Is Legg-Calvé-Perthes Disease a Local Manifestation of a Systemic Condition?
Authors: Hailer Yasmin D. , Hailer Nils P. 
Published: June 2018

Background
Osteochondrosis includes numerous diseases that occur during rapid growth, characterized by disturbances of endochondral ossification. One example, Legg-Calvé-Perthes disease, is characterized by disruption of the blood supply to the femoral head epiphysis, and a systemic etiology often has been suggested. If this were the case, secondary osteochondroses at locations other than the hip might be expected to be more common among patients with Legg-Calvé-Perthes disease, but to our knowledge, this has not been evaluated in a nationwide sample.

Questions/purposes
(1) Do patients with Legg-Calvé-Perthes disease have an increased prevalence of secondary osteochondroses at locations other than the hip? (2) Is the concept of Legg-Calvé-Perthes disease a systemic etiology supported by a higher prevalence of the metabolic diseases obesity and hypothyroidism?

Methods
We designed a retrospective population-based cohort study with data derived from the Swedish Patient Registry (SPR). The SPR was established in 1964 and collects information on dates of hospital admission and discharge, registered diagnoses (categorized along the International Classification of Diseases [ICD]), and applied treatments during the entire lifetime of all Swedish citizens with high validity. Analyzing the time span from 1964 to 2011, we identified 3183 patients with an ICD code indicative of Legg-Calvé-Perthes disease and additionally sampled 10 control individuals per patient with Legg-Calvé-Perthes disease, matching for sex, age, and residence, resulting in 31,817 control individuals. The prevalence of secondary osteochondroses, obesity, and hypothyroidism was calculated separately for patients with Legg-Calvé-Perthes disease and control individuals based on the presence of ICD codes indicative of these conditions. Using logistic regression analysis, we compared the adjusted relative risk of having either of these conditions develop between patients with Legg-Calvé-Perthes disease and their matched control subjects. The mean followup was 26.1 years (range, 2.8-65 years).

Results
The prevalence of secondary osteochondroses was greater among patients with Legg-Calvé-Perthes disease (3.11%) than among control subjects (0.31%), resulting in an increased adjusted risk of an association with such lesions in the patients (relative risk [RR], 10.3; 95% confidence interval [CI], 7.7-13.6; p < 0.001). When stratified by sex, we attained a similarly increased risk ratio for females (RR, 12.5; 95% CI, 6.1-25.8; p < 0.001) as for males (RR, 9.9; 95% CI, 7.3-13.5; p < 0.001). Patients with Legg-Calvé-Perthes disease had an increased adjusted risk of an association with obesity (RR, 2.8; 95% CI, 1.9-4.0; p < 0.001) or hypothyroidism (RR, 2.6; 95% CI, 1.7-3.8; p < 0.001) when compared with control subjects.

Conclusions
To our knowledge, this is the first population-based description of a robust association of Legg-Calvé-Perthes disease with osteochondroses at locations other than the hip, and we also found increased risk estimates for an association with obesity and hypothyroidism in patients with Legg-Calvé-Perthes disease. Our findings strengthen the hypothesis that Legg-Calvé-Perthes disease is the local manifestation of a systemic disease, indicative of an underlying common disease pathway that requires further investigation. Physicians should be aware that patients with Legg-Calvé-Perthes disease may present with secondary osteochondroses and metabolic comorbidities.

Level of Evidence
Level III, prognostic study.