Relationship between use of antidepressants and risk of fractures: a meta-analysis

Summary

It has been shown that antidepressants would have a direct action on bone metabolism and would be associated with increased fracture risk. Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types.

Introduction

This study seeks to investigate the relationship between use of antidepressants and the risk of fracture.

Methods

An exhaustive systematic research of case–control and cohort studies published or performed between 1966 and April 2011 that reported risk estimates of fracture associated with use of antidepressants was performed using MEDLINE, PsycINFO, and the Cochrane Systematic Review Database, manual review of the literature, and congressional abstracts. Inclusion, quality scoring, and data abstraction were performed systematically by three independent reviewers.

Results

A total of 34 studies (n?=?1,217,464 individuals) were identified. Compared with non-users, the random effects pooled RR of fractures of all types, among antidepressant users, were 1.39 (95%CI 1.32–1.47). Use of antidepressants were associated with a 42 %, 47 %, and 38 % risk increase in non-vertebral, hip, and spine fractures, respectively ([For non-vertebral fractures: RR?=?1.42, 95%CI 1.34–1.51]; [For hip fractures: RR?=?1.47, 95%CI 1.36–1.58]; [For spine fractures: RR?=?1.38, 95%CI 1.19–1.61]). Studies examining SSRI use showed systematically a higher increase in the risk of fractures of all types, non-vertebral, and hip fractures than studies evaluating TCA use.

Conclusions

Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types.     

Fracture rate in patients with myasthenia gravis: the general practice research database

Summary

The aim of this study was to evaluate fracture risk after onset of myasthenia gravis using the UK General Practice Research Database. Overall fracture risk is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use, but was increased in those using antidepressants, anxiolytics or anticonvulsants.

Introduction

Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. The aim of this study was to evaluate the risk of fracture after onset of MG.

Methods

We conducted a retrospective cohort study using the UK General Practice Research Database (1987–2009). Each MG patient was matched by age, sex, calendar time and practice to up to six patients without a history of MG and we identified all fractures and those associated with osteoporosis.

Results

Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84–1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67–1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31–3.14]) compared with MG patients without glucocorticoid exposure. However, fracture risk was higher in patients with MG prescribed antidepressants (AHR 3.27 [95 % CI, 1.63–6.55]), anxiolytics (AHR 2.18 [95 % CI, 1.04–4.57]) and anticonvulsants (AHR 6.88 [95 % CI, 2.91–16.27]).

Conclusion

Overall risk of fracture in patients with MG is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use but was increased in those using antidepressants, anxiolytics or anticonvulsants. These findings have implications in strategies preserving bone health in patients with MG.     

Coffee, tea, and the risk of hip fracture: a meta-analysis

Summary

The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1?4 cups of tea daily was associated with a lower risk of hip fracture.

Introduction

Prospective cohort and case–control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture.

Methods

We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95 % confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose–response, heterogeneity, publication bias, and subgroup analyses.

Results

Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case–control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95 % CI 0.71–1.17) and 0.84 (95 % CI 0.66–1.02), respectively. For the dose–response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p _nonlinearity?<?0.01). Compared to no tea consumption, 1–4 cups of tea per day may reduce the risk of hip fracture by 28 % (0.72; 95 % CI 0.56–0.88 for 1–2 cups/day), 37 % (0.63; 95 % CI 0.32–0.94 for 2–3 cups/day), and 21 % (0.79; 95 % CI 0.62–0.96 for 3–4 cups/day).

Conclusions

We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1–4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.     

Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis: a prospective observational cohort study

Summary

Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. Physical disability, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) appear to be associated with the occurrence of hip fracture.

Introduction

This study seeks to evaluate the association between potential risk factors and the occurrence of hip fractures in Japanese RA patients.

Methods

A total of 9,720 patients (82.1 % female; mean age, 55.7 years) with RA were enrolled in a prospective observational study from 2000 to 2010. Self-reported hip fractures were verified using patient medical records. Cox proportional hazards models were used to analyze independent contributions of various risk factors to hip fracture occurrence.

