fracture risk, independent of BMD. © 2014 American Society for Bone and Mineral Research.     

Hormone replacement therapy and risk for foot,distal forearm,proximal humerus,and pelvis fractures

This case-control epidemiologic study examines the relationship between hormone replacement therapy (HRT) and risk for fractures of four sites among women 45 years of age and older. From October 1996 to May 2001, incident patients with distal forearm ( n=744), foot ( n=618), proximal humerus ( n=331), and pelvis ( n=109) fractures were recruited from five Kaiser Permanente Medical Centers in northern California. Controls ( n=1617) were selected at random from the same five medical centers over the same time period within strata defined by 5-year age group, gender, and white versus nonwhite or unknown recorded race/ethnicity. Trained interviewers collected information using a standardized questionnaire. Compared with postmenopausal women who never used HRT, postmenopausal women currently using HRT for at least 3 months had a decreased risk of fracture at the distal forearm (adjusted OR=0.55, 95% CI: 0.43, 0.72), proximal humerus (adjusted OR=0.51, 95% CI: 0.36, 0.74), and pelvis (adjusted OR=0.51, 95% CI: 0.27, 0.95), but not the foot (adjusted OR=1.05, 95% CI: 0.81, 1.35). Past use of HRT for more than 7 years also appeared to be associated with a reduced risk of fracture at the distal forearm and proximal humerus. The longer a woman went without HRT after her last menstrual period, the greater her risk of fracture in the distal forearm, proximal humerus, and pelvis. The findings of this study support long-term, current use of HRT for the prevention of osteoporotic fractures, but other risks and benefits also need to be considered.