Limb Fractures in Elderly Men As Indicators of Subsequent Fracture Risk

ORIGINAL INVESTIGATION Limb Fractures in Elderly Men as Indicators of Subsequent Fracture Risk

Bruce Ettinger, MD; G. Thomas Ray, MBA; Alice R. Pressman, MS; Oscar Gluck, MD

Background: Whether limb fracture in elderly men pre- merus fracture (relative risk, 3.9; 95% confidence inter- dicts future fracture is unknown. val, 2.5-6.0), about 3 times more likely to occur in persons who experienced a previous hip fracture (relative Methods: Electronic health records were examined to risk, 2.8; 95% confidence interval, 1.7-4.5), and about 2 determine fracture incidence among men 60 years or older times more likely to occur in persons who experienced who were members of a large health maintenance orga- a previous wrist fracture (relative risk, 2.2; 95% confi- nization, experienced no fracture in the past 2 years, and dence interval, 1.4-3.5) than in controls. In contrast, per- experienced an ankle, hip, humerus, or wrist fracture be- sons who experienced a previous ankle fracture had no tween July 1, 1997, and August 31, 2001. Proportional greater risk of subsequent fracture than nonfracture con- hazards models were used to compare risk of new frac- trols (relative risk, 1.0; 95% confidence interval, 0.5-1.9). ture (ankle, hip, humerus, or wrist) between groups. Re- current fractures of the same type were excluded from Conclusions: Among men 60 years or older, a recent analysis. hip, humerus, or wrist fracture is a statistically and clinically significant predictor of future limb fracture risk. An Results: During the follow-up period (mean duration, increased risk of future fracture is greatest after a hu- 2.4 years), 0.5% of the control subjects without frac- merus fracture and is lowest after a wrist fracture; how- tures experienced a subsequent ankle fracture; 0.6%, a ever, among elderly men, a previous ankle fracture is not hip fracture; 0.2%, a humerus fracture; and 0.4%, a wrist an indicator of future fracture risk. fracture. A limb fracture was about 4 times more likely to occur in persons who experienced a previous hu- Arch Intern Med. 2003;163:2741-2747

ISK FACTORS related to os- programs aimed at preventing osteopo- teoporotic fracture in rotic fracture should receive greater em- women have been exten- phasis. sively investigated, but the Identifying persons at risk for future epidemiologic features of fracture is a key part of any prevention pro- osteoporoticR fracture in men have re- gram. Several clinical risk factors for frac- ceived attention only recently. Fracture ture are related to falls and frailty and seem among aging men is a clinically signifi- to operate similarly in men and wom- cant health problem, as indicated by the en.6,7 Low bone density6,8-10 and the re- fact that about one third of all fractures sults of serum biochemical tests6 have also among elderly persons occur in men.1,2 The been shown to predict fracture risk simi- lifetime risk of fragility fracture among larly in both sexes. The previous occur- white men at the age of 60 years has been rence of fracture can be determined dur- estimated at 21% in England and Wales1 ing patient visits or from administrative and at 15% in Australia.2 Fracture in men electronic databases available to govern- results in clinically significant morbidity, mental and managed care organizations. From the Division of Research, mortality, and cost to society.3,4 Among Such data could be used to identify pa- Kaiser Permanente Medical people older than 75 years, the hip frac- tients at increased risk for osteoporotic Care Program, Oakland, Calif ture–related mortality rate is higher in men fracture and could lead to appropriate use (Dr Ettinger, Mr Ray, and Ms Pressman); and the Arizona than in women, probably for reasons re- of interventions to reduce the number of Rheumatology Center, Phoenix lated to greater incidence of comorbid con- fractures in populations at high risk. (Dr Gluck). The authors have ditions among aging men than among Although the association between no relevant financial interest in similarly aged women.5 Given the magni- fracture occurrence and future fracture risk this article. tude of the fracture risk among aging men, has been adequately studied in women, this

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Downloaded From: https://jamanetwork.com/ on 09/26/2021 A Men Aged ≥60 y With B Men Aged ≥60 y a Potential Index Fracture With a Potential of the Ankle, Hip, Index Fracture Humerus, or Wrist of the Finger (n = 4256) (n = 983)

Membership Exclusion Membership Exclusion ∗ ∗ (n = 520) (n = 124)