Results

During a mean follow-up of 5.2 years, 152 patients reported 152 hip fractures. Among these patients, 97 hip fractures in 97 patients (15 males, 82 females) were verified with medical records. Japanese version of the Health Assessment Questionnaire (J-HAQ) disability score [per 1 score, hazard ratio (HR), 2.64; 95 % confidence interval (CI), 1.94–3.58], age (per 10 years; HR, 1.53; 95 % CI, 1.25–1.87), history of TKR (HR, 3.75; 95 % CI, 1.57–8.96), and BMI (per 1 kg/m², HR, 0.92; 95 % CI, 0.86–0.99) were significantly associated with hip fractures. Among the scores on the eight domains of the J-HAQ, J-HAQ (arising) (HR, 1.74; 95 % CI, 1.28–2.36) and J-HAQ (hygiene) (HR, 1.58; 95 % CI, 1.11–2.24) were significantly correlated with the occurrence of hip fracture.

Conclusions

High J-HAQ disability score, advanced age, history of TKR, and low BMI appear to be associated with the occurrence of hip fractures in Japanese RA patients. Among the eight domains of the J-HAQ, arising and hygiene disabilities appear to be correlated with the occurrence of hip fractures in this patient population.     

Hip fracture prevention with a multifactorial educational program in elderly community-dwelling Finnish women

Summary

Guidelines suggest identification of women at fracture risk by bone density measurement and subsequently pharmacotherapy. However, most women who sustain a hip fracture do not have osteoporosis in terms of bone density. The present non-pharmacological intervention among elderly women unselected for osteoporosis reduced hip fracture risk by 55 % providing an alternative approach to fracture prevention.

Introduction

Hip fractures are expensive for society and cause disability for those who sustain them. We studied whether a multifactorial non-pharmacological prevention program reduces hip fracture risk in elderly women.

Methods

A controlled trial concerning 60- to 70-year-old community-dwelling Finnish women was undertaken. A random sample was drawn from the Population Information System and assigned into the intervention group (IG) and control group (CG). Of the 2,547 women who were invited to the IG, 1,004 (39 %) and of the 2,120 invited to the CG, 1,174 (55 %) participated. The IG participated in a fracture prevention program for 1 week at a rehabilitation center followed by review days twice. The CG received no intervention. During the 10-year follow-up, both groups participated in survey questionnaire by mail. Outcome of interest was occurrence of hip fractures and changes in bone–health-related lifestyle.

Results

During the follow-up, 12 (1.2 %) women in the IG and 29 (2.5 %) in the CG sustained a hip fracture (P?=?0.039). The determinants of hip fractures by stepwise logistic regression were baseline smoking (odds ratio (OR) 4.32 (95 % confidence interval [CI] 2.14–8.71), age OR 1.15/year (95 % CI 1.03–1.28), fall history OR 2.7 (95 % CI 1.24–5.9), stroke history OR 2.99 (95 % CI 1.19–7.54) and participating in this program OR 0.45 (95 % CI 0.22–0.93). Starting vitamin D and calcium supplement use was more common in the IG compared with the CG.

Conclusions

The results suggest that this non-pharmacological fracture prevention program may reduce the risk of hip fractures in elderly Finnish women.     

Mediterranean diet and incidence of hip fractures in a European cohort

Summary

Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men.

Introduction

Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries.

Methods

A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders.

Results

Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI)?=?0.89–0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR?=?0.86; 95 % CI?=?0.79–0.94) and high fruit (HR?=?0.89; 95 % CI?=?0.82–0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR?=?1.18; 95 % CI?=?1.06–1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate?=?1.74; 95 % CI?=?1.32–2.31) was also a risk factor.

Conclusions

In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.     

The risk of major and any (non-hip) fragility fracture after hip fracture in the United Kingdom: 2000–2010

Summary

The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4 % of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5 % after 5 years. Subsequent fracture rates increased during the study period both for major and any (non-hip) fracture.

Introduction

Hip fractures are associated with subsequent fractures, particularly in the year following initial fracture. Age-adjusted hip fracture rates have stabilised in many developed countries, but secular trends in subsequent fracture remain poorly documented. We thus evaluated secular trends (2000–2010) and determinants for the risk of a subsequent major (humerus, vertebral, or forearm) and any (non-hip) fracture after hip fracture.

Methods

Patients ≥50 years with a hip fracture between 2000 and 2010 were extracted from the UK Clinical Practice Research Datalink (n?=?30,516). Incidence rates, cumulative incidence probabilities, and adjusted hazard ratios (aHRs) were calculated.

