Osteochondroses

Pathogenesis

The initial events in the pathogenesis of osteochondrosis remain elusive, but clinical and radiologic evidence points to ischemic necrosis of the ossification center. This process could be due to a primary vascular event, a definite traumatic event, or multiple additive traumas.

The osteochondrotic process is essentially degeneration of the epiphyseal osseous nucleus. This process is almost certainly due to either (1) interference with the blood supply, which leads to necrosis of the cartilage-canal vessels in the subchondral bone and adjacent epiphysis, or (2) failure of the bony centrum to enlarge and disordered proliferation of the cartilaginous cells in the epiphysis. Secondary changes (eg, fragmentation, collapse, and sequestrum formation) develop in accordance with the characteristics of the affected region.

The disease process can be sequential or simultaneous. It can involve a single epiphysis (isolated disease) or several (multiple-site disease), and not even the sesamoids are spared (as in Sinding-Larsen syndrome and involvement of first-metatarsal sesamoids). The underlying processes seem to be essentially the same for isolated and multiple-site disease. However, presentations may vary, depending on the stresses and strains to which the epiphyses have been subjected. The efficacy of regeneration and repair determines the patient’s long-term clinical outcome.

With complete healing, little lasting harm is done. However, partial healing or failure to heal becomes a source of chronic pain and disability later in life. Accordingly, the physician must be vigilant to avoid overlooking an osteochondrosis in a pediatric patient.

Ponseti proposed that the following features are common to all osteochondroses:

• Uncertain etiology
• Clinical pattern of progression
• Radiologic appearance of ischemic necrosis

Duthie and Houghton proposed the following models for the development of osteochondroses:

• Normal epiphysis subjected to extreme trauma (eg, pitcher’s elbow with osteochondritis dissecans of the capitellum)
• Mildly dyschondrotic epiphysis subjected to more stress than usual (eg, Perthes disease)
• Severely affected dyschondrotic epiphysis subjected to normal stress (eg, the capital femoral epiphysis in Gaucher disease)

Other proposed pathogenetic factors for which further study is warranted include an altered collagen-to-proteoglycan ratio, ^[3] biochemical abnormalities (eg, altered expression of matrix metalloproteinases [MMPs] such as MMP-1, MMP-3, and MMP-13 ^[4] ), and overexpression of glycosaminoglycans and aggrecan as a consequence of altered mechanics that exacerbate damage to the cartilage.

Classification

Earlier classifications of osteochondroses divided them into pressure, traction, and atavistic types (Burrows’s classification) or into compression, tension, and atavistic types (Goff’s classification). These systems were inadequate. Siffer proposed a classification that divided osteochondroses into articular, nonarticular, and physeal types; this schema is largely accepted today.

Articular osteochondroses exhibit the following characteristics:

• Primary involvement of the articular and epiphyseal cartilage and a subjacent endochondral ossification center – Freiberg disease ^[5]
• Secondary involvement of the articular and epiphyseal cartilage as a consequence of ischemic necrosis of subjacent bone – Perthes disease, Köhler disease, osteochondritis dissecans

Nonarticular osteochondroses occur at the following locations:

• Tendinous attachments - Osgood-Schlatter syndrome, Monde-Felix disease
• Ligamentous attachments - Vertebral ring
• Impact sites - Sever disease

Physeal osteochondroses involve the following:

• Long bones – Tibia vara (Blount disease)
• Scheuermann disease

The use of eponyms for the osteochondroses is so deeply ingrained in the literature that any discussion of these syndromes would be incomplete without the mention of these terms (see Table 1 below).

Table 1. Eponyms for Osteochondroses (Open Table in a new window)

Associated disorders

Various investigators have found that major genitourinary disorders are associated with Perthes disease. The risk of inguinal hernia increases by a factor of eight in patients with this disease. Slippage of the capital femoral epiphysis may occur in patients with Scheuermann disease.

Considerable attention has been directed toward the occurrence of growth retardation with osteochondroses. Substantiating evidence for this association includes reduced excretion of urinary deoxypyridinoline and glycosaminoglycans, as well as low plasma levels of insulinlike growth factor (IGF)-1. These changes cause a disturbance in the metabolism of collagen. ^[11] In the future, this alteration may be linked to the pathogenesis of osteochondrosis in syndromic terms.

Osteochondroses should generally be thought of as syndromes rather than diseases because multiple causes—some indeterminable—may be involved. Accordingly, the etiology is largely a matter of hypothesis. The main concern is to identify any distinct pathologic condition present that may be controlled or even corrected with proper therapy.

