“AVN (Avascular OsteoNecrosis) Is a condition where the blood supply to the bone is blocked. This leads to death and necrosis with pain and eventual collapse of the affected bone, most commonly seen in the hip (femoral head) with crippling pain. This, if identified, can be treated medically in a large number of patients, stabilised and even reversed as has been documented by me in internationally published research of medicines.”


Avascular Necrosis (AVN) or Osteonecrosis of the femoral head is a pathological process that results from interruption of blood supply to the bone which leads to the death of marrow and osteocytes resulting in collapse of the necrotic segment of the femoral head. In the early stages of the disease, there is severe pain from the dying bone. Later this leads to frank arthritis of the hip, causing stiffness, limitation of movement and adds to the disability of the patient in day to day routine life.

This is the most common cause of total hip replacement in young patients in India.

Though Avascular Necrosis (AVN) of the bone was published in 1794, Ficat and Arlet had described the pathology of this condition in 1960. It is caused by some injury or could be due to other causes. There is no reliable data on the incidence and prevalence of this disease. Approximately 15,000 to 30,000 new cases occur annually in the USA. In India as there is no statistical data available, extrapolating for a population of over a billion people probably 70,000 to 90,000 new patients get affected with AVN. The disease occurrence is more in men than in women.


Avascular Necrosis (AVN) is often seen in association with a number of different conditions. Trauma with fracture of the femoral neck, especially in the sub-capital region, interrupts the major part of the blood supply to the head and may lead to AVN. The risk has been reported to be as high as 10% -43% after a displaced femoral neck fracture. Some of the factors leading to AVN are :

  • Excess alcohol consumption, with an allergy to the chemical
  • Corticosteroid therapy, the risk of AVN with corticosteroid therapy is dose related.
  • Sickle cell disease, where the clumps of sickle cell physically block the end arteries
  • Caisson’s disease, (decompression syndrome) where escaping gas bubbles from blood block the blood vessels
  • Gaucher’s disease
  • Systemic Lupus Erythematosus
  • Rheumatoid arthritis
  • Immuno-deficiency syndrome.


The hematopoietic cells are most sensitive to Anoxia (due to interruption of blood supply causing inadequate oxygenation).

Ischaemia causes death of marrow cells, death of bone cells causing necrosis of the affected segment which leads to weakness and collapse of the femoral head. This in turn causes incongruity leading to arthritis of the hip joint. Nature tries to heal this condition through removal of dead cells by oseoclasts and layering of new bone cells by osteoblasts. This natural process of healing takes upto three years, the life cycle of the disease.

There are four stages (Ficat & Arlet) of AVN of the femoral head based on the clinical and radiological presentation. Stage 1 the normal congruity of the femoral head is maintained with minimal symptoms and Stage IV is the end stage with collapse of the hip with arthritis.


Patients with AVN have a varied presentation based on their involvement of the femoral head (Stage of AVN). In early stages, patients present with groin, buttock, thigh pain or even with the knee pain with normal x-rays and an abnormal MRI. In later stages, patient present there is a limp, limitation or decreased movements of the hip joint and restriction of activities of daily living.

Investigations :​

Standard plain x-rays of pelvis with both hips (PBH view) and MRI helps in making a diagnosis as well as prognosis of the conditions. In certain cases radio-nuclide bone scan also helps.Standard plain x-rays of pelvis with both hips (PBH view) and MRI helps in making a diagnosis as well as prognosis of the conditions. In certain cases radio-nuclide bone scan also helps.

Methods of treatment :​​

Surgical management​​​

There are various surgical procedures which have been described such as core decompression, vascular fibular bone grafting, osteotomies around the femoral head and vascular pedicle graft, with varied success rate. All these surgical procedures help in early stages of AVN with poor success and adds morbidity to the patient.

The only consistent good results are seen in total joint replacements.

Directly implanted stem cells are the latest in this long road to salvation and are still in an experimental stage.

Medical Management involves :​​​

  • Aspirin has a role with very poor results.
  • Vaso-active drugs may play a role in early AVN but never proven
  • Chinese herbal products -very suspect!
  • Pulse Electro magnetic therapy with no proven results.
  • Bisphosphonate therapy, the only currently available peer reviewed and consistently proven in world literature. Bisphosphonate therapy which was pioneered by Dr. Sanjay Agarwala has certainly changed the treatment scenario.

