Ramesh Sen AVN

AVASCULAR NECROSIS FEMUR HEAD new experiments

Ramesh K Sen MS, DNB Ortho, PhD

Professor, Department of Orthopedics

Postgraduate Institute of Medical Education and Research CHANDIGARH, INDIA

AVASCULAR NECROSIS FEMUR HEAD-EXPERIMENTS

• Diagnostic experiments

• Medical management

• Surgical salvage femur head

• Surgical nonsalvage options

AVN- MRI DIAGNOSIS

MRI T1 Image • signal from ischemic marrow

• Single band like area of low signal intensity.

• 100% sensitivity,98% specificity

MRI - T2 image • Double Line sign

• 2nd high signal intensity within the line seen on T1 images.

• Represents hyper vascular granulation tissue

MRI IN DIAGNOSIS OF AVN

Results of a rapid screening protocol (imaging

time<1 minute) similar to those of the routine protocol (an imaging time >7 minutes) for patients

99% sensitive, 98% specific

May DA, Disler DG. Screening for avascular necrosis of the hip with rapid MRI: preliminary experience. J Comput Assist Tomogr.;24:284-7. 2000

MRI EVALUATION POST HIP DISLOCATION WITH DELAYED

RELOCATION MRI EVALUATION TIME (WEEKS AFTER INJURY)

6

5 4 3 2 1 0

1 3 5 7 9 11131517192123NORMAL

AVN NUMBER OF WEEKS

Total 13/30 patients showed AVN changes, In 6 patients spotaneous slow resolution in 2 months

HOW EARLY AVN CAN BE DIAGNOSED ON MRI ?

• Traumatic hip dislocation, serial MRI in 14 patients from injury through 24 months, 5 hips transient within 3 months—4 improved,

3 hips Changes progressed to AVN

Not reliable in first week after injury for ischaemia. MRI reliable for AVN marrow changes in 4-6 weeks Poggi JJ, et al Clin Orthop. Oct;(319):249-59 1995

ISOTOPE SCANNING OF AVN

With SPECT scanning, the presence of cold spot is indicative of AVN but diagnostic

sensitivity is 58% & specificity is 78% (Steinberg ME et al 2001)

18 F-Fluoride PET/CT in Avascular Necrosis of the Femoral Head

Shankalzunnrtht• Gavana. t1BBS,'` Anish Bhattachurrn, DRa1. DAR * Rag/iata Kas!tvap, MD. Ralnesh Ktanar Se n, RMS, PhD. and Bha,trant Rai Alittal.:11D. DNB*

REFERENCES Abstract: Avascular necrosis (AVN) of the femoral head is a devastating

disease in young adults. Magnetic resonance imaging is considered the most sensitive and specific technique in the diagnosis of'this condition. The authors

present an interesting image of'bilateral AVN of the femoral heads diagnosed on 1817-fluoride positron emission tomography/computed tomography.

Kes Vlords: "'F-fluoride, PET/CT, avascular necrosis, femur

(CYi,, Vucl died 2013.38: e265 e266)

0

1. Ohzono K, Saito M. Takaoka K, et al. Natural history ofnontraumatic avascular necrosis of the femoral head../ Bone Join Stag Br. 1991;73:68-72.

2. Mont MA, Fairbank AC, Petri M, et W. Core decompression for osteonecrosis of the femoral head in systemic lupus erythematosus. C lin Orthop Relit Rec. 1997; 334:91-97.

3. Smith S' Fehring TK, Griffin WL, et al. Core decompression of the osteo-necrotic femoral head../ Bone Joint Surg Ant. 1995;77:674-680.

4. Castro FP Jr, Harris MB. Differences in age. laterality, and Steinberg stage at initial presentation in patients with steroid-induced, alcohol-induced, and idio-

40

1r4p To

Oper Tech Orthop 15:273-279 © 2005

• Hip arthroscopy can help improve overall diagnostic accuracy and serve as a direct means of treatment or adjunct to the

application of more traditional techniques in avascular necrosis management.