>24 mo of Continuous >24 mo of Continuous Health Plan Membership Health Plan Membership (n = 3736) (n = 859)

Pathologic Fracture Pathologic Fracture (n = 46) (n = 2)

Eligible Eligible (n = 3690) (n = 857)

Ankle Fracture Hip Fracture Humerus Fracture Wrist Fracture Finger Fracture (n = 1087) (n = 1175) (n = 486) (n = 942) (n = 857)

Excluded Excluded Excluded Excluded Excluded (n = 20)† (n = 61)† (n = 16)† (n = 17)† (n = 16)†

Ankle Fracture Hip Fracture Humerus Fracture Wrist Fracture Finger Fracture (n = 1067) (n = 1114) (n = 470) (n = 925) (n = 841)

Figure 1. Selection of patients with an index fracture of the ankle, hip, humerus, or wrist (A) or an index fracture of the finger (B). The asterisk indicates a health plan member for less than 24 months; dagger, excluded because of health conditions or drugs.

association in men requires further elucidation. A meta- SOURCES OF FRACTURE analysis11 of 34 studies published through September 1999 DIAGNOSIS DATA concluded that previous fracture approximately doubled the risk of future fracture in men and women; the re- Kaiser Permanente hospital diagnoses were extracted from the searchers commented on the uniformity of risk between health plan’s Admission Discharge and Transfer system, in which are maintained records for all hospital encounters (inpatient sexes and for various fracture sites. However, this sum- and ambulatory surgery) and all associated diagnoses. Diag- mary of 34 good-quality studies contained only 4 stud- 12-15 noses for emergency department visits and office visits were ies designed to examine fracture risk in men and 4 extracted from Kaiser Permanente’s Outpatient Summary Clini- 16-19 other studies that yielded usable information on frac- cal Record. At each visit, physicians and nurse practitioners se- ture risk in men after studying both sexes. Thus, a need lect from relevant diagnoses listed in specialty-specific forms; exists for data on fracture risk after various types of frac- diagnoses checked off on these forms populate the Outpatient ture in aging men and on the strength of associations for Summary Clinical Record database. Diagnoses for episodes of different types of limb fracture. hospitalization and for emergency claims made at non–Kaiser We hypothesized that limb fracture would signal Permanente sites were extracted from the Outside Medical Ser- increased skeletal fragility and, thus, increased risk of fu- vices systems, which capture diagnostic information included ture osteoporotic fracture. Therefore, we studied the as- on billing statements. sociations between 4 limb fractures considered osteopo- IDENTIFICATION OF THE FRACTURE rotic and the subsequent risk of similar fracture among AND COMPARISON COHORTS elderly men. The database for members of a large health maintenance organization was analyzed to compare the The evolution of our study cohort is depicted in Figure 1.From risk of subsequent fracture among men with each of these our automated databases, we extracted all cases of fracture di- 4 sites of index fracture with the risk among men without agnosed in men between July 1, 1995, and August 31, 2001. such a history. The analysis included adjustment for clini- By using these data, we identified all closed fractures of the ankle cal confounders related to frailty and falling. (talus or distal tibia), hip (proximal femur), humerus, or wrist (Figure 1A). We assumed that a true hip fracture would have resulted in a hospitalization; thus, to exclude spurious diag- METHODS noses, we required that hip fracture be identified from inpatient hospital stays. Similarly, we required that an ankle, hu- SETTING merus, or wrist fracture be diagnosed either in an orthopedics department or at a second visit for the same fracture within 60 The Kaiser Permanente Medical Care Program is an integrated, days after the initial fracture event. The study included only group-model, nonprofit health maintenance organization serv- men 60 years or older at the index fracture. The index fracture ing approximately 3 million members throughout Northern Cali- was defined as the first nonpathologic fracture of the ankle, hip, fornia. The Kaiser Permanente Northern California Institu- humerus, or wrist not preceded by any fracture of any kind dur- tional Review Board approved the study protocol. ing the preceding 2 years. To ensure a minimum 2 years of prior

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Downloaded From: https://jamanetwork.com/ on 09/26/2021 observation, we required that subjects be members of the health plan continuously during the 2 years before the index frac- Men Aged ≥60 y > ture. Patients who had multiple fractures occurring on the same 24 mo of Continuous Health Plan Membership Before 1/1/1999 day were excluded from the analysis to preclude the possibil- Fracture Exclusion ∗ ity of miscoding as a new fracture one that occurred concur- (n = 6962) rently with an index fracture. We also excluded from analysis persons with a history of pathologic fractures occurring be- >24 mo Without a Fracture fore the index date. Pathologic fractures were identified by In- (n = 174 387) ternational Classification of Diseases, Ninth Revision (ICD-9) code.

