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Mukharjee Regimen for

AVN of hip joint
Dr L. Prakash and Dr Aroop Mukharjee

Dr Aroop Mukharjee’s concepts about hip AVN and its reversal. His theo-
ries about why his regimen works. The same regimen is also used for treat-
ing Rheumatoid conditions with great success.

INTRODUCTION:

This chapter is a result of discussions between Dr Aroop Mukharjee and Dr

L.Prakash, over two nights in Jaipur. I heard about Mukharjee method of con-
servative management for AVN hips about three years ago from my close
friend Dr Arvind Diwakar Jain, but did not have an opportunity of trying it.
The reason was simple, I did not know what the method was!

However many young surgeons regularly asked me if there was a way to

avoid THR in the young patient with AVN. They all wanted to know some
 Orthopaedics Beyond Books

form of medical management, which would either delay, postpone or avoid

hip replacements in the very young.

I referred a few surgeons to Dr Mukharjee, who described his methods to

them, and they gave me such glowing reports of success by the medicines,
that I was impressed. I invited him to share the secrets in the Jaipur confer-
ence in December, the world’s rst conference on orthopaedics beyond books.

When I heard his talk, I was very impressed, and the sheer logic was extreme-
ly convincing. And then he showed the X-rays of his patients, with clinical re-
sults. That was the evidence I was waiting for, and in an instant I too became
a convert of his method.

We spent three days together and discussed at length about his method, the
logic, rationale, and dosages. Here I describe the original method, as well as

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Pathological appearance of AVN femoral head

my suggestions and modi cations. In Mukharjee I found a scientist twin who

spoke the same language as myself and who was as crazy about bones as Dr
L.Prakash, a rare breed indeed.

DR AROOP MUKHERJEE:

He has as done his medical graduation and post graduation from GSVM
Medical college , KANPUR in the yr 1981 and 1985. He then did his research
fellowship of ICMR on Orthopaedic bracing using for fractures and other in-
dications in the same institute.

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Femoral head blood supply has many individual variations

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After that, he had further training in Hand surgery from Stanley Medical Col-
lege Chennai, under Prof Venkataswami in 1989-90

He then went to UK for further training and completed my M Ch (orth) from

Liverpool, and worked there till 1993 at Queens Medical centre at Notting-
ham and Pulvertaft Hand centre , Derby. Fazakerley Hospital in Rheumatol-
ogy department.

He came back to India and made his own hand injury centre in the industrial
town of Kanpur and served there till 2005, managing dif cult hand and
arthritic problems.

He was invited to Max Hospital New Delhi, in the orthopaedic department to

head the Hand Surgery department, where he is still working as a senior con-
sultant .

He has a special interest in complicated reconstructive hand surgery and

Rheumatology.

He has an experience of more than 2.5 lakh patients of various autoimmune

musculoskeletal problems, travelling to him from all over the world and
bringing them and maintaining them under remission.

WHAT IS AVASCULAR NECROSIS? BONES VERSUS OTHER TISSUES:

Avascular necrosis, translated into simple English means “Death and decay
due to lack of blood supply”. AVN of the bone is just the same as myocardial
infarct or a stroke. The blood supply to a particular organ gets occluded, the
affected area dies. But unlike cardiac, neural tissue, muscle or skin, a bone is a
different structure altogether. Every tissue except bone is replaced by scar tis-
sue or inferior quality brous tissue. However bone is the only tissue which is
replaced by normal bone, if a correct stimulus is given.

If we break a bone and stretch it, new bone can be created as shown by
Ilizarov methods. Increasing the blood supply and providing precise mechan-

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ical stimulus makes bone appear and this bone is no different from the origi-
nal bone.

This is the premise under which the Mukharjee regimen works!

ISCHAEMIA, OCCLUSION AND NECROSIS:

Anatomists and pathologists, have always envisaged more interest in AVN

than an orthopaedic surgeon or rheumatologist! Scaphoid, neck of femur,
lower tibia, medial femoral condyle and lunate have always interested an
anatomist more than a surgeon. Even today a pathological classi cation of
AVN is a more precise indicator of prognosis than MRI or X-rays based or-
thopaedic Ficat classi cation.

