Weight Loss: A Determinant of Hip Bone Loss in Older Men and Women

The Rancho Bernardo Study

James D. Knoke and Elizabeth Barrett-Connor 

From the Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, San Diego, CA.

Received for publication July 22, 2002; accepted for publication June 18, 2003.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The sex-specific effect of weight change on change in total hip bone mineral density was evaluated over 4 years (1992–1996) in 1,214 community-dwelling adults whose mean age at baseline was 71 years. Weight and bone mineral density (by dual-energy x-ray absorptiometry) were assessed at two study visits. The average bone loss was 0.5% per year in both sexes; 29% of men and 28% of women lost at least 1% of bone mineral density per year. More than one in five participants lost at least 1% of their body weight per year (21% of men and 23% of women). These weight losers were twice as likely as others to lose bone at the rate of at least 1% per year. In analyses controlling for age, baseline weight, and lifestyle, weight loss was the strongest independent predictor of bone loss (odds ratios were 1.53 for men and 1.56 for women). Persons with weight loss of at least 1% per year were more likely to report fair or poor health and functional limitation at the second visit and to die within 2 years of the second visit; however, most did not report declining health, and most survived for at least 2 additional years.

aged; bone density; osteoporosis; prospective studies; weight loss

Abbreviations: Abbreviation: BMD, bone mineral density.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The adverse consequences of a hip fracture in old age are greater than the consequences of other fractures (1). Low bone mineral density (BMD) at the hip is an important risk factor for hip fracture (25). Low body weight is a recognized risk factor for bone loss. Most previous studies of the effect of weight on bone loss have included only women (613), although a few have studied both sexes (14, 15). We have found only two previous studies that investigated the effect of measured weight loss on bone loss in both sexes (16, 17).

We report here the results of a larger, longer study of weight loss and change in total hip BMD among community-dwelling older men and women. Lifestyle factors often associated with BMD, including alcohol consumption (1820), smoking (2123), physical activity (24, 25), calcium supplementation (26), and, in women, hormone replacement therapy (27), were controlled for in the analyses. We considered whether reported poor health and subclinical disease, as assessed by death within 2 years, were possible mechanisms for weight loss. A clinically important rate of hip bone loss was assumed to be an average loss of at least 1 percent per year.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Study design
The Rancho Bernardo Study was established in 1972–1974 when 82 percent of adult residents of Rancho Bernardo, California, participated in a survey of heart disease risk factors (28). Participants were Caucasian and middle- to upper-middle-class. Between February 1988 and February 1992, approximately 80 percent of surviving resident participants who were then aged 50 years or older (n = 2,031) attended an osteoporosis study visit. Between May 1992 and December 1996, a second osteoporosis study visit was conducted; all surviving attendees of the first osteoporosis visit still living in the Rancho Bernardo area were invited. The 469 men and 745 women (n = 1,214) who had complete data from both osteoporosis visits comprised our study participants.

Medical history, health habits, age, and use of dietary supplements and medications were assessed by means of standardized questionnaires at the first osteoporosis visit. Data on current health habits were dichotomized: cigarette smoking; alcohol consumption on 3 or more days per week; physical activity three or more times per week; and use of calcium supplements, estrogen, and progestin. These dichotomizations have been used in previous Rancho Bernardo reports.

At both osteoporosis visits, total hip BMD (g/cm2) was measured using the same dual-energy x-ray absorptiometer (Hologic QDR-1000; Hologic, Inc., Bedford, Massachusetts). Scans were standardized daily against a calibration phantom; the measurement error was 1.5 percent. Weight and height were measured using a balance beam scale and level while the participant stood wearing light clothing and no shoes. Body mass index was calculated as weight (kg)/[height (m)]2. After an average interval of 4 years between the two visits, changes in weight and hip BMD were expressed as percentage change per year.

General health, physical functioning, and change in exercise as compared with 10 years previously were assessed by means of standardized questionnaires at the second osteoporosis visit. General health and physical functioning were reported on a five-point scale, and change in exercise was reported as more, the same, or less. After the frequencies of the responses had been examined, these characteristics were dichotomized as excellent or good general health versus fair or poor health, little or no limitation in physical functioning versus medium or greater limitation, and exercising less than 10 years previously versus not exercising less than 10 years previously. Vital status 2 years after the second osteoporosis visit was used as another indicator of health status at that visit.

