Significant Risk Factor For Fractures Research Articles

High incidence of fracture events in patients with Long-Gap Esophageal Atresia (LGEA): A retrospective review prompting implementation of standardized protocol

PurposeTo identify factors associated with an increased risk of fractures in Long-Gap Esophageal Atresia (LGEA) patients. Following implementation of a risk-stratified program, we hypothesized a reduction in fracture incidence within this potentially high-risk population. MethodsA retrospective review of LGEA-patients admitted between 2005 and 2014 was conducted. Symptomatic fractures with radiographic confirmation were defined as events. Univariate and multivariable analysis evaluated factors including admission weight-for-age z-score, primary versus secondary Foker process (FP), weight at Foker Stage I, days and episodes of paralysis, number of parenteral nutrition (PN) days, cumulative dose of loop diuretics adjusted for body weight and days exposed, and exposure to non-loop diuretics. A fracture-prevention protocol was initiated in 2012; incidence was evaluated pre and post-intervention. ResultsFifty-nine patients met inclusion criteria. Twenty-three (39%) patients in the entire cohort incurred at least one fracture during their hospitalization utilizing the Foker process. Given this high percentage, a targeted fracture-prevention protocol was initiated in 2012. Fracture incidence decreased from 48% prior to the protocol to 21% following the protocol (P=0.046). Several variables that were associated with an increased risk of fractures on univariate analysis included prior esophageal anastomosis attempt (P=0.008), number of separate episodes of paralysis (P=0.002), exposure to non-loop diuretics (P=0.006), cumulative loop diuretic dose (P<0.001), as well as cumulative loop diuretic over days exposed (P<0.001). Intensive care unit (ICU) stay (P=0.002) and total length of hospitalization (P<0.001) were also significantly longer among patients with a fracture. Number of separate episodes of paralysis was the only independent risk factor for the development of a fracture; patients having more than 3 episodes of paralysis had an estimated risk of fracture 15 times higher than those patients paralyzed only once or twice (O.R. 15.87, 95% C.I.: 1.47–171.23, P=0.008). ConclusionEpisodes of paralysis appeared to be the most significant risk factor for fractures in patients with LGEA who underwent the Foker procedure. The incidence of symptomatic fractures decreased significantly following implementation of a standardized protocol in this series of LGEA patients with continued prospective evaluation.

Fracture incidence in pre- and postmenopausal women after completion of adjuvant hormonal therapy for breast cancer

IntroductionAlthough the effect of hormonal therapy (HT) on fracture risk during treatment of breast cancer is established, information about fracture incidence after completion of HT is scarce. In this hospital based observational study we evaluated fracture rates after completion of HT in pre- and postmenopausal women with breast cancer. MethodsAll women diagnosed with breast cancer in the VieCuri Medical Center between 1998 and 2005 who started adjuvant HT with aromatase inhibitors or tamoxifen were included (n = 289). Data on fracture rate, fracture type and risk factors for fracture after completion of HT were collected. ResultsThe overall fracture rate was 12% in pre- and 15% in postmenopausal women respectively during an average follow-up of 3.1 ± 2.9 years. The number of patients with at least one fracture was 41 (14%). There was no difference in fracture rates between different types of HT (P = 0.15). The most common types of fractures were toe/finger fractures in premenopausal- and hip and major fractures in postmenopausal women. Median time to first fracture was shorter in premenopausal women (1.4 years, IQR 0.2–3.5) than in postmenopausal women (2.4 years, IQR 0.7–5.1, P = 0.01). A history of previous fracture was a significant risk factor for fracture in postmenopausal women (HR 3.9, 95% CI 1.3–11.7). ConclusionFracture rates in the first years after cessation of HT for breast cancer were 12% and 15% for pre- and postmenopausal women respectively. The most common fractures in postmenopausal women were hip and major fractures.

