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Life Extension Magazine

LE Magazine May 2000


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imageDoing Away with... ARTHRITIS

An innovative procedure involving human growth hormone stimulates
cartilage growth and joint mobility


by Melissa Block, M.Ed.

Current statistics show that 43 million Americans have arthritis. Swollen, painful joints compromise quality of life for 38% of men and 54% of women over the age of 65. It is estimated that 15% of the U.S. population has some form of arthritic disease, and that the overall cost of the disease amounts to 1% of the gross national product. Some arthritis patients are in constant pain, day and night; others have milder pain but still can't participate in the activities they enjoy because of loss of mobility and threat of worse discomfort. The drugs that have been developed to treat arthritis only manage symptoms, and do little to stop the degeneration of cartilage caused by the disease. When a joint threatens to deteriorate completely, orthopedic surgeons can repair or replace it-but replacement parts wear away or loosen over time and often need to be operated on again. Glucosamine sulfate, a component of cartilage, has been shown to ease pain and possibly slow progress in arthritis. Still, these remedies work slowly and are not effective for everyone. Much work still needs to be done on two new experimental therapies, hyaluronic acid (Synvisc) injections and cartilage transplants. Millions of people who have found no reliable relief from their pain and debility continue to wait for a cure. Allan Dunn, M.D., an orthopedic surgeon in private practice in North Miami, Florida, may have the answer. Since 1965, he has been working on a novel method for the treatment of degenerative cartilage diseases: the injection of human growth hormone directly into affected joint spaces.

All about the doctor

Dr. Allan Dunn attended medical school at the New York State Downstate Medical Center, where he worked at the famous Kings County Hospital. There, he was exposed to uncommon, esoteric, even bizarre medical cases-patients with problems that, in other training programs, would come up only as a footnote in a medical text. Upon graduation from medical school, he was accepted for a one-year medical internship at the highly sought after Montefiore Hospital in the Bronx. He spent a second year at Montefiore as a general surgery resident. From there, he moved on to 3 1/2 years of residency in orthopedics at the Hospital for Special Surgery at the Cornell Medical Center, the top training program for orthopedic surgery in the nation. Today, he counts himself as one of the rare physicians in private practice who also engage in ongoing medical research. Dr. Dunn also finds time in his tight schedule to hone his skills as a classical violinist. When asked how he can do it all, he answers, "When you want to get something done, ask the busiest man in town."

The growth hormone-cartilage connection

Dr. Dunn's development of IAHG (IntraArticular Growth Hormone) began with his study of acromegaly, a disease caused by oversecretion of growth hormone. Acromegaly is usually caused by a benign tumor that grows in the pituitary gland. The tumor stimulates the gland to secrete far more growth hormone than is required in adulthood. Excess growth hormone causes the expansion of cartilage within the joints of the fingers and toes, as well as on the forehead and chin. Fingers and toes grow longer and thicker and the forehead and chin protrude. Dr. Dunn reasoned that if growth hormone had this kind of effect on cartilage that normally stopped growing in late adolescence, it could be injected into joints to promote the growth of cartilage that had deteriorated due to arthritis.

Bone and joint Development

One of the major functions of growth hormone, during the two-decade-long transformation from embryo to adult, is to increase the length of all bones. Virtually every bone in the body starts out as cartilage, a spongy, flexible form of connective tissue that slowly mineralizes and hardens to become bone. If you were to look at the femur (thigh bone) of a small child, you would find a short length of hard bone at its center, with softer cartilage discs-growth plates-at either end. The bone grows longer as growth hormone stimulates the growth of new cartilage in the growth plates. Behind the new growth, the cartilage skeleton mineralizes and turns to bone. At adulthood growth hormone secretion wanes, the bones stop lengthening, and the growth plates on the ends of the bones disappear. A thin layer of cartilage (about one-eighth of an inch) remains, covering the bone ends and providing cushioning and lubrication, especially in the fingers, toes, elbows, ankles, knees, hips and shoulders. This articular cartilage allows smooth, frictionless movement of the joints. Over the years, excessive wear and tear from repetitive tasks, bad posture, injury or athletics can wear down those thin cushions and expose the hard, bare bone ends to direct friction and pressure. Inflammation and arthritis pain are usually next in the progression of events.

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"I'd like to see growth hormone injections as first-line therapy, to try to restore cartilage and joint mobility before resorting to invasive and risky surgery."


