Risk of hip fracture in disabled community-living older adults

OBJECTIVES: To determine the rate of hip fracture and risk factors associated with hip fractures in disabled older persons who enroll in the Program of All-Inclusive Care for the Elderly (PACE), a program providing comprehensive care to community-living nursing-home-eligible persons. DESIGN: Prospective cohort study between January 1990 and December 1997. SETTING: The twelve PACE demonstration sites: San Francisco, California; Columbia, South Carolina; Detroit, Michigan; Denver, Colorado; East Boston, Massachusetts; El Paso, Texas; Milwaukee, Wisconsin; Oakland, California; Portland, Oregon; Rochester, New York; Sacramento, California; and the Bronx, New York. PARTICIPANTS: Five thousand one hundred eighty-seven individuals in PACE; mean age 79, 71% female, 49% white, 47% with dementia. MEASUREMENTS: Functional status, cognitive status, demographics, and comorbid conditions were recorded on all the participants, who were tracked for occurrence of a hip fracture. The goals were to determine the rate of hip fracture and identify risk factors. RESULTS: Two hundred thirty-eight hip fractures (4.6%) occurred during follow-up. The rate of hip fracture was 2.2% per person-year. Four independent predictors of hip fracture were identified using Cox proportional hazard analysis: age of 75 and older (adjusted hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.4-2.8); white ethnicity (HR = 2.1, 95% CI = 1.6-2.8); ability to transfer independently to and from bed, chair, and toilet (HR = 3.0, 95% CI = 1.2-7.2); and five or more Short Portable Mental Status Questionnaire errors (HR = 1.6, 95% CI = 1.3-2.1). The incidence of hip fracture ranged from 0.5% per person-year in persons with zero to one independent risk factors to 4.7% per person-year in those with all four independent risk factors. CONCLUSIONS: The rate of hip fracture in this cohort of disabled community-living older adults was similar to that reported in nursing home cohorts. Older age, white race, ability to transfer independently, and cognitive impairment were independent predictors of hip fracture. Persons with these risk factors should be targeted for preventive interventions, which should include strategies for making transferring safer.     

Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: a prospective analysis of the NHANES I follow-up study

BACKGROUND: Recent studies on the association between vitamin A and fracture risk have focused on samples with high vitamin A intake. We analyzed a cohort that was more representative of the overall U.S. population to test the hypothesis that both high and low serum vitamin A concentrations increase the risk of hip fracture. METHODS: We utilized data on 2799 women who were 50 to 74 years of age from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. There were 172 incident hip fractures during the 22-year follow-up period. Using Cox regression analysis, we analyzed the relation between baseline serum vitamin A (retinol and retinyl esters) concentration, as a continuous variable and by quintiles, and hip fracture risk. RESULTS: While there was no linear relation between serum vitamin A concentration and the risk of hip fracture in the multivariate analysis (hazard ratio [HR] per SD increase = 1.0; 95% confidence interval [CI]: 0.9 to 1.2), analysis by quintiles revealed a U-shaped relation between serum vitamin A concentration and hip fracture. Fracture risk was significantly higher among subjects in the lowest (HR = 1.9; 95% CI: 1.1 to 3.3) and highest (HR = 2.1; 95% CI: 1.2 to 3.6) quintiles compared with those in the middle quintiles. CONCLUSION: Both low and high serum vitamin A concentrations may be associated with an increased risk of hip fracture.     

Central nervous system active medications and risk for fractures in older women

BACKGROUND: Use of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders. METHODS: To determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports. RESULTS: During an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture. CONCLUSIONS: Community-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.     

