|
The Regeneration of
Articular Cartilage with Prolotherapy
Ross A. Hauser, MD
Journal of Prolotherapy. 2009;1:39-44.
abstract
What most people may not realize is that chondrocytes,
the cells that make articular cartilage, are metabolically active.
Chondrocytes proliferate and actively make
articular cartilage.
Osteoarthritis is an example of this, in that both the degradation and
synthesis of articular cartilage are enhanced. It is well known that in
osteoarthritis, chondrocytes retain their proliferative activity.
Osteophytes or bone spurs are an example of this activity.
Another example of adult articular cartilage cells’ replication is
acromegaly. In this condition the body produces an excessive amount of
human growth hormone and with it, articular cartilage. Acromegalics
often suffer from joint abnormalities caused by proliferation of
chondroytes in articular cartilage. In other words, they produce too
much cartilage.
When a healthy articular cartilage cell is injured, it demonstrates an
enhanced reparative response and can replicate its DNA to form new
cells. The rate of formation of articular cartilage can be enhanced by
such stimuli as altered hydrostatic pressure, varied oxygen tension,
growth factors, as well as nutrient and substrate manipulation.
If by traditional orthopedic surgery or medical standards, articular
cartilage injury or degeneration causes such symptoms as
knee pain,
stiffness, clicking, crunching, and inability to walk, then the reversal
of such symptoms with Prolotherapy must mean that articular cartilage
regeneration has taken place. In this scientific editorial, the author
makes the case for using Prolotherapy as the treatment of choice for
degenerated joints.
Simply put, I believe that articular cartilage is regenerated with
Prolotherapy.
In my opinion, Prolotherapy should be the treatment of
choice for most cases of pain involving the degeneration of a joint. It
is common knowledge that even the most effective current treatments for
osteoarthritis do not restore the joint. Conservative treatments such as
exercise, medications,
physical therapy, and lifestyle modification can
decrease symptoms and improve mobility, but they do not reverse the
disease. I believe if Prolotherapy were utilized to its fullest in the
treatment of knee,
shoulder, and other peripheral joint degenerative
conditions, it would be shown to be the one treatment that does restore
some, or most, of the degenerated structures, as well as the functions
of the joint.
What most people may not realize is that chondrocytes, the cells that
make articular cartilage, are metabolically active.1 Yes, chondrocytes
do proliferate and actively make articular cartilage. In normal
cartilage, there is a strict regulation of cartilage turnover, a
delicate balance between synthesis and degradation. The problem is, for
those suffering from osteoarthritis, the system is imbalanced. There is
more cartilage degeneration than rebuilding.
In osteoarthritis, both degradation and synthesis of articular cartilage
are enhanced. The problem is that the “messenger” molecules that allow
cells to communicate and alter one another’s functions, called
cytokines, cause more breakdown of articular cartilage than repair. The
catabolic (break down) cytokines IL-1, TNF-a, IL-17, and IL-18 act to
decrease extracellular matrix synthesis (cartilage synthesis). The
anabolic cytokines (substances that build up) IGF-1, TGF-B1, 2, and 3,
fibroblast growth factors (FGFs) 2, 4, and 8, and the bone morphogenetic
proteins act to stimulate extracellular matrix synthesis.2,3 In
osteoarthritis, unfortunately, the catabolic cytokines are winning.
It is well known that in osteoarthritis, chondrocytes retain their
proliferative activity.4-6 As a
matter of fact, a number of biochemical studies have demonstrated
enhanced synthesis of the extracellular matrix of cartilage.7-8
Chondrocytes attempt to repair the damaged matrix in osteoarthritis by
increasing their anabolic activity.9-10
One of the reasons for this is that on a molecular level, a significant
proportion of adult articular chondrocytes start to re-express a
chonodroprogenitor phenotype in osteoarthritic cartilage degeneration,
which is comparable to the chondroprogenitor phenotype observed in fetal
skeletal development.11-12 In other
words, with injury/degeneration, the adult chondrocyte cells change to
more “primitive” cells, which have more proliferative ability. In the
natural history of the disease, despite this increased activity, a net
loss of proteoglycan content (extracellular cartilage matrix) is one of
the common features of all stages of osteoarthritic cartilage
degeneration.13
One of the main hallmarks of osteoarthritis in a joint is the
development of prominent osteochondral nodules known as osteophytes.
These are also called osteochondrophytes or chondroosteophytes. Most of
us know them as bone spurs. Indeed, the presence of osteophytes in a
joint, more than any other pathological feature, distinguishes
osteoarthritis from other arthritides.14
Osteophytes are an example of new cartilage and bone development
in osteoarthritc joints, and arise from tissue associated with the
chondro-synovial junction or from progenitor cells residing in the
perichondrium.15-16 This basically
means there is a population of joint cells (pluripotential cells) that
can respond to injury and differentiate into cells that make cartilage
and bone. The purpose of osteophytes is presumed to be the stabilization
of joints affected by osteoarthritis.17
When larger osteophytes are examined from human patients, areas of
hyaline cartilage can be seen to extend to the surface of the osteophyte.
