The association between hip fracture and hip osteoarthritis: A case-control study

In Iceland, as in other Scandinavian countries, all persons have a unique personal identification number. This, combined with a highly computerized national health system, makes it possible to identify all patients operated on for a given diagnosis or by a certain procedure in Iceland[17]. We identified 806 consecutive cases of hip fracture that were admitted to Akureyri University Hospital during 1990-2008. This constitutes 24% of all hip fractures in Iceland during that time. Patients were from both rural and urban areas. As younger hip fracture patients are more likely to have sustained a high energy trauma and sustain fracture in the absence of osteoporosis, all patients younger than 60 years and all patients with a previous hip fracture were excluded. After exclusions (Figure 1), we had 636 eligible cases with a first time hip fracture, and 562 of these had pre-operative hip radiographs available.

Our control cohort was based on patients who had colon radiographs taken due to referral in routine health care. Colon radiographs taken at three different radiographic departments in Iceland during the years 1980-97 were examined. The patients were referred to these radiographic departments from four different hospitals (community and academic), as well as from the primary health care system. Patients were from both rural and urban areas. We excluded all subjects who were younger than 60 years of age, leaving 803 controls, of which 438 were women (54.5%). Iceland has a homogenous population of just over 300,000 inhabitants. The hip fracture patients were all treated at one hospital, but the controls came from three different hospitals. 38% of the controls were from the same hospital as the cases.

The double contrast (barium enema) colon radiographs included at least two anteroposterior (AP) and several oblique exposures. In this study the hip joints were assessed from a supine AP control radiograph, which was taken with the same tube to film distance of 100 cm that is used in a standard AP view of the pelvis. The x-ray beam was centered on the umbilicus. Both hips were graded and we then randomly chose the right or the left hip for our control cohort.

In our case cohort preoperative radiographs were available for 562 (88%) cases. Pelvic radiographs showing the contralateral hip were available for 457 of patients (81.3%). The hip joints were assessed from a standard supine AP pelvic radiograph, taken with a tube to film distance of 100 cm with the x-ray beam centered on the symphysis pubis. We measured hip joint space with an electronic caliper[18] and assessed osteophytes, sclerosis, cysts and any signs of secondary OA[19]. The same pre-operative radiographs were used for diagnosing the fracture and for the assessment of hip OA.

Hip fractures were classified as intra- or extracapsular[20]. We measured minimal joint space (MJS) and graded the radiographic features of OA according to Kellgren and Lawrence[19], and individual features of OA, osteophytes, sclerosis and cysts in both hips.

All radiographs of cases were examined by a single observer (JF). All controls had been previously read by a different author (TI)[21]. To calculate inter- and intraobserver reliability [22], we selected 50 radiographs of cases and 50 radiographs of controls, that included the full range of radiographic features that were read again by both these authors. We used Cohen's kappa to calculate the intra- and interobserver reliability for detecting hip OA.

For MJS both the intra- and interobserver reliability was high, but Kellgren and Lawrence grading was not as reliable (Table 1).

Pre-operative radiographs of cases were used since postoperative radiographs are now often taken in the operating theatre which yields radiographs that cannot be used to evaluate MJS. Presence of a hip fracture (displaced or not displaced) may affect the measurement of the joint space in the hip, even if subtle changes in position do not affect MJS in the hip[23]. To evaluate this we selected 50 patients where we had both pre- and postoperative standard pelvic radiographs, with an anatomic reduction of the fracture, and compared MJS measurement pre- and post-operatively. All the post-operative radiographs were taken within 10 days from the fracture. The 50 patients that were used for comparison of pre- and post-operative x-rays were not randomly chosen, since we were limited to patients that had a valid postoperative radiograph. We therefore tested if our sample adequately represented our fracture cases. Independent samples t-test for MJS was not significant (p = 0.96) and neither was Kolmogorov-Smirnov Z for OA/Not OA status (p = 0.36), which shows that this sample of 50 cases adequately represented our fracture cohort. There were 3 patients classified as having OA on a preoperative x-ray that were not classified as having OA on the postoperative x-ray. One patient was classified as having OA on the postoperative x-ray, that did not have OA on the preoperative x-ray. We calculated the p-value for pre- and postoperative readings of MJS with paired t-test (p = 0.18) and used the McNemars test to compare OA/Not OA status on pre- and postoperative x-rays (p = 0.63). Neither was significant, thereby validating the choice of using pre-operative x-ray examinations.

Unless otherwise stated, hip OA was defined as MJS of 2.5 mm or less[21, 22]. In the hip fracture cohort there were 6 women and one man that had a total hip replacement due to OA in the contralateral hip. These were classified as having OA in that hip.

Medications or diseases that cause secondary osteoporosis and thus increase the risk for hip fracture might be more common in the case or control group. To explore the association with risk factors for secondary osteoporosis in patients with hip fracture we did a prevalence study of possible risk factors for secondary osteoporosis within the hip fracture cohort using a matched design. This method was chosen as we did not have access to data on possible causes of secondary osteoporosis for the control cohort. We defined patients with hip fracture and MJS 2.5 mm or less as hip OA cases and to each of these we assigned two reference subjects, who had hip fracture, but not having hip OA (hence both hip OA cases and reference subjects came from the hip fracture cohort). The reference subjects were matched according to gender, fracture type and age ± 1 year. If more than 2 possible reference subjects were found, we randomly chose which to use. We reviewed the medical records of hip OA cases and their matched reference subjects from the fracture cohort and registered possible causes of secondary osteoporosis that we identified [24, 25].