Hip fracture in men-survival and subsequent fractures: a cohort study with 22-year follow-up

OBJECTIVES: To evaluate the influence of age on survival and risk of subsequent fracture in men with hip fracture, applying a residual lifetime perspective. DESIGN: Retrospective cohort study with 22‐year follow‐up. SETTING: Skåne University Hospital, Malmö, Sweden. PARTICIPANTS: Men aged 60 and older (N=226) with an index hip fracture during 1984/85. MEASUREMENTS: Twenty‐two‐year survival (mortality) and risk of new fractures evaluated in 5‐year age bands and age groups (<75, 75–84, ≥85). RESULTS: Mean age was 78±9. Mortality at 22 years was 98%. Survivors were all younger than 75 at inclusion. Mortality was dependent on age at all time points (18%, 38%, 69% at 1 year, increasing to 71%, 93%, 100% by 10 years in <75, 75–84, ≥85, respectively). Median survival was 5.4 years, 2.0 years, and 3 months, respectively, in these age groups, and 33%, 27%, and 13% of each age‐group sustained subsequent fractures, generally within 5 years. Overall 10‐year fracture risk was 29% (95% confidence interval (CI)=19–38%), increasing to 44% (95% CI=30–58%) when adjusted for mortality. Residual lifetime risk of new fracture was 33% (95% CI=23–43%), and mortality‐adjusted risk was 63% (95% CI=45–81%). Participants younger than 75 at index hip fracture were at greatest risk of new fracture (hazard ratio=2.7, 95% CI=1.1–6.4, P=.03). CONCLUSION: Almost one‐third of men with hip fracture have subsequent fractures during their remaining lifetime. Time at risk is highly dependent on age. Most new fractures occur in relatively younger men and within 5 years, whereas most aged 75 and older die before experiencing a new fracture.     

A national study on long-term osteoporosis therapy and risk of recurrent fractures in patients with hip fracture

ObjectiveThe study aimed to evaluate the impact of osteoporosis (OP) medication persistence on subsequent fractures and all-cause mortality in patients with hip fracture.MethodsIn this retrospective cohort study, we included patients aged ≥ 40 years with fragility hip fracture from the Taiwan’s National Health Insurance Research Database. OP medication persistence was categorized as yes (≥ 12 months) or no (< 12 months). A multivariate Cox proportional hazard model was used to evaluate the association between OP medication persistence and recurrent fractures (including hip, vertebral, and upper and lower limb fractures) and all-cause mortality.ResultsA total of 946 patients were included in the study (86.5 % of them aged ≥ 65 years) and 210 patients persistently received OP medications. Persistent OP medication use was associated with lower fracture risk (adjusted hazard ratio [aHR] = 0.64; 95 % CI = 0.41–0.99; P = .043) in the follow-up period. The strongest predictors for all-cause mortality were age ≥ 80 years (HR = 5.68, 95 % CI = 1.36–23.64, P = .017), male sex (HR = 1.55; 95 % CI = 1.18–2.03; P = .002), and Charlson Comorbidity Index ≥ 3 (aHR = 1.56; 95 % CI = 1.07–2.27; P = .022). Kaplan-Meier curves showed a lower cumulative incidence of recurrent fractures in the persistent group than that in the non-persistent group (P = .028).ConclusionPersistent OP medication use was associated with a lower risk of recurrent fractures but not with mortality in patients with hip fracture.     

Visual risk factors for hip fracture in older people

OBJECTIVES: To determine the association between poor vision and risk of hip fracture in the Blue Mountains Eye Study. DESIGN: Prospective population-based cohort study. SETTING: Two post code areas in the Blue Mountains, west of Sydney, Australia. PARTICIPANTS: Three thousand six hundred fifty-four community-dwelling Australians aged 49 and older. MEASUREMENTS: At baseline, subjects had an extensive eye examination, including refraction, contrast sensitivity and visual field testing, photographs of the lens and retina, and an interview. Hip fractures during the 5-year follow-up were identified by self-report and review of medical records and were radiologically confirmed. RESULTS: For 2-year follow-up (17 hip fractures), the adjusted hazard ratio (HR) for risk of hip fracture in those with corrected visual acuity worse than 20/60 was 8.4 (95% confidence interval (CI) = 1.5-48.5, population attributable risk (PAR) = 27%); for presence of posterior subcapsular cataract, the adjusted HR was 5.0 (95% CI = 1.1-23.0, PAR = 24%); and for visual field loss, the adjusted HR was 5.5 (95% CI = 1.0-29.8, PAR = 55%). In those aged 75 and older, visual acuity worse than 20/60 gave an adjusted HR of 40.6 (95% CI = 5.6-292.5, PAR = 49%). Visual impairment of any type did not predict risk of hip fracture after a 2-year follow-up. CONCLUSION: Visual impairment is strongly associated with risk of hip fracture in the next 2 years but not over a longer period of time.     