Results

Within 1 year following hip fracture, 2.7 and 8.4 % of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5 % after 5 years, respectively. The most important risk factors for a subsequent major fracture within 1 year were the female gender [aHR 1.90, 95 % confidence interval (CI) 1.51–2.40] and a history of secondary osteoporosis (aHR 1.54, 95 % CI 1.17–2.02). The annual risk increased during the study period for both subsequent major (2009–2010 vs. 2000–2002: aHR 1.44, 95 % CI 1.12–1.83) and any (non-hip) facture (2009–2010 vs. 2000–2002: aHR 1.80, 95 % CI 1.58–2.06).

Conclusion

The risk of sustaining a major or any (non-hip) fracture after hip fracture is small in the first year. However, given the recent rise in secondary fracture rates and the substantial risk of subsequent fracture in the longer term, fracture prevention is clearly indicated for patients who have sustained a hip fracture.     

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS)

Summary

We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors.

Introduction

Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50?+?.

Methods

We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture.

Results

Among 6,645 subjects, 192 (2.9 %) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7 %) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95 % confidence intervals (CI), 1.48–2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95 % CI, 1.32–2.14).

Conclusions

Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.     

Incidence of hip fractures in Greece during a 30-year period: 1977–2007

Summary

The incidence of hip fractures doubled in Greece from 1977 to 2007 among people aged 50 and over. A mild decrease was observed after 2002, although the future trend cannot be safely anticipated at the moment. Half of all hip fractures in 2007 were derived from the age group of 80 and over.

Introduction

The purpose of this study was to determine the incidence of hip fractures during a 30-year period in Greece among people aged 50 and over and to document possible alterations in secular trends.

Methods

We studied hip fractures during 2007 and compared them with those of previous years starting from 1977 with an in-between 5-year interval (1977, 1982, 1987, 1992, 1997, 2002). Age- and sex-specific incidence was calculated, and secular trends were recorded. The relative risk of hip fracture in every age group was estimated according to the corresponding incidence of 1977.

Results

The adjusted incidence of hip fractures increased approximately 100 % throughout the study; it progressively increased from 1977 to 2002 and exhibited a mild significant decrease thereafter. The relative risk of hip fractures among subjects aged 60–69 in 2007 has declined compared with 1977 [0.85, 95 % confidence intervals (CI) 0.79–0.92, p?<?0.0005]. Among people aged 70–79, an increased relative fracture risk (1.53, 95 % CI 1.45–1.61, p?<?0.0005) was estimated in 2007 compared with 1977. People ≥80 years old were responsible for half of the hip fractures in 2007 but only for the 22.5 % of fractures in 1977. The relative fracture risk in people aged ≥80 was 2.81 times higher (95 % CI 2.64–2.98, p?<?0.0005) in 2007 than in 1977.

Conclusions

The incidence of hip fractures doubled during the last 30 years among people aged ≥50 years, although a mild decrease was observed in almost all age groups after 2002. The most affected group is 80 and over.     

Age-adjusted incidence rates of hip fractures between 2006 and 2009 in Rabat, Morocco

Summary

This study, characterizing the incidence of hip fracture in the province of Rabat, showed that age- and sex-specific rates remained stable between 2006 and 2009. The demographic projections estimated for Morocco indicate that between 2010 and 2030, the expected annual number of hip fractures would increase about twofold.

Introduction

No data on hip fracture incidence trends exist from Africa. The aim of the study was to determine time trends in hip fracture rates for the province of Rabat and to forecast the number of hip fractures expected in Morocco up to 2030.

Methods

All hip fracture cases registered during the years 2006–2009 were collected at all the public hospitals and private clinics with a trauma unit and/or a permanent orthopedic surgeon across the province.

Results

Over the 4-year period, 723 (54.3 %) hip fractures were recorded in women and 607 (45.6 %) in men. The age- and gender-specific incidence of hip fracture rose steeply with advancing age. Hip fractures occurred later in women 75.0 (10.7) years than in men 73.3 (11.0) years (p?=?0.014), and its incidence was higher in women than in men [85.9 (95 % CI 79.7–92.2) per 100,000 person-years vs. 72.7 (95 % CI 66.9–78.5)]. The incidence remained globally stable over the period study, and the linear regression analysis showed no significant statistical difference. For the year 2010, there were 4,327 hip fractures estimated in Morocco (53.3 % in women). Assuming no change in the age- and sex-specific incidence of hip fracture from 2010 to 2030, the number of hip fractures in men is expected to increase progressively from 2,019 to 3,961 and from 2,308 to 4,259 in women.