It is logical to assume that when blood supply to bone is interrupted, the

bone cells die. Here rather than brous tissue, it is replaced by fatty non bony
tissue as shown in the pictures. As and when blood supply and oxygen to tis-
sue is restored, all of it converts to bone, as good and pristine as its original
form!

When the AVN happens in the proximity of a weight bearing joint, it would
naturally collapse and deform leading to mechanical wear and tear. And thus
if we are able to increase the blood supply by any way, while protecting the
joint, it is logical to assume that the avascular area will become healthy bone
again!

ANATOMICAL VARIATIONS IN FEMORAL HEAD BLOOD SUPPLY

AND ITS RELATION TO AVN.

Despite various causes for “Idiopathic” AVN of hip, the actual reason is the
same. Synovitis with multiple proliferation of synovial cells causing oedema
compressing blood vessels and causing thrombosis and ischemia!

Solitary vessel supplied femoral heads, i.e. those predominantly dependant

on posterior retinacular vessels are at highest risk. Those with good foveolar
supplies RARELY get AVN. Heads with good anterior, posterior and foveolar

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supply NEVER get AVN unless there is a very bad subcapital fracture with
total disruption of blood supply as shown in X-rays below.

Even untreated subcapital neck of femurs will unite in 14% of population

with good blood supply. Only about 15% population are entirely dependant
on posterior retinacular blood supply and these most often develop AVN.

Be it trauma, infection, arthritis or arthropathy, pressure on vessels, thrombo-

sis, plaque and constriction of blood supply is the culprit! As per Mukharjee
theory, it is synovitis due to rapidly proliferating synovial in ammatory cells,
that cause tissue oedema, and constriction of posterior retinacular vessels that
lead to their strangulation. And thus develops AVN.

The so called idiopathic, post partum, alcohol, or steroid induced AVN is

nothing else but highly proliferative synovitis with consequent avascularity
in those vulnerable hips which are only supplied by posterior retinacular ves-
sels!

And this brings us to Dr. Yellapragada Subbarao!

Dr. Yellapragada Subbarao!

Dr Subbarao was born in Bhimavaram in Andhra Pradesh in the year 1895.

During his early life he had to face severe hardships. After completing his
matriculation, he managed to get himself enrolled in Madras Medical Col-
lege. His education there was supported by friends.

Although he did well in college, his British professor granted him only a less-
er LMS degree instead of a full MBBS. He then became interested in Ayurve-
da and took up a job as Lecturer in Anatomy at Dr. Lakshmipathi’s Ayurvedic
College. His father in law assisted him with nances so he could nally go to
study in the US.

He sailed for the US on October 26, 1922, and took admission in the Harvard
School of Tropical Medicine. After completing his studies, he joined Harvard

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Dr. Yellapragada Subbarao!

as a Junior Faculty member. He left the this job in 1940 and took up a position
with Lederle Laboratories.

His rst tryst with success came with the discovery of the Fiske-Subbarao
method, which helped estimate the amount of phosphorous in body uids
and tissues.

This discovery was followed by a long chain of achievements, including the

discovery of the ATP molecule (which gives energy to our body), and Aure-
omycin, a rst of its kind antibiotic that was stronger than both penicillin and
streptomycin; it helped save millions of lives around the world. He also
helped develop Methotrexate, one of the rst chemotherapy agents that is
still used widely. Humans were not the only ones to bene t from his research;
Hetrazen, a drug used to treat brosis in animals, was introduced by him too.
He also spearheaded US medical research during World War II.

Despite such an amazing track record, Subbarao was relatively hidden from
the media eye. He didn’t win the Nobel Prize or even an equivalent, and of-

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ten took the backseat in terms of recognition. Often, when he his research was
being published in front of an audience, he would have to be pushed by his
colleagues to go on stage and take a bow.