Statistical analysis
Means and standard deviations for continuous variables and percentages for dichotomous variables were calculated. Sex and women’s use of estrogen were used as stratification variables. In one subanalysis, data were also stratified by age, baseline BMD, and 4-year weight change. Differences between continuous variables were assessed by means of the t test, differences between dichotomous variables by the ordinary {chi}2 test, and differences between ordinal variables by the {chi}2 test for trend.

Logistic regression analysis was used to estimate the odds ratios for hip bone loss of at least 1 percent per year, with adjustment for age and other covariates. An average bone loss of at least 1 percent per year was chosen as the endpoint because a change of at least 4 percent over a 4-year period is greater than the measurement error of the Hologic QDR-1000 absorptiometer (1.5 percent) and was thought to be clinically significant. Baseline BMD was expressed in sex-specific standard deviation units, and age was expressed in 5-year increments. All models were sex-specific.

Linear regression analysis modeling percentage of bone loss per year was used to assess the correlation between weight loss and bone loss, to explore whether the effects of weight loss were similar for younger and older participants, and to confirm the results of the logistic regression analysis. The linearity of the effects of age and weight loss on bone loss was assessed by introducing quadratic and cubic terms into the models. Similarly, the interaction between age and weight loss on bone loss was assessed by introducing cross-product terms. The SAS system was used for all data management and analyses (SAS Institute, Inc., Cary, North Carolina).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
At baseline, the average (and median) age of both men and women was 71 years (men’s ages ranged from 54 years to 87 years and women’s from 50 years to 92 years). As table 1 shows, a high proportion reported regular exercise, most commonly walking, and alcohol consumption. Less than 10 percent of all participants were current cigarette smokers. Among women, 42 percent were using estrogen and 44 percent were taking calcium supplements. One third of women taking estrogen were also taking progestin. Participants who attended the first visit but not the second, and hence were not study participants, were significantly older, had a significantly lower BMD, and were significantly less likely to regularly consume alcohol, to exercise, or to take calcium supplements. In addition, the men who did not attend the second visit had a significantly lower body mass index, and the women were significantly less likely to take hormones.


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TABLE 1. Characteristics of community-dwelling men and women aged >=50 years in a study of weight loss and change in total hip bone mineral density, Rancho Bernardo, California
 
On average, both men and women lost weight and bone over the 4-year follow-up period. The mean weight loss per year was 0.6 kg (0.2 percent) for men and 0.1 kg (0.03 percent) for women, although the percentage of men losing at least 1 percent of their weight per year (21 percent) was similar to the percentage of women (23 percent). Mean bone loss at the hip was 0.5 percent per year for both sexes. Bone loss of at least 1 percent per year was observed in 29 percent of men and 28 percent of women.

Bone loss increased with age in both sexes, and women who used estrogen lost less bone than women who did not (table 2). More than 40 percent of men and non-estrogen-taking women who were aged 75 years or older lost at least 1 percent of BMD per year. Participants with the lowest BMD at baseline were more likely to have accelerated bone loss. Men and estrogen-taking women who lost at least 1 percent of their body weight per year were twice as likely to lose bone at the rate of at least 1 percent per year as those who lost less or gained weight. Over 50 percent of men and non-estrogen-taking women who lost at least 1 percent of their weight per year lost at least 1 percent of BMD per year.


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TABLE 2. Percentage of participants who lost at least 1 percent of total hip bone mineral density per year (averaged over 4 years), by age, baseline bone mineral density, and weight change, Rancho Bernardo, California
 
In univariable logistic regression analysis, hip bone loss of at least 1 percent per year increased with age in both men and women. Similarly, in simple linear regression analysis, continuously measured hip bone loss increased with age in both men and women. As table 3 shows, after adjustment for age, the only additional significant risk factor for bone loss in both analyses for both sexes was weight loss. Age-adjusted baseline hip BMD and estrogen use were also significant in both analyses in women. Lower baseline body mass index was significant in both men and women, but only in the linear regression analysis.


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TABLE 3. Results from age and age-adjusted regression analyses of hip bone loss over a 4-year period, Rancho Bernardo, California
 
The results of multivariable logistic and linear regression analyses, including age and all other risk factors that remained significant at p = 0.05, are shown in table 4. In these multivariable analyses, weight loss was the most significant risk factor, and low baseline body mass index was also independently associated with bone loss in both sexes. Additional independent risk factors were age in men and estrogen use in women.