PREVALENCE AND RISK FACTORS OF LOW-ENERGY SKELETAL FRACTURES IN PATIENTS WITH CHRONIC INFLAMMATORY DISEASES. THE RESULTS OF A MULTICENTER STUDY OF THE RUSSIAN ASSOCIATION ON OSTEOPOROSIS GLUKOST

Objectives. This study is a part of GLUKOST study hosted and organized by the Russian Association of Osteoporosis. The aim was to estimate the incidence and risk factors of fractures in patients with chronic inflammatory diseases. Materials and Methods. A specially designed questionnaire was introduced to patients with chronic inflammatory diseases in different regions of Russia. The study included 2342 patients aged 18 to 89 years (mean age 53.02 ± 14.03 years, 591 men and 1181 women). The patients were allocated into two groups: group 1 (n = 1402) - patients never prescribed oral long acting glucocorticoids (OGC); group 2 (n = 929) - patients who received oral long acting glucocorticoids for more than 2 months or continue to take at the time of the survey. The median duration of OGC therapy was 3 years, the median daily dose - 10 mg of prednisone or equivalent. Results. Low-energy fractures of the skeleton were identified in 9.0% of patients not receiving therapy OGC, and 15.5% of patients receiving or previously treated with this therapy. Significant risk factor for fractures was the length of a chronic inflammatory disease. OGC therapy increased the risk (adjusted odds ratio (95% confidence interval (95% CI)) of osteoporotic fractures, regardless of their location by 2.2-fold (95% CI 1.63-3.02, p &lt;0,001), vertebral fractures - by 5.0 - fold (95% CI 2.05-12.37, p &lt;0.001), distal forearm 1.8-fold (95% CI 1.10-2.84, p = 0.02). The frequency of fractures in group 2 was increased in men and women of different age groups, but a significant increase in risk was demonstrated only in postmenopausal women and men 50 years and older. We were unable to identify a relationship of fractures with a daily dose of OGC. Conclusion. The main risk factors for osteoporotic fractures in patients with chronic inflammatory diseases are age, duration of the underlying disease, and long-term use of oral glucocorticoids.

Androgen ablation for low-risk prostate cancer is common among male hip fracture patients

Objective. This study aimed to evaluate the prevalence of androgen deprivation therapy (ADT) among male hip fracture patients with prostate cancer and to analyse their indications for ADT with regard to prostate cancer risk classification. Material and methods. Tampere University Hospital records were screened for International Classification of Diseases, 10th revision (ICD-10) diagnoses S72.0–72.2 in 1998–2008 to identify hip fractures among males. Prostate cancer and fracture characteristics and concomitant medications were recorded. Fracture patients with prior prostate cancer diagnosis were compared to control patients from the Tampere University prostate cancer database and the risk factors for fracture were analysed by binary logistic regression analysis. Results. In total, 133 patients (11.0% of hip fractures) had a prostate cancer diagnosis prior to fracture; of these, 111 (84.1%) had osteoporotic, 14 (10.6%) pathological and seven (5.3%) high-energy fractures. Furthermore, 117 (88.0%) of fracture patients had received ADT for their prostate cancer. The mean interval between castration and fracture was 5.9 years (median 4.6 years). Of the fracture patients with prostate cancer, 24.8% had been primarily castrated for a low-risk disease. In multivariate analysis, ADT was a significant risk factor for fracture among low [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.14–8.01, p = 0.027], intermediate (OR 4.52, 95% CI 1.32–15.40, p = 0.016) and high-risk prostate cancer patients (OR 5.85, 95% CI 1.30–26.30, p = 0.021). Conclusions. Hormonally treated prostate cancer is a major risk factor for osteoporotic hip fracture in males. Nearly a quarter of the prostate cancer patients suffering a hip fracture had been treated by primary castration despite having low-risk prostate cancer, emphasizing the importance of patient selection and timing for ADT.