Conclusion

The age-specific incidence of hip fracture between the years 2006 and 2009 remained stable in Morocco, and the number of expected hip fractures would double between 2010 and 2030.     

Diuretic initiation and the acute risk of hip fracture

Summary

We found the risk of hip fracture was transiently elevated around twofold shortly after initiation of a loop or thiazide diuretic drug in a case-crossover and case–control study. No statistical association was found following the initiation of a comparator medication: ACE inhibitors. Awareness of these short-term risks may reduce hip fractures.

Introduction

Little is known about the acute effects of initiating a diuretic drug on risk of fracture. We evaluated the relationship between initiating a diuretic drug and the occurrence of hip fracture.

Methods

The study sample included 2,118,793 persons aged ≥50 years enrolled in The Health Improvement Network (THIN) between 1986 and 2010. The effect of a new start of a diuretic drug or comparator medication (ACE inhibitor) on risk of hip fracture was assessed using a case-crossover and case–control study during the 1–7, 8–14, 15–21, and 22–28 days following drug initiation.

Results

Included were 28,703 individuals with an incident hip fracture over a mean of 7.9 years follow-up. In the case-crossover study, the risk of experiencing a hip fracture was increased during the first 7 days following loop diuretic drug initiation (OR?=?1.8; 95 % CI, 1.2, 2.7). The elevated risk did not continue during the 8–14, 15–21, or 22–28 days following drug initiation. For thiazide diuretics, the risk of hip fracture was elevated 8–14 days after drug initiation (OR?=?2.2; 95 % CI, 1.2, 3.9). No such association was observed in the 1–7, 15–21, or 22–28 days following thiazide drug initiation. ACE inhibitor initiation was not associated with a statistically significant increased risk of hip fracture. Similar results were observed using a case–control study.

Conclusions

The risk of hip fracture was transiently elevated around twofold shortly after the new start of a loop or thiazide diuretic drug. Awareness of these short-term risks may reduce hip fractures and other injurious falls in vulnerable adults.     

FRAX provides robust fracture prediction regardless of socioeconomic status

Summary

We investigated the fracture risk assessment tool (FRAX) Canada calibration and discrimination according to income quintile in 51,327 Canadian women, with and without a competing mortality framework. Our data show that, under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of socioeconomic status (SES).

Introduction

FRAX® predicts 10-year fracture risk. Social factors may independently affect fracture risk. We investigated FRAX calibration and discrimination according to SES.

Methods

Women aged ≥50 years with baseline femoral neck bone mineral density (BMD) were identified from the Manitoba Bone Density Program, Canada (n?=?51,327), 1996–2011. Mean household income, extracted from 2006 census files, was categorized into quintiles. Ten-year fracture probabilities were calculated using FRAX Canada. Incident non-traumatic fractures were studied in relation to income quintile in adjusted Cox proportional hazards models. We compared observed versus predicted fractures with and without a competing mortality framework.

Results

During mean 6.2?±?3.7 years of follow up, there were 6,392 deaths, 3,723 women with ≥1 major osteoporotic fracture (MOF), and 1,027 with hip fractures. Lower income was associated with higher risk for death, MOF, and hip fracture in adjusted models (all p?<?0.005). More women in income quintile 1 (lowest) versus quintile 5 experienced death (19 vs. 8 %), MOF (10 vs. 6 %), or hip fracture (3.0 vs. 1.3 %) (all p?≤?0.001). Adjustment for competing mortality mitigated the effect of SES on FRAX calibration, and good calibration was observed. FRAX provided good fracture discrimination for MOF and hip fracture within each income quintile (all p?<?0.001). Area under the curve was slightly lower for income quintiles 1 versus 5 for FRAX with BMD to predict MOF (0.68, 95 % CI 0.66–0.70 vs. 0.71, 95 % CI 0.69–0.74) and hip fracture (0.79, 95 % CI 0.76–0.81 vs. 0.87, 95 % CI 0.84–0.89).

Conclusion

Increased fracture risk in individuals of lower income is offset by increased mortality. Under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of SES.     

Peripheral arterial disease increases the risk of subsequent hip fracture in older men: the Health in Men Study

Summary

The aim of the present study was to assess whether peripheral arterial disease is associated with an increased risk of hip fracture in a cohort of 12,094 older men. There was no association between claudication and hip fracture, but there was a significant association with an ankle brachial index (ABI) <0.9.