The primary comparison group was randomly selected from Excluded all men who were 60 years or older on January 1, 1999, and (n = 985)† who had continuous health plan membership but no fracture of any kind during the previous 2 years (Figure 2). The in- Eligible dex date for these men was January 1, 1999. A second com- (n = 173 402) parison group was composed of men who sustained a closed finger fracture (Figure 1B). This group was selected using the About 50% Random Sample same inclusion and exclusion criteria as used for the 4 limb frac- (n = 86 408) ture groups, but because a closed fracture of the finger rarely requires multiple visits or a visit to an orthopedist, a single di- Figure 2. Selection of patients in the control group without fractures. agnosis from any source was considered sufficient for selec- The asterisk indicates fracture of any kind before January 1, 1999; tion of the second comparison group. dagger, excluded because of health conditions or drugs. Among the fracture and comparison cohorts, we excluded persons who, before the index date, received treatment known to affect risk of osteoporosis. Therefore, we excluded 3 current with the index fracture but had not been included in groups of men: those diagnosed as having Paget disease, those the Outpatient Summary Clinical Record or the Admission who used the equivalent of2gormoreofprednisone-equiva- Discharge and Transfer system until a later time. Most cases of lent glucocorticoid agents in the year before the index date, incorrect coding of a presumed subsequent fracture were and those who used osteoporosis prevention–related drugs because of continuing care for the index fracture and seemed (alendronate sodium, calcitonin, etidronate disodium, or to be caused by physicians or nurse practitioners inadvert- risedronate sodium) during the year before the index date. ently checking a different fracture type on the Outpatient The level of prednisone equivalent was chosen because intake Summary Clinical Record diagnosis form. Therefore, errors of of 5 mg/d or more for more than 3 months is considered by this type were associated with the index fracture, and we did experts a level of use likely to increase the risk of osteoporotic not expect to find them for the comparison group with no fracture.20 index fracture. Our final cohort consisted of 3576 men 60 years or older with an index fracture as defined for this study in the follow- ANALYSIS ing areas: ankle (n=1067), hip (n=1114), humerus (n=470), and wrist (n=925). The comparison group with a finger frac- We used a separate proportional hazards model to estimate the ture consisted of 841 men, and the nonfracture comparison increased hazard of a subsequent fracture for each index frac- group consisted of 173402 men, of whom 86408 (about half ture type. The outcome of interest was the first fracture after the sample) were randomly selected for study. the index date. Data for any person were censored if the person died or otherwise discontinued health plan membership IDENTIFICATION OF before the end of follow-up. Separate models compared per- SUBSEQUENT FRACTURES sons with each type of index fracture with persons who had no previous fracture and with persons whose index fracture was For men in the fracture and nonfracture groups, we identified of the finger. ankle, hip, humerus, and wrist fractures that occurred after the Because our analysis excluded subsequent fractures of index dates. Follow-up from the index date ended when 1 of 4 the same site as the index fracture, the same fracture was nec- conditions was met: (1) the first ankle, hip, humerus, or wrist essarily excluded as an outcome in the nonfracture and finger fracture was sustained; (2) health plan membership was dis- fracture comparison groups. Thus, for example, a person in continued; (3) death; or (4) the end of the study period was the nonfracture comparison group who had a hip fracture on reached (August 31, 2001). Without examining written medi- March 1, 2000, and an ankle fracture on August 1, 2000, was cal records, we could not always distinguish between continu- counted as having an ankle fracture when compared with men ing care for a fracture and a new fracture of the same type; there- who had an index hip fracture and was counted as having a fore, we considered only subsequent fractures that differed in hip fracture when compared with men who had an index site from the index fracture. For example, for men who had an ankle fracture. index hip fracture, only a subsequent ankle, humerus, or wrist All proportional hazards models were adjusted for the fol- fracture counted as an event; subsequent diagnoses of hip frac- lowing factors: (1) age, (2) cardiac-related drug use, (3) cen- ture were ignored. tral nervous system–related drug use, (4) diabetes mellitus– related drug use, (5) hospitalizations, and (6) office visits. Each REVIEW AND VERIFICATION drug use variable was modeled dichotomously and refers to any OF SUBSEQUENT FRACTURES use in the year before the index fracture. Hospitalization and visit counts were each modeled as a continuous variable and One of us (B.E.) reviewed the radiographic reports of all men were measured in the 395 to 30 days before the index fracture. with an index fracture who subsequently had a new fracture When deriving hospitalization and office visit measures, we ex- during the study period. Cases were excluded if electronically cluded the period 30 days before the index date so as not to available radiology reports failed to confirm a subsequent frac- include health care use that might have been associated with ture or if the presumed subsequent fracture was, in fact, con- the fracture event.