Age differences between groups were tested with the independent samples t-test. We age standardized the observed prevalence of hip OA in both hip fracture cases and controls against the Icelandic population from the year 2000 (using 5 year age strata and direct external standardization)[26]. Intra- and interobserver reliability was calculated using Cohen's Kappa. Paired t-test and McNemar test were used to compare readings of pre- and postoperative x-rays and we used independent samples t-test and Kolmogorov-Smirnov Z to see that this not randomly selected sample had approximately the same mean MJS and distribution of values as the entire group of cases. Chi-square was used in calculations for difference in crude rate and binary logistic regression for age-adjusted calculation of odds ratios for having OA amongst cases vs. controls. We considered a p-value of less than or equal to 0.05 to be significant, and all tests were 2-tailed. Calculations were done using SPSS v. 16.0. (SPSS Incorporated 2007).

The male to female ratio was about 1:3 in the fracture cohort, while it was close to one in the control cohort (Table 2). The number of basocervical and subtrochanteric fractures was small, so these were grouped together with pertrochanteric fractures as extracapsular fractures (Figure 1). There was no difference in mean age between the two fracture types, neither for men (p = 0.85), nor women (p = 0.48). The mean age of controls was significantly lower than that of subjects with fracture (p < 0.0001).

There was a significant difference in the crude prevalence of hip OA between fracture cases and controls for men (p = 0.02), but not for women (p = 0.3). Following a direct external standardization of the crude prevalence, the differences between our cases and controls increased, especially for women where the age difference between cases and controls was greater (Table 3).

There was no significant difference in mean age when comparing men with or without hip OA (Table 4). However, women with hip OA were significantly older than women without hip OA.

The age difference between cases and controls emphasized the need to take that into account when assessing the association between hip fracture and hip OA. We therefore did an age-adjusted binary logistic regression with hip OA as the dependent variable. All groups of hip fracture patients had a significantly reduced odds ratio of hip OA (comparing cases with controls) regardless of gender and classification system of hip OA. The odds ratio for hip OA was significantly reduced in both the fractured hip and the contralateral hip (Figure 2 and 3). For the fractured hip in men the OR was 0.30 (95%CI 0.12-0.74) when defining OA by MJS and 0.31 (95% CI 0.12-0.76) when defining OA by Kellgren and Lawrence. Corresponding results for the fractured hip in women were 0.33 (95%CI 0.19-0.58) and 0.38 (95% CI 0.21-0.69) when defining OA by Kellgren and Lawrence. For the contralateral hip in men the OR was 0.38 (95%CI 0.16-0.90) when defining OA by MJS and 0.38 (95% CI 0.16-0.91) when defining OA by Kellgren and Lawrence. Corresponding results for the contralateral hip in women were 0.55 (95%CI 0.32-0.96) and 0.52 (95% CI 0.29-0.94) when defining OA by Kellgren and Lawrence.

In this study we have primarily used MJS 2.5 mm or less as definition of OA[21, 22], but used the Kellgren and Lawrence classification as well to enable comparison to previously published studies. We also tested our data using MJS 2.0 mm or less as definition of OA. The ORs were lower (meaning a greater difference between cases and controls), although the difference from MJS 2.5 mm or less definition was not statistically significant. Using MJS 2.0 mm or less as definition the crude prevalence of OA was 9.3% for male controls, 3.1% for male cases, 8.9% for female controls and 3.7% for female cases. For hip OA in men with hip fracture, we obtained the OR 0.18 (95%CI 0.06-0.57) and in women with hip fracture the OR 0.12 (0.05-0.28).

When defining hip OA by MJS we found no statistical difference in the age adjusted estimate of association for hip OA between the two different fracture groups, neither for men (OR = 0.96, 95% CI 0.21-4.5), or for women (OR = 1.5, 95% CI 0.75-2.8). When using Kellgren and Lawrence definition of OA, we again found no difference between the fracture types for men (OR = 0.96, 95% CI 0.21-4.5), but a significant difference for women, with extracapsular more frequently having hip OA than intracapsular fractures (OR = 2.5, 95% CI 1.2-5.2). We then repeated the calculations, using presence of OA in the contralateral hip. Again, there was no difference for men (OR = 2.3, 95% CI 0.52-10.4), regardless of classification system for OA. For women there was no difference for OA classified by MJS (OR = 1.8, 95% CI 0.92-3.5) or by Kellgren and Lawrence (OR = 1.5, 95% CI 0.73-3.2).

There were 40 women and seven men who had hip fracture and hip OA in the same fractured hip according to definition by MJS. We reviewed the medical history for all, except one woman whose patient records were not found. We thus had 46 cases with hip fracture and hip OA matched by age, gender and fracture type to 92 reference subjects with hip fracture without hip OA. Patients were defined as having possible secondary osteoporosis if they had at least one of the conditions listed in Table 5. Three of 7 men and 15 of 39 women had at least one potential cause of secondary osteoporosis (Table 5). The probability of having a possible cause of secondary osteoporosis was 3 times higher for those with hip fracture and hip OA than for those with hip fracture, but without hip OA.