Probable causes

Various factors have been proposed as potential causes of osteochondroses. The oldest, most controversial, and therefore least widely accepted of these are social deprivation, dietary deficiency, and passive exposure to smoke (an unknown industrial factor). The studies that proposed these factors as causes were geographically specific, and their results might have been confounded by the etiologic fallacy.

The factors that have been more broadly accepted as the most probable causes of osteochondrosis—alone or in various combinations (in multifactorial disease)—are these:

• Genetic predisposition ^[12]
• Environmental factors
• Thrombotic predisposition
• Acute or repeated trauma
• Embolism
• Copper (trace element) deficiency
• Infection
• Mechanical factors

With respect to genetic predisposition, Blount disease is known to be inherited in an autosomal dominant pattern; however, inheritance patterns of other potentially inheritable disorders (eg, Scheuermann disease ^[13] ) remain to be characterized.

An area deserving of further study is the genetic predisposition that produces a hypercoagulable state due to a deficiency in tissue factor pathway inhibitor (TFPI). ^[14] Others include fibrinolysis defects involving protein S, protein C deficiency, ^[15] and resistance to activated protein C. Likewise, there is no consensus regarding the inheritable disorders of thrombophilia due to mutations in the genes for prothrombin (mutation G20210A), factor V Leiden (mutation G1691A), methylene tetrahydrofolate reductase (C677T mutation), or anticardiolipin antibodies. ^{[16, 17]}

With respect to both genetic predisposition and environmental factors, exposure to secondhand smoke may be related to the development of Perthes disease as a consequence of the G-455-A polymorphism of the beta-fibrinogen gene.

Deficiencies in trace elements (eg, copper and zinc) have been proposed as probable causes on the basis of animal studies. ^[18]

Infection, which at one time appeared to have been unanimously discredited as a cause of osteochondrosis, has subsequently been shown to trigger or potentiate the disease process. Its effect may be direct or related to autoimmune mechanisms.

Individual mechanical factors may be related to the development of specific diseases, such as Osgood-Schlatter ^{[19, 20]} disease and Sinding-Larsen-Johansson disease. Examples of such factors are a long patella (Grelsamer type II) and extensor apparatus and external tibial torsion. Various authors have suggested that Osgood-Schlatter syndrome is traumatic in origin and that it does not involve ischemic necrosis.

Compounding factors

Compounding factors associated with osteochondrosis have also been identified. These include hormonal imbalance (hypothyroidism), sickle cell anemia, Gaucher disease and mucopolysaccharidoses, tetany due to magnesium deficiency, and cystic fibrosis, among others. However, all of these conditions are now well-established diseases on their own and, in the authors’ view, should not be linked with osteochondroses.

The frequency with which osteochondroses affect different sites varies. Because these disorders are self-limiting, they often go undiagnosed; consequently, exact documentation is difficult. Perthes disease is considered to be the most common disabling osteochondrosis, but it is not the most common of all osteochondroses. Some osteochondroses occur so infrequently that a physician may never encounter them in his or her whole period of practice.

Age-related demographics

Most osteochondroses occur shortly after the bony nucleus appears, around the middle of the growth spurt. At this time, the epiphysis is mainly cartilaginous and growing rapidly; therefore, it is susceptible to injury. Exceptions to this general statement include osteochondritis dissecans, Scheuermann disease, and Osgood-Schlatter disease, which predominantly occur during the adolescent growth spurt.

Sex-related demographics

Freiberg disease is more common among females than among males, and juvenile osteochondritis dissecans of the elbow (capitellum) is common among female javelin throwers. All other osteochondroses occur most frequently in males. The delayed appearance and maturation of the growth center in boys may account for this difference. In addition, the high activity level further traumatizes the immature epiphysis.

Race-related demographics

Some of the common and well-studied osteochondroses have definite racial and ethnic differences in incidence and prevalence. For example, Perthes disease is uncommon among persons of African or Chinese descent, whereas Blount disease is common in Africa but uncommon in Western Europe and North America.

Because osteochondrosis is a self-limiting disorder, the prognosis is usually good. ^[21]  More often than not, in fact, the syndrome goes unnoticed. However, when osteochondrosis does not remit with conservative treatment or surgery, the patient’s prognosis is usually poor. In these cases, patients may need salvage interventions or joint replacement later in life to manage secondary changes. Patients should be properly informed and educated before such interventions are undertaken.