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Downloaded From: https://jamanetwork.com/ on 09/26/2021 Table 1. Characteristics of Male Patients 60 Years or Older With an Index Fracture and a Comparison Group With No Index Fracture*

Group With an Initial Index Fracture Comparison Group Ankle Hip Humerus Wrist Finger With No Index Fracture Characteristic (n = 1067) (n = 1114) (n = 470) (n = 925) (n = 841) (N = 86 408) Baseline Data Age group at the index date, y† 60-69 55 10 39 46 51 54 70-79 32 36 35 38 36 35 Ն80 13 54 26 16 13 12 Age at the index date, mean, y 70 81‡ 74‡ 72‡ 71‡ 70 Health status–related variables used as covariates Hospitalization between 395 and 30 d before 0.4‡ 0.6‡ 0.5‡ 0.4‡ 0.3 0.3 the index date, mean Office visits between 395 and 30 d before 9‡ 11‡ 11‡ 9‡ 9‡ 7 the index date, mean Cardiac-related drug prescribed in the year 59‡ 67‡ 58‡ 56‡ 57‡ 51 before the index date Active central nervous system–related drug 47‡ 58‡ 57‡ 47‡ 50‡ 33 prescribed in the year before the index date Diabetes mellitus–related drug prescribed 17‡ 18‡ 17‡ 12 10 12 in the year before the index date Follow-up Data Died before the end of follow-up 7 41‡ 15‡ 9 5‡ 8 Length of follow-up, mean, mo§ 22‡ 15‡ 20‡ 22‡ 23‡ 29 Fracture occurred after the index date࿣ Subsequent fracture of the hip, humerus, 0.8 NA NA NA 1.0 1.2 or wrist Subsequent fracture of the ankle, humerus, NA 2.0‡ NA NA 1.0 1.1 or wrist Subsequent fracture of the ankle, hip, NA NA 5.1‡ NA 1.3 1.5 or wrist Subsequent fracture of the ankle, hip, NA NA NA 2.5‡ 1.4 1.3 or humerus

Abbreviation: NA, data not applicable. *Data are given as percentage of each group unless otherwise indicated. Data are from the Kaiser Permanente Medical Care Program, Oakland, Calif, from July 1, 1997, through August 31, 2001. †Percentages may not total 100 because of rounding. ‡PϽ.05 vs persons with no index fracture, unadjusted. §Calculated only for persons who did not have a fracture after the index date; for those who did have a fracture after the index date, follow-up ended when the fracture occurred. ࿣For persons with an index fracture of the ankle, hip, humerus, or wrist, outcome at a site other than the index fracture site. For persons with an index fracture of the finger or for those who were in the nonfracture comparison group, the outcome fracture site was matched with the site used for the fracture comparison group.

RESULTS ture. This difference was in part explained by a higher mortality rate among some of the fracture groups (par- PATIENT CHARACTERISTICS ticularly those with a hip or humerus fracture) but was AND UNADJUSTED ANALYSES also due to the study chronology. Follow-up for the nonfracture group began on January 1, 1999, whereas fol- On average, men who had an index ankle, hip, hu- low-up for patients with an index fracture started at a later merus, or wrist fracture differed from each other and from date (ie, when the index fracture occurred). Figure 3 men in the nonfracture comparison group. Men with a shows the proportions of these groups who were free from limb fracture tended to be older than men without an in- fracture over time; the hazard function was linear for all dex fracture, had more hospitalizations and outpatient types of fracture, and no excessive risk was observed dur- visits, and were more likely to have received a prescrip- ing the early months after the index fracture occurred. tion for one of the high-risk drugs (Table 1). More men The proportion of men with 1 or more subsequent frac- with an index hip or humerus fracture died during fol- tures of a type different from that of the index fracture low-up compared with men without an index fracture. was higher for men after an index fracture of the hip When follow-up was calculated for persons who did not (2.0%), humerus (5.1%), or wrist (2.5%) than for men have a subsequent fracture (because follow-up “artifi- who had a similar fracture outcome but no index frac- cially” ended for them at that point), follow-up ranged ture. Among those men, a subsequent fracture at a dif- from 15 to 23 months for persons with an index frac- ferent location occurred in 1.1% of those who previ- ture but was 29 months for men without an index frac- ously had a hip fracture, 1.5% of those who previously