These cartilaginous tissues resemble genuine articular cartilage in
chondrocyte morphology and in extracellular matrix. Interestingly, the
anabolic factors TGF-B and TGF-B2 have been found in
 osteophytes from
human femoral heads.18 Again this
signifies that adult articular cartilage retains repair (anabolic)
activity.
INCREASED ARTICULAR CARTILAGE THICKNESS IN ACROMEGALY
One of the major problems in osteoarthritis care today is traditional
medicine’s inability to promote effective cartilage regeneration in the
presence of adult chondromalacia (cartilage degeneration). Yet such
regeneration is consistently present in acromegalics. Acromegaly is a
condition whereby the pituitary gland secretes too much human growth
hormone (HGH). It is a disease characterized by the gradual enlargement
of the bones of the hands, feet, head and chest, and thickening of the
skin, lips and vocal cords. What is also characteristic of this
condition is that there is an excessive amount of articular cartilage in
both weight-bearing (knees) and non-weight-bearing joints.19 Acromegalics often suffer from joint abnormalities caused by the
proliferation of chondrocytes in articular cartilage. Since this
condition typically occurs after puberty, the increased human growth
hormone secretion in acromegaly somehow, either directly or indirectly,
stimulates adult chondrocytes (cartilage cells) to make cartilage.
People with acromegaly have tremendously thick articular cartilage,
which can be diminished by decreasing their HGH secretion.20
HGH is known to cause the liver to increase production of
Insulin-like
growth factor-1 (IGF-1). Circulating and locally produced IGF-1 is known
to stimulate DNA synthesis, cell replication, and proteoglycan and
glycosaminoglycan synthesis in articular chondrocytes.21 IGF-1 and HGH
have both been shown to stimulate the growth and repair of adult
articular cartilage.22-24 One reason for this cartilage growth can be
that some cartilage cells have HGH receptors.25
MORE EVIDENCE OF ARTICULAR CARTILAGE REGENERATION
What happens to articular cartilage when it is subjected to mechanical
trauma? It is important to consider the main issue. Can adult articular
cartilage respond to appropriate stimuli by an increase in its synthetic
activities for DNA and matrix components? In other words, can
chondrocytes replicate and make cartilage? Central to this discussion is
the consideration of the ability of any tissue to increase its rate of
DNA and protein synthesis. Regardless of the tissue involved, the
process of repair is a cellular one in the sense that fibroblasts, or
specific cells (osteoblasts, chondrocytes for example), must synthesize
the repair material. For the most part, these are “new” cells that
evolve by cell replication and modulation of existing cells, or from
cells that have migrated either from the margins of the wound or from
blood vessels entering the tissue. It is therefore important to
recognize that DNA replication and cell division are essential
characteristics of any repair process.
The confusion in regard to articular cartilage repair stems from the
fact that chondrocytes from immature cartilage are capable of dramatic
repair and synthesis, whereas aging chondrocytes show much lower rates
of cell replication.26-27 This is where the notion of “cartilage cells
don’t replicate” stems from. The problem with this logic is that a
normal adult chondrocyte is phenotypically different from an injured
chondrocyte. Analysis of cartilage from joints with osteoarthritis has
demonstrated, over and over again, an increased number of cells in
clones and evidence for DNA synthesis by a number of means including
3H-thymidine metabolic studies, autoradiography, and even histological
demonstration of mitotic figures.28-30 These data suggest that under
circumstances of chronic injury, such as is seen in osteoarthritis or
trauma, chondrocytes are capable of mounting a significant reparative
response and can replicate their DNA to form new cells.31 This is fact. Chondrocytes can divide, and do so in the adult animal/human with
osteoarthritis and from other stimuli. Ample evidence now exists that
articular chondrocytes from immature and adult animals can vary the rate
at which they make cartilage matrix necessary for repair. This rate of
proteoglycan synthesis can change in response to such diverse physical
and pathological states as osteoarthritis (as discussed), altered
hydrostatic pressure, varied oxygen tension, alternations in pH, calcium
concentration, substrate concentration, and the presence of growth
hormone (as discussed), growth factors, ascorbate, vitamin E, and so
on.32-36 I could easily elaborate on each of these, but the
reader is encouraged to check the references for further information.
Therefore, it is reasonable to conclude from the above that injured
adult articular cartilage chondrocytes have the capacity to
substantially increase their rate of matrix synthesis, and that the
possibility exists of chondrocyte participation in the repair of
articular cartilage. All that is really needed is a method to stimulate
that repair maximally. This is where Prolotherapy fits in.