Subbarao succumbed to cardiac arrest on the August 9, 1948. He was just 53

years of age.

It is the miracle drug methotrixate, that helps us to achieve miracles by the

Mukharjee regimen, and “Aroop’s folic neutralisation theory” helps to coun-
teract the side effects of the drug with a combination of low but effective dos-
es, followed by neutralisation produces wonders!

Aroop’s folic neutralisation theory

Synovitis, and rapidly proliferating synovial cells cause compression and

strangulation of femoral head blood supply.

Methotrixate will inhibit these rapidly proliferating cells.

Methotrixate however is a very powerfully toxic drug with systemic effects,

and as methotrixate acts on mutant, or rapidly neoplastic cells by interfering
with folic acid metabolism and cycle, alternating MTX with folic acid will
neutralise its ill effects.

Blood thinners like warfarin and aspirin with low dose steroids will allow
more of the drugs to reach the site.

Key words
• Creeping substitution.
• Avascular zone or necrotic zone.
• Bone is the only tissue which rejuvenates without scar tissue.
• That means bone which is dead today (avascular) will be living tomorrow
and fully functional.
• To achieve this, we prevent structural collapse of bone which is avascular.
• Avascularity is due to thrombosis of artery, arterioles, capillary, veins in
the Haversian system.

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• Because of the rich collateral and interconnectivity of Haversian systems,

AVN is not a usual occurrence.
• Areas of solitary blood supply suffer from AVN.
• 1/3 rd of the population has solitary blood supply in the femoral head
and 20% population has solitary dorsal blood supply in lunate.
• Removal of thrombosis and revascularisation in femoral head may take
about 2 years time.
• Thrombosis is the most common complication in arthritis. 80-90% of
lower limbs show blood clots/ thrombosis in doppler studies in all pa-
tients of arthritis which may cause or may not cause pulmonary em-
bolism. So all patients are kept in LMWH in THR/TKR.
• Principles of treatment in AVN.
• Start anti-arthritis treatment (without pain killers/NSAIDS) in AVN.
• Add blood thinners to increase blood permeability to the peripheral areas
of bone necrotic zone.
• Continue Anti-arthritic treatment (Low dose DMARDS) or Mukharjee’s
Regime which is safe in long term use.
• Still; monster blood test and other parameters to ensure patient safety.
• Monitor Xray pelvis AP and in 30 degrees hip exion AP to check skeletal
integrity of the femoral dome and ISN every two months.
• Avoid smoking/ alcohol intake, weight gain in order to increase possibili-
ty of collapse of avascular zone (Dietary restrictions).
• Intermittent attacks of pain is possibility (after remission) which can be
managed by rest and low dose steroid along with regular intake of
Mukharjee’s Regime.
• Any surgical intervention will increase the intensity of arthritis and joint
replacement is not a long term solution in young individuals.

Arthritis is the most common cause of thrombosis which increases in inci-

dence (of thrombosis) with age.

It has been documented in many studies that all cases of knees hip arthritis
has 80-90% incidence of venom thrombosis I the lower limbs, that is reason all

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the cases of arthroplasty are given pre operative/ peri operative low molecu-
lar weight heparin (LMWH) to prevent pulmonary embolism which can be
total at times.

So naturally arthritis is next commonly attributed, cause of proximal a distal

thrombosis which leads to AVN where there is solitary blood supply.

Radiological variations in the AVN picture and its causes

Grossly there are two mai types of AVN pictures seen in the x ray picture
1. AVN without reduction in joint space (JSW) that is pure AVN without
arthritis.
2. AVN with reduction in the joint space (JSW) and arthritic changes.

1. Why there is AVN without reduced JSW?

Reason: Here we see pure proximal/thrombosis of the femoral head vessels
due to any reason like, arthritis tendency, sickle cell disease as a complication
of steroid therapy, post dislocation of the hip and its sequel etc. Here we see
little or no synovitis in MRI picture.