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Downloaded From: https://jamanetwork.com/ on 09/26/2021 A B 1.00

0.98

0.96

0.94 Nonfracture Comparison Group Nonfracture Comparison Group Ankle Fracture Group Hip Fracture Group Probability of No Subsequent Fracture 0.92

C D 1.00

0.98

0.96

0.94 Nonfracture Comparison Group Nonfracture Comparison Group Humerus Fracture Group Wrist Fracture Group Probability of No Subsequent Fracture 0.92 0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28 Follow-up, mo Follow-up, mo

Figure 3. Probability of remaining free of fracture during follow-up by type of index fracture. A, Ankle fracture. B, Hip fracture. C, Humerus fracture. D, Wrist fracture.

Table 2. Hazard Ratios of Incurring a Subsequent Fracture for Male Patients 60 Years or Older With an Initial Fracture of the Ankle, Hip, Humerus, or Wrist Compared With Persons Who Had an Initial Fracture of the Finger and Persons in the Nonfracture Comparison Group, After Adjustment*

Hazard Ratio (95% Confidence Interval)

Compared With the Compared With the Nonfracture Comparison Group Finger Fracture Group Type of Initial Fracture Age Adjusted Only All Adjustments† Age Adjusted Only All Adjustments† Ankle 1.0 (0.5-1.9) 1.0 (0.5-1.9) 1.0 (0.4-2.6) 1.0 (0.4-2.6) Hip 2.5 (1.6-3.9)‡ 2.8 (1.7-4.5)‡ 2.5 (1.1-5.6)‡ 2.6 (1.1-5.9)‡ Humerus 4.1 (2.7-6.1)‡ 3.9 (2.5-6.0)‡ 3.6 (1.7-7.3)‡ 3.5 (1.7-7.1)‡ Wrist 2.2 (1.4-3.4)‡ 2.2 (1.4-3.5)‡ 1.7 (0.9-3.5) 1.7 (0.9-3.4)

*Data are given only for a subsequent fracture of a form different than that of the initial fracture. Data are from the Kaiser Permanente Medical Care Program, Oakland, Calif, from July 1, 1997, through August 31, 2001. †Proportional hazard models were adjusted for (1) age, (2) cardiac-related drug use, (3) central nervous system–related drug use, (4) diabetes mellitus–related drug use, (5) hospitalizations, and (6) office visits. Each drug use variable was modeled dichotomously, and is based on use in the year before the index date. Hospitalization and visit counts were each modeled as a continuous variable, and were measured in the 395 to 30 days before the date of the index fracture. ‡PϽ.05.

had a humerus fracture, and 1.3% of those who previ- ture was more likely to occur in men with an index hip, ously had a wrist fracture. These results, however, are humerus, or wrist fracture than in men who had either based on differing lengths of follow-up and on differing no fracture or an index fracture of the finger (Table 2). baseline risk factors. Compared with men who had no index fracture, men with an index fracture of the humerus were nearly 4 times more ADJUSTED HAZARD RATES likely to have a subsequent nonhumerus fracture (ankle, OF SUBSEQUENT FRACTURES hip, or wrist). Compared with men who had no index fracture, men with an index fracture of the hip were about After adjusting for follow-up time, age of the patient, and 3 times more likely to have a subsequent fracture, and baseline measures of health status, a subsequent frac- men with an index fracture of the wrist were about 2 times

