Fondazione Ospedale “San Camillo-Forlanini” - Roma

Giovanni Minisola

Osimo, 13 settembre 2019

OSTEOPOROSI E ARTROSI

CONVERGENTI O DIVERGENTI?

Direttore Scientifico

CONFLITTI D’INTERESSE

• Nessuno

BMD NELL’OP E NELL’OA

• Correlazione inversa tra OPe BMD

• Correlazione diretta tra OAe BMD

• Fattori confondenti:– presenza di osteofiti

– entesofiti

– HBM (dimensioni dell’osso)

– BMI

• Vari subset di OAe OP

• 140 patients with upper femoral fractures and 100cases of OAof the hip have been studied.

• This study shows:• most patients who suffer fromOA of the hip joint have

a (metacarpal) bone density that is greater than normalfor their age

• an association between fracture of the upper end of thefemur and OP

• OA of the hip is hardly ever found in OP patients

0

10

20

30

40

1 2 3 4

PREVALENCE OF RADIOGRAPHIC KNEE OA AMONG 473 WOMEN IN THE FRAMINGHAM STUDY ACCORDING TO AGE-SPECIFIC

QUARTILES OF FEMORAL NECK BMD

Low High

FN BMD quartiles

Rad

iog

rap

hic

knee

OA

Pre

vale

nce

(%

)

Zhang Y et al. J Rheumatol 2000; 27: 1032-7

• This twin study confirms the existence of aninverse relationship between OAand OPatthe hip.

• The inverse relationship was localized to theOA-affected hip.

• There is overwhelming evidence that OAcases have increased

BMD or BMC at all sites.

• This increased BMDis related to high peak bone mass, as

shown in mother-daughter studies.

• With aging, the bone loss in OAis lower, except when

measured near an affected joint (hand, hip, knee).

• The lower degree of bone loss with aging in OAis explained

by lower bone turnover.

ODDS RATIO FOR HAVING OA IN DIFFERENT JOINTS OF 27 4

INDIVIDUALS ACCORDING TO DIFFERENT BIOPARAMETERS

Karlsson MK et al. Open Orthop J 2014; 8: 450-6

• OP occurs worldwide in 20-32% of patients with advanced OA.

• Because of clinical implications of OP in patients being

managed for OA, it is important to identify and refer for OP

evaluation those patients at risk.

• A subset of OApatients with advanced age and lowBMI may

have lowbone density at non-OAsites and if left untreated may

be at risk of fragility fracture.

BMI E SINDROME METABOLICA NELL’OP E NELL’OA

• Un basso BMI è considerato un fattore di rischio per OPe per complicanze fratturative correlate.

• Un alto BMI è considerato un fattore di rischio per OAeun fattore protettivo rispetto a fratture da fragilità.

• Nelle donne in PMe negli uomini adulti un alto BMI(obesità) è fattore protettivo per fratture di bacino efemore.

• Gli studi sui rapporti intercorrenti tra OP e SMhannodato risultanti contrastanti e non definitivi.

• Nei soggetti con OAè frequente l’associazione con SM.

GENETIC BACKGROUND

• Both OP and OAhave a considerable hereditary component

• Both OP and OAare considered polygenic diseases

• Size and shape of the femoral head and femoral neck are

related to genetic influences in both OP and OA

• Genetics play a role in the age of development of both OP

and OA

THE BASIS OF CROSSTALK IN EARLY AND LATE STAGES OF OA

“BONE MARROW LESIONS”

• Sono associate a varie condizioni (traumi, neoplasie, OA, artropatieinfiammatorie, neoplasie, infezioni, ischemia, malattie metaboliche,endocrinopatie, infezioni).

• Sono aree circoscritte che appaiono chiare e luminose (ipodense)nelle sequenze RMNfluido-sensibili (T2 pesate) e grigio-opache(iperdense) nelle sequenze grasso-sensibili (T1 pesate).

• Dipendono da inadeguata riparazione di una zona circoscrittadell’osso subcondrale a causa di eccessivo stress meccanico e/oinfiammazione e/o ischemia (per aumento della necrosi adipocitariae/o ipertensione del microcircolo e/o aumento dello spessore dellaparete vasale).

• Rappresentano una risposta (flogistica?) dell’osso localizzata eprecoce in una fase iniziale dell’OA.

• Sono associate a progressione dell’OAe a dolore.• Solitamente le biopsie delle BML in corso di OAnon mostrano

segni di edema ma piuttosto segni di elevato turnover osseo e ditentativi di riparazione.

CARTILAGE AND SUBCHONDRAL BONE CHANGES IN OA AND OP

Geusens PP et al. Curr Opin Rheumatol 2016; 28: 97-103

THE ROLE OF INFLAMMATION

• Local and systemic inflammation is a risk factor for both OP andOA.