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TABLE 4. Results from multivariable regression analyses* of hip bone loss over a 4-year period, Rancho Bernardo, California
 
The results from the linear regression models shown in table 4 were augmented to investigate the possibility of an interaction between age and weight loss by adding the cross-product term of age and weight loss. Neither the cross-product term for men nor that for women was significantly different from zero. Similarly, the models were augmented to investigate the linearity of the effects of age and weight loss by the addition of quadratic and cubic terms. For men, there was no evidence of nonlinearity in the effect of age, but there was a small, significant nonlinearity in the effect of weight loss. For women, both age and weight loss were significantly nonlinear (data not shown).

In addition to the risk factor analysis, the associations of weight loss with general health, physical function, and exercise habits, as reported at the second osteoporosis visit, were studied as possible mechanisms for weight loss (table 5). Participants who lost at least 1 percent of their baseline weight per year were more likely to have reported their health as fair or poor than those who did not lose weight. Similarly, participants who lost weight were more likely than those who did not to have reported medium or greater functional limitation and to have reported exercising less than 10 years previously. Participants older than the mean (71 years) as compared with those younger were also more likely to have reported their health as fair or poor, to have reported their physical functioning as limited, and to be exercising less (results not shown).


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TABLE 5. Prevalence (%) of selected health indicators at the study second visit according to weight loss of at least 1% per year over a 4-year period, Rancho Bernardo, California
 
Functional limitation, added to the multivariable analysis of table 4, was an additional independent risk factor for bone loss in men (although it did not appreciably change the odds ratios reported in table 4) but not in women. Poor general health and exercising less, while associated with bone loss, were not independent risk factors for bone loss.

Although most participants who lost weight survived for more than 2 years after the second visit, participants who lost at least 1 percent of their weight per year were significantly more likely to die during the following 2 years than those who lost less or gained weight (12.4 percent vs. 4.7 percent in men (p = 0.004) and 8.6 percent vs. 2.4 percent in women (p < 0.001)).


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Although results may differ for other sociodemographic groups, weight loss was the most important risk factor for bone loss in these community-dwelling older men and women. This effect was independent of low baseline body mass index (also an independent risk factor in both sexes) and of estrogen supplement use in women. These results are concordant with two previous reports showing that both low baseline body mass index and weight loss were independent risk factors for hip bone loss in both sexes (16, 17). Our results additionally show that these risk factors are unchanged when a categorical, clinically important decrease in BMD is modeled as the response variable instead of a continuous measure of BMD change. Our results differ from those of the Longitudinal Aging Study Amsterdam (29), which found that the effect of weight change on BMD was diminished by inclusion of a measure of body size; this difference may be due to different baseline weight patterns or to the use of self-reported weight at age 25 years as the baseline weight in the Amsterdam study.

There was no significant interaction between weight loss and age in men or women, although both weight loss and age were important main effects. The slight but generally significant nonlinearity of age and weight loss on continuously measured bone loss suggests that the logistic regression models on dichotomized bone loss may be more appropriate than the linear models, although the results of both models were similar. The effects of percentage of weight loss on percentage of bone loss were similar in men and women, although women weighed less, had a lower BMD at baseline, and lost fewer pounds on average over 4 years. Thus, the effects of weight loss on bone loss were proportional to baseline size and weight loss but were not otherwise different for men and women. Neither baseline hip BMD nor health habits were significant predictors of bone loss in multivariate analysis. The absent lifestyle associations possibly reflect the low proportion of participants who were current smokers and the high proportion who reported regular exercise and alcohol consumption.

In these older adults, weight loss may have been a surrogate for underlying illness, in that participants who had lost weight were more likely at the second visit to report fair or poor general health, functional limitation, and less exercise and were more likely to die within the next 2 years. Thus, many who lost weight may have done so unintentionally, consistent with the low prevalence of dieting (30) and the high frequency of unintentional weight loss in old age (31). Some weight loss may parallel unexplained muscle loss; sarcopenia is associated with physical disability (32), and immobility is associated with bone loss.