Multisite quantitative ultrasound for the prediction of fractures over 5 years of follow-up: The Canadian Multicentre Osteoporosis Study

This study assessed the ability of multisite quantitative ultrasound (mQUS) to predict fracture over a 5-year follow-up. Participants were a subset of the Canadian Multicentre Osteoporosis Study. mQUS-assessed speed of sound (SOS in m/s) at three sites (distal radius, tibia, and phalanx) and extensive questionnaires were completed, after which participants were followed for 5 years and incident fractures recorded. Two survival analyses were completed for each site--a univariate analysis and an adjusted multivariate analysis controlling for age, antiresorptive use, femoral neck bone mineral density, number of diseases, previous fractures, body mass index (BMI), parental history of hip fracture, current smoking, current alcoholic drinks >3 per day, current use of glucocorticoids, and rheumatoid arthritis diagnosis (variables from the FRAX 10-year fracture risk assessment tool). The unit of change for regression analyses was one standard deviation for all measurement sites, specific to site and sex. Separate analyses were completed for all clinical fractures, nonvertebral fractures, and hip fractures by sex. There were 2633 women and 1108 men included, and they experienced 204 incident fractures over 5 years (5.5% fractured). Univariate models revealed statistically significant (p < 0.05) predictive ability of mQUS for all three measurement sites for women alone for all three fracture types (one standard deviation decrease in SOS was associated with a 52% to 130% increase in the risk of fracture), but not for the men's group. The adjusted model found that measures at the distal radius and tibia in the women's group could significantly (p < 0.05) predict all clinical fractures and nonvertebral fractures within the next 5 years (one standard deviation decrease in SOS was associated with a 25% to 31% increase in the risk of fracture). mQUS provided significant 5-year clinical fracture prediction in women, independent of bone mineral density and other significant risk factors for fracture, when measured at the distal radius and tibia sites.

Identification of risk factors for fracture of veneering materials and screw loosening of implant‐supported fixed partial dentures in partially edentulous cases

This retrospective study identified the risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases. The study group included a total of 182 patients who were installed 219 suprastructures at the Fixed Prosthodontic Clinic of Okayama University Dental Hospital between February 1990 and March 2005 and were subdivided in two subgroups: 120 patients (149 facing suprastructures) were included in the subgroup to investigate the risk factors of fracture of veneering materials, and 81 patients (92 suprastructures) were included in the subgroup to identify the risk factors of abutment screw loosening. Each patient was followed up from the day of suprastructure installation until March, 2005. A Cox proportional hazards regression model was used to identify the risk factors related to technical complications, and eight factors were regarded as candidate risk factors. Screw retention was the significant risk factor for fracture of veneering materials, whereas connection of suprastructures with natural tooth was the significant risk factor for screw loosening. It was suggested that screw retention was a significant risk factor for the fracture of veneering materials, and connection of suprastructures with natural tooth was a significant risk factor for screw loosening. Future studies, involving dynamic factors (e.g. bruxism) as predictors as well, are more helpful to discuss the risk factor of fracture of veneering materials and screw loosening.

Musculoskeletal deformities and fractures in Parkinson&amp;rsquo;s disease

Parkinson’s disease (PD) is a neurodegenerative condition that is characterized by a variety of severely debilitating motor and non-motor symptoms. Further, an increased risk of skeletal deformities and fractures, conditions ranging from scoliosis to osteoporosis, is of noteworthy importance. Following are some of the skeletal deformities seen in PD. Scoliosis, a lateral curving of the spine, is more common in PD patients than in the general population. Although the exact relationship between scoliosis and PD is not clearly known, it has been suggested that scoliosis is closely related to the dopamine deficiency associated with PD. Several studies have noted that the direction of the spinal curvature is correlated with the laterality of the major signs and symptoms of PD. It has been suggested that patients may slowly develop a tendency to lean towards the affected lagging side of PD during walking. This may result in the curvature of the spine seen in scoliosis, although genetic, biomechanical, or hormonal factors may play a role as well. Osteoporosis is a skeletal condition that is characterized by bone wasting and loss of bone density. This is a significant risk factor for fractures in the elderly population. Within PD patients, there is an increased frequency of osteoporosis in both males and females. Commonly bone mass is maintained by bone formation/re-absorption and is reliant on day-today mobility and exercise. However, for PD patients, this mobility and exercise are significantly reduced as most of their time is spent sitting or lying down. This is especially prevalent in the moderate to advanced stages of PD. The results may include an increased rates of bone re-absorption, loss in bone density, and fractures particularly around the hip. Combined with the inherent disposition of falling among PD patients, due to postural imbalance and neurological impairment, the risk of fracture is certainly a cause for concern. Bone mass is measured by a bone density test which should be used for elderly PD patients to establish a baseline. Thereafter, they should be monitored periodically for the occurrence of osteoporosis.