2. Why there is AVN with reduced JSW?

Here the picture is due to direct effect of hip joint synovitis which is pressing
its thrombotic effect on the retinacular vessels in the posterior part of the
femoral neck, its solitary blood supply.

Here we can see the synovitis (soft tissue) swelling in the MRI picture en-
croaching on the femoral neck

• The picture is a mixture of hip arthritis

• Femoral head AVN

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Principles of therapy

To start medication to control auto Immune reaction leading to decreasing

levels of toxics like PG1, PG2, TNF2, Cytokynes and prevent degeneration
and tissue breakdown. Control acidity and G1 irritability for better absorp-
tion of DMARDS.

Give DMARDS, not all of them daily, but 2 drugs alternative rays.

Since Methyl Prednisolone (steroid) is given in small doses regularly hence

supplement vitamin A ( Becadexamine) to reduce the oxidative stress pro-
duced by steroid.

Supplement Vitamin B12 as antibodies against Neurotransmitters are pro-

duced in Arthritis.

Add Blood thinner (Acetron/ Warfarin) to allow more blood perfusion with
medication, to disease affected area and promote creeping substitution. Keep
the level of vitamin D nearly 100 mum/ml to promote maximum bone heal-
ing

Supplement easily digestible bio-protiens to encourage quick healing and re-

pair

Supplement probiotics (4 billion spores) every day to promote protein ab-

sorption from the gut (which is in amed most of the time)

High protein diet is essential for the protein matrix of bony tissue, and vita-
min D and B complex are essential helpers!

Fasting
1) Tab Folic Acid 5mg on Mon/Wed/Fri
2) Tab Methotrexate 2.5mg on Tue/Thu/Sat
3) Cap Vitamin D 6000 units on sunday
4) Tab pantoprazole 40mg daily

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After Lunch
1) Capsule Vitamin A 5000 units alternate day
2) Capsule Vitamin B 1500 mg alternate day
3) Tab Hydroxychloroquine 400 mg alternate day
4) Tab sulfasalazine 1gm alternate day
5) Tab Lefunamide 20 mg alternate day
6) Cap Probiotic (3 billion spores) alternate day
After Dinner
1) Tab Calcium Citrate 1gm 1 tab daily
2) Tab vitamin E with Levocarnitine 1 tab daily
3) Tab Methyl Prednisolone
• 4 mg daily * 1 month
• 2 mg daily * 2 month
Add: Tab Warfarm 2 mg daily (fasting) daily (except Sunday) in AVN cases

BLOOD THINNERS:

Warfarin2 mg daily fasting 6 days a week, except Sunday for two months or
till pain disappears. Monitor PT every week. Then aspirin 75 mg daily after
dinner six days a week.

Mederol to be tapered. 2 mg bd for 15 days, 2 mg bd for 30 days, 2 mg daily

thereafter.

Protein supplementation:

6 egg whites, Protinules, or Whey protein, 125 grams per day every day

As no NSAID is added, pain relief is the best indicator for success of treat-
ment!

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Examples are given on the subsequent pages

Before beginning treatment :

CBC phosphatase SGPT Alkaline PT/APTT ESR Sugar(F) Hb A1C USG

whole Abdomen To See

1. Fatly Liver

2. Renal Calculus

3. IBs

MRI Pelvis

Every 6 months

Creatinine Uric acid Lipid

TSH

How long to continue treatment?

Until complete revascularisation of the head, which may take up to 24

months depending on the size of the area affected and the degree of AVN.

As no NSAID is added, pain relief is the best indicator for success of treat-
ment! Examples are given on the subsequent pages

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Example 1 Feb 2015

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Example 1 September 2016

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Example 1 clinical picture

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Example 2 MRI sequence and nal clinical picture

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Example 3 Sequential progress. Dates on lms, with clinical

pictures

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Diminished joint space (JSW) and associated synovitis in the right hip
causing arthritis and direct AVN

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Same patient with sequencing of X-ray pictures with treatment and

follow up

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