No correlation to collagen synthesis disorders in patients with Perthes' disease: a nationwide Swedish register study of 3488 patients.

BACKGROUND: Mutations of the COL2A1 gene have been identified in patients with Perthes' disease. Several studies have hypothesised a connection between Perthes' disease and collagen synthesis disorders, especially COL2A1-related disorders, but no large studies on the subject have been made. The aim of this study was thus to discover if there is a connection between patients presenting with Perthes' disease, and collagen synthesis disorders. A secondary aim was to see if the children with both disorders had less optimal birth characteristics than the rest. METHODS: Swedish national registers were used to collect data on children diagnosed with Perthes' disease or a collagen synthesis disorder. These registers include all births in Sweden, and data from both outpatient and in-hospital visits. A wide range of data is included besides diagnoses. All children with follow-up data to the age of 15 years were included. Pearson's chi-square was used for analysis. Statistical significance was further analysed with Fisher's Exact Test. RESULTS: In total, 3488 children with either diagnosis were included. 1620 children had only Perthes disease, while 1808 children had only a collagen synthesis disorder. Five children were found to have both the diagnosis Perthes' disease and a collagen synthesis disorder. One child was large for their gestational age and none of the children had a low birthweight. Two of the children were moderately preterm. CONCLUSIONS: The distinct lack of overlap in such a large body of material raises doubt about a connection between the presentation of Perthes' disease and collagen synthesis disorders, either COL2A1-related or not. We could not find an overrepresentation of less optimal birth characteristics either.

[Legg-Calvé-Perthes disease]. / Morbus Perthes.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is an important cause of limping and/or hip pain in preadolescent children. OBJECTIVE: Pathogenesis and epidemiology of LCPD, classification of disease stages, quantitative femoral head involvement and prognosis based on X­ray images and magnetic resonance imaging (MRI). MATERIAL AND METHODS: Summary and discussion of the basic research and recommendations. RESULTS: Boys between 3 and 10 years of age are mostly affected. The etiology of the femoral head ischemia is still unknown. Commonly used classifications are the stages of disease according to Waldenström and the extent of the femoral head involvement according to Catterall. Head at risk signs are used for early prognosis, and after completion of growth Stulberg's end stages are applied for long-term prognosis. CONCLUSION: Based on X­ray images and MRI, different classifications can be used for an assessment of progression and prognosis of LCPD. This systematic approach is essential to identify cases that require surgical treatment and to avoid complications such as early onset osteoarthritis of the hip.

Incidence of total hip arthroplasty in patients with Legg-Calve-Perthes disease after conservative or surgical treatment: a meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the incidence of total hip arthroplasty (THA) in patients with Legg-Calve-Perthes disease (LCPD) treated conservatively or surgically and factors influencing the incidence of THA. METHODS: Long-term follow-up studies on the conservative or surgical treatments of LCPD from 1950 to 2021 were conducted using six public databases. Articles were screened by two investigators (PRISMA guidelines), and the quality of the included publications (n = 27) was assessed (MINORS criteria). R version 4.2.1 was used for statistical analysis. RESULTS: The overall incidences of THA were 6.8% and 5.14% in patients who were treated conservatively and surgically, respectively. At disease onset, the incidences of THA were 6.79% and 6.17% after conservative treatment and surgery in patients aged < seven years, respectively, and 16.97% and 3.61% in patients aged > seven years, respectively. The incidences of THA were 4.91%, 5.19%, and 23.18% in patients who were treated conservatively with ≤ 30, 30-40, and > 40 years of follow-up, respectively, and 3.68%, 3.11%, 9.66%, and 17.92% in patients who were treated surgically with ≤ ten, ten to 20, 20-40, and > 40 years of follow-up, respectively. In patients who received conservative treatment, the incidences of THA were 5.79% and 5.29% in patients with Stulberg I-II and III-V, respectively. In surgically treated patients, the incidence of THA was 0% in Stulberg I-II and 8% in Stulberg III-V. CONCLUSION: Patients with LCPD had relatively low incidences of THA. The greater the age at disease onset and longer the follow-up, the higher the incidence of THA; however, the Stulberg classification was not directly associated with the incidence of THA.