Pathologic femur fractures after limb-sparing treatment of soft-tissue sarcomas

Local control for sarcomas of the long bones includes limb sparing surgery and radiotherapy. While effective, there are potential complications. Patients treated for a soft tissue sarcoma of the thigh with limb-sparing surgery and radiation therapy between 1986 and 2000 at the University of Minnesota Masonic Cancer Center (n=89) were identified. Demographic, tumor, and treatment characteristics were abstracted from the medical record. Univariate analysis was conducted to identify significant risk factors for fracture. Survivors (58% male), median age of 50 (7-88) years, reported 8 (9%) fractures at a median of 7.3 (0.8-21.9) years from diagnosis after a median of 6300 (2000-7020) cGy of radiation. All fractures occurred within the previous radiation field, after no trauma. Three of the 8 (37.5%) had delayed union, 2 (25%) nonunion healing. Significant risk factors included periosteal stripping (p=0.006), anterior compartment location (p=0.022), and having 100% of the femoral circumference irradiated (p=0.018). Taking into account time to fracture using Kaplan Meier and log rank tests, these same predictors were identified. Older age, female sex, use of chemotherapy, and timing of radiation were not predictive of femoral fracture. Anterior tumor location, periosteal stripping, and radiation to 100% of the femur circumference are associated with femoral fracture. These patients require long-term monitoring and may warrant prophylactic intramedullary pinning or other protective measures. Survivors of soft tissue sarcomas of the femur may be at risk for the development of femur fractures and warrant close observation.

Femur fractures after limb-sparing treatment of soft-tissue sarcomas: One institution's experience.

e19601 Background: Local control for soft tissue sarcomas of the long bones often includes limb sparing surgery with the addition of radiation therapy. While effective, there are potential complications including poor wound healing and late-onset fractures. Methods: This analysis includes patients treated for a soft tissue sarcoma of the thigh with limb-sparing surgery and radiation therapy between 1986 and 2000 at the University of Minnesota Masonic Cancer Center (n=89). Demographic, tumor, and treatment characteristics including age, sex, histology, location (anterior, posterior, medial, buttock, popliteal fossa), use of adjuvant chemotherapy (yes/no), use of periosteal stripping (yes/no), timing of radiation (pre-/post-operative, both), radiation dose [high (>60 Gy), low (</+60 Gy), radiation field length [> 30 centimeters (cm), </= 30 cm], circumference of radiation field (100%/< 100% of femur) were abstracted from the medical record. Univariate analysis was conducted to identify significant risk factors for fracture. Given the small numbers of patients with a femoral fracture, multivariate analysis was unable to be performed. Results: Survivors (58 % male) with a median age of 50 (7-88) years reported_8 (9%) fractures at a median of 7.3 (0.8 – 21.9) years from diagnosis after a median of 6300 (2000-7020) cGy of radiation. All fractures occurred within the previous radiation field, after minimal or no trauma. Three of the 8 (37.5%) had delayed union, 2 (25%) nonunion healing. Significant risk factors included periosteal stripping (p=0.006), anterior location (p=0.022), and having 100% of the femoral circumference irradiated (p=0.018). Taking into account time to fracture using Kaplan Meier and log rank tests, these same predictors were identified. Older age, female sex, use of chemotherapy, and timing of radiation were not predictive of femoral fracture. Conclusions: Anterior tumor location, the presence of periosteal stripping, and radiation to 100% of the femur circumference are significantly associated with femoral fracture. These patients require long-term monitoring and may warrant prophylactic intramedullary pinning or other protective measures. No significant financial relationships to disclose.