However, the majority of participants in this study did not report poor health or impaired physical functioning and survived for at least 2 years after the second visit—indirect evidence that BMD loss accompanying weight loss is not always a result of age and illness (10). Two studies of BMD change in overweight adults who were dieting to lose weight confirmed this thesis: In both studies, one in men (33) and one in postmenopausal women (34), diet-induced weight loss reduced total body BMD as well as weight. In both studies, an exercise group lost weight without significant bone loss, which shows that bone loss associated with voluntary weight loss can be reduced or prevented if it is paired with weight-bearing exercise. Calcium supplementation has also been shown to partially ameliorate the bone loss that accompanies voluntary weight loss in women (35), although the effect of calcium supplementation on bone loss in dieting postmenopausal women may be slight (36). In the present study, calcium supplementation did not significantly interact with the effect of weight loss on bone loss, although the interaction was of borderline significance in women (0.05 < p <= 0.10).

In summary, weight loss is common with aging, such that more than one in five of these ambulatory, community-dwelling men and women lost an average of at least 1 percent of their body weight per year. After 4 years, this weight loss doubled the risk of clinically important bone loss (table 2). This association was similar in men and women and increased with age. The strength of the association may have been underestimated, since Rancho Bernardo participants principally did not return for the second osteoporosis visit because of death or institutionalization, which probably removed many persons who lost weight after the first osteoporosis visit. Accumulated bone loss and weight loss are likely to be important factors in the exponential increase in hip fractures with aging (37). Health care providers should consider the frequency of voluntary or involuntary weight loss in elderly patients and its portent for significant bone loss. The ideal body weight for older adults remains a subject of controversy (38, 39); however, in older adults, weight loss from any cause appears to have dangerous effects on skeletal health.


    ACKNOWLEDGMENTS
 
This research was supported by National Institute on Aging grant AG07181.


    NOTES
 
Correspondence to Dr. Elizabeth Barrett-Connor, 349 Stein Clinical Research Building, Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0607 (e-mail: ebarrettconnor{at}ucsd.edu). Back


