Clinical Fragility Fractures Research Articles

Frequency of FRAX risk factors in osteopenic postmenopausal women with and without history of fragility fracture

Fractures associated with bone fragility represent a major public health concern. Although the risk of bone fracture is higher among patients with osteoporosis, the number of fractures is usually higher among patients with osteopenia due to its higher prevalence. This is an observational case series study that compares the frequencies of nonskeletal risk factors for osteoporotic fractures in osteopenic postmenopausal women with previous clinical fragility fractures (FFs) and osteopenic postmenopausal women without previous FF. Risk factors included in the FRAX algorithm and other selected risk factors, including asymptomatic vertebral fractures, were evaluated. A total of 735 (50.3% with prior FF and 49.7% without prior FF) postmenopausal women were evaluated (median age, 60 y; mean bone mineral density [BMD] femoral neck T score of -1.67). The frequency of the following risk factors was significantly higher among women with FF-FRAX algorithm: age, use of corticosteroids, and BMD femoral neck T score; other factors: Hispanic ethnicity, falls during the last year, and BMD lumbar T score. In addition, the frequency of previously undetected asymptomatic vertebral fractures was four times higher among women with a history of FF. The results of the present study support the need to assess the presence of asymptomatic vertebral fractures and BMD T scores in osteopenic postmenopausal women. The risk evaluation of this subpopulation can be accomplished by using some of the risk factors included in the FRAX algorithm combined with other conventional risk factors.

Low 25-Hydroxyvitamin D Levels and Low Bone Density Assessed by Quantitative Ultrasonometry in a Cohort of Postmenopausal Italian Nuns

This study was aimed at evaluating the effect of clothing style on bone mass and fractures in 70 postmenopausal nuns residing in a monastery in Naples. Sixty healthy women matched for age, body mass index, and menopausal status were enrolled as controls. Each participant underwent measurement by quantitative ultrasonometry (QUS) using a DBM Sonic Bone Profiler (IGEA S.p.A., Carpi, Modena, Italy) at proximal phalanges, responded to questionnaires regarding lifestyle, calcium intake, medical history, including clinical fragility fractures, and was submitted to routine biochemical assessment. A significant reduction in ultrasonometric parameters of bone mass was found in nuns compared with controls (p from 0.007 to <0.0001). 25-hydroxyvitamin D (25-OH vit D) levels were reduced by more than 50% in nuns (9.8±4.2 vs 23.5±5.7nmol/L; p<0.0001), whereas their estimated daily calcium intake was higher (1.004±0.23 vs 0.721±0.25g of controls; p=0.0007). Age at menopause was significantly lower in nuns' group (p=0.016). Incidence of fractures was higher in nuns (39% vs 10%; p=0.0029), and the best predictors of fractures were age at menopause (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.01–1.30), amplitude-dependent speed of sound T-score (OR: 1.15; 95% CI: 1.03–1.63), and bone transmission time T-score (OR: 1.30; 95% CI: 1.15–1.81). This study documented low 25-OH vit D levels, increased frequency of clinical fractures, and low bone mass detected by QUS in Southern Italian nuns.

Fragility fractures and the osteoporosis care gap in women: the Canadian Multicentre Osteoporosis Study

Canadian women over 50years old were studied over a 10-year period to see if those who sustained a fracture (caused by minimal trauma) were receiving the recommended osteoporosis therapy. We found that approximately half of these women were not being treated, indicating a significant care gap in osteoporosis treatment. Prevalent fragility fracture strongly predicts future fracture. Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment. We aimed to describe post fracture care in Canadian women using a large, population-based prospective cohort that began in 1995-1997. We followed 5,566 women over 50years of age from across Canada over a period of 10years in the Canadian Multicentre Osteoporosis Study. Information on medication use and incident clinical fragility fractures was obtained during a yearly questionnaire or interview and fractures were confirmed by radiographic/medical reports. Over the 10-year study period, 42-56% of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication. During year1 of the study, 22% of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26% were on hormone therapy (HT). We were not able to differentiate HT use for menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over time; odds ratio (OR) for use at year10 compared to use at year1 was 3.65 (95% confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of 0.07 (95%CI 0.02-0.24) at year10 compared to year1 of the study. In a large population-based cohort study, we found a therapeutic care gap in women with osteoporosis and fragility fractures. Although bisphosphonate therapy usage improved over time, a substantial gap remains.