Subsequent fracture in nursing home residents with a hip fracture: a competing risks approach

OBJECTIVES: To determine the incidence and predictors of subsequent fracture in nursing home residents with a hip fracture, accounting for the competing risk of death. DESIGN: Dynamic cohort study. SETTING: Hebrew Rehabilitation Center, a 725‐bed, long‐term care facility in Boston, Massachusetts. PARTICIPANTS: Long‐term care residents with a surgically repaired hip fracture (1999–2006) followed through June 30, 2007, for the occurrence of subsequent fracture at any skeletal site. MEASUREMENTS: Information on age, sex, anatomic location, type of repair, body mass index (BMI), comorbidities, functional status, cognitive status, and medication use were evaluated as potential risk factors for subsequent fracture. RESULTS: The study included 184 residents with a baseline hip fracture. Thirty‐nine residents (7 men, 32 women) experienced a subsequent fracture over a median follow‐up of 1.1 years. After the baseline hip fracture, 6% of residents experienced a subsequent fracture within 6 months, 12% within 1 year, and 21% within 5 years. In addition, 23% of residents died within 6 months, 31% within 1 year, and 60% within 5 years. High functional status was associated with a five times greater risk of subsequent fracture (high vs low functional status, hazard ratio=5.10, P<.005). Age, sex, BMI, comorbidities, cognitive status, and medication use were not associated with subsequent fracture. CONCLUSION: Hip fractures are a sentinel event in nursing home residents, with a high incidence of subsequent fracture and death occurring within 1 year. Identification of prefracture characteristics and postfracture complications associated with mortality should help guide secondary prevention efforts in nursing home residents.     

Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study

OBJECTIVES: To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability. DESIGN: Prospective study, the Women's Health Initiative Observational Study. SETTING: Forty U.S. clinical centers. PARTICIPANTS: Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline. MEASUREMENTS: Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up. RESULTS: Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions. CONCLUSION: These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.     

Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study

BACKGROUND: Data on the influence of gonadal hormones on incident fracture risk in elderly men are limited. We prospectively examined the relationship between serum levels of testosterone and estradiol and future fracture risk in community-dwelling men. METHODS: A total of 609 men older than 60 years had been observed between January 1989 and December 2005, with the median duration being 5.8 years (up to 13 years). Clinical risk factors, including bone mineral density and lifestyle factors, were assessed at baseline. Serum testosterone and estradiol levels were measured by tandem mass spectrometry. The incidence of a low-trauma fracture was ascertained during follow-up. RESULTS: During follow-up, 113 men had at least 1 low-trauma fracture. The risk of fracture was significantly increased in men with reduced testosterone levels (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.09-1.62). After adjustment for sex hormone-binding globulin, serum testosterone (HR, 1.48; 95% CI, 1.22-1.78) and serum estradiol (HR, 1.21; 95% CI, 1.00-1.47) levels were associated with overall fracture risk. After further adjustment for major risk factors of fractures (age, weight or bone mineral density, fracture history, smoking status, calcium intake, and sex hormone-binding globulin), lower testosterone was still associated with increased risk of fracture, particularly with hip (HR, 1.88; 95% CI, 1.24-2.82) and nonvertebral (HR, 1.32; 95% CI, 1.03-1.68) fractures. CONCLUSION: In community-dwelling men older than 60 years, serum testosterone is independently associated with the risk of osteoporotic fracture and its measurement may provide additional clinical information for the assessment of fracture risk in elderly men.     

Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study

BACKGROUND: Breast cancer and its treatment may compromise bone health. We tested the hypothesis in the Women's Health Initiative Observational Study that postmenopausal survivors of breast cancer have a higher risk for fractures compared with women who have no cancer history. METHODS: A prospective cohort (5.1 years' follow-up) study design was used. Breast cancer survivors were women who reported a history of breast cancer (n = 5298). A reference group included women who had no cancer history at baseline (n = 80 848). Fracture occurrence was ascertained from annual self-reports. Hip fractures were confirmed by reviewing medical records. RESULTS: After adjustment for age, weight, ethnicity, and geographic region of enrollment, the hazard ratios (HRs) of breast cancer survivors to women in the reference group were 0.93 (95% confidence interval [CI], 0.64-1.33) for hip; 1.36 (95% CI, 1.16-1.59) for forearm or wrist; 1.31 (95% CI, 1.19-1.43) for eligible fractures other than hip, vertebral, and forearm or wrist; and 1.31 (95% CI, 1.21-1.41) for these fractures combined. The increased risk for clinical vertebral fracture was statistically significant only among survivors who had a breast cancer diagnosis before age 55 years (HR, 1.78; 95% CI, 1.28-2.46). After adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle, the increased risk for all fractures studied among survivors was reduced to 15% (HR, 1.15; 95% CI, 1.05-1.25). CONCLUSIONS: Postmenopausal survivors of breast cancer are at increased risk for clinical fractures. Preventions and therapeutic interventions are needed to reduce fracture risk in this large and growing population.     

Risk factors associated with incident clinical vertebral and nonvertebral fractures in Japanese women with rheumatoid arthritis: a prospective 54-month observational study

OBJECTIVE: To evaluate the association between potential risk factors and incident clinical fractures in Japanese patients with rheumatoid arthritis (RA). METHODS: A total of 1733 female patients with RA over age 50 years were enrolled in a prospective observational cohort study. Participants were followed for 54 months from October 2000 to March 2005, and classified into 4 groups according to incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture); and those with any new nonvertebral fracture. Cox proportional hazard models were used to analyze independent contributions of various risk factors to fracture incidence. RESULTS: During the followup period, 33, 34, and 98 patients developed a vertebral, a main nonvertebral, and any nonvertebral fracture, respectively. The Japanese Health Assessment Questionnaire (J-HAQ) score was associated with relative risks (RR) of 2.42 (95% confidence interval 1.42-4.14), 1.76 (95% CI 1.07-2.89), and 1.73 (95% CI 1.29-2.32) for vertebral, main nonvertebral, and all nonvertebral fractures. The risks of vertebral and any nonvertebral fractures were increased for age over 70 years compared with age in the 50s (RR 3.25, 95% CI 1.19-8.86; and RR 2.22, 95% CI 1.20-4.10, respectively). Clinical variables and medications were associated with a new fracture. CONCLUSION: HAQ, age, history of any prior fracture, and orthopedic surgery for RA appear to be associated with fractures in Japanese women with RA.     

Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk

Aims/hypothesis We studied the association between fractures and type 1 and type 2 diabetes mellitus.Methods In this case-control study, all subjects diagnosed with a fracture (n=124,655) in Denmark served as cases, and for each case three control subjects (n=373,962) matched for sex and age were retrieved from the general population.Results Type 1 and type 2 diabetes were associated with an increased risk (1) of any fracture (odds ratio [OR]=1.3, 95% CI: 1.2–1.5 for type 1 diabetes and 1.2, 95% CI: 1.1–1.3 for type 2 diabetes after adjustment for confounders) and (2) of hip fractures (OR=1.7, 95% CI: 1.3–2.2 for type 1 diabetes, and 1.4, 95% CI: 1.2–1.6 for type 2 diabetes). Furthermore, type 2 diabetes was associated with a significant increase in forearm fractures (OR=1.2, 95% CI: 1.0–1.5), and type 1 diabetes was associated with an increased risk of spine fractures (OR=2.5, 95% CI: 1.3–4.6), whereas type 2 diabetes was not. Use of metformin and sulphonylureas was associated with a significantly decreased risk of any fracture, whereas a non-significant trend towards decreased risk of any fracture was associated with the use of insulin. Except for a decrease in hip fractures with use of sulphonylureas, no change in fracture risk in the hip, spine or forearm was associated with the use of insulin or oral antidiabetic drugs.Conclusions/interpretation Type 1 and type 2 diabetes are associated with an increased risk of any fracture and hip fractures. The use of drugs to control diabetes may reduce the association between diabetes and fractures.     

Opioid analgesics and the risk of fractures in older adults with arthritis

OBJECTIVES: To compare the risk of fracture associated with initiating opioids with that of nonsteroidal anti‐inflammatory drugs (NSAIDs) and the variation in risk according to opioid dose, duration of action, and duration of use. DESIGN: Retrospective cohort study. SETTING: Two statewide pharmaceutical benefit programs for persons aged 65 and older. PARTICIPANTS: Twelve thousand four hundred thirty‐six initiators of opioids and 4,874 initiators of NSAIDs began treatment between January 1, 1999, and December 31, 2006. Mean age at initiation of analgesia was 81; 85% of participants were female, and all had arthritis. MEASUREMENTS: Cox proportional hazards models, adjusted for several potential confounders, quantified fracture risk. Study outcomes were fractures of the hip, humerus or ulna, or wrist, identified using a combination of diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification) and procedure (Common Procedural Terminology) codes. RESULTS: There were 587 fracture events among the participants initiating opioids (120 fractures per 1,000 person‐years) and 38 fracture events among participants initiating NSAIDs (25 fractures per 1,000 person‐years) (hazard ratio (HR)=4.9, 95% confidence interval (CI)=3.5–6.9). Fracture risk was greater with higher opioid dose. Risk was greater for short‐acting opioids (HR=5.1, 95% CI=3.7–7.1) than for long‐acting opioids (HR=2.6, 95% CI=1.5–4.4), even in participants taking equianalgesic doses, with differential fracture risk apparent for the first 2 weeks after starting opioids but not thereafter. CONCLUSION: Older people with arthritis who initiate therapy with opioids are more likely to experience a fracture than those who initiate NSAIDs. For the first 2 weeks after initiating opioid therapy, but not thereafter, short‐acting opioids are associated with a greater risk of fracture than are long‐acting opioids.     

Osteoporotic fractures and heart failure in the community

Purpose

Recent findings suggest a role for heart failure in the etiology of osteoporotic fractures, yet the temporal sequence of occurrence of the 2 conditions needs clarification.

Methods

Using the Rochester Epidemiology Project, the authors conducted a 2-phase study: a case-control study compared osteoporotic fracture history among Olmsted County, Minnesota, residents newly diagnosed with heart failure in 1979-2002 with age- and sex-matched community controls without heart failure (961 pairs; mean age 76 years; 54% women). Both groups were then followed to July 2009 to evaluate their subsequent fracture risk in a cohort study.

Results

Prior fractures were more frequent in heart failure cases than controls (23.1% vs. 18.8%, P = .02). The adjusted odds ratio (OR) for heart failure associated with prior fracture was 1.39 (95% confidence interval [CI], 1.07-1.81), mainly driven by hip fractures (OR 1.82; 95% CI, 1.25-2.66) with little or no association with other fractures. Over a mean follow-up of 7.5 years, 444 individuals developed subsequent osteoporotic fractures. The adjusted fracture risk was marginally elevated in heart failure patients compared with controls (hazard ratio [HR] 1.32; 95% CI, 0.98-1.79), again largely attributable to hip fractures (HR 1.58; 95% CI, 1.03-2.41).