Non-surgical Interventions in AVN

RESTRICTED WEIGHT BEARING

Meta-analysis of protected weight bearing in 819 patients demonstrated a failure rate of >80% at a mean of 34 months. conservative treatment of osteonecrosis femoral head by protected weight bearing is not appropriate.

Mont MA, Carbone JJ, Fairbank AC.

Clin Orthop Relat Res.;324:169-78. 1996

1997 early 1997 late 1998 2001

1997 1998 2001

Patient restricted activity & pain 2007

Opts for THR







PHARMACOLOGICAL AGENTS • Anabolic steroids

Stanozolol (6mg/day) decreases AVN symptoms at 1 year following treatment. Glueck et al. Am J Hematol.;48:213-20. 1995

• Enoxaparin

On 60 mg/day for 12 weeks, 89% did not require surgery Glueck et al CORR;435:164-70 2005

• Iloprost - prostacyclin derivative

a vasodilator, usedul in AVN FH & BMES. Disch et al,J Bone Joint Surg Br.;87:560-4. 2005

• Hyperoxygenation mediated relief of ischaemia enhances the fibroblastic, angioblastic and osteoclastic activities

• After RPMF treatment, osteogenesis regeneration of necrotic femoral head markedly improved (micro-CT). • RPMF could affect various critical aspects in the

course of femoral head necrosis, a promising measure in the treatment of avn of femoral head, in the early stage.

• Surgery can be prevented/deferred in AVN.

• Improvement objective clinical assessments but also in radiological parameters.

• a trial of alendronate for all patients with early AVN of the hip, i.e. stages I and II and early stage III will be beneficial.


BISPHOSPHONATES Increased resorption contributes

to collapse of the femoral head.

Alendronate Inhibits osteoclast activity & thus curtail bone

Experimental studies: resorption.Tagil et al. in rats Acta Orthop Scand.; 75:756-61. 2004 Bowers et al. in canines. J Surg Orthop Adv.;13:210-6. 2004 Kimet al, in immature pigs. J B J S Am.;87:550-7, 2005.

Clinical studies: Lai et al, J Bone Joint Surg Am.;87:2155-9. 2005

• ESWT and alendronate produced comparable result as compared with ESWT without alendronate in early ONFH. ESWT is effective with or without the concurrent use of alendronate.






ARCO meeting Chicago March 2013

Surgical Interventions in AVN CORE DECOMPRESSION

Meta-analysis of CD in 1206 hips in 24 studies

84% Ficat-I & 65% Stage-II had successful result.

22 studies: success rate of CD significantly higher than that of conservative treatment for early-stage disease

(p < 0.05)

Castro FP Jr, Barrack RL.. Am J Orthop.;29:187-94. 2000

CD USING PERCUTANEOUS MULTIPLE SMALL-DIAMETER DRILLING

• Multiple small drillings with a 3-mm Steinman pin to effectuate the core decompression.

Successful outcomes in:

• 24/30 Stage I hips (80%;23 patients) had

• 8/15 Stage II hips (57%; 12 patients)

Mont MA et al Clin Orthop Relat Res. Dec;(429):131-8, 2004

CORE DECOMPRESSION WITH BMP

Partially purified human BMP combined with allogeneic antigen-extracted autolyzed human bone and introduced CD.

At a mean of 53 months, 14/17 hips showed a clinical success, with HHS of >80 points and no patient requiring conversion to a total hip replacement.

Lieberman JR, Conduah A, Urist MR. Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic

protein. Clin Orthop Relat Res.;429:139-45. 2004

GROWTH FACTORS & GENE THERAPY

• vascular endothelial growth factor (VEGF) stimulate angiogenesis and promotes healing.

• use of a recombinant plasmid pCD-hVEGF165 mixed with collagen for the treatment of an animal model of osteonecrosis

new bone was observed in the channel of the drill hole and on the surface of the dead trabeculae.