Pediatric Hip Disease Increases the Risk for Opioid Use in Adulthood: Long-term Burden of Pain and Depression.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) and slipped capital femoral epiphysis (SCFE) can result in painful deformation of the hip joint with impaired range of motion and early development of secondary osteoarthritis. It has not been investigated whether having LCPD or SCFE is associated with increased use of pain or antidepressant drug prescriptions later in life. OBJECTIVE: With this study, we aimed to investigate if patients with a history of LCPD or SCFE have an increased risk of prescription analgesic or antidepressant drugs in adulthood compared with matched controls. STUDY DESIGN: The included patients were identified by the Swedish Patient Register and matched for age, gender, and residency with 10 control individuals not exposed to any of the mentioned pediatric hip diseases, by the Swedish National Population Register. SETTING: This was a nationwide, registry-based cohort study which included 1,292 patients diagnosed with LCPD at age 2-15 years and 1,613 patients diagnosed with SCFE at age 5-16 years and > 17 years from 2005 through 2011. METHODS: Prescription data of first-line analgesic drugs (acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids), or first-line antidepressant drugs (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants) were derived from the Swedish Prescribed Drugs Register. Conditional logistic regression models were fitted to estimate the relative risk for the prescription in exposed compared with unexposed individuals. Adjustment was performed for gender and birth year. RESULTS: In the group with an LCPD diagnosis, the adjusted odds ratio for analgesic prescriptions overall was 1.3 (95% CI, 1.2-1.5). For patients with an SCFE diagnosis, the adjusted odds ratio for analgesic prescriptions overall was 1.4 (95% CI, 1.3-1.6). Among patients with an LCPD diagnosis, the adjusted odds ratio for antidepressant prescriptions overall was 1.0 (95% CI, 0.8-1.2). For patients with an SCFE diagnosis, the adjusted odds ratio was 1.2 (95% CI, 1.1-1.4). LIMITATIONS: As with all register studies, there are known associated biases such as selection, detection, and observational bias as well as the uncertain quality of input data. Further, the Swedish Prescribed Drugs Register only includes drugs that were prescribed by a physician and dispensed at a pharmacy. This is also a factor that may lead to underestimating the use of acetaminophen and nonsteroidal anti-inflammatory drugs, as these drugs can be acquired "over the counter." CONCLUSION: During childhood, patients with LCPD or SCFE seem to suffer long-term pain and have an increased risk of requiring analgesic medication in adulthood, including opioids. It is important to assess the causes, type, and severity of pain to optimize pain management to counteract possible overuse in these patients. Seemingly, patients with LCPD do not have an increased risk for antidepressant drug therapy in adulthood whereas we did see an increased risk for that in patients with previous SCFE compared with the general population.

Impacto de la enfermedad de Legg-Calvé-Perthes en un área de salud mediterránea / Impact of Legg-Calve-Perthes disease in a Mediterranean health area

Introducción: Se han relacionado varios factores poblacionales socioeconómicos en la etiología de la enfermedad de Legg-Calvé-Perthes (ELCP), como son su mayor incidencia en población urbana, vivir en la periferia de núcleos urbanos o residir a una determinada latitud con respecto al ecuador terráqueo. Es conocida la incidencia en algunos otros países, pero se desconoce la incidencia del proceso en nuestro medio, hecho importante para acomodar los recursos sociosanitarios necesarios para el tratamiento de la enfermedad. Por todo ello, el objetivo del presente estudio es determinar la incidencia de la ELCP en el Área de Salud 2 de Madrid. Material y métodos: Se analiza la incidencia de ELCP en el Área de Salud 2 de Madrid por ser el área mediterránea una zona poco estudiada. Se trata de una zona con muy escasa movilidad geográfica, de nivel socioeconómico medio-bajo, e integrada en su mayoría por trabajadores de empresas del sector secundario y terciario. Los datos se han obtenido a partir de las bases de datos hospitalarias del Área 2 entre los años 1994 y 2010. Los criterios de inclusión fueron padecer la ELCP y la distribución territorial de la población en el Área 2 de Madrid. Conclusiones: La incidencia de ELCP en esta población mediterránea de un área industrial fue de 1,59 casos por 100.000 habitantes-año, próxima a la encontrada en poblaciones de latitudes similares; pero, sin embargo, se trata de un área industrial con un nivel socioeconómico parecido al de las poblaciones de Reino Unido con una incidencia mucho mayor.(AU)

