Hip fractures are a major public health problem in the United States, and often lead to devastating consequences. Hip fractures are associated with substantial morbidity and mortality. Approximately, 15% to 25% of hip fracture patients die within 1 year. Hip fractures lead to hospitalization, disability, and loss of independence for an estimated 270,000 to 350,000 persons annually. About 9 of 10 hip fractures occur in individuals over 60 years of age, more commonly among women, and are usually the result of a fall. However, osteoporosis and other disorders can weaken the bone and a hip fracture may result from the stresses of ordinary activity, such as getting in and out of a chair.

In 1995, medical treatment for hip fractures, including inpatient care, nursing home care, and outpatient services, cost an estimated $8.68 billion. With the aging of the U.S. population, the number of hip fractures is expected to increase in the near future. Approximately, 50% of patients who lived independently before sustaining a hip fracture are unable to regain their independent lifestyle postfracture; instead, they face ongoing disability and prolonged institutionalization. Given these serious consequences, it is vital to detect and appropriately treat patients who develop a hip fracture.

Preventing hip fractures is the key, and that involves preventing falls, strengthening bones to prevent osteoporosis, and protecting bones. The following research articles address a number of concerns along these lines: (a) Albertsson, Mellstrom, Petersson, and Eggertsen (2007) developed and validated a tool for hip fracture risk assessment; (b) Oliver et al. (2007) evaluated strategies to prevent falls; (c) Yang, Lewis, Epstein, and Metz (2006) tried to determine the association between proton pump inhibitors (PPIs) therapy and the risk of hip fracture; (d) Wagner et al. (2007) determined whether a statewide policy that decreased the use of benzodiazepines among the elderly by more than 50% decreased the incidence of hip fractures; (e) De Vries, Souverein, Cooper, Leufkens, and van Staa (2007) assessed the strength of the association between use of [beta]-blockers and the risk of hip/femur fractures; and (f) Lipscombe, Jamal, Booth, and Hawker (2007) compared the risk of hip fractures among men and women with and without diabetes.

Albertsson, D. M., Mellstrom, D., Petersson, C., & Eggertsen, R. (2007). Validation of a 4-item score predicting hip fracture and mortality risk among elderly women. Annals of Family Medicine, 5(1), 48-56.

Hip fractures are an increasing problem worldwide. These Swedish authors state that approximately one in four Swedish women (23%) experiences a hip fracture in her lifetime, an event that has high concomitant morbidity and mortality (20%) within 1 year. Although there are several methods for fracture prevention, they are underused in routine healthcare. Thus, the goal of this study was to develop and validate a practical tool for hip fracture risk assessment and evaluate its ability to predict fractures and total mortality.

The study population was drawn from 1,498 women aged 70 years or older living in three rural primary healthcare districts in southern Sweden. The participants were recruited from the National Swedish Population Register in November 2001. The entire female population in the Vislanda district was selected, and a similar number of age-matched women from each of two other districts, Tingsryd and Emmaboda. Each woman was sent a 22-item questionnaire that focused on risk factors for fracture (items such as age, weight, height, mobility, previous fractures, smoking, medication use, and housing), combined with brief advice on fracture prevention. Nonresponders were twice reminded by mail within 2 months.

The authors developed two risk models before data collection. Model 1 (which was renamed the Fracture and Mortality [FRAMO] Index) had four items: age more than 80 years, weight less than 60 kg, previous fragility fracture after an age of 40 years, and having to use arms to rise from a sitting position. Model 2 included the same risk factors, except that having to use arms to rise was replaced by falls during the last 12 months. For both models, women with at least two of the four risk factors were compared with women with zero or one risk factor. Each model was tested as a predictor of future hip fractures, fragility fractures, and total mortality during a 2-year period.

Odds ratios (ORs) and hazard ratios (HRs) were calculated with logistic and Cox regression analysis for variables with cell values greater than 4. Women with missing data were recoded as having a low fracture risk to avoid overestimating the risks, while still evaluating the remaining risk factors for all participants. Fisher's exact test or the chi-square test was used to compare binary variables between two independent groups. Variables with cell values of less than 5 were analyzed with the Fisher exact test only. The Wilcoxon test or the t test was used for continuous, symmetric, or skewed variables. Kaplan-Meier curves were compared by the Breslow test. The authors regarded two-tailed p < .05 to be significant and used exact tests whenever possible.

