OSTEOPOROSI E DOLORE OSSEO: MECCANISMI E TRATTAMENTO FARMACOLOGICO: Prof. Davide Gatti - MuseiOn

Prof. Davide Gatti
                        OSTEOPOROSI E DOLORE OSSEO:
UOC di Reumatologia            MECCANISMI
Università di Verona                 E
                       TRATTAMENTO FARMACOLOGICO:

CON ETA’        CON ETA’
CALA       MA
                NON SI RIDUCONO
L’OSSO          LE FIBRE NERVOSE
                SENSITIVE

Sistema                              Sistema
                     Allarme                            Maladattativo
                    vs danno                             patologico

                   DOLORE                                DOLORE
                   ACUTO                                 CRONICO

                   FLOGOSI

Modificato e tratto da :
JI RR ET AL
NEUROINFLAMMATION AND CENTRAL SENSITIZATION IN CHRONIC AND WIDESPREAD PAIN. ANESTHESIOLOGY. 2018

DOLORE ACUTO LOCALIZZATO

                 DOLORE DIFFUSO

               DOLORE CRONICO

Understanding osteoporotic pain and its pharmacological treatment:
Vellucci et al. Osteoporos Int 2018

A new definition for neuropathic pain

The new definition is                                 The older definition was

PAIN                                                  PAIN
CAUSED BY                                             INITIATED OR CAUSED BY
LESION,                                               PRIMARY LESION,
DISEASE                                               DYSFUNCTION,
OF THE SOMATOSENSORY                                  TRANSITORY PERTURBATION
NERVOUS SYSTEM.                                       OF THE PERIPHERAL OR
                                                      CENTRAL NERVOUS SYSTEM’.

- the term dysfunction was thought to be over-inclusive and did not reflect the
  pathophysiology.
- Neuropathic pain is a number of diseases or lesions with a cluster of symptoms and signs,
  where understanding of pathophysiology is evolving

Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, et al.
A new definition of neuropathic pain. Pain 2011;152:2204-5.
International Association for the Study of Pain. IASP
Taxonomy. Pain terms. Neuropathic pain. Updated 2017 Dec 14.
www.iasp-pain.org/Taxonomy#Neuropathicpain [cited 2018 May 1]

NEUROINFIAMMAZIONE

Sprouting and formation of neuroma-like
      structures in chronic bone pain

CGRP+ sensory fibers   Sprouting and neuroma-like structures
  in normal bone              in cancer-induced bone
                                      Mantyh PW. Eur J Neurosci, 2014

Ab anti-NGF counteract bone marrow
         CGRP+ fibers sprouting

Bone marrow CGRP+ fibers in      Bone marrow CGRP+ fibers in
   cancer-induced bone        cancer-induced bone after anti-NGF

                                         Denk F et al. Ann Rev Neurosci, 2017

NGF binds to receptors (TrkA), promoting multiple pain signaling pathways, leading to nociceptive pain.

                                                                            CGRP = calcitonin gene-related peptide
                                                                            SP,= substance P
                                                                            TRPV1= transient receptor potential vanilloid receptor 1
                                                                            ASIC= acid-sensing ion channel;
                                                                            TrkA= tropomyosin receptor kinase A

Xiushuai Shang et al. Therapeutics and Clinical Risk Management 2017:13 951–956

Sensory nerve fibers
  expressing TrkA

Futuro: blocco NGF ??

ANTINFIAMMATORI

 PARAC.+CODEINA

ANALGESICI CENTRALI

NNT: 4,5

  Terapia
analgesica!

Nei primi 6 mesi RR= 2,78 p

Futuro: blocco NGF ??

        ?
ANTINFIAMMATORI
                                    ?
                         Qualche settimana/mese
 PARAC.+CODEINA
                         Terapia cronica

ANALGESICI CENTRALI

5 euro
10 pastiglie
 da 200mg
     =
 2000 mg

NSAIDs /selective COX-2 inhibitors are effective in bone pain
but have limitations in their dosage and duration of treatment due
to adverse events

Osteoporosis affects elderly with cardiovascular disease and age-
related decline in renal function, also taking multiple medications

13 RCTs
                   5366 pazienti

                       PROBABLY
 -3 % vs Placebo         SAFY

                        PROBABLY
                       INEFECTIVE

-4% vs Placebo

Codeine
Metabolism
 Pathway

 INTERAZIONI FARMACOLOGICHE !!
      VARIABILITA’ GENETICA
                
 AUMENTO EFFETTI COLLATERALI !!
      RIDUZIONE EFFICACIA !!

                                  Racoosin et al, N Engl J Med 368;23 June 6, 2013

 Comunicato AIFA 29/07/2013 - Misura Restrittiva EMA/249413/2015
  I farmaci contenenti codeina non devono essere somministrati a persone di ogni età
   note per essere metabolizzatori CYP2D6 ultra-rapidi
  Devono essere usati alla dose minima efficace, per il più breve periodo di tempo

Tramadolo

  INTERAZIONI FARMACOLOGICHE !!
       VARIABILITA’ GENETICA
                 
  AUMENTO EFFETTI COLLATERALI !!
       RIDUZIONE EFFICACIA !!

10% ca

Analgesici e oppioidi: tollerabilità
Effetti collaterali                             Strategia
                       Switch
Nausea e vomito        Antiemetici
                       Abbassare la dose
Sedazione
                       Aggiungere farmaci non oppioidi
                       Switch
Costipazione           Trattare con farmaci favorenti il transito
                       Switch
Prurito
                       Anti-istaminici
                       Switch
Calo della libido      Monitoraggio testosterone
                       Consulto endocrinologo
Edema                  Switch
                       Switch
Confusione
                       Titolazione di dose

Associazione più tollerata
          Associazione più efficace
p

…

                                Pain
                              Intensity   terapia più tollerata
                                          terapia più efficace

                                                             p

Molti pazienti con fratture osteoporotiche possono essere pauci-sintomatici

Il dolore acuto da frattura  nocicettivo  neuroplastico  cronico

           I farmaci attuali ci permettono di gestire
               adeguatamente queste condizioni

                                    TRATTARE
                                       IL
                                    DOLORE