New findings on cartilage growth

The first step toward development of a scientific rationale for intra-articular (within the joint) growth hormone injections was to discover exactly how growth hormone stimulates the growth of cartilage. It has been known since the 1930s that it has this effect, but the exact physiological chain of events has proved difficult to discern. In textbooks on orthopedics, it is stated that cartilage is avascular (contains no blood vessels). This theory is used to explain the fact that damaged cartilage regenerates either slowly or not at all. With the use of fluorescent antibody markers and other special techniques, Dr. Dunn found that the cartilage surface has a previously undiscovered, specialized microvascular system, consisting of tiny blood vessels that fold in on one another in loops and swirls. The cartilage vessels bear a strong resemblance to the vascular loops called glomeruli, which are found in the kidneys. This resemblance inspired Dr. Dunn to dub these vascular cartilage structures Glomeruloids. While they may look alike, these two types of vessels have entirely different functions. In the kidney, the glomeruli filter wastes from the blood to produce urine. At the ends of bones, Glomeruloids produce cartilage cells. During infancy and childhood, when growth is rapid, stem cells-immature cells formed in the bone marrow and the linings of blood vessels-are moved to the growth plate through the Glomeruloids. Within these cartilage vessels, stem cells are transformed into cartilage cells. They then pass into the growth plate or the joint surfaces. An understanding of the presence and function of the glomeruloids is essential to the understanding of how IAGH stimulates the restoration of cartilage in arthritic joints. Because of the enormous cost of the research that would be required to overturn the standard beliefs about cartilage regeneration, however, Dr. Dunn has not had the opportunity to publish these findings in major medical journals.

Clinical applications

Several studies on isolated cartilage and on the joints of rabbits and dogs have shown that cartilage rapidly grows when exposed to growth hormone. Dr. Dunn's research has been designed to illustrate that this effect is due to direct growth hormone stimulation of Glomeruloid formation. In one of his experiments, all cartilage and vascular tissue was scraped from the knees of large, mature adult rabbits, leaving only the bare bone ends. After the surgery, a single dose of growth hormone was injected. In only a matter of days, hundreds of thousands of new Glomeruloids sprang up on the exposed bone surfaces in the joint. Once the Glomeruloids have formed, claims Dr. Dunn, "their only function is to produce cartilage cells." Growth hormone also increases production of collagen, a strong, fibrous connective tissue that attaches cartilage to bone and provides a framework for the matrix. Matrix is the gelatinous, resilient part of cartilage, and its production, too, is increased by growth hormone. Cells called chondrocytes manufacture the matrix. Local administration of growth hormone causes a local increase in insulin-like growth factor I (IGF-I), which sends a message to the chondrocytes to build more matrix. IAGH gives the body the cues it needs to set the cartilage growth process in motion. Stimulation of cartilage regeneration with growth hormone reproduces the same environment in which joint tissues grow during childhood. It is a completely natural therapy.

IAGH success stories

While an understanding of the physiological mechanisms is important, the real test is how well the treatments work. Normal, structurally sound cartilage has been restored with local application of growth hormone in both animal experiments and in Dr. Dunn's patients. Dr. Dunn has successfully treated 35 patients with IAGH thus far. Dr. Dunn's patented procedure entails three to six separate injections in the affected joint. Between injections, x-rays are taken to monitor cartilage regrowth. The regrowth is visible on the x-ray as increased space between the ends of the bones. Patients have consistently shown an increase from zero space to about four millimeters, a difference that can transform a nearly crippled person into one who can move again without stiffness and who can sleep through the night without waking in pain. One young patient went from being debilitated by knee pain to complete healing, which allowed him to return to his sport of pole vaulting. Another was amazed to find himself well enough to hike up Mt. St. Helens and back with no symptoms in his knee. Patients followed for up to 16 months have had no recurrence of "water on the knee," pain, swelling or heat in treated joints. They continue to improve. Some previously bowlegged patients have even reported that their knees became straighter following IAGH! The procedure has been performed on hips, knees, ankles, shoulders and elbows. Dr. Dunn hopes to soon conduct a study on IAGH for deteriorated spinal discs. The cost of growth hormone is an obstacle for many, and it is a new therapy that will require continual refinement, but the results Dr. Dunn has achieved so far are certainly impressive. Dr. Dunn does not believe that growth hormone will be a substitute for total joint replacement surgeries in all cases. He would, however, like to see growth hormone injections as first-line therapy, to try to restore cartilage and joint mobility before resorting to invasive and risky surgery.

The cost per injection of IntraArticular Growth Hormone (IAGH) is $375. Usually, three injections are suggested. For more information on IAGH, please contact Allan Dunn, M.D. in North Miami Beach, Florida, at (888) 848-6534.


References

Chrisman OD, "The effect of growth hormone on established cartilage lesions. A Presidential address to the Association of Bone and Joint Surgeons, 1974," Clin Orthop 1975;107:232-8.

Halbrecht J, et al, "The influence of growth hormone on the reversibility of articular cartilage degeneration in rabbits," Clin Orthop 1990 Oct;259:245-55.

Hendricson AS, Havdrup T, Telhag H, "The effect of growth hormone and thyroxine on adult joint cartilage," Clin Orthop 1982 Jan-Feb;162:270-5.

Isaksson OG, Jansson JO, Gause IA, "Growth hormone stimulates longitudinal bone growth directly," Science 1982 Jun 11;216(4551):1237-9.

Livne E, Laufer D, Blumenfeld I, "Comparison of in vitro response to growth hormone by chondrocytes from mandibular condyle cartilage of young and old mice," Calcif Tissue Int 1997 Jul;61(1):62-7.

Madsen K, et al, "Growth hormone stimulates the proliferation of cultured chondrocytes from rabbit ear and rat rib growth cartilage," Nature 1983 Aug 11-17;304(5926):545-7.

Muir H, "The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules," Bioessays 1995 Dec;17(12):1039-48.



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