The questionnaire response rate was 83% (N = 1,248). The 63% of women with zero to one risk factors had a 2-year hip fracture risk of 0.8% and a mortality risk after fracture of 3.2%. In contrast, women with two to four risk factors had a 2-year hip fracture risk of 5.4% (OR = 7.5; 95% confidence interval [CI], 3.0-18.4) and a postfracture mortality risk of 23.7% (OR = 9.5; 95% CI, 6.0-14.9). Those differences remain significant after adjustment for age as a continuous variable. Mortality increased with the number of risk factors. The proportion of women reporting previous vertebral fractures was higher among the group specifically questioned about vertebral radiographs.

The FRAMO Index identified the majority of women who experienced hip fractures during a 2-year follow-up, who might have been candidates for intensified preventive measures. The FRAMO Index, based on four binary risk factors, would be practical for routine use in primary care.

The study demonstrates some good measures for identifying risk factors, but leaves some concerns. First, it was limited to White, rural, Swedish women, nearly all of whom had parents of Nordic origin. Not included were urban women, who had a higher fracture risk, more often had a history of fractures, and were less physically active. Second, the study needs to be replicated with a larger and more diverse population. Third, the observation period should be extended. Fourth, bone mineral density measurement may improve the risk model. Fifth, more information is needed to define different preventive treatments for different levels of risk.

Oliver, D., Connelly, J. B., Victor, C. R., Shaw, F. E., Whitehead, A., Genc, Y., et al. (2007). Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: Systematic review and meta-analyses. British Medical Journal, 334, 82.

The objectives of the study were to evaluate the effectiveness of strategies to prevent falls or fractures in residents in care homes and hospital inpatients, and to investigate the effect of dementia and cognitive impairment. In 2004-2005, 275,000 falls were reported in hospitals in the United Kingdom, 60% of all reported incidents. Cohort studies in the United Kingdom have shown that residents in care homes fall two to six times a year (Dickson & Woodward, 2000). Up to 20% of admissions to general hospitals for hip fractures are from care homes. The results of falls may lead to loss of function, anxiety, depression, impaired rehabilitation, increased length of hospitalization, and inability to return to previous residence. Falls are often an indication of an underlying frailty or illness that requires a broader approach to assessment and management.

For the study, the authors designed a systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression was used to investigate the effects of dementia and study quality and design. The data used were from MEDLINE, CINAHL, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews, and the Clinical Trials Register. Of the 1,207 references identified, 115 were systematic reviews, expert reviews, or guidelines. The authors used the following core search terms: (a) accidental fall, (b) fracture, (c) accident prevention, (d) risk management, (e) wounds and injuries, (f) hospital, (g) hospitalization, (h) residential facilities, (i) care home, (j) wounds and injuries, (k) dementia, (l) delirium, (m) cognitive disorder, (n) clinical trials, (o) restraint physical, and (p) protective devices.

Although the initial criteria were very broad, for inclusion in the study, the data had to be reported in such a way that log rate ratios or log relative risks and their variances could be determined. The studies included trials with individual or cluster randomization, case-control studies, and observational cohort studies. The variety reflected the methodological and logistical difficulties of performing randomized controlled trials in these settings.

The authors used the quality score of Downs and Black to assess articles because it enabled assessment of studies with various designs. However, after initial piloting on five articles to assess interrater reliability, the authors determined that the statistical items on the score needed to be independently scored by a statistician. The authors also piloted and refined a data extraction form summarizing key features of trial design, study populations, and interventions regarding the five studies. Working independently, one of three pairs of peer assessors scored each included study and extracted data.

For presentation of the results and meta-analyses, studies were grouped into nine categories according to type and setting of the intervention. The prevalence of dementia in study participants was categorized by using: (a) 0 for unknown, (b) 1 for less than 40%, (c) 2 for 40% to 69%, and (d) 3 for more than or equal to 70%.