Research Done by Dr. Sanjay Agarwala​

Dr. Sanjay Agarwala had started the research regarding management of AVN with bisphosphonate therapy and reported on it in 2001. Probably one of the only surgeons reporting in medical journal!

His index case was of a patient who refused any surgical intervention. Dr Agarwala analysed the cause of pain as collapse of bone due to weakness of the weakened bone. Weakened bone from osteoporosis was already being treated with bisphosphonates ! And therein lies the start of the story where legends spring from.

This pilot prescription of bisphosphonate therapy worked wonders and triggered off this methodological research at P.D. Hinduja National Hospital & Medical Research Centre. Bisphosphonates are poorly absorbed. At the best of times less than 1 % get absorbed from the GI tract. Hence daily intake is preferable in the first 3 to 6 months. The original treatment involved one tablet of Alendronate (10mg) to be taken on an empty stomach with two glasses of water.

For financial rather than medical reasons Pharma supported the dispensing of weekly dosage tablets 70 mg once weekly. Some formulations of 35 mg are also available. Keeping in mind that bisphosphonates are poorly absorbed in the GI tract, the current regimen advocates 35 mg tablets taken twice weekly. This ensures that the patient receives 70 mg on a weekly basis.

Bending forward or lying down or having food for 45 minutes after consumption of the tablet is to be avoided as the resultant acidic solution in the stomach can regurgitate and cause oesophagitis. Hence, patients are advised to take the tablet before brushing their teeth and the 45 mins are covered during the time of the morning rituals. Thereafter the patients can resume their normal daily activities and have tea/coffee, breakfast etc.

Recognising that there is poor absorption of oral bisphosphonates, hence poorer blood levels and hence slower efficacy , the current protocol includes an initial IV top up with 5 mg zolendronic acid. This ensures immediate blood levels of bisphosphonates, hence early response. The blood levels are maintained by the oral alendronate as described above. This particular regimen has been published internationally in the peer reviewed journal ‘Global oncology ‘.

Calcium and Vitamin supplementation are to be taken with bisphosphonate therapy for better efficacy.

This treatment needs to be continued for up to 3 years in view of the natural history to AVN being 3 years and the known safety profile of oral bisphosphonates which is for 3 years as well.

Patients were followed up with their clinical presentation and a radiological presentation including x-rays and MRI and their pain scores.

The Mechanism of action of Alendronate is described below :

  • Critical ischemia Alendronate
  • Necrosis
  • Inflammatory response Anti- inflammatory
  • Osteoclastic bone resorption Anti osteoclastic

Neo-osteogenesisThe results of the initial study was published in December 2001 in the Journal of the Association of Physicians in India and was honoured with the Best Paper Award and subsequently extended studies were published in Rheumatology Journal by 2005.

Dr. Sanjay Agarwala has published his 8 year follow-up in the JBJS, (British Journal of Bone and Joint Surgery -2009) and in 2011 the 10 year results were confirmed in JOA (Journal of Arthroplasty). These studies have shown 98% success rate in Stage I, 92% with Stage II and 70% with Stage III which is far better than various studies done in the past which had a success rate of only around 30%.


The cost involved for this treatment is a bare minimum of Rs. 150/- per month, which is affordable to the common man, and this avoids or postpones the requirement of total hip replacement surgery, the cost of which is very high.

This path breaking research on Bisphosphonate therapy in the management of AVN has paved the way for an economic mode of treatment while at the same time postponing or even avoiding the need for a hip replacement surgery.

This amazing discovery from an Indian surgeon, done with dogged persistence over 20 years, is now internationally acclaimed and cited in all legendary textbooks of Rheumatology and Orthopaedics. It has spawned new research in the previously difficult disease and is even used in paediatric conditions like Perthes disease.

Some patients who have advanced disease and who cannot or do not benefit from these methods can still have outstanding results by total hip replacements – THR. Patients can hope to be restored to their former functions within the ambit of norms for these artificial joints.
Continuing in the traditions of the surgical masters of legend like Sushruta, Indian surgical care is writing a new chapter in world literature.



In a groundbreaking discovery Dr. Sanjay Agarwala & his team has established a new hope for painful joints stricken by Avascular Necrosis / Osteonecrosis.

