Hazard Ratio For Hip Fracture Research Articles

Effect of New York State Regulatory Action on Benzodiazepine Prescribing and Hip Fracture Rates

Medicare Part D excludes benzodiazepines from coverage, and numerous state government policies limit use of benzodiazepines. No data indicate that such policies have decreased the incidence of hip fracture. To assess whether a statewide policy that decreased the use of benzodiazepines among elderly persons by more than 50% has decreased the incidence of hip fracture. A quasi-experiment comparing changes in outcomes before and after a policy change in a study U.S. state (New York) and a control state (New Jersey). Two U.S. state Medicaid programs, 1988-1990. Medicaid enrollees in New York (n = 51 529) and New Jersey (n = 42 029) who received or did not receive a benzodiazepine. Benzodiazepine prescribing and hazard ratios for hip fracture, adjusted for age and eligibility category. A statewide policy, implemented in New York in 1989, that required triplicate forms for benzodiazepine prescribing to allow surveillance by health authorities. The triplicate prescription policy immediately resulted in a 60.3% (95% CI, -66.3% to -54.2%) reduction in benzodiazepine use among women and 58.5% (-64.3% to -52.8%) among men. Benzodiazepine use in New Jersey remained stable. Hazard ratios for hip fracture that were adjusted for age and eligibility category did not change in New York or New Jersey when the periods before and after use of the triplicate prescription policy were compared (change from 1.2 to 1.1 among female benzodiazepine recipients [P = 0.70], 1.3 to 1.1 [P = 0.08] among female nonrecipients, 0.8 to 1.1 [P = 0.56] among male recipients, and 1.1 to 1.3 [P = 0.46] among male nonrecipients). Information was lacking on race, benzodiazepine dose, and other potential determinants of continued benzodiazepine prescribing. Policies that lead to substantial reductions in the use of benzodiazepines among elderly persons do not necessarily lead to decreased incidence of hip fracture. Limitations on coverage of benzodiazepines under Medicare Part D may not achieve this widely assumed clinical benefit.

Integrin β3 Leu33Pro polymorphism and risk of hip fracture: 25 years follow-up of 9233 adults from the general population

Integrin alphavbeta3 is essential for mature osteoclast function and therefore important for the development of osteoporosis and osteoporotic fractures. Integrin alphavbeta3 antagonists have antiresorptive effects in bone. We tested the hypothesis that the Leu33Pro polymorphism in the integrin beta3-subunit associates with risk of hip fracture. We included 9233 men and women selected at random to represent the Danish general population as participants in the Copenhagen City Heart Study. First-ever hip fractures (n=267) were registered during 25 years follow-up. Log-rank statistics and Cox regression were used to compare fracture incidences and risk estimates between genotypes. Genotyping rendered 69.9% noncarriers, 27.3% heterozygotes and 2.7% homozygotes. Incidence of hip fracture was 2.8 and 1.5 per 1000 person-years in homozygotes and noncarriers (log-rank: P=0.02), respectively. Multifactorial adjusted Cox regression revealed a hazard ratio of 2.0 (95% confidence interval: 1.1-3.5) for hip fracture in homozygotes versus noncarriers. After stratification by sex, equivalent hazard ratios were 2.0 (1.0-4.1) in women and 2.0 (0.8-5.0) in men. In the 2193 postmenopausal women, hazard ratio for hip fracture in homozygotes versus noncarriers after additional adjustment for age at menopause and use of hormone replacement therapy was 2.6 (1.2-5.3). Hazard ratio for hip fracture in heterozygotes versus noncarriers did not differ from 1.0. Individuals homozygous for the integrin beta3 Leu33Pro polymorphism have a two-fold risk of hip fracture, mainly confined to postmenopausal women. Integrin beta3 Leu33Pro homozygosity could prove a useful marker for risk of future hip fracture and may contribute to pharmacogenetic variation in effects of integrin alphavbeta3 antagonists.

Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women

Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed. Recently, the association between high serum homocysteine (Hcy) levels and an increased risk of fracture has been described. Hcy levels were measured at baseline in 996 women, all 75 years old. Vitamin B(12), folate, serum cross-linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin, urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound (QUS), and physical performance were assessed at baseline. Fractures and mortality were recorded during a mean follow-up of 7.0 years. Bone marker levels were higher in women with Hcy in the highest quartile compared with all other women (p < 0.05). The most evident correlation between Hcy and a bone marker was seen with CTX (r = 0.19, p < 0.001). aBMD (hip) was 4% lower, QUS was up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest quartile compared with the other women (p < 0.05). During the follow-up, 267 women sustained at least one low-energy fracture (including 69 hip fractures). When women in the highest Hcy quartile were compared with all other women, the hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89-1.36) and for hip fracture was 1.50 (95% CI, 0.91-1.94). For the same group of women, the mortality risk was 2.16 (95% CI, 1.58-2.55). Adjustments for confounders did not substantially change these associations. Adjustment for PTH increased the HR for hip fracture to 1.67 (95% CI, 1.01-2.17). Low vitamin B(12) or folate was not associated with increased fracture risk or mortality. High Hcy levels were associated with higher bone turnover, poor physical performance, and lower BMD. There was no clear association to fracture risk. The increased mortality among women with high Hcy levels indicates that a high Hcy level may be a marker of frailty.

Calcium plus Vitamin D Supplementation and the Risk of Fractures

The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

Maternal height, childhood growth and risk of hip fracture in later life: a longitudinal study.

Although measures to enhance bone mineralization during childhood and adolescence are widely incorporated into preventive programmes against osteoporotic fracture, there are no published data directly linking growth rates in childhood with the risk of later hip fracture. We addressed this issue in a unique Finnish cohort in whom birth and childhood growth data were linked to later hospital discharge records. This permitted follow-up of 3639 men and 3447 women who were born in Helsinki University Central Hospital between 1924 and 1933, who went to school in Helsinki and still lived in Finland in 1971. Body size at birth was recorded and an average of 10 measurements were obtained of height and weight throughout childhood. We identified 112 subjects (55 men and 57 women) who sustained a hip fracture during 165 404 person-years of follow-up. After adjustment for age and sex in a proportional hazards model, we identified two major determinants of hip fracture risk: tall maternal height (p < 0.001) and a low rate of childhood growth (height, p = 0.006; weight, p = 0.01). The hazard ratio for hip fracture was 2.1 (95% CI 1.2-3.5) among men and women born to mothers taller than 1.61 m, when compared with those whose mothers were shorter than 1.54 m. The ratio was 1.9 (95% CI 1.1-3.2) among those whose rate of childhood height gain was below the lowest quartile for the cohort, compared with those whose growth rate was above the highest quartile. The effects of maternal height and childhood growth rate were statistically independent of each other, and remained after adjusting for socioeconomic status. The patterns of childhood growth that predicted future hip fracture differed between boys and girls. In boys, there was a constant deficit in height and weight between ages 7 and 15 years among those later sustaining fractures; in girls, there was a progressively increasing deficit in weight but a delayed height gain among those later sustaining fractures. This epidemiologic study provides the first direct evidence that a low rate of childhood growth is a risk factor for later hip fracture. Whether reduced growth rate is a consequence of childhood lifestyle, genetic background or intrauterine hormonal programming, the data support measures to optimize childhood growth as part of preventive strategies against osteoporotic fracture in future generations.

Cohort study of risk of institutionalisation after hip fracture.

The purpose of this study was to describe the rate of permanent placement in aged care institutions (nursing homes and hostels) after hip fracture and to assess whether or not hip fracture is an independent risk factor for institutionalisation. It was a cohort study with median follow-up time of 14 months. Subjects were 291 people living in the community in western Sydney: 13] with hip fractures and 160 controls. Permanent admission to an aged care institution and/or death during follow-up was assessed by telephone interview with study subjects of carers. Data on potential confounders were collected with an interviewer-administered questionnaire at the time of recruitment into the study. During follow-up, 27 per cent of hip fracture cases and 5 per cent of controls were admitted to an aged care institution. The age- and sex-adjusted hazard ratio for hip fracture and institutionalisation was 5.1 (95 per cent confidence interval (CI) 2.2 to 11.9). Adjusting for multiple health-related factors reduced the strength of association but the hazard ratio remained high at 4.0 (CI 1.7 to 9.5). The risk of institutionalisation after hip fracture is high; this is only partly explained by the poor pre-fracture health status of many people who fracture their hips.

Health status before and mortality after hip fracture.

A cohort study was done to determine the direct impact of hip fracture on mortality in older people. Survival was compared between 211 hip fracture patients from a defined area and 201 non-hip fracture control subjects randomly selected from the same area. The mortality rate 1 year after hip fracture was 21.7%; 1-year mortality in the comparison group was 4.7%. The crude hazard ratio for hip fracture and mortality was 4.0 (95% confidence interval [CI] = 2.2, 7.4); adjusting for multiple health-related variables reduced it to 3.3 (95% CI = 1.7, 6.5). This finding suggests that the observed excess mortality after hip fracture is not explained by poor prefracture health status.