Backround: The etiology of Legg-Calvé-Perthes disease (LCPD) is incompletely understood. Previous studies suggest associations with coagulation problems, anatomical abnormalities in the femoral head blood supply and risks for cardiovascular disease. Therefore, we hypothesized that patients with LCPD might have a higher risk of cardiovascular diseases and diseases of blood and blood-forming organs.

Methods: 3,141 patients with LCPD aged 2–15 years, diagnosed between 1965 and 2005 were identified using the Swedish inpatient register. 15,595 individuals without LCPD were randomly selected from among the Swedish general population, matched by year of birth, age, sex, and region of residence. Cox proportional hazard regression, adjusted for socioeconomic index, was used to estimate the relative risks. The patients were also compared with their same-sex siblings.

Results: Patients with LCPD had a hazard ratio (HR) of 1.70 (95% CI 1.39–2.09) for cardiovascular disease compared with individuals without LCPD. The point estimate was slightly higher among those older than 30 at follow-up (HR=2.10, 95% CI: 1.52–2.91). There were statistically significant higher risks for diseases of blood and blood-forming organs (1.41, 1.07–1.86), which were more pronounced among those older than 30 years at follow-up (2.70. 1.50–4.84). Patients had also statistically significant higher risks for hypertensive disease (2.97, 1.87–4.72), and nutritional anemia (2.92, 1.58–5.40). When siblings were used as the comparison group, the results were consistent for cardiovascular disease.

Conclusion: The results are consistent with the hypothesis that an insufficient blood supply to the femoral head due to vascular pathology and other causes are involved in the etiology of LCPD.

In dogs, resection of a length of the ulna equal to twice the diameter of the mid-shaft leaves a defect which consistently fails to unite. In response to an implant of 100 mg of bovine bone morphogenetic protein (BMP), the defect becomes filled by callus consisting of fibrocartilage, cartilage and woven bone within four weeks. The cartilage is resorbed and replaced by new bone in four to eight weeks. Woven bone is then resorbed, colonised by bone marrow cells and remodelled into lamellar bone. Union of the defect is produced by 12 weeks. Control defects filled with autogeneic cortical bone chips unite after the same period. In regeneration induced by bone morphogenetic protein (BMP) and in repair enhanced by bone graft, union depends upon the proliferation of cells within and around the bone ends. Our working hypothesis is that BMP induces the differentiation of perivascular connective tissue cells into chondroblasts and osteoprogenitor cells and thereby augments the process of bone regeneration from the cells already present in the endosteum and periosteum.