Introduction

It is uncertain whether peripheral arterial disease (PAD) is associated with an increased risk of subsequent hip fracture. The aim of the present study was to assess this in a large cohort of men aged 65 years and over.

Methods

Claudication was assessed by means of the Edinburgh Claudication Questionnaire in 12,094 men, and the ABI was measured in 4,321 of these men. Hospitalisations with hip fracture were identified by record linkage. The association between both claudication and an ABI <0.9 and subsequent hip fractures was assessed using survival curves and Cox regression models.

Results

Amongst the 12,094 men, the baseline prevalence of claudication according to the ECQ was 5.3 %. Amongst the 4,321 men with ABI results, the prevalence of an ABI <0.9 was 11.7 %. Of the 506 men with an ABI <0.9, 129 (25.5 %) also had claudication. Over a median (range) follow-up of 10.8 (0.3–12.7) years, 343 (2.8 %) of the 12,094 men were admitted to hospital with a hip fracture. There was no association between claudication and subsequent hip fractures (hazard ratio (HR)?=?0.95; 95 % confidence interval (CI), 0.60, 1.52). Over a median (range) follow-up of 11.1 (0.06–12.3) years 135 (3.1 %) of the 4,321 men with ABI data were admitted to hospital with hip fractures. There was a significant association between an ABI <0.9 and subsequent hip fracture (HR?=?1.69; 95 % CI, 1.08, 2.63).

Conclusion

Older men with PAD defined as ABI?<?0.9 are at increased risk of hip fracture, whereas the symptom of claudication is not an independent predictor of hip fracture.     

All-cause and cause-specific mortality after hip fracture among Chinese women and men

Summary

All-cause mortality risk persisted for 5 years after hip fractures in both men and women. There may be gender-specific differences in effect and duration of excess risk for cause-specific mortality after hip fracture.

Introduction

To determine all-cause and cause-specific mortality risk in the first 5 years after hip fracture in an Asian Chinese population.

Methods

The Singapore Chinese Health Study is a population-based cohort of 63,257 middle-aged and elderly Chinese men and women in Singapore recruited between 1993 and 1998. This cohort was followed up for hip fracture and death via linkage with nationwide hospital discharge database and death registry. As of 31 December 2008, we identified 1,166 hip fracture cases and matched five non-fracture cohort subjects by age and gender for each fracture case. Cox proportional hazards and competing risks regression models with hip fracture as a time-dependent covariate were used to determine all-cause and cause-specific mortality risk, respectively.

Results

Increase in all-cause mortality risk persisted till 5 years after hip fracture (adjusted hazard ratio, aHR = 1.58 [95 % CI, 1.35–1.86] for females and aHR = 1.64 [95 % CI, 1.30–2.06] for males). Men had higher mortality risk after hip fracture than women for deaths from stroke and cancer up to 1 year post-fracture but women with hip fracture had higher coronary artery mortality risk than men for 5 years post-fracture. Men had higher risk of death from pneumonia while women had increased risk of death from urinary tract infections. There was no difference in mortality risk by types of hip fracture surgery.

Conclusions

All-cause mortality risk persisted for 5 years after hip fractures in men and women. There are gender-specific differences in effect size and duration of excess mortality risk from hip fractures between specific causes of death.     

Direct health-care costs attributed to hip fractures among seniors: a matched cohort study

Summary

Using a matched cohort design, we estimated the mean direct attributable cost in the first year after hip fracture in Ontario to be $36,929 among women and $39,479 among men. These estimates translate into an annual $282 million in direct attributable health-care costs in Ontario and $1.1 billion in Canada.

Introduction

Osteoporosis is a major public health concern that results in substantial fracture-related morbidity and mortality. It is well established that hip fractures are the most devastating consequence of osteoporosis, yet the health-care costs attributed to hip fractures in Canada have not been thoroughly evaluated.

Methods

We determined the 1- and 2-year direct attributable costs and cost drivers associated with hip fractures among seniors in comparison to a matched non-hip fracture cohort using health-care administrative data from Ontario (2004–2008). Entry into long-term care and deaths attributable to hip fracture were also determined.