The effect of toremifene citrate on BMD in men on ADT: A phase III clinical trial

5055 Background: Androgen deprivation therapy decreases bone mineral density and increases fracture incidence. In a recently completed two-year randomized controlled trial of 1382 men, toremifene increased BMD and decreased vertebral fracture incidence in men receiving ADT for prostate cancer. We now describe the effects of toremifene on BMD in various subject subgroups. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Key entry criteria included age ≥ 50 years, continuous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for the duration of their time on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included BMD, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: In the overall study population, toremifene increase BMD of the hip and lumbar spine by 1.6% and 2% after two years compared to placebo. Similar beneficial effects of toremifene were observed in each of the subgroups ( Table ). Conclusions: Toremifene significantly increases bone mineral density of the hip and spine in every subgroup including those men who were older or had prevalent vertebral fractures, longer exposure to ADT, or lower baseline BMD. [Table: see text] [Table: see text]

Use of age and BMD to predict fracture risk in men on androgen deprivation therapy

9517 Background: Androgen deprivation therapy (ADT) decreases bone mineral density by reducing estrogens to castrate levels and, as a result, increases fracture risk. We recently completed a two-year trial in 1382 men in which we examined the ability of toremifene to reduce fracture risk in men on ADT. Herein we describe analyses of the placebo group to assess the baseline characteristics associated with new fractures. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Entry criteria included age ≥ 50 years, continous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for their duration on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included bone mineral density, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: The modified intent to treat (MITT) population included subjects who took study medication and had an on-study radiograph. There were 467 subjects in the placebo MITT population. To identify factors associated with fracture risk in men on ADT we compared placebo subjects who suffered a fracture or during the first year on study suffered 7% or greater bone loss with those placebo subjects who did not. Baseline characteristics included: BMD (spine, hip, femoral neck), Age, history of fracture, ADT duration, bone turnover markers, and race. Logistic regression models of the probability of fracture/bone loss as a function of country showed that each of BMD at all sites, age, race, CTX, and history of previous fracture independently predicted fracture/7% bone loss. When all characteristics were analyzed in a multivariable model lower spine BMD (p=0.006) and older age (p=0.018) were significantly associated with incident fractures. Conclusions: In prostate cancer patients on ADT older age and lower baseline spine BMD were associated with a greater risk of fracture in untreated patients. [Table: see text]

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women

In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.

The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study

We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

Effect of Selective Serotonin Reuptake Inhibitors on the Risk of Fracture

Depression and osteoporotic fractures are common ailments among elderly persons. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of depression in this population, and the association between daily SSRI use and fragility fractures is unclear. Our objective was to examine the effect of daily SSRI use on the risk of incident clinical fragility fracture. A population-based, randomly selected, prospective cohort study of 5008 community-dwelling adults 50 years and older, followed up over 5 years for incident fractures. Clinical fragility fractures were classified as minimal trauma fractures that were clinically reported and radiographically confirmed. The risk of fragility fracture associated with daily SSRI use was determined while controlling for relevant covariates. Daily SSRI use was reported by 137 subjects. After adjustment for many potential covariates, daily SSRI use was associated with substantially increased risk of incident clinical fragility fracture (hazard rate, 2.1; 95% confidence interval, 1.3-3.4). Daily SSRI use was also associated with increased odds of falling (odds ratio, 2.2; 95% confidence interval, 1.4-3.5), lower bone mineral density at the hip, and a trend toward lower bone mineral density at the spine. These effects were dose dependent and were similar for those who reported taking SSRIs at baseline and at 5 years' follow-up. Daily SSRI use in adults 50 years and older remained associated with a 2-fold increased risk of clinical fragility fracture after adjustment for potential covariates. Depression and fragility fractures are common in this age group, and the elevated risk attributed to daily SSRI use may have important public health consequences.