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Sernbo I, Johnell O. Consequences of a hip fracture: a prospective study over 1 year. Osteoporos Int 1993;3:148–53.[ISI][Medline]
  2. Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for the prediction of hip fractures. The Study of Osteoporotic Fractures Group. Lancet 1993;341:72–5.[ISI][Medline]
  3. Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Group. N Engl J Med 1995;332:767–73.[Abstract/Free Full Text]
  4. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254–9.[Abstract/Free Full Text]
  5. Nguyen TV, Center JR, Sambrook PN, et al. Risk factors for proximal humerus, forearm, and wrist fractures in elderly men and women: The Dubbo Osteoporosis Epidemiology Study. Am J Epidemiol 2001;153:587–95.[Abstract/Free Full Text]
  6. Ravn P, Cizza G, Bjarnason NH, et al. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (ERIC) Study Group. J Bone Miner Res 1999;14:1622–7.[ISI][Medline]
  7. Stone K, Bauer DC, Black DM, et al. Hormonal predictors of bone loss in elderly women: a prospective study. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1998;13:1167–74.[ISI][Medline]
  8. Reeve J, Walton J, Russell LJ, et al. Determinants of the first decade of bone loss after menopause at spine, hip, and radius. QJM 1999;92:261–73.[Abstract/Free Full Text]
  9. Brot C, Jensen LB, Sorensen OH. Bone mass and risk factors for bone loss in perimenopausal Danish women. J Intern Med 1997;242:505–11.[ISI][Medline]
  10. Chao D, Espeland MA, Farmer D, et al. Effect of voluntary weight loss on bone mineral density in older overweight women. J Am Geriatr Soc 2000;48:753–9.[ISI][Medline]
  11. Van Loan MD, Johnson HL, Barbieri TF. Effect of weight loss on bone mineral content and bone mineral density in obese women. Am J Clin Nutr 1998;67:734–8.[Abstract]
  12. Sirola J, Kroger H, Honkanen R, et al. Risk factors associated with peri- and postmenopausal bone loss: does HRT prevent weight loss-related bone loss? Osteoporos Int 2003;14:27–33.[ISI][Medline]
  13. Nguyen TV, Sambrook PN, Eisman JA. Bone loss, physical activity, and weight change in elderly women: The Dubbo Osteoporosis Epidemiology Study. J Bone Miner Res 1998;13:1458–67.[ISI][Medline]
  14. Burger H, De Laet CE, Van Daele PL, et al. Risk factors for increased bone loss in an elderly population: The Rotterdam Study. Am J Epidemiol 1998;147:871–9.[Abstract]
  15. Yoshimura N, Hashimoto T, Morioka S, et al. Determinants of bone loss in a rural Japanese community: The Taiji Study. Osteoporos Int 1998;8:604–10.[CrossRef][ISI][Medline]
  16. Dennison E, Eastell R, Fall CH, et al. Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 1999;10:384–91.[CrossRef][ISI][Medline]
  17. Hannan MT, Felson DT, Dawson-Hughes B, et al. Risk factors for longitudinal bone loss in elderly men and women: The Framingham Osteoporosis Study. J Bone Miner Res 2000;15:710–20.[ISI][Medline]
  18. Holbrook TL, Barrett-Connor E. A prospective study of alcohol consumption and bone mineral density. BMJ 1993;306:1506–9.[ISI][Medline]
  19. Felson DT, Zhang Y, Hannan MT, et al. Alcohol intake and bone mineral density in elderly men and women: The Framingham Study. Am J Epidemiol 1995;142:485–92.[Abstract]
  20. May H, Murphy S, Khaw KT. Alcohol consumption and bone mineral density in older men. Gerontology 1995;41:152–8.[ISI][Medline]
  21. Hollenbach KA, Barrett-Connor E, Edelstein SL, et al. Cigarette smoking and bone mineral density in older men and women. Am J Public Health 1993;83:1265–70.[Abstract]
  22. Kiel DP, Zhang Y, Hannan MT, et al. The effect of smoking at different life stages on bone mineral density in elderly men and women. Osteoporos Int 1996;6:240–8.[ISI][Medline]
  23. Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med 1994;330:387–92.[Abstract/Free Full Text]
  24. Greendale GA, Barrett-Connor E, Edelstein SL, et al. Lifetime leisure exercise and osteoporosis: The Rancho Bernardo Study. Am J Epidemiol 1995;141:951–9.[Abstract]
  25. Taunton JE, Martin AD, Rhodes EC, et al. Exercise for the older woman: choosing the right prescription. Br J Sports Med 1997;31:5–10.[Abstract]
  26. Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990;323:878–83.[Abstract]
  27. Felson DT, Zhang Y, Hannan MT, et al. The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 1993;329:1141–6.[Abstract/Free Full Text]
  28. Criqui MH, Barrett-Connor E, Austin M. Differences between respondents and non-respondents in a population-based cardiovascular disease study. Am J Epidemiol 1978;108:367–72.[Abstract]
  29. Pluijm SM, Visser M, Smit JH, et al. Determinants of bone mineral density in older men and women: body composition as mediator. J Bone Miner Res 2001;16:2142–51.[ISI][Medline]
  30. Horm J, Anderson K. Who in America is trying to lose weight? Ann Intern Med 1993;119:672–6.[ISI][Medline]
  31. Wedick NM, Barrett-Connor E, Knoke JD, et al. The relationship between weight loss and all-cause mortality in older men and women with and without diabetes mellitus: The Rancho Bernardo Study. J Am Geriatr Soc 2002;50:1810–15.[CrossRef][ISI][Medline]
  32. Baumgartner RN, Koehler KM, Gallagher D, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998;147:755–63.[Abstract]
  33. Pritchard JE, Nowson CA, Wark JD. Bone loss accompanying diet-induced or exercise-induced weight loss: a randomised controlled study. Int J Obes Relat Metab Disord 1996;20:513–20.[Medline]
  34. Ryan AS, Nicklas BJ, Dennis KE. Aerobic exercise maintains regional bone mineral density during weight loss in postmenopausal women. J Appl Physiol 1998;84:1305–10.[Abstract/Free Full Text]
  35. Jensen LB, Kollerup G, Quaade F, et al. Bone minerals changes in obese women during a moderate weight loss with and without calcium supplementation. J Bone Miner Res 2001;16:141–7.[ISI][Medline]
  36. Ricci TA, Chowdhury HA, Heymsfield SB, et al. Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. J Bone Miner Res 1998;13:1045–50.[ISI][Medline]
  37. Melton LJ III. Epidemiology of hip fractures: implications of the exponential increase with age. Bone 1996;18(suppl):121S–5S.[CrossRef][Medline]
  38. Allison DB, Gallagher D, Heo M, et al. Body mass index and all-cause mortality among people age 70 and over: The Longitudinal Study of Aging. Int J Obes Relat Metab Disord 1997;21:424–31.[CrossRef][Medline]
  39. Grabowski DC, Ellis JE. High body mass index does not predict mortality in older people: analysis of the Longitudinal Study of Aging. J Am Geriatr Soc 2001;49:968–79.[CrossRef][ISI][Medline]