Survey of spine surgeons on attitudes regarding osteoporosis and osteomalacia screening and treatment for fractures, fusion surgery, and pseudoarthrosis

Background context Osteoporosis and osteomalacia are significant risk factors for fracture and spine instrumentation failure. Low-energy fractures are becoming increasingly more common because of an increase in life expectancy and age of the population. Decreased bone density is an independent risk factor for instrumentation failure in spinal fusion operations. Purpose To assess the awareness and practice patterns of spine surgeons regarding metabolic bone disorders and osteoporosis with emphasis on fracture care and arthrodesis. Study design/setting Questionnaire study. Patient sample Spine surgeons attending the “Disorders of the Spine” conference (January 2007, Whistler, British Columbia, Canada). Outcome measures Respondent reported frequencies of diagnostics, screening, and treatment methods for patients with low-energy spine fractures, pseudoarthrosis, and those undergoing spinal arthrodesis. Methods A ten-question survey was administered to orthopedic surgeons and neurosurgeons who treated spine fractures and degenerative spine conditions in their practice. The survey was given to those who were attending a continuing medical education spinal disorders conference. The survey asked about treatment patterns with respect to osteoporosis and osteomalacia workup and treatment for patients with low-energy spine fractures, pseudoarthrosis, and those undergoing spinal arthrodesis. Results Of the 133 surgeons to whom the questionnaire was distributed at this meeting, 114 questionnaires were returned that corresponds to a response rate of 86%. Twenty-one surveys were excluded because of incomplete biographical information, resulting in a total of 93 completed questionnaires that were available for analysis. When treating patients with low-energy spine fractures, 60% checked dual-energy X-ray absorptiometry (DEXA) and 39% checked metabolic laboratories (of those who did not order laboratories and DEXA about 63% refer for treatment). Before instrumented fusion, 44% of those queried checked DEXA and 12% checked metabolic laboratories (vitamin D, parathyroid hormone [PTH], and calcium [Ca]). Before noninstrumented fusion, 22% checked DEXA and 11% checked metabolic laboratories. Before addressing pseudoarthrosis, 19% checked DEXA and 20% checked metabolic laboratories. Conclusions Despite of the large number of elderly patients undergoing spine care and the high incidence of osteoporosis and/or osteomalacia in this population, a large portion of the spine surgeons who responded to the survey reported that they do not perform routine osteoporosis/osteomalacia workups. Of those who do perform workups, some commented that it will change their surgical plan or preoperative treatment. It appears that there is a need for increased awareness among spine specialists regarding osteoporosis screening and treatment. Osteoporosis practice patterns may also be affected with newly evolving government quality reporting regulations.

55. Practice Patterns Among Spine Specialists Regarding Metabolic Bone Disorder Screening and Treatment in Spine Fusion and Low Energy Fracture Patients

BACKGROUND CONTEXT: Low energy fractures are becoming increasingly more common due to an increase in life expectancy and age of the population. Osteoporosis and osteomalacia are significant risk factors for fracture and spine instrumentation failure. Decreased bone density is an independent risk factor for instrumentation failure in spinal fusion operations. The Center for Medicare and Medicaid Services has recently established the Physician Quality Reporting Initiative and links compliance with a financial incentive.