CORE DECOMPRESSION BONE MARROW AUGMENTATION

Marrow contains

BMP+

Angiogenic factors.

BONE MARROW osteoblast progenitor cells from pluri-potential connective-tissue stem cells proliferate to form colonies that express AKP & subsequently, a mature osteoblastic phenotype

Since bone marrow contains progenitor cells it may be

associated to core decompression.

It is a simple and easy adjuvant to core decompression.

In 2003 …..DR PR…

48 years male with Fracture Dislocation hip in MVA, reduction in 2 hours but got MRI at 8 weeks after injury

P R- 8 years FU in 2011

AUTOLOGUS BONE MARROW GRAFTING OF AVN

• Hernigou et al (2000, 2002, 2004, 2005) Experience of 189 hips.

No control group, surgical technique variable.

Gangii V et al JBJS Am. Jun; 86-A(6):1153-60 2004 Experience of BMSC+CD in 10 AVN hips, compared 8 controls with CD.

BONE MARROW STEM CELL CONC.

•Total 100-180 mL marrow (100 ml Unilateral and 180 for Bilateral Hip AVN patients)

1. Ficoll layering on marrow in 1:3 ratio 2. Centrifuged at speed 400/m for 30 min. at 250C. 3. Plasma layer aspirated, discarded 4. BMSC into another sterile tube + PBS buffer 5. Washed thrice re-suspension in 2.5 ml buffer.

BMSC content : mononuclear stem cells + monocytes, lymphocytes, PMNs

(MNC count with CD34+ more than 5X107 )

NON-TRAUMATIC AVN MANAGEMENT CD+BMSC

Idiopathic bil. AVN with 3 months painful hip & restricted hip ROM

E. FU after 18 months of CD+BMSC, MRI lesion in healing phase, no edema or effusion

After 6 years FU in 2011

51 AVNFH randomly divided. group A (25) treated with CD, group B (26) received autologous BMMNC instillation after CD. Outcome compared clinically (HHS), x-ray and MRI, & by Kaplan-Meier hip survival analysis at 12 & 24 months FU

• Clinical score & mean hip survival better in group B than in group A (p<0.05).

BMSC AFFECT AVN HIP ?

Hernigou et al (2005) Instillation of MNC into the necrotic area in AVN enhances vascularization and the oxygen flow to the ischemic tissues

Tzaribachev et al (2008) autologous MSCs could potentially complement AVN treatment by adding fresh "osteogenic cells" to the healing process.

• case of a patient with bilateral osteonecrosis of the femoral head treated with autologous cultured osteoblast injection. • Experience is limited to one patient, autologous cultured osteoblast transplantation appears to be effective for treating the osteonecrosis of femoral head.

CD+ CULTURED OSTEOBLASTS instillation

Biol Bloril.1 Grr•ro;:• 7i•rnn'yhnrt 14: 1081- 1087 (?O/)S) ) 0('M' .-l merica,, Society for Blood ,n►d .11rn•ro 7 rurr+pLiit rti ;� � i

REVIEW

Cell-Based Therapies for Osteonecrosis of the FemoralHead

CeI Iular- Based Therapy B. Jones, 1'3 Tara Seshadri,2'3 Roselynn Krantz,2 Armand Keating, 2,3 Peter C. Ferguson 1'3

for Osteonecrosis

Valerie Gangji, MD, PhDa•*, Jean-Philippe Hauzeur, MD, PhDb

KEYWORDS

• Osteonecrosis • Bone marrow • Stem cell • Cellular therapy

CORE DECOMPRESSION WITH MARROW STEM CELLS

0-I LI==E HERN GC.,, MD CL `e FP. `,IAN -CM. L'D. A_EXANDRE -OISNARD. P.O. ALEXIS NOGIER. MD. nACLO FlLIR?INl. MC. and LID A CE ABR MD

