The Association between Gender and Familial Prevalence of Hip Dysplasia in Danish Patients

Abstract

Background

The development of hip dysplasia is associated with several risk factors. 1 of these risk factors is gender, since 80% of patients with symptomatic hip dysplasia are females. Another risk factor for hip dysplasia is familial predisposition of hip dysplasia. Several studies indicate that the risk of hip dysplasia is increased with familial prevalence of hip dysplasia. However, little is known about the association between the familial prevalence and gender and the development of hip dysplasia.

Purpose

The aim of the study was to estimate the prevalence of hip dysplasia among relatives to Danish patients with hip dysplasia operated with periacetabular osteotomy (PAO), and the degree of relationship of affected family members. Furthermore, to assess the association between gender and family predisposition in the same group of patients.

Method

The study is a cross-sectional study, with a descriptive and an analytical part. The study population consists of 676 patients drawn from a clinical database of patients operated with PAO at Aarhus University hospital from 1998 to 2014. Information about gender, operated hip side and age was collected from the clinical PAO database, while information about familial prevalence was collected through questionnaires. The association between gender and familial prevalence of hip dysplasia was presented as the prevalence proportions ratio (PPR), tested by χ² test. Stratification was conducted for the variables age and operated hip side, with the Mantel-Haenszels analytical method, and tested for statistical significance by χ².

Results

The familial prevalence of hip dysplasia in the study population was 30% (95% CI, 27%-34%), with 73% reporting affected first-degree relatives. Females have 32% increased risk of familial prevalence of hip dysplasia compared to males, but this difference in risk was not statistically significant (p = 0.10).

Conclusions

The study shows that females have 32% increased familial prevalence of hip dysplasia compared to males, but the increased prevalence was not statistically significant probably due to the low power of the study.

Keywords

Familial prevalence Gender Hip dysplasia

Introduction

Developmental dysplasia of the hip is a spectrum of anatomical abnormalities, which beside subluxated and dislocated hip conditions includes hip dysplasia (HD) (1). In developed countries, the incidence of HD is reported to be 1.5 to 20 cases per 1,000 births (1, 2). Variation in incidence is in part due to different kind of diagnosis criteria, environmental factors and ethnicity (2, 3). Approximately 80% of cases with HD resolve spontaneously without any intervention within the first months of life and only a minor part of patients develop symptoms later on in life where surgical treatment is necessary (1, 4).

Epidemiological studies have estimated a prevalence of HD in the Danish population of 5-10% and predict that HD occurs as frequently in males as in females (5). In spite of these findings, the major part of patients presenting with symptomatic HD are females in the age of 20-40 years and 30%-40% of those have HD bilaterally (5 –7).

HD is characterised by a pathological anatomy of the hip joint resulting in reduced acetabular coverage of the femoral head (5, 8 –11). The abnormal anatomy increase stress on bone, cartilage and the labrum, which leads to an increased risk of developing osteoarthritis in the hip joint (12, 13). In patients with symptomatic HD periactebular osteotomy (PAO) has become the treatment of choice in Denmark.

The aetiology of HD is thought to be multifactorial (6, 14 –16). A meta-analysis has studied 31 primary studies with the aim to assess the association between most mentioned risk factors and HD in newborns. The risk factors considered were gender, breech birth presentation, hip side, family history, first born and caesarean section. The meta-analysis concluded that all the mentioned risk factors were significantly associated with the presence of HD (14).

Studies show that among patients developing symptomatic HD and receiving PAO, females are highly overrepresented, accounting for 80% (14, 15, 17, 18). An Egyptian study assessed the hip morphology in 244 healthy adults of whom 134 were males and 110 were females. The study found that Egyptian females had more dysplastic hips compared to the Egyptian males. The prevalence of hip dysplasia in females was estimated to 3.6% while the prevalence among males was estimated to 2.3% (19). However, the reason why females to a larger degree develop symptomatic hip dysplasia that requires surgical treatment is not fully established (16).

A positive family history is mentioned in the literature as another significant risk factor connected to HD (15, 18, 20). In the mentioned meta-analysis it is reported that newborns with diagnosed HD has a statistical significant increased risk for a positive family history of HD of 1.39 (14). An American case-control study outlined the risk of family history out of a database concerning demographic and health status of over 6 million individuals. Based on this database they were able to identify 141 families with 4-30 family members with HD in each family. The results of the study were that first-degree relatives to the index cases had a 12.1 higher risk of diagnosed HD compared to a control group (18).

A Chinese case-control study performed assessed the risk of family history of HD in siblings to cases with HD with siblings in a healthy control group. The prevalence of HD in siblings to cases was estimated to 13.85 compared to 1.57 in siblings in the healthy control group. Furthermore, the study found that sisters to cases had a prevalence of HD of 19.85% compared to brothers to cases who had a prevalence of HD of 9.12%. This indicates that the family history of HD in patients with HD may be related to gender (20).

