Hip Fracture Risk in Older White Men Is Associated With Change in Body Weight From Age 50 Years to Old Age FREE

HIP FRACTURES in men are projected to account for one third of all hip fractures¹ worldwide and are associated with higher mortality than in women.² Relatively few studies,^3- 8 however, have investigated risk factors for hip fracture in men, especially those aged 65 years and older who are at highest risk of a hip fracture.² Because the risk of hip fracture in men is not linked to accelerated bone loss attributable to a distinct menopause equivalent, understanding the reasons for the increase in the risk of hip fracture with aging in men and identifying prevention strategies presents a greater challenge.

Changes in body weight occur commonly with aging.⁹ Low body weight is a risk factor for hip fracture among men.^3- 6 Weight loss may explain at least part of the risk of hip fracture associated with low weight because weight loss is related both to decreased bone mineral density^10- 13 and to declines in health and physical function¹⁴ that may increase the risk of falls. Among women aged 65 years and older, weight loss is associated with an increased risk of hip fracture^15- 17 and other osteoporotic fractures.¹⁸ Weight loss also is associated with an increased risk of hip fracture in middle-aged men.⁷ Because substantially greater weight loss among men occurs between middle age and old age than during middle age,⁹ it is important to investigate directly the association between weight loss and the risk of hip fracture among older men. To our knowledge, the relationship between change in body weight between middle and old age and the risk of hip fracture in older men has not been studied.

We used data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE) to study the risk of hip fracture associated with weight change between middle (50 years) and old age in white men aged 67 years and older.

Data collected about older white men from 3 sites of the EPESE were studied. The EPESE, sponsored by the National Institute on Aging, is a longitudinal study initially designed to identify predictors of mortality, hospitalization, chronic diseases, and disability in community-dwelling elderly individuals. Community surveys were conducted on all people aged 65 years or older living in East Boston, Mass, and Iowa and Washington counties, Iowa. The third population, from New Haven, Conn, was drawn from a stratified random sample defined according to sex, to ensure an adequate number of men, and housing status (public housing for the elderly, private housing for the elderly, or community residence). Details of the study have been described elsewhere.^19- 20

During 1981 through 1983, household interviews were conducted with more than 80% of the more than 10000 eligible study participants. From 1983 through 1989, annual follow-up interviews were conducted. The third and sixth in-person interviews updated the detailed information about health characteristics that were obtained in the initial interview. The remaining brief telephone surveys ascertained health status and health events from the previous year. More than 90% of the people initially interviewed participated in each of the follow-up interviews. The occurrence of hip fracture was ascertained from Medicare hospitalization data for 8 years (1985-1992) beginning with the third follow-up interview. Thus, the third follow-up serves as the baseline for our analyses.

The study population consisted of 2878 white men aged 67 years and older who participated in the baseline interview. Eliminated from the analyses were 21 men who could not be matched to the Medicare hospitalization files, 82 men who reported previous hip fracture, 347 men with missing body weight data (269 at age 50 years and 78 at the third follow-up), and 15 men with missing height data (used to calculate body mass index [BMI], which is a measure of weight in kilograms divided by the square of the height in meters, at age 50 years). The men excluded because of missing data were significantly older, reported a greater number of medical conditions and greater physical disability, had lower mental status scores, were less physically active, and were less likely to be current smokers or to have consumed alcohol in the past year than those included in the analyses (P<.05). The final sample included 2413 men aged 67 through 104 years (943 from East Boston, 876 from Iowa, and 594 from New Haven). Nonwhite men were excluded from the analyses because there was insufficient statistical power to examine them separately.

Men hospitalized with a hip fracture (principal diagnosis code 820 in the International Classification of Diseases, Ninth Edition, Clinical Modification)²¹ occurring between January 1, 1985, and December 31, 1992, were included in the study. Hospitalization data obtained from the Medicare Provider Analyses and Review Files maintained by the Health Care Financing Administration were matched to EPESE data by using identification codes or Social Security numbers. Details of the matching procedure have been described elsewhere.²² Data from these files are estimated to include 100%, 95.5%, and 86.7% of the hip fracture hospitalizations among individuals aged 65 years or older in Iowa, Connecticut, and Massachusetts, respectively.²³ In the final study sample, the total number of hip fracture cases was 72 (29 in East Boston, 21 in Iowa, and 22 in New Haven).