• The risk of local and systemic bone loss (and fracture risk) isincreased in inflammatory rheumatic diseases and other chronic(inflammatory) conditions, such as the metabolic syndrome.

• In hand OA, systemic and local inflammation are associated withthe development of bone erosions.

• In knee (and hip) OA, different patterns of local synovitis can befound, with variable correlation with the degree of inflammationand pain.

A relevant mechanism for the (increased) fracture risk in OAand OP involves the role of systemic and local inflammation.

AGE-ADJUSTED RELATIVE RISK FOR HIP FRACTURE

IN PATIENTS WITH OA (The MEDOS study)

Dequeker J, Johnell O. Bone 1993; 14 Suppl 1: S51-6

CONCLUSIONS. These findings seemto confirm earlierobservations that OAand OP are two distinct diseases andnot phenomena related solely to aging.

Parameters All Women Men

n 7,539 5,584 1,950

RR 0.64 0.68 0.48

ASSOCIATION OF RADIOGRAPHIC OA OF THE KNEE WITH

VERTEBRAL AND NONVERTEBRAL FRACTURES (2773 ELDERLY PATIENTS FROM THE ROTTERDAM STUDY)

Bergink AP et al. Arthritis Rheum 2003; 49: 648-57

Castaño-Betancourt MC et al. Bone 2013; 57: 284-9

MALE SUBJECTS WITH LUMBAR DISC DEGENERATION HAVE A HIGHER OSTEOPOROTIC FRACTURE RISK IN SPITE OF HIGHER BMD

(

Bolland MJ et al.Lancet Diabetes Endocrinol 2018; 6: 847-58.

Our findings (froma systematic review) suggest thatvitamin D supplementation does not prevent fracturesor falls, or have clinically meaningful effects onBMD.

OP AND VITAMIN D SUPPLEMENTATION

Bischoff-Ferrari HA . Dtsch Med Wochenschr.2019; 144: 1018-21.

Based on our critical reviewof the meta-analyses onvitamin D and fracture prevention, vitamin Dsupplementation with or without calciumis stilluseful in older adults, aged 65 and older, with anincreased risk of vitamin D deficiency and anincreased risk of fracture.

VITAMINA D E OA

• La presenza del VDRè stata dimostrata neicondrociti di cartilagine artrosica ma non inquelli di cartilagine sana.

• L’1,25(OH)2D è implicata nella regolazionedelle MMPs 1, 3 e 13 e nella sintesi deiproteoglicani.

• Non c’è un razionale che possa spiegare uneventuale effetto antidolorifico della vitamina D.

• È verosimile un’effetto favorevole sull’ossosubcondrale.

OPINIONE PERSONALE

• Anche se l’effetto antifratturativo della vitamina D è

(probabilmente) modesto, i soggetti con OP/OAe

con deficit (accertato o verosimile) possono trarre

beneficio da una correzione terapeutica

economicamente poco onerosa.

• Vanno evitate le dosi molto elevate e molto

distanziate.

• Spesso è necessario prevedere anche un programma

di rinforzo muscolare personalizzato.

ConclusionsOur analysis showed that BPs neither provide symptomaticrelief nor defer radiographic progression in knee OA. However,these agents may still be beneficial in certain subsets of patientswho display high rates of subchondral bone turnover. Futurestudies should be directed at defining such OAsubsets andinvestigating the effects of BPs in those patients. BPs displayedgood tolerability, with no statistically significant differences inAE outcomes vs placebo.

Lems WF. Ann Rheum Dis 2018 Sep; 77: 1247-8

Conclusions.Two comparable and high-quality studies(FuSH et al. J Bone Joint Surg Am 2017; 99: 938-46 - Neogi T et al. AnnRheum Dis 2018; 77: 92-7) have documented and suggestedthat BP use is associated with a 25% reduction in KRs.Since KRis a clinically relevant and hard endpoint, thesestudies hopefully might stimulate further research in therole of subchondral bone in OA, which is still urgentlyneeded given the paucity of therapeutic options in OA.

INTRAVENOUS NERIDRONATE IN THE TREATMENT OF ACUTE P AINFUL KNEE OSTEOARTHRITIS: A RANDOMIZED CONTROLLED STUDY

Pain trend at baseline and afterneridronate treatment or placebo.

Varenna M et al. Rheumatology 2015; 54: 1826-32

CONCLUSIONS

• The pathophysiology of OP and OAdepends on acomplex interaction of BMD, BMI, falls, genetics andinflammation.

• Classical epidemiological data indicate that OP and OAare inversely related.

• (Recent) epidemiological data indicate that OP and OAshare some common mechanisms and can coexist.

• Subchondral bone changes and cartilage/bone interactionsplay a crucial role in the pathogenesis of OA.

• Treatment should be personalized and should take intoaccount the heterogeneous nature and the stage of bothconditions (early, late, severe).