Materials and Methods

The study was designed as a cross-sectional study based on data from questionnaires and from a clinical database. The study was performed in the autumn of 2014 at Aarhus University Hospital, Denmark. Patients invited to participate in the study were registered in the clinical database on all patients operated with a PAO since 1998 at Aarhus University Hospital. The database contains information on the patients’ names, civil registrations numbers, gender, date of surgery and on which side of the hip the procedure is performed.

The questionnaires were sent by mail along with an explanatory letter and a stamped addressed envelope. The questionnaires were mailed to the patients in 2 separate periods during the spring of 2008 and the spring of 2014. Patients who did not return the questionnaire within 2 months received the same questionnaire for the second time. The patients had to report if there was anyone else in their family with hip dysplasia. If this was the case they were asked to report of the genealogy degree of their relatives. To avoid an overestimation of the familial prevalence, patients who placed their answer between the 2 categories “yes” and “no” or added, “don't know” as answer to familial prevalence were all registered in the “no” category. Patient gender, year of birth and operated hip side was collected from the database.

In March 2014, the PAO database comprised of 1,042 patients and all patients were considered eligible for inclusion (Fig. 1). Initially 83 patients were excluded from the study. 77 were excluded because of foreign or incorrect registered civil registration numbers, while 5 patients were excluded because of unknown home address. A total of 959 patients were invited to participate in the study and out of those 687 responded with signed consents. 11 patients were excluded afterwards because they reported that their PAO surgery was performed as treatment of Legg-Calvé-Perthes disease and 1 patient withdrew consent to participate. The remaining study group consisted of 676 patients: 551 females and 125 males.

Fig. 1

Flowchart of the study population.

Information on gender, year of birth, operated hip side and year of operation was collected for nonparticipants to assess whether they differed from the participants on those variables.

Statistical analysis

Data are presented as prevalence proportions (PP) and prevalence proportion ratios (PPR) with 95% confidence intervals (CI). X² test was used to estimate the association between the familial prevalence and gender. The statistical analysis were performed using STATA version 13 (StataCorp LP, College Stations), and the significance level was set at p<0.05.

Results

A total of 959 patients received the questionnaire and 687 responded. Out of the respondents, 11 reported an alternative diagnosis other than HD and were excluded. The response rate was 71.6% and data on the included patients is presented in Table I.

Table I

Data on gender, age and side of operation from clinical database for patients (n = 676) with hip dysplasia operated with periacetabular osteotomy

	Number (n)	Percentage %
Gender
Females	551	82%
Males	125	18%
Age
Born before 1972	299	44%
Born after 1972	377	56%
Operated hip side
Left side	189	28%
Right side	294	43%
Bilaterally	193	29%

Prevalence of family history of HD

A total of 204 patients reported a positive family history of HD, which corresponds to a prevalence of 30% (95% CI, 27%-34%). As shown in Table II, the prevalence of affected family members among first-, second-, and third-degree relatives were 148 (73%), 28 (14%), and 27 (13%), respectively.

Table II

Number of affected relatives among first-, second-, and third-degree relatives to patients with hip dysplasia (n = 204)

Degree of relationship	n (%)
First-degree	148 (73%)
Second-degree	28 (14%)
Third-degree	27 (13%)
Missing	1
Total	204

The association between the family history of HD and gender

As summarised in Table III, females had a prevalence proportion (PP) of positive family history of HD of 0.32 while the corresponding PP for males was 0.24. This leads to a prevalence proportion ratio of 1.32, which means that when compared to males, females had an increased prevalence of positive family history of HD. Meanwhile this result was not statistically significant.

Table III

The association between gender and the family history of hip dysplasia in 676 patients with hip dysplasia operated with periacetabular osteotomy

	Positive family history
	Yes	No	PP	PPR	(95% CI)	p value
Females	174	377	0.32	1.32	[0.94-1.84]	0.10
Males	30	95	0.24	1	[Reference]

PP = prevalence proportion; PPR = prevalence proportion ratio. p value derived using χ² test.

As presented in Table IV when stratified for age groups and hip side, the PPR did not differ in the strata and no significant difference was found between crude and adjusted PPR.

Table IV

Stratification by age groups and hip side

	PPR	95% CI	p-value
Age group
Born before 1972	1.40	[0.84-2.33]
Born after 1972	1.26	[0.81-1.97]	0.80
Crude	1.32
Adjusted^*	1.32
Hip side
Left	1.85	[0.85-4.01]
Right	0.93	[0.61-1.42]
Bilaterally	1.90	[0.85-4.27]	0.13
Crude	1.32	[0.94-1.84]
Adjusted^*	1.29	[0.92-1.81]

Adjusted PPR estimated by Mantel-Haenszel analysis. PPR = prevalence proportion ratio.