Conclusions

In this community, the association with fracture risk was about as strong before as after the diagnosis of heart failure and was nearly entirely attributable to hip fractures. Additional work is needed to identify common underlying mechanisms for heart failure and hip fracture, which may define prevention opportunities.     

Amount of social contact and hip fracture mortality

OBJECTIVES: To study the association between amount of social contact and mortality after hip fracture in elderly participants.
DESIGN: Prospective cohort.
SETTING: Community residents of Baltimore, Maryland.
PARTICIPANTS: Six hundred seventy-four elderly participants.
MEASUREMENTS: Amount of telephone and direct personal contact between participants and their relatives and friends and mortality up to 2 years after fracture.
RESULTS: No social contact with friends during the 2 weeks before the fracture was associated with a five times greater risk of death over 2 years than daily contact with friends during the 2 weeks before the fracture (hazard ratio (HR)=5.04, 95% confidence interval (CI)=2.75–9.23). Participants with less than daily contact were also at greater risk of dying, although the CI spanned 1 (HR=1.76, 95% CI=0.99–3.13). Participants who had no contact with family members prefracture were more than twice as likely to die as those who communicated daily during the 2 weeks before fracture (HR=2.26, 95% CI=1.36–3.77). Participants who had less than daily contact were also more than twice as likely to die (HR=2.55, 95% CI=1.65–3.94).
CONCLUSION: This study suggests that lower social contact before hip fracture is associated with poorer survival after 2 years.     

Risk of hip fracture in Addison's disease: a population-based cohort study

Abstract. Björnsdottir S, Sääf M, Bensing S, Kämpe O, Michaëlsson K, Ludvigsson JF (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; and Örebro University Hospital, Örebro; Sweden). Risk of hip fracture in Addison’s disease: a population‐based cohort study. J Intern Med 2011; 270 : 187–195. Objectives. The results of studies of bone mineral density in Addison’s disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study, we compare hip fracture risk in adults with and without AD. Design. A population‐based cohort study. Methods. Through the Swedish National Patient Register and the Total Population Register, we identified 3219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964–2006 and 31 557 age‐ and sex‐matched controls. Time to hip fracture was measured. Results. We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture [hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6–2.1; P < 0.001]. This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95 % CI, 1.6–4.5). We found a positive association between hip fracture and undiagnosed AD [odds ratio (OR) = 2.4; 95 % CI, 2.1–3.0] with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95 % CI, 1.8–4.2). Conclusion. Both clinically undiagnosed and diagnosed AD was associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age.     

Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders

OBJECTIVES: Herpes zoster (HZ) is a common disorder that causes substantial pain and morbidity. We examined its rate and predictors in rheumatoid arthritis (RA) and non-inflammatory musculoskeletal (MSK) disorders to determine if HZ was increased in RA and whether treatment contributed to the risk of HZ. METHODS: After excluding patients witzh prior HZ, we assessed 10 614 RA and 1721 MSK patients by semi-annual questionnaires during 33 825 patient-years of follow-up. Predictors of HZ were determined by Cox regression and expressed as hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The annualized incidence rate per 1000 patient-years was 13.2 (95% CI 11.9-14.5) in RA and 14.6 (95% CI 11.2-18.1) in MSK, and did not differ significantly after adjustment for age and sex. HZ was predicted by impaired functional status, as measured by the Health Assessment Questionnaire (HAQ), [HR 1.3 (95% CI 1.1-1.5)] and by the use of COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs) [HR 1.3 (95% CI 1.1-1.6)] in RA and MSK. In multivariable analyses in patients with RA, cyclophosphamide HR 4.2 (95% CI 1.6-11.5), azathioprine HR 2.0 (1.2-3.3), prednisone HR 1.5 (1.2-1.8), leflunomide HR 1.4 (1.1-1.8) and COX-2 NSAIDs HR 1.3 (95% CI 1.1-1.6) were significant predictors of HZ. CONCLUSION: The incidence of HZ is increased in RA and MSK compared with population-based rates. However, the rate of HZ in RA is not increased compared with MSK. After adjustment for severity, various treatments, but not methotrexate or biologics, were risk factors for HZ.     

