RAZIONALE DEL TRATTAMENTO FARMACOLOGICO DA ASSOCIARE AD UN IMPIANTO DA REVISIONE Paolo Sirtori, Rashwan Gogue*, Riccardo Cecchinato e Gianfranco Fraschini This tolk concerning our esperience in resurfacin procedures IRCCS Ospedale San Raffaele Milano U.O. Ortopedia e Traumatologia *Scuola di Specializzazione di Ortopedia Perugia

Total Hip Arthroplasty Failure Malchau H, Herberts P, Ahnfelt L. Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 1978-1990. Acta Orthop Scand 1993;64(5):497-506 2

Total Hip Arthroplasty Failure Prosthetic Dislocation (2%)

Total Hip Arthroplasty Failure Periprosthetic Fractures (< 2%) 4

Total Hip Arthroplasty Failure Infections (10%)

Total Hip Arthroplasty Failure Fatigue Breakage (<2%) 6

Total Hip Arthroplasty Failure Aseptic Loosening (79%) Malchau H, Herberts P, Ahnfelt L. Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 1978-1990. Acta Orthop Scand 1993;64(5):497-506 7

FIRST ACETABULAR IMPLANT’S SURVIVAL (Baker 2009 - Clin Orth Rel Resear) (69 pz) 88.8% to 15 years 8

FIRST ACETABULAR IMPLANT’S SURVIVAL (Clarius 2009 – Int. Orthop.) (127 pz) 75% to 17 years 9

FIRST ACETABULAR AND FEMORAL UNCEMENTED IMPLANT’S SURVIVAL YOUNG SUBJECTS (< 50 ANNI) (Kearns 2006 - Clin Orth Rel Resea) (221 pz) ACETABULAR CUP FEMORAL STEM 98.7% to 5 years 84.6% to 10 years 52.5% to 15 years 98.7% to 5 years 84.6% to 10 years 52.5% to 15 years 99.3% to 5 years 98.9% to 10 years 96.8% to 15 years 10

EARLY FAILURE IN TOTAL HIP ARTHROPLASTY (Dobzyniak M. G. 2006 – Clin Orthop Rel Res) (824 pz) 35 % of revision were performed during the first 5 years

CAUSES OF FAILURES in THA Absence of primary stability Implant instability Infections Painful THA/ discrepancy in leg lengthening Periprosthetic fractures Aseptic bone loosening HARRIS 2006 - Clin Orth Rel Resear HOPLIN 2008 – RadioGraphics 12

MOST FREQUENT CAUSE OF FAILURES IN THA Aseptic Bone Loosening The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene 13

Aseptic Bone Loosening FAILURES IN THA Aseptic Bone Loosening Multifactorial etiology Aging and systemic bone loss Adaptive bone remodeling or stress shielding Individual cellular response to wear debries Bone metabolic status The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene SUNDFELDT 2006 – Acta Orthopaedica 14

Aseptic Bone Loosening Aseptic Bone Loosening FAILURES IN THA FAILURES IN THA Aseptic Bone Loosening Aseptic Bone Loosening Multifactorial events those lead to mid and long term failures, secondary to……. The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene Absence of osteo-integration Lost of osteo-integration 15

Come è fallito il primo impianto fallirà anche la revisione?!! La qualità dell’osso in una revisione è più scadente!?! Come è fallito il primo impianto fallirà anche la revisione?!! Quali fattori devo considerare per affrontare bene una revisione?!!

Revision for Aseptic Bone Loosening Extrinsic Factors Implant typology Bone graft Coating The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene 17

Revision for Aseptic Bone Loosening Intrinsic Factors Bone Metabolic Alterations Osteoporosis/Osteopenia Genetic Predisposal The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene 18

ORA TI MOSTRO I FATTORI ESTRINSECI PREFERISCO BERE LA MIA BIRRA

THA REVISION – EXTRINSIC FACTORS IMPLANT TYPOLOGY Optimal stability of revision socket device Good proximal encourage with wings and screws Good osteo-conductive surface Good distal encourage with obturatoris hook 20