The literature search resulted in the inclusion of 43 studies. Sixteen studies were individually randomized controlled trials, 12 were cluster randomized, 9 were prospective (historical controls), 2 were retrospective observational cohort, 2 were prospective observational cohort, 1 was a prospective case-control study, and 1 was quasi-experimental study with a multiple interrupted time series.

The meta-analysis for multifaceted interventions in hospitals (13 studies) showed a rate ratio of 0.82 (95% CI, 0.68-0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies), the rate ratio for hip fractures was 0.67 (95% CI, 0.46-0.98), but there was no significant effect on falls and not enough studies on fallers. For the other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication reviews in hospitals), meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment.

REFERENCE

Dickson, B., & Woodward, M. (2000). Accident prevention in the elderly in nursing homes. 2nd Year report. Newcastle: Gateshead, South Tyneside, Sunderland and Northumberland and Inspection Areas for Care Homes.

Yang, Y.-X., Lewis, J. D., Epstein, S., & Metz, D. C. (2006). Long-term proton pump inhibitor therapy and risk of hip fracture. Journal of the American Medical Association, 296(24), 2947-2953.

More than 47,000 hip fractures occur annually in the United Kingdom. These researchers worked with the premise that hip fracture is the main manifestation of senile osteoporosis, which results from secondary hyperparathyroidism associated with calcium malabsorption, low calcium intake, and other factors. In the United Kingdom, the mortality rate during the first year after a hip fracture is 20% and among those surviving the first year, one in five requires nursing home care.

The objective of the study was to determine the association between PPI therapy and the risk of hip fracture. (PPIs are a group of drugs that are given for long-lasting reduction of gastric acid production.) PPIs have largely superseded another group with similar effects, but a different mode-of-action, called histamine-2 receptor antagonists (H2RA).

A nested case-control study was conducted using the General Practice Research Database (GPRD) for 1987-2003. The GPRD is a computerized medical record system of a selected group of general practices in the United Kingdom, and is representative of the UK population in terms of sex, age, and geography. Information on the database includes demographics, prescription use, clinical diagnoses, specialty consultation notes, and hospital discharge diagnoses. It is essentially an electronic version of the actual patient medical record.

From the 9.4 million patients who started follow-up in the full version of the GPRD between May 1987 and March 2003, individuals meeting at least one of the following four criteria were excluded: (a) less than 365 days of total up-to-standard database follow-up (n = 2.3 million), (b) younger than 50 years at the time of database enrollment (n = 6.9 million), (c) having a documented hip fracture before the start of up-to-standard database follow-up or during the first year of up-to-standard database follow-up (n = 15,871), and (d) having received H2RA or PPI therapy exclusively during non-up-too-standard periods of database follow-up (n = 21,011). The remaining 1.8 million patients made up the eligible study cohort, which consisted of 192,028 users of PPI therapy who received at least one prescription for PPIs during their up-too-standard database follow-up, 187,686 users of H2RA who received at least one prescription during their up-to-standard database follow-up but no PPI therapy, and 1.4 million acid suppression nonusers who had no documented prescriptions for PPI or H2RA therapy.

The primary nested case-control analysis was conducted within the study cohort consisting of all of the PPI users and the acid suppression drug nonusers. The secondary nested case-control analysis was conducted within the study cohort and included the users of H2RA only and the nonusers of acid suppression. Patients who received both PPI and H2RA therapies were considered in the primary analysis for PPIs only. Cases and controls were sampled using incidence sampling. Incidence density sampling yields ORs interpretable as unbiased estimated of the incidence rate ratios.

Conditional logistic regression was used to estimate the unadjusted and adjusted ORs and CIs. In addition to matching factors of age and sex, a comprehensive list of potential confounders that are risk factors for falling, including a known association with osteoporosis, and/or determined comorbidity status was examined.

Among the acid suppression nonusers, 10,834 incident hip fractures were identified. These fractures were added to the 2,722 incident hip fractures identified among the PPI users to make up the case group. Those cases were matched with 135,386 controls, with at least one eligible control patient to each case. The crude incidence rate of hip fracture was estimated to be 4.0 per 1,000 person-years among patients with more than 1 year of PPI therapy and 1.8 per 1,000 person-years among acid suppression nonusers. The hip fracture cases were more likely to have received medications or medical diagnoses that had a known association with either osteoporosis or the risk of falling. High body mass index, hormone therapy, and long-term statin therapy were associated with a reduced risk of hip fracture in the analysis.

