**Author details**

A large number of sessions showed to be effective on pain relief and mobility improvement and avoided arthroplasty, in about 80% of cases. In particular, about 90% of Ficat I and II patients and half of Ficat III patients after HBOTs had no more need of surgery and all related

Despite the several clinical studies that support the benefits of HBOT in patients afflicted with osteonecrosis [1, 5], therapy is still not worldwide approved. This could be due to several factors including the apparent high number of HBO treatments necessary plus limited amount of clinical evidence for FHN, the majority of the evidence relies on ex vivo and in vitro studies, and the molecular mechanisms responsible for the regenerative responses of HBOT are still

A recent study investigated HBO upregulation on serum osteoprotegerin (OPG) and/or inhibition of osteoclast activation [50]. Twenty-three patients suffering from unilateral FHN at stage I, II, and III consented to the study: patients received standard HBOT; nineteen patients com-

), after 15

and about

), and at the end of our treatment pro-

pleted the study. Serum OPG levels were obtained at the beginning of HBOT (T0

), after a 30-day break (T<sup>3</sup>

1 year from the end of HBO treatments to compare pre-HBOT with post-HBOT lesion size.

• HBOT significantly reduced lesion size in all stage I and II patients and in 2 of 11 stage III

• HBOT increased serum OPG levels, but receptor activator of nuclear factor kappa-B ligand

These evidences proposed an influence of HBO on the immune system and inflammatory processes. Indeed, one of the initial studies by Lukich et al. suggested an immunosuppressive effect of HBO therapy in patients suffering from rheumatoid arthritis [51]. Later, other studies reinforced these findings. Specifically, authors showed TNF-alpha and interleukin-1β (IL-1β) inhibition after HBO therapy in indomethacin-induced enteropathy and in chronic constriction injury-induced neuropathy [52, 53]. The following are some examples of tissue cytokine

IL-1β is a pro-inflammatory cytokine that responds to injury or infection by binding to the type-1 IL-1 receptor (IL-1R) and IL-1R accessory protein [54]. Although belonging to a structurally different cytokine class, IL-1 resembles many of the biological activities of TNF-α; IL-1 activation results in downstream activation of NF-kB and JNK [55, 56]. Fukushima et al. found that IL-1β has a stimulatory effect on osteoclast formation via increasing expression of RANKL [57]. IL-1β, like TNF-α and IL-6, is produced by stromal cells and monocytes. These

). Magnetic resonance imaging (MRI) was obtained at T0

debatable. Thus, the underlying mechanism of action is still unclear.

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

complications for at least 4 years [47].

), after 30 sessions (T2

• HBOT reduced pain symptoms in all patients.

(RANKL) levels did not change.

changes proposed after HBO.

**7. New perspectives**

sessions (T1

tocol, after 60 sessions (T4

The findings were:

patients.

Gerardo Bosco1 \*, Alex Rizzato1 , Giuliano Vezzani1 , Vincenzo Zanon1 and Enrico Camporesi2

\*Address all correspondence to: gerardo.bosco@unipd.it

1 Master Level II in Diving and Hyperbaric Medicine and Physiological Lab, Department of Biomedical Sciences, University of Padova, Padova, Italy

2 Anesthesia, Tampa General Hospital, TEAM Health, Tampa, Florida, USA