Vital status was ascertained for almost 100% of the population at each study site. Vital status was determined for men from East Boston through the sixth follow-up period, New Haven through the seventh follow-up, and Iowa through 1992 using information collected at annual interviews and by local surveillance procedures, including monitoring obituary notices and review of state vital statistics records. The remaining data on vital status through 1992 were obtained from the National Death Index.

Weight change was estimated by using the reported weight at baseline and the reported weight at age 50 years. The percentage of weight change was calculated as ([weight at age 50 years (weight at baseline)/weight at 50 years] × 100). Weight change was categorized as a loss of 10% or more, a loss of 5% to less than 10%, a loss or gain of less than 5%, a gain of 5% to less than 10%, and a gain of 10% or more. The percentage of weight change was used because it provides a more meaningful comparison between individuals with widely differing weights and is a more clinically relevant measurement than absolute weight change.²⁴

Body mass index at age 50 years was calculated based on reported weight at age 50 years and height reported at the initial EPESE interview. Body mass index at age 50 years was used as a continuous variable.

Other risk factors assessed at baseline that were used in the analyses were age; number of medical conditions from a self-reported history of having been told by a physician or other health care provider that they had cancer, diabetes, heart attack, or stroke; low mental status score (≥3 errors on the Short Portable Mental Status Questionnaire)²⁵; physical disability, determined using measures of mobility and activities of daily living (ADL): no disability, mobility disability (report of the need for help with walking 12 mile (0.8 km), climbing a flight of stairs, or doing heavy housework, but no limitations in ADL), and ADL disability (report of the need for help with ≥1 ADL that included bathing, dressing, eating, walking across a room, and transferring from bed to chair). Physical activity level was measured using 3 items concerning the frequency of walking, gardening, and doing vigorous exercise.²⁶ For each activity, subjects were classified into 3 categories: frequently (≥3 times per week), sometimes (twice weekly, weekly, or several times per month), and rarely or never. For the multivariable analysis, a value of 3 was assigned when the activity was performed frequently, 2 when the activity was performed sometimes, and 1 when the activity was performed rarely or never. The scores for each activity were summed to create a total score for physical activity and categorized into 3 groups based on the distribution of scores: low physical activity level (score, 3-5), moderate (score, 6), and high (score, 7-9). Other behavioral variables included cigarette smoking (current, former, or never); use of alcohol (none or any consumed in the past year); and use of thiazide diuretics (current or none). Data about disability, physical activity, smoking, and alcohol were missing for fewer than 2%, mental status score data were missing for 8.0%, and use of thiazide diuretics data were missing for 15.8% of the men in our study.

The incidence rates of hip fracture per 1000 person-years were calculated by age. Person-years were calculated by summing the time from baseline until the occurrence of a hip fracture, death, or the end of follow-up, whichever came first. Age-adjusted means and percentages of men with risk factors for hip fracture were compared by hip fracture status and by level of weight change using the SAS general linear models procedure.²⁷ Adjusted relative risks (RRs) for hip fracture by category of weight change from age 50 years were calculated from a Cox proportional hazards model stratified by community using the STRATA option of the SAS proportional hazards regression procedure to obtain a summary estimate across the communities.²⁸ Men reporting little change in weight (loss or gain <5%) were used as the reference group. The model controlled for BMI at age 50 years (ie, BMI at the start of the weight change interval) and all other covariates. Statistical interaction between weight change and both age at baseline and BMI at age 50 years was tested by entering the interaction terms separately into the final model.

The 2413 men were observed for a total of 13620 person-years during the 8-year follow-up. During the follow-up period, 72 men had a hip fracture, yielding an overall incidence rate of 5.3 per 1000 person-years. The incidence rate of hip fracture was substantially higher among men aged 75 years and older (9.0 per 1000 person-years) than among men aged 65 to 74 years (2.6 per 1000 person-years).