Characteristics of elderly patients admitted to an urban tertiary care hospital with osteoporotic fractures: correlations with risk factors, fracture type, gender and ethnicity

Osteoporosis is a major public health problem in the United States of America and around the world, largely due to the morbidity and mortality associated with osteoporotic fractures. In the past decade, large epidemiologic studies have contributed greatly to our understanding of patients who fracture. However, most studies are limited to postmenopausal white women. In this retrospective review, we analyze data from 185 men and women with acute fragility fractures who received osteoporosis consultations during admission to a single urban hospital between 2001 and 2003. Men and women differed in terms of risk factors for falls and osteoporosis but had areal bone mineral density (BMD) measurements remarkably similar, except at the total hip. Black and Hispanic subjects with fractures were significantly younger than whites yet were much more likely to have serious co-morbidities, such as diabetes mellitus and hypertension. In spite of significantly higher BMD measurements, black patients had the highest rates of vitamin D deficiency and secondary hyperparathyroidism. Patients admitted with hip fractures differed from those with non-hip fractures on a number of important variables. Based on these data, we conclude that elderly subjects admitted to an urban hospital with osteoporotic fractures are a heterogeneous group, with features that vary according to fracture type, gender and ethnicity. Future studies of patients with clinical fragility fractures should include ample numbers of men and ethnic minorities, since differences in underlying risk factors may suggest alternative strategies for fracture prevention.

Prevalence of vitamin D inadequacy in Scottish adults with non-vertebral fragility fractures

ABSTRACTBackground: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age, or below the normal range.Objectives: To investigate the prevalence of vitamin D inadequacy in an elderly population presenting to the South Glasgow Fracture Liaison Service with non-vertebral fragility fractures in order to assess the extent of the problem.Research design and methods: The retrospective arm of this study used data from an established database to identify patients aged over 50 years admitted to South Glasgow University Hospitals over the previous 4 years with hip fracture. The prospective arm identified the first 50 patients aged over 50 presenting with a clinical non-vertebral fragility fracture with osteoporosis as measured by axial spine and/or hip DEXA (T‐score < –2.5) after November 2004.Results: In the retrospective arm, 626 patients were identified from the database: mean age 80.5 years; 94% were aged over 60 and 74% were aged over 75. Data analysis was limited to 548 patients aged over 60 years with vitamin D recordings and not receiving supplementation with calcium and vitamin D. The mean vitamin D level was 24.7 nmol/L (9.9 ng/ml) SD = 17, however, it is likely that the true mean is lower since in approximately 25% of cases vitamin D levels were reported as < 15 nmol/L (effectively unrecordable). These were transcribed as 15 nmol/L in order to permit a numerical value to be calculated. In the absence of an agreement on what should constitute a diagnostic serum level of vitamin D inadequacy, a number of thresholds were considered – 97.8% had vitamin D levels below 70 nmol/L and 91.6% had vitamin D levels below 50 nmol/L. There were no significant differences by patient sex, age or season of presentation.The mean age of patients in the prospective arm was 65.8 years (range 50.6–83.8), 72% were aged over 60 and 16% were aged over 75. The mean vitamin D level was 44.1 nmol/L (18.4 ng/ml) SD = 25.3; 82% had vitamin D levels below 70 nmol/L and 72% had vitamin D levels below 50 nmol/L. Although numbers were too small to justify extensive subgroup analyses, the mean vitamin D level in the 13 patients with hip fracture (34.5 nmol/L) was lower than in the 37 with non-hip fractures (48.2 nmol/L).Conclusions: This study confirms almost universal vitamin D inadequacy among 548 elderly patients admitted to hospital with hip fracture, regardless of whether a threshold of 50 nmol/L or 70 nmol/L was used. However, among a prospective subset of 50 patients with clinical fragility fractures, especially those with non-hip fractures, the prevalence of inadequacy was substantially lower. It may be that vitamin D represents a correctable risk factor for fragility fracture in the elderly, possibly specifically for the hip.