Fracture risk assessment in frail older people using clinical risk factors

this study aims to develop and evaluate a simple fracture risk index for use in frail older people. clinical risk factors were assessed at baseline for 2,005 older people (473 males, 1,532 females; mean age 85.7 years, SD 7.1 years) living in aged-care facilities. Fractures were ascertained for 2 years from baseline. Cox regression model was used to identify significant risk factors for fracture. Hazard ratios (HRs) from the model were assigned as weights. The risk index was calculated by multiplying the weights of all risk factors. during a mean follow-up of 1.64 years, 401 fractures occurred in 338 participants. Significant independent clinical risk factors for fracture were institution type, balance, history of previous fracture, cognitive function, number of medications, weight and lower leg length (n = 1,813). The index was capable of identifying higher-risk individuals, with almost an 8-fold increase in the risk of fracture for residents from the lowest 15% to the highest 18% of the score. Among 1-year survivors, a high score (>or=15) indicated approximately a one-in-six chance of fracture, while a low score (<8) indicated only a one-in-forty chance of fracture within a year. The area under the receiver operating characteristic (ROC) curve was 0.69 (95% CI: 0.65-0.72) and 0.68 (95% CI: 0.65-0.71) for identifying someone who would have a fracture in 1 and 2 years respectively. this risk index could identify individuals at higher fracture risk among institutionalised older people, and thus, could help to rationalise the provision of fracture prevention programs in this population.

Does Diabetes Increase the Risk for Fractures After Solid Organ Transplantation? A Nested Case-Control Study

To assess the risk of fractures after a solid organ transplantation among diabetic versus nondiabetic patients, we conducted a nested case-control study. Pretransplant diabetes was associated with a 2-fold increase in post-transplant fractures. Diabetes has been associated with osteoporosis in the general population. However, among patients receiving solid organ transplantation, the association between pretransplant diabetes and post-transplant fractures is not clear, although both diabetes and fractures are prevalent among this patient population. We aimed to determine whether pretransplant diabetes increases the risk of fractures among patients receiving solid organ transplantation. We conducted a nested case-control study in a cohort of subjects 18 years and older, enrolled in the Quebec Drug Insurance Plan, who received a first solid organ transplantation between January 1986 and December 2005. Cases had sustained a fracture between the date of discharge from the hospitalization for solid organ transplantation and the end of the study period. All remaining patients were eligible controls. The fracture date was the case index date. Cases were matched to up to four controls on the type of organ transplanted and the date of transplantation. The index date of a control patient was that of his/her matched case. Crude and adjusted ORs were obtained with univariate and multivariate conditional logistic regression models. The study included 238 cases and 873 controls. Pretransplant diabetes was present in 30% of the cases and 22% of the controls (crude OR: 2.16; 95% CI: 1.7-2.8). After adjusting for age, sex, previous fractures, past hyperthyroidism, hospitalization duration, use of narcotics, benzodiazepines, antidepressants, loop diuretics, thiazide diuretics, glucocorticoids, immunosuppressants, estrogens, bisphosphonates, calcium, vitamin D, and calcitonin, pretransplantation diabetes remained a significant risk factor for fractures (adjusted OR: 1.94; 95% CI: 1.5-2.6). Use of narcotics (OR: 3.0; 95% CI: 2.0-4.4) and antidepressants (OR: 1.9; 95% CI: 1.2-3.1) in the month preceding the index date and use of loop diuretics in the year preceding the index date (OR: 1.4; 95% CI: 1.1-1.9) were also associated with increased risks of fractures. Pretransplant diabetes seemed to significantly increase post-transplant fractures among adults receiving solid organ transplantation. Pretransplant fracture prophylaxis should be considered in these patients.

A meta-analysis of prior corticosteroid use and fracture risk.

The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.

