8/6/2019 Biology of Legg-Calve-Perthes Disease. Nuno Craveiro Lopes; Carolina Escalda and Carlo Villacreses

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Biology of Legg-Calv-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-Calv-

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 internalrotation 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 theepiphysis. 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 - IDGHSub-chondral weakening, double layer lamellae,

normal myeloid tissue

Experimental Model five weeks - LCPDSubchondral fracture, woven bone and fibrous

tissue proliferation

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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 withTNHD, 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

Ischemic event over a reparative process of a recen

necrosis. Myeloid tissue beguns to be substituted byfibrous tissue

LCPD Stage I

Woven bone, substitution of myeloid tissue by

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-Calv-Perthes disease.