Trabecular Metal Modular Augmentation THA REVISION IMPLANT TYPOLOGY Trabecular Metal Modular Augmentation 21

THA REVISION – EXTRINSIC FACTORS IMPLANT TYPOLOGY 22

THA REVISION - EXTRINSIC FACTORS BONE GRAFTS Bone Allograft integration Morsellised Chips – Optimal Shape (2x2x4 mm) Bone Allograft 23

THA REVISION - EXTRINSIC FACTORS BONE GRAFTS Morsellised chips to fill the cavity; They posses osteoconductive and limited osteoinductive properties. Hypothetical use of osteoinductive factors like PRP or stem cells. 24

THA REVISION - EXTRINSIC FACTORS BONE GRAFTS Synthetic bone graft substitutes Bone substitutes calcium/phosphate + Mg Macro e micro porosity Osteoconductive capabiility 25

ORA TI MOSTRO I FATTORI INTRINSECI NON HO ANCORA TERMINATO DI BERE LA BIRRA

THA REVISIONS (Intrinsic Factors) Bone Metabolic Alterations 43% 21% 36% Vitamin D active metabolite: 25 OH D3 Hypo and Deficiency of Vitamin D3 27

THA REVISIONS (Intrinsic Factors) Bone Metabolic Alterations 4% 84% 5% 7% Parathyroid Hormones: PTH vs Ca++ Hyperparathyroidism 28

Bone Metabolic Alterations THA REVISIONS (Intrinsic Factors) Bone Metabolic Alterations (n=62) 66% 44% Index of osteoblast activity BGP 65% 35% Index of osteoclast activity D-Pyr Higth bone turnover and uncopling of bone remodeling 29

THA REVISIONS (Intrinsic Factors) Osteoporosis (n=62) 82% 18% Vertebral BMD 75% 25% Femoral BMD (neck) Osteoporosis has been releved in interesting amount of subjects, with prevalence in femoral site. 30

THA REVISIONS (Intrinsic Factors) Genetic Predisposal Polymorphism in metalloproteases MMP-1 and interleuchin IL-6 Gender-dependent role of the T393C polymorphism in aseptic loosening “Calcium Sensing Receptor” unspecific alterations 1) Malik MHA; Ann Rhem Dis 2007 2) Godoy Santos AL; J Arthroplasty 2009 3) Bachmann HS; J Orthopaedic Research 2008 4) Gallo J; BMC Medical Genetics 2009 31

THA REVISIONS (Intrinsic Factors) Genetic Predisposal Calcium-Sensing Receptor (CaSR) PARATHYROIDS regulation in PTH secretion THYROID regulation in Calcitonin secretion KIDNEY riduced the phosphaturic activity of PTH BONE inibizione osteoclastica 32

THA REVISIONS (Intrinsic Factors) Genetic Predisposal PTH suppression test (CaSR) in hip fracture subjects Secondary Hyperparthyroidism due to unspecific alterations in CaSR Secondary Hyperparthyroidism due to hyocalcemia P<0.005 33

Factors should be considered in revision surgery of THA Extrinsic Factors Implant typology Bone graft Coating Bone Mineral Metabolism Alterations; Osteoporosis Intrinsic Factors Genetic Factors Polymorphism in metalloprotease MMP-1 Gender-dependent T393C polymorphism Calcium Sensing Receptor unspecific alterations 34

Stress meccanico dell’impianto sulla struttura ossea accettante Fattori intrinseci coinvolti nel fallimento di una revisione di artroprotesi di anca Iperparatiroidismo Microparticelle di materiale proveniente dall’usura delle componenti protesiche Stress meccanico dell’impianto sulla struttura ossea accettante Attivazione OC Deficienza di Vit D Inibizione OB Fallimento della REVISIONE Difetto di integrazione protesica Riassorbimento periprotesico Osteoporosi Diminuito “Bone Stock”

il metabolismo minerale e di trattare il paziente Ricordati di valutare il metabolismo minerale e di trattare il paziente Domani farò una revisione di anca