Results

We successfully matched 22,418 female (mean age?=?83.3 years) and 7,611 male (mean age?=?81.3 years) hip fracture patients. The mean attributable cost in the first year after fracture was $36,929 (95 % CI $36,380–37,466) among women and $39,479 (95 % CI $38,311–$40,677) among men. These estimates translate into an annual $282 million in direct attributable health-care costs in Ontario and $1.1 billion in Canada. Primary cost drivers were acute and post-acute institutional care. Approximately 24 % of women and 19 % of men living in the community at the time of fracture entered a long-term care facility, and 22 % of women and 33 % of men died within the first year following hip fracture. Attributable costs remained elevated into the second year ($9,017 among women, $10,347 among men) for patients who survived the first year.

Conclusions

We identified significant health-care costs, entry into long-term care, and mortality attributed to hip fractures. Results may inform health economic analyses and policy decision-making in Canada.     

Non-linear relationship between serum 25-hydroxyvitamin D concentration and subsequent hip fracture

Summary

Serum 25-OH vitamin D levels were compared in 254 hip fracture subjects and 2,402 matched control subjects. There was a significant inverse association between 25-OH vitamin D and hip fracture only between 0 and 70 nmol/L.

Introduction

Vitamin D is integral to bone metabolism, however the utility of serum 25-OH vitamin D as a risk marker for hip fractures is controversial.

Methods

We conducted a case–control study of patients admitted to the hospitals with hip fractures in Calgary, Alberta, (catchment population 1.4 million) between January 1, 2007 and August 31, 2011. We searched the laboratory information system of Calgary Laboratory Services for serum 25-OH vitamin D levels within 6 months prior to admission on patients admitted to hospital with hip fractures. Cases were identified through the Calgary Laboratory Services laboratory information system and were matched to controls for age, sex, and month of testing. The hip fracture–25-OH vitamin D association was examined using multiple linear and spline regression.

Results

Of 305 subjects initially identified with hip fractures, serum 25-OH vitamin D levels were available for 254 (83 %). These were matched to 2,402 control subjects. We observed a significant (p?<?0.01) non-linear relationship such that 25-OH vitamin D was inversely associated with hip fracture only below 70 nmol/L (odds ratio?=?0.81 per 10 nmol/L increase; 95 % CI 0.86–0.93).

Conclusions

The utility of 25-OH vitamin D level as a risk marker for hip fracture depends on the cut-off level used and was of potential use only for lower levels of 25-OH vitamin D.     

Forecasting the burden of future postmenopausal hip fractures

Summary

A growing elderly population is expected worldwide, and the rate of hip fractures is decisive for the future fracture burden. Significant declines in hip fracture rates in Norway, the USA, France, Germany, and the UK are required to counteract the impact of the ageing effects.

Introduction

This study aims to evaluate the consequences of the expected growth of the elderly population worldwide on the hip fracture burden using Norway as an example. Furthermore, we wanted to estimate the decline in hip fracture rates required to counteract the anticipated increase in the burden of hip fracture for Norway, the USA, France, Germany, and the UK.

Methods

The burden of future postmenopausal hip fractures in Norway were estimated given (1) constant age-specific rates, (2) continued decline, and (3) different cohort scenarios. Based on population projection estimates and population age-specific hip fracture rates in women 65 years and older, we calculated the required declines in hip fracture rates needed to counteract the growing elderly populations in Norway, the USA, France, Germany, and the UK.

Results

The level of age-specific hip fracture rates had a huge impact on the future hip fracture burden in Norway. Even if the hip fracture rates decline at the same speed, a 22 % increase in the burden of hip fractures can be expected by 2040. An annual decline in hip fracture rates of 1.1–2.2 % until 2040 is required to counteract the effects of the growing elderly population on the future burden of hip fractures in Norway, the USA, France, Germany, and the UK.

Conclusions

Hip fracture rates have a great impact on the burden of hip fractures. The rates will have to decline significantly to counteract the impact of a growing elderly population. A change in preventive strategies and further studies are warranted to identify the complex causes associated to hip fractures.     

Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study

Summary

We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile.

Introduction

Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up.

Methods

We performed a case-cohort analysis among 21,774 men and women aged 65–79 years who participated in four community-based health studies in Norway 1994–2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n?=?1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed.

Results

Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) μmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04–1.20) per 10-μmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17–1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05–1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio.

Conclusions

Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.     