Men who had hip fractures were significantly older than those who did not (Table 1). Although the men with and without hip fracture were not significantly different with respect to mean weight at baseline or at age 50 years, those with hip fractures were nearly twice as likely to have been obese (BMI >30) at age 50 years. Men with hip fracture were also nearly twice as likely to have a low mental status score and ADL disability at baseline, and were less likely to have consumed alcohol in the past year. A larger proportion of the men with hip fracture had mobility disability and a low level of physical activity; however, the differences were not statistically significant. The 2 groups also were not significantly different (P>.05) in their reported number of medical conditions, cigarette smoking, and use of thiazide diuretics.

Overall, one third of the older men in our study lost weight and one third gained weight between age 50 years and old age. Extreme weight loss was more common among very old men. A total of 26.5% of men aged 75 years and older reported loss of 10% or more of their body weight since age 50 years, compared with 16.0% of men aged 67 to 74 years (P=.001).

Men who lost 10% or more body weight between age 50 years and the study baseline (extreme weight loss) were older and weighed less at baseline than those with little change in weight (Table 2). Men who lost weight reported heavier weights and were nearly 4 times as likely to have been obese (BMI >30) at age 50 years. They also were more likely to report a low level of physical activity. Those who had extreme weight loss were more likely to have 2 or more medical conditions, a low mental status score, and to have mobility and ADL disability; they were less likely to have never smoked or to have consumed alcohol in the past year. Men who gained weight reported heavier weights at baseline and lower weights at age 50 years than those with little change in weight. Those who gained 5% to less than 10% of their weight since age 50 years were more likely to have consumed alcohol and to have reported use of thiazide diuretics at baseline. Men with extreme weight gain (≥10% weight from age 50 years) were more likely to have been underweight at age 50 years (BMI <19), to have a low physical activity level at baseline, and to be former smokers.

The older men who lost 10% or more body weight between age 50 years and old age (extreme weight loss) had the highest incidence rate of hip fracture (Table 3). The unadjusted RR of hip fracture among older men with extreme weight loss was 3 times that of both men with lesser weight loss and those with little change in weight. Men who gained 10% or more body weight had the lowest risk of hip fracture.

After adjustment for other risk factors for hip fracture, including BMI at age 50 years, the older men with a weight loss of 10% or more between age 50 years and the study baseline had a significantly increased risk of hip fracture (RR, 1.85; 95% confidence interval [CI], 1.04-3.31) (Figure 1). Conversely, men with extreme weight gain had a borderline significant decreased risk of hip fracture (RR, 0.38; 95% CI, 0.14-1.00). Men with lesser decreases in weight (5%-<10%) did not have a significantly increased risk of hip fracture (RR, 0.78; 95% CI, 0.33-1.83). Likewise, men with lesser increases in weight did not have a significantly decreased risk of hip fracture (RR, 0.60; 95% CI, 0.24-1.48).

The interactions of weight change and age at baseline and weight change and BMI at age 50 years were not statistically significant (P>.05). Stratified analysis of the association between weight change and risk of hip fracture by tertiles of BMI at age 50 years revealed an elevated RR only among the men who were thinnest at age 50 years (RR, 2.13; 95% CI, 0.88-5.14; P=.09) although the RR was not statistically significant.

The results of this study show that weight loss of 10% or more from age 50 years to old age is associated with a nearly 2-fold increased risk of hip fracture among white men aged 67 years or older. The association of weight loss with several indicators of poor health suggests that weight loss is a marker of frailty that increases the risk of hip fracture among older men. Weight gain of 10% or more is associated with a borderline significant reduction in the risk of hip fracture. The incidence rate of hip fracture in our study, 5.3 per 1000 person-years, was similar to the rates of 4 to 5 per 1000 person-years reported in previous studies.^29- 30 A major strength of our study is the relatively large population of nearly 2500 community-dwelling older men that allowed us to investigate specifically the risk of hip fracture as opposed to all osteoporotic fractures.³¹