Evaluation of Bone Metabolic Alterations THA REVISIONS (Intrinsic Factors) Evaluation of Bone Metabolic Alterations Biochemical Index of Bone Metabolism Calcio ionico serico (Ca2+ ) Vitamina D (25OHD) Paratormone (PTH) Biochemical Index of Bone Remodeling Osteocalcina (BGP) Lisilpiridinolina urinaria (D-Pyr) The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene 37

THA REVISIONS (Intrinsic Factors) Evaluation of Bone Mineral Density MOC - DXA scan Lumbar site Femoral site The hip resurfacing’s past was a disaster…. Because of the materials …………olso metal when coupled with polythylene 38

il rimodellamento osseo Attivare Deprimere Modulare il rimodellamento osseo Mesenchymal stem cell Hematopoetic stem cell Stromal cell macrophage Adipocyte Pre-osteoblast Osteoblast Pre-osteoclast Lining cell Osteocyte Osteoclast

1) ATTIVARE 1,25 (OH)2 - Vitamin D (+) Promotes differentiation of Mesenchymal stem cell Hematopoetic stem cell 1) ATTIVARE Stromal cell 1,25 (OH)2 - Vitamin D macrophage (+) Adipocyte Promotes differentiation of osteoblast and osteoclast precursors Pre-osteoblast Osteoblast Pre-osteoclast Lining cell Osteocyte Osteoclast

2) DEPRIMERE Bisphosphonates (-) Inhibits pre-osteoclast (-) Mesenchymal stem cell Hematopoetic stem cell 2) DEPRIMERE Stromal cell Bisphosphonates macrophage (-) Inhibits pre-osteoclast (-) Inhibits osteoclast function Adipocyte Pre-osteoblast Osteoblast Pre-osteoclast Lining cell Osteocyte Osteoclast

MODULARE Strontium-R (+) Increases expression of RANK-L + OPG (-) Mesenchymal stem cell Hematopoetic stem cell MODULARE Stromal cell Strontium-R macrophage (-) Inhibits osteoclast function (+) Increases expression of RANK-L + OPG Adipocyte Pre-osteoblast Osteoblast Pre-osteoclast Lining cell Osteocyte Osteoclast

Lo Stronzio è un modulatore del turnover osseo a vantaggio della attività osteoblastica Ranelato di Stronzio Osteoblasta Osteoclasta CaSrRan Replicazione1 RANKL expression2 Apoptosi4 Differenziazione5 Sopravvivenza3 Voici en résumé l’ensemble des effets de PROTELOS sur les OB impliquant le CaSrRan. Afin de compléter ces résultats, il serait intéressant d’étudier si les effets induits par PROTELOS, l’augmentation de la quantité d’IGF-1 aux niveaux osseux et circulant et l’augmentation de la survie des OB, sont liés et et impliquent le CaSrRan comme démontré récemment par l’équipe de Shoback. Espressione di OPG & RANKL2 (4) Hurtel et al, J Biol Chem 2009 (5) Hurtel et al, submitted (1) Chattopadyay et al, Biochem Pharmacol 2007 (2) Brennan et al, Br J Pharmacol 2009 (3) Fromingué et al, JCMM 2009

ALLO SCOPO DI FACILITARE LA OSTEOINTEGRAZIONE DEL NUOVO IMPIANTO TRATTAMENTO FARMACOLOGICO DA ASSOCIARE AD UN IMPIANTO DA REVISIONE (ADM) Attivazione del rimodellamento osseo con: 1,25(OH)2 D3 Depressione della attività osteoclastica con: DIFOSFONATI Modulazione del rimodellamento osseo sbilanciandolo a favore della attività osteoblastica con: R. di STRONZIO ALLO SCOPO DI FACILITARE LA OSTEOINTEGRAZIONE DEL NUOVO IMPIANTO 44

MODALITA’ DI TRATTAMENTO (ADM) Attivazione: ROCALTROL 0.5 µg/die per 30 gg. Depressione: ALENDRONATO/RISENDRONATO (70 o 35 mg/ sett) per 6 mesi. Modulazione: RANELATO di STRONZIO 2g/die per 6 mesi NB: mantenere adeguato apporto del metabolita 25OHD durante la fase D e M 45

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