The study results show that the risk of hip fracture is positively associated with PPI use. Long-term PPI therapy, at high doses in particular, is associated with an increased risk of hip fracture. Positive association between long-term PPI therapy and hip fracture was stronger in men.

On the other hand, PPI therapy is widespread, and may have an exaggerated effect among those at risk for osteoporosis. Further studies are definitely needed to confirm this study's findings and clarify the underlying mechanisms. At this point, practitioners should be aware of the potential risk when considering PPI therapy, and should use the lowest effective dose for patients with appropriate indications. For the elderly patients who require long-term and particularly high-dose PPI therapy, it may be prudent to reemphasize increased calcium intake.

Wagner, A. K., Ross-Degnan, D., Gurwitz, J. H., Zhang, F., Gilden, D. B., Cosler, L., et al. (2007). Effect of New York State regulatory action on benzodiazepine prescribing and hip fracture rates. Annals of Internal Medicine, 146, 96-103.

Concerns about benzodiazepine abuse, misuse, and adverse events, including hip fractures among the elderly, prompted state and national policies intended to regulate access to benzodiazepines. In 1990, after the first landmark study describing the risk for hip fractures associated with benzodiazepine use, the U.S. Congress passed the Omnibus Budget Reconciliation Act, which allowed states to restrict coverage of benzodiazepine in Medicaid programs or exclude them from coverage. Although no state excluded benzodiazepines from coverage after this act, about one third of the states imposed limits on the number of prescriptions covered, required authorization before a patient could fill a prescription, or implemented other statewide policies that restricted access. Since January 2006, benzodiazepines have been explicitly excluded from coverage through the Medicare Part D drug benefit.

On January 1, 1989, the New York State Department of Health implemented a triplicate prescription policy (TPP) for benzodiazepines. Since that time, all physicians in New York State are required to obtain, pay for, and use special serially numbered, triplicate forms to prescribe benzodiazepines. Pharmacists would then forward one copy to the state health authorities for surveillance. The TPP allows monitoring of each physician's prescribing, each pharmacy's dispensing, and each patient's receipt of benzodiazepines. The policy works as a barrier to accessing benzodiazepines and resulted in an immediate and sustained decrease of 55% overall in the number of benzodiazepine recipients in a continuously enrolled Medicaid cohort. Benzodiazepine prescribing decreased by 30% in a privately insured sample, and by 44% statewide. One expected benefit of the policy was that limited access to benzodiazepines would decrease the incidence of falls and hip fractures associated with benzodiazepine use among the elderly.

The objective of this study was to assess whether a statewide policy that substantially decreased the use of benzodiazepines actually decreased the incidence of hip fracture. Using a longitudinal, controlled, quasi-experimental research design, the authors compared monthly rates of benzodiazepine use and HRs for hip fracture among the elderly Medicaid enrollees in New York (the intervention state) and New Jersey (the comparison state) during the 12 months before and the 21 months after implementation of the New York TPP.

While the triplicate prescription policy immediately reduced benzodiazepine use in New York, benzodiazepine use in New Jersey remained stable. HRs for hip fracture that were adjusted for age and eligibility category did not change in either New York or New Jersey when the periods before and after use of the triplicate prescription policy were compared.

Thus, in conclusion, policies that led to substantial reductions in the use of benzodiazepines among the elderly persons did not lead to decrease in fractures. Limitations on coverage of benzodiazepines under Medicare Part D may also not achieve this widely assumed clinical benefit. A limitation of the study is the lack of information on race, benzodiazepine dose, and other potential determinants of continued benzodiazepine prescribing. Further research is needed to replicate this finding.

De Vries, F., Souverein, P. C., Cooper, C., Leufkens, H. G. N., & van Staa, T. P. (2007). Use of [beta]-blockers and the risk of hip/femur fracture in the United Kingdom and the Netherlands. Calcified Tissue International, 80(2), 69-75.