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Downloaded From: https://jamanetwork.com/ on 09/26/2021 more likely to have a subsequent fracture. In contrast to unlike the strong age-related relation we observed be- men with a history of these sites of limb fracture, men tween hip and humerus fractures, we did not find any with an index fracture of the ankle had no greater risk age-related increase in the rate of ankle fracture among of subsequent fracture than men in the nonfracture con- men at our health maintenance organization. Other re- trol group. searchers21-23 have suggested that ankle fractures may not When the ankle, hip, humerus, and wrist fracture indicate osteoporosis. Lauritzen and Lund21 failed to find cohorts were compared with those who had an index frac- a statistically significant association between ankle fracture of the finger, results were similar. Men with a fracture and subsequent hip fracture in women. In that study,21 ture of the humerus or hip were still more likely to have elbow and knee fractures showed a statistically signifi- a subsequent fracture, although the hazard ratios for this cant association with hip fracture. Moreover, an ankle group were somewhat lower and the confidence inter- fracture in women does not show the usual relation to vals were wider. Men with a wrist fracture were also more age and bone mineral density22,23 seen for other fragility likely to have a subsequent fracture than those with an fractures. index fracture of the finger, but this difference was not A major strength of our report is its large sample size, statistically significant (P=.13). which included hundreds of fractures of each type. In addition, we were able to validate all fracture outcomes COMMENT among persons with an index limb fracture. We also were able to adjust for measures of medical use, general health In our study of aging men, we found a strong associa- status, and prescription use, which we interpreted (from tion between a hip, humerus, or wrist fracture and the existing medical literature) to be related to falls or to low risk of a subsequent fracture, but this association did not bone mineral density. Certain drugs are associated with exist for an ankle fracture. Compared with either men a high risk of dizziness, a condition that may lead to falls who had no recent fracture or men with an index frac- and, therefore, to fracture. The risk of falls and fracture ture of the finger, men in our study who had a previous may be increased about 2-fold in persons who use psy- humerus, hip, or wrist fracture were about 2- to 3-fold choactive medications, including antidepressant agents24 more likely to have a subsequent limb fracture. A recent and benzodiazepine drugs.25 However, we found that ad- summary11 of 34 studies found a 2- to 3-fold increase in justing for these health conditions and medications did the risk of a subsequent fracture for both sexes. Most pub- not consistently reduce the strength of the association lished studies on the subject have reported an associa- between fracture and subsequent fracture, perhaps be- tion in women or in men and women, but relatively few cause the index fracture variable subsumed factors re- men were studied. These studies focused primarily on a lating to frailty and falls. fracture of the hip or spine. A limitation of our study was that we did not vali- Compared with community-derived fracture rates, date fracture outcome in the large group of nonfracture 243 men 35 years or older in Rochester, Minn, who had controls. This omission could produce a conservative bias an index wrist fracture had a 2.7-fold greater risk of a because possible incident fracture was removed from the subsequent hip fracture.17 A similar epidemiologic study16 limb fracture groups but not from the nonfracture con- of fracture rates among 212 Swedish men 40 years or older trols. In addition, we found it necessary to examine only who had an index wrist fracture compared this group fractures differing from the index fracture because of the against a population registry of men free of fracture and difficulty in distinguishing between continuing care for found a relative risk (RR) of 2.3 of subsequent hip frac- the original fracture and care for a new fracture of the ture in the study group. In cohort studies12,13 of aging men, same type; this problem is especially difficult during ex- the RR of prior fracture was estimated after multiple sta- amination of a hip fracture, a condition for which the ex- tistical adjustments, including an adjustment for bone pected annual rate of readmission for initial fracture (about mineral density. A study13 of 654 Swedish men com- 10%) is considerably higher than the risk of new hip frac- pared those with and without a previous fracture and ture (about 1%). Another limitation of our study was its found that 82 men with a previous wrist fracture had an relatively short follow-up period, which was mandated RR of 1.8 of a subsequent fragility fracture of the verte- by the availability of historical data in our database; bra, wrist, humerus, pelvis, tibia, or hip, whereas 39 men however, a linear hazard function constructed for pa- with a previous hip fracture had a 1.6-fold higher RR (nei- tients in the study suggests that the RR remains stable ther RR was statistically significant). Another similar co- for 1 to 2 years. hort study12 of men 60 years or older living in Australia Our study was limited to limb fracture because we found that those with a history of nontraumatic or low- were unable to adequately document cases of incident trauma fracture in the previous 5 years had a 1.4-fold in- vertebral fracture treated at our health maintenance or- creased risk of subsequent nontraumatic or low-trauma ganization. Postmenopausal women with a recent ver- fracture during a 5-year follow-up period. In a study19 tebral deformity are well known to be at substantial risk designed to examine the risk of recurrent hip fracture, for subsequent fracture, especially in other vertebrae.26 men with a previous hip fracture had an RR of 3.2 of a However, only about 1 in 4 vertebral deformities ob- subsequent hip fracture. Beyond hip and wrist fracture served radiologically will manifest clinically as fracture data, to our knowledge, predictive values of other spe- events,27 and a diagnosis of spinal fracture is frequently cific limb fractures have not been described in men. overlooked by those reading radiographs in the clinical In our study, an ankle fracture among aging men setting.28 Moreover, among hospitalized women 60 years was not associated with a subsequent limb fracture. And or older in whom radiographs showed moderate to se-