Our findings of an increased risk of hip fracture with weight loss are consistent with those from a study that included middle-aged Norwegian men.⁷ In this study, men who lost more than 3 kg of body weight during an average 11 years of follow-up had a 2.5-fold increased risk of hip fracture compared with a reference group of men who gained between 1.3 and 5.5 kg.⁷ Of note, the comparison of men who lost weight with a reference group of men who gained weight resulted in a substantially higher estimate of the RR than would have been obtained if, as in our study, the reference group were composed of men with little change in weight. Although older men have a lower overall risk of hip fracture than older women,² we found that the pattern among older men of greater risk of hip fracture associated with greater weight loss, and lesser risk associated with greater weight gain, from age 50 years to old age was comparable with the findings for older women from the same (EPESE) population.¹⁵ This suggests that the overall influence of weight change on risk of hip fracture is similar in both sexes.

In both cross-sectional^10,12,32 and longitudinal¹³ studies, weight loss has been shown to be associated with decreased bone mineral density. In a cross-sectional study,³² weight loss accounted for one third of the decline in bone mineral density with aging among older men.

Weight loss may contribute directly to a decline in bone mineral density by decreasing the frequency or intensity of stimuli to bone formation, probably as a result of reduced mechanical loading.³³ The specific changes in soft tissue body composition that accompany weight loss, ie, decreased lean (muscle) and fat mass, may also be important in determining bone mineral density. Heavier individuals carry more weight and have both greater lean body mass and greater fat mass.³⁴ Weight loss that results in the loss of lean mass may result in decreased strength, decreased physical activity, and reductions in mechanical stress on bone.³⁵ This may be a relatively more important mechanism among men³⁶ because of their greater muscle mass³⁷ and thus the greater likelihood of muscle loss with weight loss³⁸ compared with women. Fat mass appears to be of greater importance to the maintenance of bone mineral density among postmenopausal women³⁹ than among men.^40- 41 Among overweight women, weight loss that results in loss of fat may result in decreased bone mineral density through decreased adipose-based production of estrogen⁴² or through decreases in the efficiency of absorption and utilization of calcium.^43- 44 Because men do not have a menopause equivalent with related acceleration in bone loss, testosterone or one of its conversion products, estradiol,^45- 46 may be more important to maintenance of bone mineral density in men⁴⁷ than estrogen from adipose tissue; however, the relationship between fat mass and hormonal levels^48- 49 and the influence of both on maintenance of bone in men⁴⁰ is not fully understood. Weight loss that includes loss of fat from around the hip may result in less natural protective padding to reduce the risk of hip fracture in the event of a fall.^50- 51

Weight loss may be associated with reduced dietary intake of nutrients¹⁴ such as protein and calcium that are necessary for maintenance of bone mineral density. Protein-energy undernutrition may cause both reduced weight and accelerated bone loss⁵² since adequate protein intake is necessary for production of skeletal growth factors. Higher levels of calcium intake and combined calcium and vitamin D supplementation⁵³ have been shown to be associated with decreased risk of hip fracture among older men.^54- 55

Perhaps most important in this population of older men, involuntary weight loss may be a marker of increased risk of hip fracture associated with impaired health because underlying illness may be both the cause of weight loss and a risk factor for decreased bone mineral density, falls, and hip fracture. Poor et al⁸ found that medical conditions accounted for nearly three fourths of the hip fractures among the men in their study. Although we did not specifically determine whether weight loss was voluntary or involuntary, the men who lost the most weight in our study had more indicators of poor health than those with little change in weight. These indicators included a greater number of medical conditions and a higher proportion with physical disability, a low mental status score, a low level of physical activity, or current smoking. Even after adjustment for health status, however, weight loss of 10% or more between age 50 years and old age was associated with an increased risk of hip fracture.

