Biology of Legg-Calvé-Perthes Disease. The Beginning.
Nuno Craveiro Lopes; Carolina Escalda and Carlo Villacreses.
Orthopedic and Traumatologic Department, Pediatric Orthopedic Unit.
Garcia de Orta Hospital, Almada, Portugal
The existence of several fractional and sequential ischemic episodes on the onset of Legg-Calvé-
Perthes (LCPD) is well documented.
It is also known that multiple factors are involved in the pathogenesis of the disease and that a
specific sequence of chained events is necessary to trigger LCPD in a susceptible child.
To clarify the pathogenesis of LCPD, the senior Author (NCL) developed an animal model and
analysed the data of patients treated with Transphyseal Neck-Head Drilling (TNHD), in the stage of
sequential ischemic episodes and initial necrosis.
For the experimental model, 27 White New Zealand rabbits, seven to eight weeks old, were used.
This growth stage of the rabbit is equivalent to that of a 5-6 year old child. To try to reproduce the
morphologic, radiological and histological aspects of LCPD, an no invasive method was used,
consisting on the use of flexible splints to place the legs of the rabbits in extension and internal
rotation for 6 hours, promoting an effusion and secondary collapse of the retinacular vessels without
causing their destruction. In the following day micro-trauma was produced on the right hip only, using
a vibratory motor for a period of 30 minutes. This sequence was repeated twice a week.
We observed that the prolonged and repeated positioning of the legs of the rabbit induced an intra
articular pressure level sufficient to produce an ischemic episode at the proximal femoral epiphysis.
After this episode, we observed a process of rapid revascularization of the preserved vascular canals
with repositioning of myeloid and osteoid tissues by differentiation of endothelial cells in
mesenchymal progenitor cells, without distortion of the epiphyseal structure or loss of its mechanical
resistance. When a new ischemic episode was produced after the completion of the repairing process,
all the reparative sequence was repeated, again without loss of the mechanical resistance of the
epiphysis. However, the repetition of an ischemic episode during the reconstruction of a previous
episode, lead to an alteration of the reparative response, with osteoclastic hyperactivity in the
subchondral zone and formation of a distorted bone structure in the epiphysis by osteoblastic
hyperactivity, which leads to a mechanically weak bone structure, similar to that described in LCPD as
"woven bone". In these conditions, the existence of trauma or micro-trauma on the right hip, lead to
the appearance of a sub-chondral pathological fracture and collapse of the structure of the epiphysis,
with formation of a true bone sequestum on that side only. This represents the initial stage of LCPD.
Experimental Model two week - IDGH Experimental Model five weeks - LCPD
Sub-chondral weakening, double layer lamellae, Subchondral fracture, woven bone and fibrous
normal myeloid tissue tissue proliferation
The results of this experimental model suggests the existence of a pathologic entity, prior to
LCPD, characterized by the existence of successive ischemic events at the level of the femoral
proximal epiphysis, that in certain circumstances can develop into LCPD. We call this entity Ischemic
Disease of the Growing Hip (IDGH).
The image data and histological examinations from 19 patients who presented signs and symptoms
compatible with the existence of IDGH under risk of development to DLCP, and 17 patients with
LCPD in the initial stage, were analysed. These patients were treated between 1995 and 2006 with
TNHD, and had samples for histological examination. The analysis of those samples, has shown that
patients where IDGH was detected, presented histological signals of a recent ischemic event of the
osteoid and myeloid or recent ischemia over a remodelled anterior ischemic event. In all the cases
where the bone samples showed profuse “woven bone” and total substitution of the myeloid by fibrous
tissue rich in fibroblasts, progressed into LCPD. Such biopsies were consistent with failure of
immediate revascularization, as the vascular canals had collapsed.
IDGH Stage III LCPD Stage I
Ischemic event over a reparative process of a recent Woven bone, substitution of myeloid tissue by
necrosis. Myeloid tissue beguns to be substituted by fibrous tissue
fibrous tissue
As a conclusion, this study confirms the existence of a period of fractional and sequential ischemic
episodes before the onset of LCPD. These ischemic events lead to weakening of the epiphyseal bone
structure at two levels: subchondral cortical bone weakening by osteoclastic hyperactivity and
epiphyseal cancellous bone weakening by osteoblastic hyperactivity and woven bone formation. If a
trauma or microtrauma happens at that timing, then a pathologic subchondral fracture triggers the
beginning of Legg-Calvé-Perthes disease.