Avascular necrosis (AVN) of bone is a painful, progressively disabling disorder. The hip (femoral head) is the most common site. Untreated, it progresses to frank hip arthritis needing surgical intervention (Total hip replacement).

The team has been using Alendronate, a Bisphosphonate, to treat AVN of the hip for the last fifteen years with great success. Alendronate is most commonly used to treat osteoporosis. It prevents bone resorption. An initial report appeared as a letter in the Journal of Association of Physicians of India (Vo. 49, Dec’01 issue) and was awarded the Patel-Mehta Prize. Subsequently extended studies were published in Rheumatology Journal in 2005.

Dr. Sanjay Agarwala published his 8-year follow-up in the JBJS, (British Journal of Bone and Joint Surgery) 2009 and in 2011 the 10-year results were confirmed in JOA (Journal of Arthroplasty). These studies have shown 98% success rate in Stage I, 92% with Stage II and 70% with Stage III, which is far better than various studies done in the past, which had a success rate of only around 30%.

Most of the patients were referred to him for surgical treatment. In 80% of these, surgical intervention was avoided. The relief from pain was seen within 3-6 weeks. Most become freely ambulant. Those that needed surgery had advanced disease with hip joint damage already set in. In advanced stages of AVN there is resultant osteoarthritis of the joint.This requires the management of the joint arthritis and may need hip replacement.

Concurrent animal experiments done elsewhere, independent of our studies have also confirmed the scientific efficacy of this study, and are quoted in original papers published in scientific journals.


The tablet is to be taken on an empty stomach with one/two (preferably two) glasses of Water only. (Tea, coffee or juice WILL NOT do) and dissolves to become acidic. While the stomach lining can withstand this acidity, bending forwards, or lying down, brings the acid to the mouth and food-pipe (esophagus). Hence after taking the tablet please do not bend forward or lie down for a period of half an hour.

Likewise eating or drinking for up to half an hour will change the acidity of the stomach and prevent the activity of the tablet. Hence, do not take anything to eat or drink for up to half an hour. Therefore, I recommend you take it before you brush your teeth in the morning and continue with the rest of your daily morning rituals like bathing / shaving etc.

Alendronate is now available as 35mg and 70mg preparation. The dose is 35 mg twice a week or 70mg weekly. (35 mg twice a week works better in the initial 3 to 6 months).

Combination of oral alendronate and intravenous zolendronic acid is safe and effective, which has been published by Dr. Sanjay Agarwala in Journal of Global Oncology, Jan 2018. Hence,

To potentiate the action of the bisphosphonates, Dr. Agarwala feels it is advisable to ADDITIONALLY take (ONCE A YEAR) 5mg of Zolendronic Acid (I.V. form of bisphosphonate available from various companies with different brand names).

For 24 to 48 hrs after the slow I.V. injection, there could be some Fever / Flu like symptoms like bone pain and fever. This is easily treated with Paracetamol (Crocin 500mg tablets or Combiflam) 2-3 times a day. If pain and discomfort persists, two tablets of 10 mg Wysolone (Prednisolone) as a single dose will further help.

Bisphosphonates do not work in the absence of Calcium and Vitamin D Hence….Please continue taking Calcium with Vitamin D Supplementation for the 3 years that this treatment will be continued for. At the end of 3 years this bisphosphonate medicine has to be DISCONTINUED, whereas the Calcium & Vitamin D medication may be continued life-long.

Publications and Awards​​​

Bisphosphonate Therapy : A New Paradigm In AVN Management​​​​

In 2001, Dr Sanjay Agarwala reported on AVN management with bisphosphonte therapy in medical journals. Recognizing that bisphosphontes were FDA approved and routinely used to treat osteoporotic weakened bones, he hypothesized that a viable treatment for AVN may include the use of bisphosphonates. This treatment needs to be continued for at least three years in view of the natural history of AVN and the known safety profile of bisphosphontes which too is three years. The studies done by Dr Sanjay Agarwala have shown 98% success rate in Stage I, 92% with stage II and 70% with stage III, which is far better than various studies done in the past which had a success rate of only around 30%. This pathbreaking research on bisphonate therapy in the management of AVN has paved the way for an economic mode of treatment while at the same time postponing or even avoiding the need for hip replacement surgery.

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