Introduction: Several socioeconomic population factors have been related to the aetiology of Legg-Calve-Perthes disease (LCPD), such as its higher incidence in the urban population, living on the periphery of urban centres or residing at a certain latitude with respect to the world equator. The incidence in some other countries is known but the incidence of the process in our environment is unknown an important fact to allocate the social and health resources necessary for the treatment of the disease. Therefore, the aim of the present study is to determine the incidence of LCPD in Health Area 2 of Madrid. Material and methods: The incidence of LCPD is analysed in Healthcare Area 2 of Madrid because it is the Mediterranean area that has been scarcely studied. It is an area with very low geographic mobility, a medium-low socioeconomic level, and mostly composed of workers in companies in the secondary and tertiary sectors. The data were obtained from the hospital databases of Area 2 between the years 1994 and 2010. The inclusion criteria were the presence of LCPD and the territorial distribution of the population in Area 2 of Madrid. Conclusions: The incidence of LCPD in this Mediterranean population of an industrial area was 1.59 cases/year and 100,000 inhabitants, close to that found in populations of similar latitudes, but nevertheless it is an industrial area and socioeconomic level similar to United Kingdom populations with a much higher incidence.(AU)

Impact of Legg-Calve-Perthes disease in a Mediterranean health area / Impacto de la enfermedad de Legg-Calvé-Perthes en un área de salud mediterránea

Introduction: Several socioeconomic population factors have been related to the aetiology of Legg-Calve-Perthes disease (LCPD), such as its higher incidence in the urban population, living on the periphery of urban centres or residing at a certain latitude with respect to the world equator. The incidence in some other countries is known but the incidence of the process in our environment is unknown an important fact to allocate the social and health resources necessary for the treatment of the disease. Therefore, the aim of the present study is to determine the incidence of LCPD in Health Area 2 of Madrid. Material and methods: The incidence of LCPD is analysed in Healthcare Area 2 of Madrid because it is the Mediterranean area that has been scarcely studied. It is an area with very low geographic mobility, a medium-low socioeconomic level, and mostly composed of workers in companies in the secondary and tertiary sectors. The data were obtained from the hospital databases of Area 2 between the years 1994 and 2010. The inclusion criteria were the presence of LCPD and the territorial distribution of the population in Area 2 of Madrid. Conclusions: The incidence of LCPD in this Mediterranean population of an industrial area was 1.59 cases/year and 100,000 inhabitants, close to that found in populations of similar latitudes, but nevertheless it is an industrial area and socioeconomic level similar to United Kingdom populations with a much higher incidence.(AU)

Introducción: Se han relacionado varios factores poblacionales socioeconómicos en la etiología de la enfermedad de Legg-Calvé-Perthes (ELCP), como son su mayor incidencia en población urbana, vivir en la periferia de núcleos urbanos o residir a una determinada latitud con respecto al ecuador terráqueo. Es conocida la incidencia en algunos otros países, pero se desconoce la incidencia del proceso en nuestro medio, hecho importante para acomodar los recursos sociosanitarios necesarios para el tratamiento de la enfermedad. Por todo ello, el objetivo del presente estudio es determinar la incidencia de la ELCP en el Área de Salud 2 de Madrid. Material y métodos: Se analiza la incidencia de ELCP en el Área de Salud 2 de Madrid por ser el área mediterránea una zona poco estudiada. Se trata de una zona con muy escasa movilidad geográfica, de nivel socioeconómico medio-bajo, e integrada en su mayoría por trabajadores de empresas del sector secundario y terciario. Los datos se han obtenido a partir de las bases de datos hospitalarias del Área 2 entre los años 1994 y 2010. Los criterios de inclusión fueron padecer la ELCP y la distribución territorial de la población en el Área 2 de Madrid. Conclusiones: La incidencia de ELCP en esta población mediterránea de un área industrial fue de 1,59 casos por 100.000 habitantes-año, próxima a la encontrada en poblaciones de latitudes similares; pero, sin embargo, se trata de un área industrial con un nivel socioeconómico parecido al de las poblaciones de Reino Unido con una incidencia mucho mayor.(AU)

Legg-Calvé-Perthes disease overview.