The distribution of gender, age and operated side for participants and nonparticipants are summarised in Table V. More females and fewer males participated in the study compared to those who did not want to participate. More participants were born before 1972 compared to the nonparticipants. More participants were operated bilaterally compared to non-participants.

Discussion

We found a clear preponderance of first-degree relatives with HD, which can have several causes. If genetic factors is a contributing factor to the aetiology of HD, first-degree relatives have a higher proportion of genes shared, compared to second- and third-degree relatives. Additionally, the respondents may have most information of diagnoses in their first-degree relatives.

In this study, we found that in a large group of patients with symptomatic HD, females have a 32% increased risk of familial prevalence of HD compared to males. Although the risk was clearly increased for females, the results were not statistically significant. We calculated the power of the study post hoc based on the actual distribution of familial HD in the participating males and females and found our study had a power of 0.41 to detect a difference of 32% between the groups. Hence, our study is underpowered to detect a potential association between gender and family prevalence of HD. To our knowledge, the only study concerning the association between gender and family history of HD, was conducted by Li Lianyong et al (20). Li Lianyong et al found that the sisters of patients with HD had a significant increased risk for HD of 19.86 compared to brothers of patients with HD with the risk for HD of 9.12. Despite differences in our study and Li Lianyong et al (20) both studies indicate, that females have an increased familial prevalence of HD compared to males.

Internal validity

Data on family history of HD are self-reported, which may lead to incorrect assumptions, since we have not verified these data. The lack of verification of the diagnosis is a study limitation since, the diagnosis of HD should have been supported by objective criteria from clinical examinations and x-rays.

All patients who answered, “yes” to the question “Are there others in your family with congenital hip dysplasia?”, were included in the statistical analysis, as having familial prevalence of HD. There may be a risk of an overestimation of the familial prevalence of HD, because it is likely that a proportion of the patients, who answered “yes”, are uncertain about the diagnosis of the relatives. Conversely, patients who answered “no” due to lack of knowledge of HD in the family, contribute to an underestimation of the familial prevalence of HD. It is believed that males and females over- and underestimates the familial prevalence of HD equally, which leads to nondifferential misclassification. It seems unlikely that the outcome of the study may be influenced by differential information bias, since there is no indication that the collected information regarding family history is unequally distributed on gender.

The nonparticipants analysis (Tab. V) indicates that patients, who have chosen not to participate in the study, differ significantly from participating patients in regard to gender, age, and bilateral PAO operation. The literature shows a general tendency that nonparticipants tend to be younger males, which is in line with that found in our study since younger males to a larger extent did not want to participate in the study (21). In the literature the left hip side is identified as a risk factor for HD. In contrast, our findings show that the majority (43%) of patients undergoing a PAO surgery have a right hip side operation (Tab. V). The opposing results may be explained by differences in the choice of study population. In our study, the participants are adults who have had a PAO surgery, while studies examining the left side as a risk factor often includes newborns, who are part of a screening programme (14, 15). Another explanation may be that for the majority of people the right leg is their dominant leg, leading to increased strain on the joint in certain sports activities and possibly contribute to HD in the right side to become symptomatic.

Table V

Distribution of gender, age and operated hip side in participants and nonparticipants (%)

	Participants (n = 676)	Nonparticipants (n = 271)	p-value
Gender
Females	551 (82%)	201 (74%)
Males	125 (18%)	71 (26%)	0.01
Age group
Born before 1972	299 (44%)	85 (31%)
Born after 1972	377 (56%)	187 (69%)	<0.001
Operated hip side
Left	189 (28%)	94 (35%)
Right	294 (43%)	121 (45%)
Bilaterally	193 (29%)	57 (21%)	0.03

Confounding

Since operated hip side is a known risk factor for hip dysplasia, an adjustment was made. After adjusting for hip side there was a minor difference of 0.03 in the association between gender and the family history of HD, but it was considered clinically irrelevant.

Effect modification

We stratified for age to assess whether it could enhance the association between gender and familial prevalence of HD. The stratification showed no significant difference in familial prevalence of HD for participants born before or after 1972. Similarly, stratifying for hip side as a modifier of the relationship between gender and the familial prevalence of HD, also showed no significantly difference between participants operated on the left, right side and bilateral.

Conclusion

This study indicates that females have 32% increased familial prevalence of HD compared to males. However, the association between gender and the familial prevalence of HD was not significant. The statistical power of the study was only 41%, which affects both the internal and external validity, and the results must be interpreted with caution. An intensive screening of newborns in families with dysplastic mothers is of importance in order to help patients at risk of developing HD.

Footnotes

Financial support: This study has been financially supported by the Danish Rheumatism Association, Bevica Foundation and Toyota-Fonden.

Conflict of interest: None.

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