Research studies have indicated a role for [beta]-blockers in the prevention of bone loss. Some epidemiological studies have found protective effects of [beta]-blockers on fracture risk. For example, in the early 1990s, Propranolol was found to increase bone formation. There are also conflicting research studies that found no association with fractures. However, there is limited information on the influence of cumulative dose and type of [beta]-blockers used.

A possible role for [beta]-blockers in the prevention of fractures is of major clinical interest, given that fractures are a major source of morbidity, disability, hospitalization, and mortality. Hip fractures resulting from accidental falls being one of the most serious.

The objective of the study was to assess the strength of the association between use of [beta]-blockers and risk of hip/femur fractures using data from two different large population-based data sets in the United Kingdom and the Netherlands.

Data for the study were obtained from the UK GPRD and the Dutch PHARMO Record Linkage System (RLS). GPRD contains the computerized medical records of general practices across the United Kingdom, approximately 6% of the total registered population of England and Wales (an accumulation of more than 5 million adult patients). The database includes demographic information, diagnoses, prescription details, preventive care provided, referrals to specialist care, hospital admissions, and related major outcomes. The authors state that previous independent validation studies have shown that the GPRD has a high level of completeness and validity, including for hip fractures.

The PHARMO RLS includes the demographic details and complete medication history of 950,000 community-dwelling residents of more than 25 population-defined areas in the Netherlands from 1985 onward. The database is linked to hospital admission records as well as health registries, including pathology, clinical laboratory findings, and general practitioners data. The pharmacy records are virtually complete with regard to prescription drugs, since all patients are registered with only one community pharmacy.

The study utilized drug-dispensing and hospitalization data. The computerized histories records provided information on the type of drug dispensed, dispensing date, prescriber, amount dispensed, and prescribed dosage regimen. Hospital discharge records provided detailed information on the primary and secondary discharge diagnoses; diagnostic, surgical and treatment procedures; type and frequency of consultations with medical specialists; and dates of hospital admission and discharge.

A case-control study was conducted by the researchers using GPRD data collected from January 1987 to July 1999 and published previous to this report. In this study, cases were defined as patients aged 18 years and older with a first record of a hospital admission for a hip/femur fracture recorded in their medical records between their enrollment date in the GPRD and the end of data collection. Each patient was matched by year of birth, sex, medical practice, and calendar time to one control patient without a history of a fracture. If no eligible control patient was available, the age criterion was expanded consecutively by 1-year intervals to a maximum of 10 years. If no eligible control patient could be found, then an age- and sex-matched control patient from another practice was selected. The date of the hip/femur fracture was the index date.

The PHARMO RLS cases were patients aged 18 years and older with a first admission for a hip/femur fracture between January 1, 1991, and December 31, 2002. Up to four control patients, who did not have a history of any type of fracture, were matched to each case by year of birth, gender, region, and calendar time. The date of hospitalization was the index date.

The study cases were patients with a first hip or femur fracture: controls were individually matched on practice/region, gender, year of birth, and calendar time. Current use of [beta]-blockers was defined as a prescription within 90 days before the index date. The researchers adjusted for medical conditions and drugs associated with falling or bone mineral density. Thus, the study population included 22,247 cases and controls in the GPRD and 6,763 cases and 26,341 controls in the PHARMO RLS.

The strength of the association between use of [beta]-blockers and risk of hip/femur fractures was estimated using conditional logistic regression analysis and expressed as ORs) with 95% CIs. Final regression models were determined by stepwise backward elimination using a significance level of .05. Smoothing spline regression plots were used to visualize the effect of cumulative [beta]-blocker dose on risk of hip/femur fracture.

Current use of [beta]-blockers was associated with a reduced risk of hip/femur fracture in both groups. However, this reduction of risk was not associated with cumulative dose, lipophilicity, or receptor selectivity of [beta]-blockers. The protective effect of [beta]-blockers was only present among patients with a history of use of other antihypertensive agents, but not in patients using [beta]-blockers only. In patients with a history of use of such other antihypertensive agents, no dose-response relationship with [beta]-blocker use was found. The OR was below 1.0 even among patients who just started treatment with [beta]-blockers.