BACKGROUND: Legg-Calvé-Perthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. Although LCPD was first described in the beginning of the past century, limited is known about its etiology. Our objective is to describe the main areas of interest in Legg-Calve-Perthes disease. METHODS: A review of the literature regarding LCPD etiology was performed, considering the following inclusion criteria: Studies reporting clinical or preclinical results. The research group carried out a filtered search on the PubMed and Science Direct databases. To maximize the suitability of the search results, we combined the terms ''Perthes disease" OR "LCPD" OR "children avascular femoral head necrosis" with "diagnostic" OR "treatment" OR "etiology" as either key words or MeSH terms. RESULTS: In this article been described some areas of interest in LCPD, we include topics such as: history, incidence, pathogenesis, diagnosis, treatment and possible etiology, since LCPD has an unknown etiology. CONCLUSIONS: This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved.

Co-occurrence of Blount's disease and Legg-Calvé-Perthes disease: is obesity a factor?

Legg-Calvé-Perthes disease (LCPD) and Blount's disease share a similar presenting age in addition to similar symptoms such as limp or knee pain. A little overlap is mentioned about both diseases. We sought to present cases of children having both conditions to discuss the implications of this co-occurrence on diagnosis and management. After institutional review board approval, we retrospectively reviewed records of four children who developed both Blount's disease and LCPD. Patient details and outcomes were analyzed. Radiographs were evaluated for the lateral pillar classification, Stulberg classification, tibial metaphyseal-diaphyseal angle and tibiofemoral angle. Two of the cases were initially diagnosed with Blount's disease and subsequently developed Perthes, one case presented initially with both disorders and the final case had Perthes followed by Blount's. Three children were obese and one was overweight. The common symptom to all patients was an abnormal gait, which was painless in two children and painful in two. Blount's disease required surgery in three children. Radiographs showed Lateral Pillar B, B/C border and C hips, and the final Stulberg was stage II (n = 2) or stage IV (n = 2). Obesity is associated with Blount's disease and LCPD, so obese children can be at an increased risk of developing both disorders. Therefore, a child with Blount's disease who has persistent, recurrent or worsening symptoms such as gait disturbance or thigh or knee pain might benefit from a careful physical exam of the hips to prevent a delayed or even missed LCPD diagnosis.

High blood pressure and overweight in children with Legg-Calvé-Perthes disease: a nationwide population-based cohort study.

PURPOSE: Legg-Calvé-Perthes disease (LCPD) and its association with cardiovascular diseases, obesity and hypertension has been consistently observed but remains cloudy. This study aimed to investigate the presence of hypertension and overweight/obesity at diagnosis of LCPD and at a 2-year follow-up and its association with age, sex and lateral pillar classification. METHOD: We compared blood pressure (BP) (n = 93) and body mass index (BMI) (n = 125) in patients registered in the Perthes' register - a part of the Swedish pediatric orthopedic quality register (SPOQ) - with normative data for children with the same age and sex. RESULTS: In children with LCPD 19% had high BP. At the 2-year follow-up, 13% had high BP. For children with LCPD, 30% were either overweight or obese. At the 2-year follow-up, 32% were either overweight or obese. Paired analysis showed stable BMI z-score between these 2 measurements. The sample size of this study was too small to analyze possible associations of high BP or BMI with age, sex and lateral pillar classification. CONCLUSIONS: The prevalence of hypertension was higher in children with LCPD compared to general pediatric normative data. The same pattern was seen for overweight/obesity. Further studies are needed to investigate whether BP and obesity are catalyzing factors in the etiology of LCPD.

Demographics and Clinical Presentation of Early-Stage Legg-Calvé-Perthes Disease: A Prospective, Multicenter, International Study.