Bone Densitometry in Premenopausal Women: Synthesis and Review

Abstract Bone loss prior to menopause is being increasingly identified in women. Clearly, low bone mineral density (BMD) is a significant risk factor for fracture in the estrogen-deficient female postmenopause. The significance of low bone density prior to menopause needs to be addressed. Low bone density in the premenopausal female may reflect attainment of a lower peak bone mass. It may also be secondary to progressive bone loss following achievement of peak bone density. The etiology of low bone density in the premenopausal female needs to be clarified with meticulous exclusion of secondary causes of bone loss. Menstrual status is an important determinant of peak bone mass as well as the development of bone loss in women prior to the onset of menopause. Subclinical decreases in circulating gonadal steroids may be associated with a lower peak bone mass as well as progressive bone loss in otherwise reproductively normal women. Elevations of follicle-stimulating hormone (FSH) of greater than 20 miu/L are associated with evidence of increased bone turnover marker activity and correlate with progressive bone loss in perimenopausal women. This transitional period requires further study with respect to the magnitude of bone loss experienced and the potential benefits of antiresorptive therapy. Detailed assessment of menstrual status is necessary in the evaluation of low bone density in premenopausal women. The majority of the cross-sectional and longitudinal studies completed evaluating BMD in the premenopausal years suggest that minimal bone loss does occur prior to menopause after attainment of peak bone mass. The magnitude of premenopausal bone loss, however, is controversial and may be site-dependent. More rapid rates of bone loss are seen in the transitional period beginning 2–3 yr prior to the onset of menopause. Prospective data are needed to understand further the relationship between BMD and fracture in the premenopausal period. Women with steroid-induced bone loss as well as other secondary causes of osteoporosis respond to antiresorptive therapy with documented improvements in BMD. Biomarkers can identify perimenopausal women with increased bone turnover. Lifestyle modification can improve BMD in the pre- and the perimenopausal period. Antiresorptive therapy has not been evaluated in pre- or perimenopausal women with low BMD in the absence of secondary causes of osteoporosis. As new treatment options are evaluated and become available, biomarker assessment may be of value in identifying women at risk of fracture. This paper provides a review of the literature and recommendations with respect to management of low bone density in the premenopausal female.

Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group.

Previous studies have suggested that depression is associated with falls and with low bone density, but it is not known whether depression leads to an increased risk of fracture. We conducted a prospective cohort study in elderly white women who were recruited from population-based listings in the United States. At a second visit (1988-1990), 7414 participants completed the 15-item Geriatric Depression Scale and were considered depressed if they reported 6 or more symptoms of depression. We measured bone mineral density (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second visit, and asked participants about incident falls (yes/no) at 4 follow-up visits. Nonvertebral fractures were ascertained for an average of 6 years following the depression measure, and verified radiologically. We determined incident vertebral fractures by comparing lateral spine films obtained at the first visit (1986-1988) with repeat films obtained an average of 3.7 years later (1991-1992). The prevalence of depression (Geriatric Depression Scale score > or = 6) was 6.3% (467/7414). We found no difference in mean BMD of the hip and lumbar spine in women with depression compared with those without depression. Women with depression were more likely to experience subsequent falls than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9; P<.001), an association that persisted after adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P=.004). Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2-1.7; P<.001) increased rate of nonvertebral fracture (124 fractures in 3805 woman-years of follow-up) compared with women without depression (1367 fractures in 59 503 woman-years of follow-up). This association remained strong after adjusting for potential confounding variables, including medication use and neuromuscular function (HR, 1.3; 95% CI, 1.1-1.6; P=.008). Further adjustment for subsequent falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P = .06). Women with depression were also more likely to suffer vertebral fractures than women without depression, adjusting for history of vertebral fracture, history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P<.001). Depression is a significant risk factor for fracture in older women. The greater frequency of falls among individuals with depression partially explains this finding. Other mechanisms responsible for the association between depression and fracture remain to be determined.

Trauma type, age, and gender as determinants of hip fracture.

We determined the trauma type of femoral neck and trochanteric fractures in men and women aged greater than or equal to 20 years in 19, 128 fractures reported to a computerized medical information register during 1972-1981. We found that the earlier known exponential increase of fracture incidence by age started in early adulthood rather than during middle age. An age-related increase was found for each type of injury as well, although the incidence of fractures resulting from severe trauma increased less than that of fractures associated with moderate trauma. The incidence of low-energy fractures in men as well as in women displayed a constant increase rate with age from young adulthood on, impugning the widely held belief that the menopause is a significant risk factor for fractures. The dominating risk factor for proximal femoral fracture in adults appears to be age, irrespective of the cause of injury, with a chronological decline in bone strength as the most likely cause of the exponential increase in the fracture incidence during adult life.