Diet-induced weight loss also has been shown to result in decreased bone mineral density in a study of healthy older women.¹¹ Although the need for information on the efficacy of weight loss regimens, especially pharmacotherapeutic interventions, has received increasing attention,⁵⁶ little is known about their health effects, including their effects on bone, in older people. Future studies must address this issue. In the interim, weight loss programs for older men should encourage appropriate levels of physical activity and nutrient intake, including calcium, to maintain bone.

The finding of a higher percentage of older men who were obese (BMI >30) at age 50 years among those with hip fracture than among those with no hip fracture is intriguing. Greater BMI has been shown to be associated with lower growth hormone secretion and clearance in men,⁵⁷ and lower growth hormone secretion may be associated with decreased bone mineral density.⁵⁸ Heavier weight in middle age also may be associated with the development of a greater burden of disease in old age, resulting in involuntary weight loss and disability that increase the risk of hip fracture. These hypotheses are speculative and should be investigated in other studies of men with follow-up of body composition and health status from middle through old age.

We found that a weight gain of 10% or more from age 50 years to old age was associated with a borderline significant reduction in the risk of hip fracture among the older men in our study. Contrary to weight loss, weight gain may contribute to decreased risk of hip fracture by increasing bone mineral density through increased gravitational force on bone, increased adipose-based production of estrogens, or reduced likelihood of injury in the event of a fall because of increased protective padding around the hip.^50- 51 Men who gained weight also may have had a reduced exposure to the risk of falling associated with a lower physical activity level. Use of thiazide diuretics by some men who gained weight may have contributed to a reduced risk of hip fracture.³¹ Of particular interest, the older men who gained 10% or more weight from age 50 years were less likely to be current smokers and more likely to be former smokers than those with little change in weight. In addition to contributing to lower body weight,⁵⁹ smoking may increase hip fracture risk^3,60 through its association with decreased bone mineral density.⁶¹ In older men as in older women, the positive effects of smoking cessation, including the avoidance of further weight loss and the slowing or halting of bone loss even among those who quit smoking cigarettes in old age¹² may decrease the risk of hip fracture. Although heavier weight may contribute to a reduced risk of hip fracture, the negative health effects, including increased risk of a wide range of chronic health conditions^62- 63 and physical disability,²⁶ outweigh the potential benefits. To promote overall health and maintenance of bone, physicians and other health care providers should encourage older men to achieve and to maintain an appropriate weight.

Some limitations of our study should be considered. First, the older men (16%) excluded from the analysis because of missing weight and/or height data were older and were less healthy than the men included in the analysis. The exclusion of men with poorer health likely resulted in an underestimate of the association between weight change and hip fracture in our study. Second, we were limited to the use of self-reported data from only 2 points in time in selecting a reference group with little change in weight (ie, men whose weight at baseline was only 5% more or less than their weight at age 50 years). The inclusion in our reference group of some men whose weight may have increased after age 50 years and then returned in old age to within 5% of their weight at age 50 years may have resulted in a bias toward the null in the association of weight loss with risk of hip fracture. Third, the body weight data in our study were self-reported. Data from the older men participating in the sixth follow-up of the Iowa EPESE revealed a high correlation between self-reported and measured weights (Pearson r = 0.96). Weight recalled even from many years earlier by elderly men has been found to be relatively accurate^64- 65 although men may be more likely to overestimate their past weight.⁶⁶ Such a recall bias may have resulted in an overestimate of the weight loss and an underestimate of the weight gain in our study. Future studies should obtain measured weights at frequent intervals to identify a truly weight-stable reference group, and should determine the circumstances related to changes in weight among older men.

Weight loss is common among older men and contributes to a substantial increase in the risk of hip fracture. Physicians and other health care providers should obtain a weight history as part of an overall assessment of the risk of hip fracture in older men and should encourage them to achieve and maintain a healthy weight.

Accepted for publication September 25, 1997.

We thank Eric Orwoll, MD, and Cliff Rosen, MD, for their valuable comments on the manuscript.

Reprints: Jean A. Langlois, ScD, MPH, Division of Acute Care, Rehabilitation Research and Disability Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Hwy NE (MS-F-41), Atlanta, GA 30341-3724.