BACKGROUND: Children with Legg-Calvé-Perthes disease (LCPD) are classically described as small, thin, high-energy children presenting with a painless limp. Epidemiologic studies have historically been retrospective and regional in nature. The purpose of this study was to determine the demographic and clinical features of children presenting in the early stages of LCPD in an international, multicenter cohort. METHODS: Children (6 to 10 years) in the early stages of LCPD (modified Waldenström stage I to IIa) were enrolled in a prospective, multicenter study. Demographic and clinical data at presentation were analyzed. Body mass index percentiles were determined using country-specific growth charts for children in the United States and India, two countries with largest enrollment. Statistical analyses included t-tests and chi-square. RESULTS: A total of 209 children (86% males; mean age 7.9 ± 1.2 years) from 25 centers (six countries) were included. Eight-four percent of children presented with pain with or without a limp. Average pain score at presentation was 3 ± 2 (range 0 to 9), and 63% of children (n = 105) used pain medications. Of these children 65% required medication more than once per week. Thirty percent of children missed school due to pain in the past month, and of those, 74% missed at least 1 day per week. Twenty-nine percent of children from the United States and 20% of children from India were overweight or obese. Nineteen percent reported household smoking. DISCUSSION: This prospective study provides a new international multicenter representation of early LCPD. The frequency of pain and missed school highlights the substantial morbidity and potential social cost and burden for children and families. The prevalence of being overweight/obese in our LCPD cohort was comparable to rates within the pediatric cohort as a whole, and fewer children have a history of smoke exposure than in previous reports. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Range of abduction in patients with Legg-Calvé-Perthes disease - a nationwide register-based cohort study.

BACKGROUND: Range of abduction often decreases during Legg-Calvé-Perthes Disease (LCPD) disease. However, a good range of abduction is required during the course of LCPD, especially when containment surgery should be performed. This study aimed to investigate how many patients registered in the Swedish Pediatric Orthopedic Quality register (SPOQ) with LCPD had reduced range of abduction at diagnosis in relation to sex or age at diagnosis or severity of disease (lateral pillar class at the time at diagnosis), if physiotherapy (PT) was prescribed and has a beneficial impact in maintaining (or increasing) abduction and if the range of abduction at diagnosis before fragmentation stage is predictive for the lateral pillar classification at fragmentation stage. METHODS: The national Swedish Pediatric Orthopedic Quality Register (SPOQ), established in 2015, is used to identify patients with LCPD. The patients are registered at three time points: at diagnosis, at potential surgery and 2 years after diagnosis. Range of abduction and information on PT are required to register at all registration sessions. One hundred ninety-nine hips from 192 children were registered in the SPOQ. RESULTS: Of all hips, the mean range of abduction at diagnosis was 39 degrees (range 0 to 90). One hundred twenty-six patients (63%) either received instructions for PT or were referred to a physiotherapist; two patients were treated additionally with an abduction brace. There was a trend that patients who received PT, compared to patients without PT, either maintained or increased their range of abduction at the 2-year follow-up. Older age at diagnosis correlated with decreased range of abduction at the 2-year follow-up (Estimate [Est]: - 3.1, 95% confidence interval [CI]: - 4.4 to - 1.7). The degree of abduction at diagnosis before fragmentation stage correlated with the lateral pillar group at the fragmentation stage (Est: -5.3, 95% CI: - 10.0 to - 1.1). CONCLUSION: In all, 63% of the children with LCPD in SPOQ received either written instructions or were referred to PT or both. PT seems to have a favorable impact for maintaining the range of abduction in children with LCPD. Children with a lower range of abduction at diagnosis (before the fragmentation stage) developed a higher degree of lateral pillar involvement as measured by the lateral pillar classification.

Risk factors during pregnancy and delivery for the development of Perthes' disease, a nationwide Swedish study of 2.1 million individuals.

BACKGROUND: To ascertain or disprove a correlation between suboptimal birth characteristics, breech position at delivery and development of Perthes' disease. METHODS: Study material was collected from nationwide registers regarding diagnoses, birth statistics and delivery data. As study population were included children with a diagnosis code for Perthes' disease who were alive and living in Sweden at age 13. Children with missing birth statistics were excluded. All children with no Perthes' disease diagnosis were used as control group. Both single and multiple logistical regression analyses were used to calculate OR for the included characteristics. RESULTS: Children in breech position had a higher risk for developing Perthes' disease. Children with Perthes' disease had also a higher probability of having been born pre-term, very pre-term or post-term. Lower than normal birth weight and a lower Apgar-score were also associated with Perthes' disease. CONCLUSIONS: There is a correlation between breech birth and development of Perthes' disease. There is also correlation to suboptimal birth characteristics. Despite our findings this should not be used for screening of Perthes' disease as the percentage of children who actually develop it is very low. Also, as of yet there is no possibility to diagnose Perthes' disease before the presence of skeletal changes. Our findings could be important in finding the cause of Perthes' disease and therefore developing better diagnostics, treatment and prevention.