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Downloaded From: https://jamanetwork.com/ on 09/26/2021 vere vertebral deformity, only 8% had this diagnosis noted tures in the Longitudinal Aging Study Amsterdam. J Bone Miner Res. 1998;13: at discharge from the hospital.28 Thus, unless patients with 1932-1939. 8. Melton LJ 3rd, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL. Bone den- a vertebral deformity are carefully scrutinized, this con- sity and fracture risk in men. J Bone Miner Res. 1998;13:1915-1923. dition will not be discovered by clinicians or included 9. Nyquist F, Ga¨rdsell P, Sernbo I, Jeppsson JO, Johnell O. Assessment of sex hor- in administrative databases. This fact is true of our health mones and bone mineral density in relation to occurrence of fracture in men: plan also and was the reason for our exclusion of spinal a prospective population-based study. Bone. 1998;22:147-151. fractures from the present epidemiologic study. A pro- 10. De Laet CE, Van Hout BA, Burger H, Weel AE, Hofman A, Pols HA. Hip fracture 29 prediction in elderly men and women: validation in the Rotterdam Study. J Bone spective study of vertebral deformity in men and women Miner Res. 1998;13:1587-1593. based on radiologic assessment has been performed. 11. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M. Patients We conclude that among elderly men, a recent his- with prior fractures have an increased risk of future fractures: a summary of the tory of a humerus, hip, or wrist fracture is a statistically literature and statistical synthesis. J Bone Miner Res. 2000;15:721-739. significant and clinically relevant predictor of future os- 12. Nguyen TV, Eisman JA, Kelly PJ, Sambrook PN. Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol. 1996;144:255-263. teoporotic fracture risk but that a previous ankle frac- 13. Ga¨rdsell P, Johnell O, Nilsson BE. The predictive value of forearm bone mineral ture is not. Use of fracture history can provide a simple content measurements in men. Bone. 1990;11:229-232. way to identify patients at increased risk for future frac- 14. Mussolino ME, Looker AC, Madans JH, Langlois JA, Orwoll ES. Risk factors for ture. Further definition of future fracture risk could be hip fracture in white men: the NHANES I Epidemiologic Follow-up Study. J Bone based on other clinical risk factors and on bone density. Miner Res. 1998;13:918-924. 15. Poo´r G, Atkinson EJ, O’Fallon WM, Melton LJ 3rd. Predictors of hip fractures in Identification and risk assessment could ultimately lead elderly men. J Bone Miner Res. 1995;10:1900-1907. to more appropriate use of fracture risk reduction strat- 16. Mallmin H, Ljunghall S, Persson I, Naesse´n T, Krusemo UB, Bergstro¨m R. Fracture egies, including medication. Bisphosphonates30 and para- of the distal forearm as a forecaster of subsequent hip fracture: a population-based thyroid hormone31 have enhanced bone mineral density cohort study with 24 years of follow-up. Calcif Tissue Int. 1993;52:269-272. in men and hold promise for reducing the risk of subse- 17. Cuddihy MT, Gabriel SE, Crowson CS, O’Fallon WM, Melton LJ 3rd. Forearm fractures as predictors of subsequent osteoporotic fractures. Osteoporos Int. 1999; quent fracture in men. Other types of interventions de- 9:469-475. 32 signed to reduce fracture risk—calcium with vitamin D 18. Melton LJ 3rd, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL. Vertebral frac- or use of hip protectors33—have proved as effective in tures predict subsequent fractures. Osteoporos Int. 1999;10:214-221. men as in women. Thus, programs aimed at identifying 19. Melton LJ 3rd, Ilstrup DM, Beckenbaugh RD, Riggs BL. Hip fracture recurrence: men with limb fractures may provide a simple low-cost a population-based study. Clin Orthop. 1982;No. 167:131-138. 