Incident long-term warfarin use and risk of osteoporotic fractures: propensity-score matched cohort of elders with new onset atrial fibrillation

Summary

Association between warfarin use and fracture risk is unclear. We examined the association between long-term warfarin use and fracture risk at the hip, spine, and wrist in elders. No significant association was found between long-term warfarin use and fracture risk, despite biological plausibility.

Introduction

Prior studies examining the association of warfarin use and osteoporotic fractures have been conflicting, potentially related to methodological limitations. Thus, we examined the association of long-term warfarin use with risk of hip, spine, and wrist fractures among older adults with atrial fibrillation, attempting to address prior methodologic challenges.

Methods

We included men and women ≥65 years of age with incident atrial fibrillation and without prior history of fractures from The Health Improvement Network followed between 2000 and 2010. Long-term warfarin use was defined in two ways: (1) warfarin use ≥1 year; (2) warfarin use ≥3 years. Propensity-score matched cohorts of warfarin users and nonusers were created to evaluate the association between long-term warfarin use and risk of hip, spine, and wrist fractures separately as well as combined, using Cox-proportional hazards regression models.

Results

Among >20,000 participants with incident atrial fibrillation, the hazard ratios (HR) for hip fracture with warfarin use ≥1 and ≥3 years, respectively, were 1.08 (95%CI 0.87, 1.35) and 1.13 (95 % CI 0.84, 1.50). Similarly, no significant associations were observed between long-term warfarin use and risk of spine or wrist fracture. When risk of any fracture was assessed with warfarin use, no association was found [HR for warfarin use ≥1 year 0.92 (95%CI 0.77, 1.10); HR for warfarin use ≥3 years 1.12 (95%CI 0.88, 1.43)].

Conclusions

Long-term warfarin use among elders with atrial fibrillation was not associated with increased risk of osteoporotic fractures and therefore does not appear to necessitate additional surveillance or prophylaxis.     

Association between use of benzodiazepines and risk of fractures: a meta-analysis

Summary

Benzodiazepines (BZDs) are some of the most commonly prescribed drugs in the world. It has been shown that BZD use could be associated with increased fracture risk. However, studies on the use of BZDs and fracture risk have yielded inconsistent results. Results from the present meta-analysis show that BZD use is associated with a moderate and clinically significant increase in the risk of fractures.

Introduction

The relationship between the use of BZDs and fracture risk has been neither well identified nor summarized. This meta-analysis reports on the use of BZDs, especially short-acting BZDs, and their correlation with a moderate and clinically significant increase in fracture risk. This analysis will provide evidence for clinicians to consider fracture risk when prescribing BZDs among the elderly population. This study was conducted to determine whether people who take BZDs are at an increased fracture risk.

Methods

A systematic search of studies published through January 2013 was conducted using MEDLINE, EMBASE, OVID, and ScienceDirect. Case–control and cohort studies that assessed the relationship between BZD use and the risk of fractures were identified. Literature searches, study selections, methodological assessments, and data mining were independently conducted by two reviewers. Disagreements were resolved by consensus. STATA 12.0 software was used for the meta-analysis. Random effects models were used for pooled analysis due to heterogeneity among the studies.

Results

There were 25 studies, including 19 case–control studies and 6 cohort studies, that met the inclusion criteria. Overall, the results of the meta-analysis indicated that BZD use was associated with a significantly increased fracture risk (relative risk (RR)?=?1.25; 95 % confidence intervals (CI), 1.17–1.34; p?<?0.001). Increased fracture risk associated with BZD use was observed in participants aged ≥65 years old (RR?=?1.26; 95 % CI, 1.15–1.38; p?<?0.001). When only hip fractures were included as the outcome measure, the RR increased to 1.35. However, subgroup meta-analyses showed that there was no significant association between BZD use and fracture risk in Eastern countries (RR?=?1.27; 95 % CI, 0.76–2.14; p?=?0.362) as well as between long-acting BZD use and risk of fractures (RR?=?1.21; 95 % CI, 0.95–1.54; p?=?0.12). After accounting for publication bias, we observed that the overall association between BZD use and fracture risk to be slightly weaker (RR?=?1.21; 95 % CI, 1.13–1.30) but still significant.

Conclusion

The results of this meta-analysis demonstrate that the use of BZD, especially short-acting BZD, is associated with a moderate and clinically significant increase in fracture risk. However, large prospective studies that minimize selection bias are necessary to determine a more accurate fracture risk associated with BZD use.