Influence of passive smoking on the onset of Legg-Calvè-Perthes disease: a systematic review and meta-analysis.

The relationship between passive smoking and the onset of Legg-Calvè-Perthes disease is still controversial. Therefore, we conducted the study to systematically evaluate and analyze the relationship. A comprehensive search was conducted. Meta-analysis was performed with RevMan 5.3 software, with the odds ratio as the effect size. Eight English articles with a total of 1379 Legg-Calvè-Perthes disease patients were eventually included. Passive smoking type of family members smoking in indoor (odds ratio = 2.53), paternal smoking (odds ratio = 2.76), maternal smoking (odds ratio = 2.02), maternal smoking during pregnancy (odds ratio = 1.68), using stove indoor (odds ratio = 2.56) are statistically significant (P < 0.05). For the family members smoking indoor, region may be a confounding factor (European group I = 92%, odds ratio = 2.51; USA group I = 5%, odds ratio = 3.26; and Asian group I = 0%, odds ratio = 2.25). In addition, the type of maternal smoking (odds ratio = 0.80, for 1-10 per day; odds ratio = 2.73, for 10-20 per day; odds ratio = 2.78, for >20 per day) and the type of maternal smoking during pregnancy (odds ratio = 1.36, for 1-9 per day; odds ratio = 2.02, for ≥10 per day) may show a dose-effect relationship. Passive smoking is a risk factor for the onset of Legg-Calvè-Perthes disease, but the specific types of passive smoking (haze, etc.), dose, dose-effect relationship, regional confounding, pathological mechanisms, etc. also require clinicians and researchers to continue exploring.

Comparison of surgical and nonsurgical containment methods for patients with Legg-Calvé-Perthes disease of the onset ages between 6.0 and 8.0 years: Salter osteotomy versus a non-weight-bearing hip flexion-abduction brace.

Since bone healing potential decreases with age, patients with Legg-Calvé-Perthes disease should receive treatment appropriate to their age group. Nonsurgical treatment is commonly applied to patients under 6.0 years of age at the onset and surgical treatment is recommended for those over 8.0 years of age, but it remains unclear which is better for those between 6.0 and 8.0 years. The aim of this retrospective study was to compare outcomes of Salter osteotomy and a non-weight-bearing brace in this age group. Inclusion criteria were unilateral Legg-Calvé-Perthes disease patients who were 6.0-8.0 years of age at the onset, who had more than 50% femoral head involvement without hinge abduction, and who underwent either Salter osteotomy (n = 35) or a non-weight-bearing hip flexion-abduction brace (n = 18). Radiological and clinical outcomes at skeletal maturity were compared between the two groups. The mean follow-up durations were 9.4 years in the Salter osteotomy group and 10.0 years in the brace group. There was no significant difference in the modified Waldenström classification at the beginning of treatment and the Catterall and modified lateral pillar classifications evaluated at the fragmentation stage between the groups. At skeletal maturity, the Stulberg classification, the sphericity deviation score, femoral head overgrowth, and the articulo-trochanteric distance were similar between the groups, but the Salter osteotomy group showed significantly smaller lateralization of the femoral head and better acetabular shape and coverage than the brace group: femoral head lateralization (P < 0.001), acetabular depth-to-width ratio (P = 0.002), Sharp angle (P < 0.001), lateral acetabular shape (P = 0.027), acetabular head index (P < 0.001). There was no significant difference in hip pain and motion between the groups. In this age group, Salter osteotomy provides better femoral head position and acetabular shape and coverage than a non-weight-bearing brace.

What are the Demographics and Epidemiology of Legg-Calvé-Perthes Disease in a Large Southern California Integrated Health System?