As the mechanism by which [beta]-blockers could influence bone mineral density is likely to need some time to exert a clinically relevant effect, all these findings suggest that the association between [beta]-blockers and fracture risk is not causal.

The strengths of this study are that it was population-based and the results were the same for both the United Kingdom and Dutch data. However, some potential weakness are following: (a) observational studies have the potential for bias and confounding and can lead to disputes about interpretation and credibility, (b) an alternative explanation for the findings could be that the protective effect of [beta]-blockers on fractures is an artifact caused by selective underuse in patients with an unmeasured comorbidity, (c) a limitation is that the study was confined to hip/femur fractures and did not evaluate other types of fractures, and (d) the reduction in hip/femur fracture risk might be related to an interaction between [beta]-blockers and other antihypertensive drugs, which was not examined.

Lipscombe, L. L., Jamal, S. A., Booth, G. L., & Hawker, G. A. (2007). The risk of hip fractures in older individuals with diabetes: A population-based study. Diabetes Care, 30, 835-841.

An association between diabetes and hip fractures is becoming increasingly recognized. Both cross-sectional and prospective studies have shown that type 1 diabetes mellitus is associated with a decrease in bone mineral density (BMD) and an increased risk of osteoporotic hip and other fractures. However, in contrast, studies in patients with type 2 diabetes mellitus have demonstrated that these patients have higher BMD, probably because of increased body weight, but have found inconsistent associations between type 2 diabetes mellitus and fractures. Most of these findings have been documented in women.

The objective of the study was to compare the risk of hip fractures among men and women with and without diabetes. Using a retrospective cohort design, the study population utilized Ontario residents aged 66 years and older with diabetes from a validated registry from 1994 to 1995 (n = 197,412) and then followed them for their first hip fracture until March 31, 2003 (mean 6.1-year follow-up). Hip fracture rates were compared with those of age-matched Ontario residents without diabetes (n = 401,400), and results were stratified by sex and adjusted for age and other covariates.

Data were obtained from anonymized, administrative healthcare databases that include records for all individuals eligible for the provincial health plan. Databases included were (a) Canadian Institute for Health Information database, which provides hospital discharge abstracts containing up to 16 diagnoses; (b) the Registered Persons Database, which contains demographic and residential information; (c) the physician service claims database, which include billing claims for physicians for consultations, visits, and procedures; (d) the Ontario Diabetes Database, which is a validated database of diabetic patients created from hospital and physicians' claims data; and (e) the drug prescription database, which lists prescriptions provided under the provincial formulary for all residents aged 65 years or older. Individuals excluded from the study were (a) those with a prior hip fracture or a bilateral hip replacement, (b) those using oral corticosteroids at any time from January 1, 1991, to study entry, (c) residents of a long-term care facility, and (d) those lacking contact with the healthcare system during the follow-up period.

Baseline characteristics among individuals with and without diabetes were examined using means and t tests for continuous variables and proportions and [chi]² tests for categorical variables. Distributions of the continuous variables were examined and those not normally distributed were converted into categorical variables based on distribution. Cox proportional hazards regression was used to estimate the HR of a hip fracture by diabetes status. A multivariate model was used to adjust for covariates that were significantly associated with hip fractures on univariate analyses. Multivariate subgroup analyses were done within diabetes groups to assess for the effect of incident versus prevalent diabetes and insulin treatment.

Individuals with diabetes had greater comorbidity, were less likely to have had a BMD test, and were more likely to be taking medications that increase risk of falling and decrease BMD than individuals without diabetes. After adjusting for these difference and age, the study found that diabetes increased fracture risk in both men (HR = 1.18) and women (HR = 1.11).

In sum, men and women with diabetes have a higher risk of hip fractures than individuals without diabetes. However, further research is needed to elucidate the mechanisms underlying this increased risk of fracture. Another limitation of the study is that it was not possible to distinguish between type 1 and type 2 diabetes within the Ontario Diabetes Database; even though it is estimated that the vast majority (c. 90%) of patients in the age group studied have type 2 diabetes mellitus.