Natural history of radiographic hip osteoarthritis: A retrospective cohort study with 11-28 years of followup

Objective

To evaluate the association between radiographic hip osteoarthritis (OA) and future total hip replacement (THR) due to OA or hip fracture.

Methods

We studied a cohort of individuals who had colon radiography from 1980–1997. Minimal joint space (MJS) was measured and each hip was graded for radiographic OA according to the Kellgren/Lawrence scale. Subjects were followed until the end of 2008. A Cox proportional hazards model, adjusted for age and sex, was used to evaluate factors associated with THR and hip fracture.

Results

A total of 2,953 hips were studied (57% women). The cumulative incidence of THR was 2.5% and the cumulative incidence of hip fracture was 2.6%. For hips with radiographic hip OA (MJS of 2.5 mm or less), the cumulative incidence of THR was 16.9% and the hazard ratio (HR) for THR was 13.2 (95% confidence interval [95% CI] 8.1–21). Using Kellgren/Lawrence grading, the HR for THR was 12.9 (95% CI 7.9–21) for hips with radiographic OA compared to those without. The HR for all types of hip fracture for hips with radiographic OA (MJS of 2.5 mm or less) was 0.47 (95% CI 0.15–1.5), for intracapsular fractures was 0.29 (95% CI 0.04–2.1), and for extracapsular fractures was 0.67 (95% CI 0.16–2.8).

Conclusion

The risk of THR due to OA is substantially increased in patients with radiographic hip OA, regardless of symptoms, and increases with decreasing MJS. However, 11–28 years after having had radiographic hip OA, more than 4 of 5 of those having radiographic signs of hip OA had not had a THR for OA.     

Renal function and risk of hip and vertebral fractures in older women

BACKGROUND: An increased rate of hip fractures has been reported in patients with end-stage renal disease, but the effect of less severe renal dysfunction on fracture risk is uncertain. METHODS: We conducted a case-cohort study within a cohort of 9704 women 65 years or older to compare baseline renal function (estimated glomerular filtration rate [eGFR] using the Cockcroft-Gault equation) in 149 women who subsequently had hip fractures and 150 women who subsequently had vertebral fractures with eGRF in 396 randomly selected women. RESULTS: In models adjusted for age, weight, and calcaneal bone density, decreasing eGFR was associated with increased risk of hip fracture. Compared with women with an eGFR 60 mL/min per 1.73 m(2) or greater, the hazard ratio (95% confidence interval [CI]) for hip fracture was 1.57 (95% CI, 0.89-2.76) in those with an eGFR 45 to 59 mL/min per 1.73 m(2) and 2.32 (95% CI, 1.15-4.68) in those with an eGFR less than 45 mL/min per 1.73 m(2) (P for trend = .02). In particular, women with a reduced eGFR were at increased risk of trochanteric hip fracture (adjusted hazard ratio, 3.93 [95% CI, 1.37-11.30] in women with an eGFR 45-59 mL/min per 1.73 m(2) and 7.17 [95% CI, 1.93-26.67] in women with an eGFR <45 mL/min per 1.73 m(2); P for trend = .004). Renal function was not independently associated with risk of vertebral fracture (adjusted odds ratio, 1.08 [95% CI, 0.61-1.92] in women with an eGFR 45-59 mL/min per 1.73 m(2) and 1.33 [95% CI, 0.63-2.80] in women with an eGFR <45 mL/min per 1.73 m(2); P for trend = .47). CONCLUSION: Older women with moderate renal dysfunction are at increased risk of hip fracture.