BACKGROUND: Although many authors have reported the incidence of Legg-Calvé-Perthes disease (LCPD), there have been few incidence studies in the United States on large, self-contained populations such as those within an integrated health system. Understanding the epidemiology and demographics of LCPD in this setting may help clinicians identify patients at the greatest risk and aid in diagnosis and subsequent treatment. QUESTIONS/PURPOSES: In this study we sought (1) to determine the incidence and demographics of LCPD in a large cohort of children and adolescents in a Southern California integrated healthcare system, and (2) to identify any demographic or clinical factors (such as age, sex, race/ethnicity, or BMI) that are independently associated with LCPD. METHODS: A retrospective chart analysis was done on patients diagnosed with LCPD within our integrated healthcare system in patients aged 2 to 12 years over a 3-year period between 2010-2012. There were nearly 800,000 children in this cohort. Patient demographics were recorded; the incidence of LCPD was determined for the entire group and by sex, age, and race/ethnicity. Odds ratios for an association with LCPD based on age, sex, BMI and race/ethnicity were determined using logistic regression models. RESULTS: The LCPD incidence per 100,000 for all children was 2.84, with the highest incidence in 2- to 5-year-old children (3.05; 95% CI, 1.51-4.59) and the lowest in 9- to 12-year-old children (1.06; 95% CI, 0.21-1.91). Incidence varied markedly among ethnicities, with the highest incidence in whites (5.69; 95% CI, 3.13-8.24) and the lowest in Asians (0.78; 95% CI, 0.00-2.32). Data analysis revealed a 3.13-times increased odds ratio (OR) of LCPD in 2- to 5-year-old patients versus 9- to 12-year-olds (p = 0.011), and boys had a 12.44 times greater OR of LCPD than girls (p < 0.001). Data analysis showed an increased OR for LCPD (3.41; 95% CI, 1.28-9.09) in patients with extreme obesity (BMI-for-age ≥ 1.2 × 95th percentile or a BMI ≥ 35 kg/m) compared with patients with a normal BMI. CONCLUSIONS: Our study of a large integrated healthcare system in Southern California revealed an increased association of male sex and young age (2 to 5 years old) with LCPD. The overall incidence was lower overall than previously reported, although the incidence seen in white patients was similar to that in prior studies. The finding that patients with extreme obesity may have an increased association with LCPD merits further study. These findings may increase providers' awareness of the risk of the disease in younger patients and in extremely obese patients, and it also merits further future investigation as to whether there is a cause or effect relationship between extreme obesity and LCPD. LEVEL OF EVIDENCE: Level IV, prognostic study.

Is Legg-Calvé-Perthes Disease a Local Manifestation of a Systemic Condition?

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.

A case control study to determine the association between Perthes' disease and the recalled use of tobacco during pregnancy, and biological markers of current tobacco smoke exposure.

AIMS: It is well established that there is a strong association between Perthes' disease and worsening socioeconomic deprivation. It has been suggested that the primary determinant driving this association is exposure to tobacco smoke. This study aimed to examine this hypothesis. PATIENTS AND METHODS: A hospital case-control study (n = 149/146) examined the association between tobacco smoke exposure and Perthes' disease, adjusting for area-level socioeconomic deprivation. Tobacco smoke exposure was assessed by parental questionnaire of smoking habits during pregnancy, and by quantitative assay of current exposure using the urinary cotinine-creatinine ratio, which is a widely used and validated measure of tobacco smoke exposure. RESULTS: The odds of Perthes' disease significantly increased with reported in utero exposure after adjustment for socioeconomic deprivation (maternal smoking odds ratio (OR) 2.06, 95% confidence interval (CI) 1.17 to 3.63; paternal smoking OR 2.09, 95% CI 1.26 to 3.46). The cotinine-creatinine ratio was significantly greater in cases, OR 1.63 (95% CI 1.09 to 2.43), suggesting a greater 'dose' of current tobacco exposure. CONCLUSION: An association exists between tobacco smoke exposure and Perthes' disease but we remain unable to disentangle the association with socioeconomic deprivation. Cite this article: Bone Joint J 2017;99-B:1102-8.

The Declining Incidence of Legg-Calve-Perthes' Disease in Northern Ireland: An Epidemiological Study.

