**5. Clinical presentation**

An early detection of FHN is of paramount importance as clinical success of the therapy is closely related to the stage which the treatment started in [42]. There are several procedures capable to intercept a suspected FHN at the onset or eventual early stages of the disease: at the present time, histological studies, scintigraphy, functional bone evaluation, radiography, magnetic resonance imaging (MRI), and computer-assisted tomography (CAT) are the most current diagnostic methods available. At an early stage, FHN is usually asymptomatic or characterized by slight pain radiating to the knee and/or ipsilateral buttock.

as well as of reactive nitrogen species (RNS), these last ones due to hyperoxia [37]. Controlled

intracellular transduction cascades, driving to synthesis of growth factors, promoting the

case is still depending on the lack in Level 1 evidence [1, 11]; as a matter of fact, the current scientific literature does not yet allow a clear identification of the optimal treatment protocol.

provide a delay in undergoing hip arthroplasty surgery; it is a reasonable postulate that such therapy can show a beneficial effect without having the invasiveness of a surgical approach.

an increased oxygen delivery to ischemic cells, thus relieving compartment syndrome so to prevent a progression in a further necrosis, stimulating angiogenesis and oxygen-dependent cells, and enhancing osteoclast and osteoblast function for remodeling and repair. Moreover,

In FHN treatment HBO facilitates oxygenation of hypoxic tissue and reduces edema by creating a high concentration of dissolved oxygen and inducing vasoconstriction. This may explain the early pain relief noticed in patients treated with this modality; by saturating the extracellular fluid with diffused oxygen, HBO treatment will lead to a better oxygenation of the ischemic bone cells, independently of circulating hemoglobin and without the extra-energy requirement to provide for the dissociation of oxygen from hemoglobin. Late effects of HBO

Yang et al. quantitatively evaluated the hemodynamic flow in animal models with steroidinduced FHN by using multi-slice CT perfusion imaging. Especially in the early stage, they assessed how HBO therapy resulted in regional blood flow improvement in the ischemic tissues. Additionally, they found high-grade new bone formation and a well-regenerated hematopoietic tissue [39]. Moreover, recent studies focusing among osteoblasts differentiation and suppression osteoclasts showed positive results due to hyperbaric oxygen treatment. In particular, HBO shifted the balance between bone formation and bone resorption promoting regeneration [40, 41].

An early detection of FHN is of paramount importance as clinical success of the therapy is closely related to the stage which the treatment started in [42]. There are several procedures capable to intercept a suspected FHN at the onset or eventual early stages of the disease:

 increases extracellular oxygen concentration and reduces cellular ischemia and edema by inducing vasoconstriction [38]. Studies have already reported radiographic improvement in FHN at stage I according to the Steinberg classification, as well as a better pain control, compliance, and range of motion (ROM) in FHN at Ficat stages I–II [36]. Amid the possible effects

, there is a reduced bone marrow pressure, leading to a significant pain relief, and

is also able to stimulate the multipotent fibroblasts in the bone marrow with an addi-

is positioned among the possible and feasible therapies which allow to

wound healing, and ameliorating postischemic and post-inflammatory injuries [36].

depends on modulation of

to administer in each

studies have already shown as the clinical efficacy from HBO<sup>2</sup>

Nevertheless, HBO2

tional aid in the osteogenesis process [37].

**5. Clinical presentation**

are bone resorption, revascularization, and osteogenesis [5, 36].

HBO2

of HBO2

HBO2

The actual inability to establish which will be the correct dose of HBO2

14 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

It may present with a limited range of hip movement as well as stabbing pain, especially during a forced intra-rotation. FHN should be considered if the patient feels pain in the hips and has no risk factors in his clinical history. In particular, plain radiographs can often appear as normal in the early stages of necrosis. Patients with a history of previous necrosis should be observed for bilateral FHN; this condition has been reported up to 70% of the observations [43].

Classification systems currently in use for FHN include the Ficat and Steinberg systems [15].

The Ficat classification substantially relies on standard radiographic presentations, where phase I shows normal images; phase II indicates a normal contour, with evidence of a bone remodeling; stage III is characterized by subchondral collapse or flattening of the femoral head; and phase IV indicates a narrowing of the joint space, with secondary degenerative changes in the acetabulum. The Ficat classification system is however based on radiographic imaging; therefore, the real size of the lesion cannot be quantified up to a more proper and accurate measure of the radiological appearance of the disease.

Steinberg expands the Ficat system into six stages, including quantification of involvement of the femoral head within stages I–VI, with three further subsets each: mild (less than 15% radiographic involvement of the head's articular surface), moderate (with a 15–30% involvement of the head's articular surface), and severe (greater than 30% involvement of the head's articular surface) stages.

Recently, the Association Research Circulation Osseous (ARCO) has recommended a third standardized classification system relying on an interpolated comparison of different procedure findings: radiographic, MRI, bone scan, and histologic findings [15]. Anyhow, not even this can eliminate completely the intrinsic operator-dependent variability, making Ficat and ARCO classification systems still not sufficiently reliable to assess FHN occurrence [44].

FHN is currently diagnosed by plain anterior-posterior and frog leg lateral radiographs of the hip, followed by MRI; this is considered the most accurate benchmark. Other existing tools for assessing the FHN presentation, such as venography, bone marrow pressure measurements, and core biopsy, are rarely used.