20. American College of Rheumatology Ad Hoc Committee on Glucocorticoid- means of focused fracture prevention in these high-risk, Induced Osteoporosis. Recommendations for the prevention and treatment of but frequently overlooked, patients. glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001;44: 1496-1503. Accepted for publication January 24, 2003. 21. Lauritzen JB, Lund B. Risk of hip fracture after osteoporosis fractures: 451 women This study was supported by an unrestricted educa- with fracture of lumbar spine, olecranon, knee or ankle. Acta Orthop Scand. 1993; 64:297-300. tional grant from Merck & Co, Inc, West Point, Pa. 22. Greenfield DM, Eastell R. Risk factors for ankle fracture. Osteoporos Int. 2001; We thank the Medical Editing Department, Kaiser 12:97-103. Foundation Research Institute, Oakland, Calif, for edito- 23. Seeley DG, Kelsey J, Jergas M, Nevitt MC, the Study of Osteoporotic Fractures rial assistance. Research Group. Predictors of ankle and foot fractures in older women. J Bone Miner Res. 1996;11:1347-1355. Corresponding author: Bruce Ettinger, MD, Division 24. Thapa PB, Gideon P, Cost TW, Milam AB, Ray WA. Antidepressants and the risk of Research, Kaiser Permanente Medical Care Program, 3505 of falls among nursing home residents. N Engl J Med. 1998;339:875-882. Broadway, Oakland, CA 94611 (e-mail: [email protected]). 25. Herings RM, Stricker BH, de Boer A, Bakker A, Sturmans F. Benzodiazepines and the risk of falling leading to femur fractures: dosage more important than elimi- nation half-life. Arch Intern Med. 1995;155:1801-1807. REFERENCES 26. Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001;285:320-323. 1. Van Staa TP, Dennison EM, Leufkens HG, Cooper C. Epidemiology of fractures 27. Silverman SL. The clinical consequences of vertebral compression fracture. Bone. in England and Wales. Bone. 2001;29:517-522. 1992;13(suppl 2):S27-S31. 2. Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA. Symptomatic 28. Gehlbach SH, Bigelow C, Heimisdottir M, May S, Walker M, Kirkwood JR. Recog- fracture incidence in elderly men and women: the Dubbo Osteoporosis Epide- nition of vertebral fracture in a clinical setting. Osteoporos Int. 2000;11:577-582. miology Study (DOES). Osteoporos Int. 1994;4:277-282. 29. Van der Klift M, De Laet CE, McCloskey EV, Hofman A, Pols HA. The incidence of 3. Randell A, Sambrook PN, Nguyen TV, et al. Direct clinical and welfare costs of os- vertebral fractures in men and women: the Rotterdam Study. J Bone Miner Res. teoporotic fractures in elderly men and women. Osteoporos Int. 1995;5:427-432. 2002;17:1051-1056. 4. Poo´r G, Atkinson EJ, Lewallen DG, O’Fallon WM, Melton LJ 3rd. Age-related hip 30. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteopo- fractures in men: clinical spectrum and short-term outcomes. Osteoporos Int. rosis in men. N Engl J Med. 2000;343:604-610. 1995;5:419-426. 31. Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. Para- 5. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after thyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone all major types of osteoporotic fracture in men and women: an observational study. mineral density and bone markers. J Clin Endocrinol Metab. 2000;85:3069-3076. Lancet. 1999;353:878-882. 32. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin 6. Center JR, Nguyen TV, Sambrook PN, Eisman JA. Hormonal and biochemical D supplementation on bone density in men and women 65 years of age or older. parameters and osteoporotic fractures in elderly men. J Bone Miner Res. 2000; N Engl J Med. 1997;337:670-676. 15:1405-1411. 33. Kannus P, Parkkari J, Niemi S, et al. Prevention of hip fracture in elderly people 7. Tromp AM, Smit JH, Deeg DJ, Bouter LM, Lips P. Predictors for falls and frac- with use of a hip protector. N Engl J Med. 2000;343:1506-1513.

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