BACKGROUND: Legg-Calve-Perthes' disease (LCPD) is an idiopathic disease of the femoral head affecting the pediatric population. The causative factors remains poorly understood and it is associated with significant hip pathology in adult life. Research has demonstrated wide geographical variation in the incidence rates of LCPD with a relatively high incidence occurring in Northern Ireland (NI) shown in a previous study of incidence from the same unit. The number of new diagnoses of LCPD seems to be declining over time. This study aimed to track changes in the incidence of LCPD within the 0- to 14-year-old population over a 15-year period in NI. METHODS: An established database was utilized to collate information of any individual between the ages of 0 to 14 years with a diagnosis of LCPD. The data were compared with electronic radiologic records to confirm the diagnosis. Postal code data were used to the determine location of residence and used as a proxy measure of deprivation. RESULTS: The results of this epidemiological study have demonstrated a 61% decrease in the incidence of LCPD over a 15-year period within the pediatric population of NI. Comparison between 2 cohorts reveals no distinguishable change in distribution of age or sex. The relationship between geographical proxy measures of deprivation in NI and LCPD remains evident. CONCLUSIONS: The number of new cases of LCPD is decreasing over time. The epidemiological data are unchanged between 2 cohorts over a 15-year period, and this therefore supports a change within the patients' environment relating to this decline. This change could relate to a number of factors including smoking rates, breastfeeding, lead use, and vaccination implementation. LEVEL OF EVIDENCE: Level IV-retrospective cohort study.

Incidence of Perthes' disease in children born between 1973 and 1993.

Background and purpose - The incidence of Perthes' disease as reported in the literature varies widely between and within countries. The etiology of the disease is still unknown. Both environmental and genetic factors have been suggested to play a part in either causing the disease or increasing the susceptibility of an individual. We determined the incidence of Perthes' disease in Sweden and investigated possible relationships to parental socioeconomic status, ethnicity, marital status, mothers' age when giving birth, parity, number of siblings, and smoking habits. Patients and methods - Six Swedish population-based registers were used, together covering all children born in Sweden from 1973 through 1993. Results - The incidence of Perthes' disease in Sweden was 9.3 per 100,000 subjects. The ratio between boys and girls was 3.1:1. The educational level of the father and the mother of a child with Perthes' disease was lower than in the controls. The incidence was lower when the fathers were in the highest income bracket (above the 90th percentile). A higher proportion of parents of Nordic lineage had children with Perthes' disease than parental pairs with one or both who were not of such lineage. Interpretation - This study confirms that there is an association between the incidence of Perthes' disease and the socioeconomic status of the parents.

The lognormal age of onset distribution in Perthes' disease: an analysis from a large well-defined cohort.

AIMS: To explore the of age of onset distribution for Perthes' disease of the hip, with particular reference to gender, laterality and conformity to the lognormal distribution. PATIENTS AND METHODS: A total of 1082 patients were identified from the Liverpool Perthes' Disease Register between 1976 and 2010, of which 992 had the date of diagnosis recorded. In total, 682 patients came from the geographical area exclusively served by Alder Hey Hospital, of which 673 had a date of diagnosis. Age of onset curves were analysed, with respect to the predefined subgroups. RESULTS: The age of onset demonstrated a positive skew with a median of 5.8 years (interquartile range 4.6 to 7.5). Disease onset was a mean five months earlier in girls (p = 0.01) and one year earlier in those who went on to develop bilateral disease (p < 0.001). There was no difference in the age of onset between geographical districts with differing incidence rates. The entire dataset (n = 992) conformed to a lognormal distribution graphically and with the chi-squared test of normality (p = 0.10), but not using the Shapiro-Wilk test (p = 0.01). The distribution for the predefined geographical subgroup (n = 673) conformed well to a lognormal distribution (chi-squared p = 0.16, Shapiro-Wilk p = 0.08). Given the observed lognormal distribution it was assumed that Perthes' disease followed on incubation period consistent with a point-source disease exposure. The incubation period was further examined using Hirayama's method, which suggested that the disease exposure may act in the prenatal period. CONCLUSION: The age of onset in Perthes' disease conforms to a lognormal distribution, which allows comparisons with infectious disease epidemiology. Earlier onset in girls and those who develop bilateral disease may offer clues to understanding the aetiological determinants of the disease. The analysis suggests that an antenatal aetiological determinant may be responsible for disease. TAKE HOME MESSAGE: Perthes' disease age of onset conforms to a lognormal model, which is most typical of infectious diseases. The shape of the distribution suggests that an aetiological trigger in the pre-natal period may be an important determinant of disease. Cite this article: Bone Joint J 2016;98-B:710-14.