Treatment of Osteonecrosis of the Femoral Head with Implantation of

Autologous Bone-MIarrow Cells V'ale:ie Craaj3 and :ear-?_:ippe Hauzeur j Bone join Surg. Am. 8-.106-111.2005. do::102106 JBJS.D.02662

hoN . ■ ASPECTS OF CURRENT MANAGEMENT

� „• The use of percutaneous

autologous bone marrow

transplantation in nonunion and

avascular necrosis of boneP. Hcmigou, Bone marow and orthopaedic surgery Burwell' showed that primitive ostcogcni.A. Poignard. During the development of normal bone in the cells in bone marrow are responsible for much0. Manicom, young child, osteoblasts and then haematopoi- of the biological efficacy of cancdloua bone

BMSCs-seeded BBM combined with rhBMP-2 are capable of improving the quantity and quality of new bones to grow in the subchondral defects of the

femoral head, and repairing early-stage osteonecrosis of the femoral head in rabbits.

• local application of traditional Chinese medicine, Danshen, the dried root of Salvia miltiorrhiza, promotes blood flow and resolves blood stasis. also provides mechanic buttress in the weight loading

• minimal invasion surgery for ischemic necrosis of the femoral head at Stages I, II and III of ARCO.

NON-VASCULARIZED IMPACTION BONE-GRAFTING

P.S.R. 9 yrs FU

At 18 months AVN on imaging

41 R Sen PPT

NON-VASCULARIZED BONE-GRAFTING

Removing osteonecrotic bone impacting autogenous cancellous bone grafts

Lateral approach Of 28 hips followed for a 42 months Of

18/20 hips survived, successful result (minimal pain) 70% no progression

Rijnen WH, Gardeniers JW, Buma P, Yamano K, Slooff TJ, Schreurs BW. Treatment of femoral head osteonecrosis using bone impaction grafting. Clin Orthop Relat

Res.;417:74-83. 2003

• successful in Ficat and Arlet stage-III

• osteonecrosis of the hip in patients with small- to medium-sized lesions.

LIGHT BULB PROCEDURE

2 years PO

At mean 4 years (range, 3-4.5 years), 18/21 hips clinically successful result (HHS>80 points , no additional procedures). Mont MA, Etienne G, Ragland PS. Outcome of non-vascularized bone grafting for

osteonecrosis of the femoral head. Clin Orthop Relat Res.;417:84-92. 2003

EXPANDABLE DRILLING SYSTEM& CURRETTAGE WITH BONE GRAFTING

FREE FIBULAR GRAFTING

• survival rate of 59% five years after surgery. • significant difference (p = 0.002) in survivorship, when using a clinical and radiological end-point, between the two grafts, in favour of the tibial autograft.

TRABECULAR METAL AVN INTERVENTION

metal tantalum (Trabecular Metal) that’s full of pores. The rod-shaped implant available in various lengths. has threads at the end of the rod away from the hip that screw into healthy bone on the outer edge of the

femur

QUADRATUS FEMORIS/TFL MUSCLE PEDICLE GRAFT

(FU >4 years)

• FU of 10 to 21.5 years Excellent & good results in Hospital for Special Surgery (HSS) score obtained in 100% of cases in Stage I, 92% in Stage II and 80.4% in stage III, with a survivorship of 91% in Stage II and 82% in Stage III cases.

VASCULARIZED FIBULAR GRAFTING

Vascularized fibula into osteonecrotic femur head

VASCULARIZED FIBULAR GRAFTING

11 YEARS FOLLOWUP

• 124 hips, mean FU , 13.9 years; Mean HHS improved from 72 to 88.

• Unchanged radiographs in 37 of 59 hips initially Stage II hips and 39 of 65 Stage III hips. Thirteen hips (13 patients) (10.5%) failed treatment and underwent total hip

arthroplasty.

VASCULARIZED ILIAC GRAFTING

• 35 operations pedicle iliac bone, 28 patients stage II

• 13/17 hips no collapse deep circumflex iliac pedicle bone graft indicated for stage 2 type C-1 necrosis,

Nagoya et al, Predictive factors for vascularized iliac bone graft for non-traumatic

osteonecrosis of the femoral head. J Orthop Sci.;9(6):566-70. 2004

BONE GRAFT + VASCULAR MUSCLE PEDICLE

INTER-TROCHANTERIC OSTEOTOMY

Angular osteotomies best results in young active patients not on corticosteroids,unilateral involvement

with a good preoperative ROM of hip, and a small lesion without collapse.

96% success at 3-26 years postoperatively

Mont et al (76%) a good or excellent result, and nine (24%) had a fair or poor result

TROCHANTERIC ROTATION OSTEOTOMY

• Sugioka rotation osteotomy delays hip degradation • patients with AVN Stage II disease.

may be a role in selected patients, difficult to perform and a high potential for morbidity,

including nonunion Results variable, with success

rates around 40%

Shannon BD, Trousdale RT. Femoral osteotomies for avascular necrosis of the

femoral head. Clin Orthop Relat Res.;418:34-40. 2004

OSTEOTOMY+VASCULARIZED GRAFT

•Conversion to endoprosavoided in all except one.

•For advanced and extensiveosteonecrosis of the femoral head, especially in young patients, to preserve the joint.

•Relatively complex procedure.

CEMENTATION OF FEMORAL HEAD

relying on the fact that the cartilage cells will survive because the articular cartilage is nourished by the synovial fluid

Ph. HERNIGOU, D. GOUTALLIER :, Ed. J. Arlet, B. Mazieres,

Springer Verlag, 353-355. 1990

CEMENTATION OF FEMORAL HEAD

Wood et al. treated 19 patients (20 hips) with open reduction augmented with methyl methacrylate cement and followed them for 6 months to 12 years. 3 patients had a conversion to a THR The long-term results of this procedure are unknown.

Wood ML, McDowell CM, Kerstetter TL, Kelley SS. Open reduction and cementation for femoral head fracture secondary to avascular necrosis: preliminary report. Iowa

Orthop J. 2000;20:17-23.





• Surgical non-salvage options

TOTAL HIP ARTHROPLASTY AVN vs. OA as Etiology

• Failure rate in AVN higher than OA group (33%);

1, Bilateral Occurrence of the disease with bilateral THA

2, Extensive bone necrosis

• Femoral component loosening more frequently in the ON (28%) than in the OA group (5%).

TOTAL HIP ARTHROPLASTY FOR OSTEONECROSIS

• Meta-analysis - Before 1990

• 83% survival

- After 1990 • 97% survival

• Second generation cementing techniques

• Proximally coated femoral stems

MANY CHOICES OF BEARINGS • Metal on polyethylene • Metal on highly cross linked polyethylene • Metal on metal • Ceramic on ceramic • Ceramic on metal • Ceramic on polyethylene

Which is better for osteonecrosis??

TOTAL HIP ARTHROPLASTY • Non cemented acetabular

component

• Porous-coated components

• THA reliable treatment for

- patients >45 years of age

- In patients with post-traumatic necrosis

SURFACE ARTHROPLASTY Resurfacing of the femoral head successful interim

procedure for Ficat and Arlet stage-III or early stage-IV disease

HUNGERFORD et al JBJS 80:1656-64 (1998)

PREVENTION OF AVN

STATIN THERAPY Patients on steroids on mean of 7.5 years

(minimum 5 years), also given lipid clearing agents that reduce lipid levels.

Osteonecrosis in only 3 (1%) of 284 patients who were taking high-dose corticosteroids + statin drugs

Statins might offer protection against AVN when corticosteroid treatment is necessary

Pritchett JW. CORR ;386:173-8 2001

A

Thank You

Health & Medicine

Ramesh Sen AVN