PROLOTHERAPY: THE TREATMENT OF CHOICE FOR DEGENERATED JOINTS
George S. Hackett, MD coined the term Prolotherapy. As he describes it,
“To the treatment of proliferating new cells, I have applied the name
Prolotherapy from the word prolix (Latin), meaning offspring;
proliferate-to produce new cells in rapid succession. My definition of
Prolotherapy as applied medically in the treatment of skeletal
disability is ‘the rehabilitation of an incompetent structure by the
generation of new cellular tissue.’”37 While traditionally used for
ligament and tendon repair, Prolotherapy has a long history of being
used for
Degenerative
Joint Disease.38-41 Like the chronic knee pain study
published in February 2009 issue of the Journal of Prolotherapy,42 Prolotherapy has remarkable pain-relieving effects. But
when a person with degenerative
knee arthritis reports less stiffness
and crunching in the knee, as well as improved motion, are we to assume
that there has been cartilage repair? I would answer the question with
an emphatic “yes” in most cases. But some would remain skeptical. This
is why the February 2009 issue of the Journal of Prolotherapy also
presented five before and after X-rays of knees showing cartilage
regeneration.43 Does this prove that all Prolotherapy treatments on
degenerated knees stimulate cartilage regeneration?
Absolutely not! But it surely shows that
Prolotherapy treatments to human knees do have the potential to
regenerate articular cartilage. For those who have had numerous
treatments and have seen the function, signs, and symptoms of their
degenerated joints reverse with Prolotherapy, is it reasonable to assume
that the articular cartilage is being stimulated to repair? How else
would you explain a decline in stiffness, clicking, and crunching in the
person’s knee treated with Prolotherapy? How do you explain the
inability to walk or do any athletics, but yet with a number of
Prolotherapy injections,
(Watch where do
Prolotherapy injections go and do they hurt?)
into and around the knee, the person regains his
walking ability and is now able to perform athletics? How about
improvement with Prolotherapy in those patients who have been told they
need knee replacements, or those whose doctors say there is no other
treatment available for them? What about in these cases? If the person
receives Prolotherapy to their end-stage osteoarthritic joint and not
only do they not need a knee replacement, they are back to dancing, how
do you explain it? Placebo? I think not. Something has changed. Their
joint architecture has changed. There has been some rebuilding inside
their joints. In essence, they have a regenerated joint. The
chondrocytes have been activated to start making cartilage and that
cartilage has been laid down.
I believe in changed lives. I believe a changed life is enough. In other
words, if a person cannot walk much because of a degenerated knee and
has been told by an orthopedist that he needs a knee replacement, but he
refuses and decides instead to get Prolotherapy, and if after
Prolotherapy treatments he can walk well with virtually no symptoms, I
am satisfied. Their life was changed with Prolotherapy. I believe the
patients when they tell me that it was the Prolotherapy that turned
their lives around. I believe that the Prolotherapy regenerated the
injured tissues. I believe that the person can now have a full life.
That full life is because of Prolotherapy. Prolotherapy worked for them.
I do not need an MRI or X-rays or a biopsy of cartilage cells to know
that Prolotherapy worked!
The bottom line is you can’t have it both ways. If the orthopedist is
saying to a patient that your knee pain, grinding, crunching, pain upon
bending your knee, and your inability to walk without a limp is from
your cartilage degeneration and you need a knee replacement, then the
opposite must also be true. If that same patient, after receiving
Prolotherapy to the knee, has no more, or very little, pain, grinding,
etc., can walk unlimited and does hiking and climbing, then it must mean
that their degenerated cartilage has been regenerated! To put it
bluntly, Prolotherapy regenerated their cartilage! This is my main
point!
I know there are a lot of skeptics out
there. They want “evidence” that Prolotherapy works. They need to see
before and after X-rays and MRIs. Well, that is part of the purpose of
the Journal of Prolotherapy. The goal is to educate the world
on the life-changing effects of Prolotherapy. Some of the people in the
world who need educating are the traditional doctors who treat pain
patients. They need to know of the life-changing effects of Prolotherapy
on degenerated joints. One of the effects of Prolotherapy is to change a
degenerated joint without much cartilage to a joint that has more
cartilage. How will that appear to the physician examining the joint?
The doctor would notice a smooth-gliding joint instead of a joint that
makes grinding, clicking, and popping sounds while the physician puts
the joint through its range of motion. It is definitely noticeable and
demonstrable. To the patient, the joint after Prolotherapy will produce
much less crunching or clicking sounds when the knee or joint is moved,
as well as when going up and down stairs. As a given, he will experience
less pain and stiffness.
CALL TO ACTION
Here are some suggestions to those with degenerated joints that were
regenerated with Prolotherapy, and for those who use Prolotherapy in
their practices. Let’s start obtaining before and after Prolotherapy
X-rays, and if possible even MRIs. Make sure the X-rays and MRIs taken
after Prolotherapy are compared to the ones taken before Prolotherapy,
and are evaluated by an independent radiologist who understands that the
patient had Prolotherapy. I believe that you will most likely see
structures be regenerated! The average radiologist has never seen
menisci or cartilage tissue regeneration. (See
A Retrospective Study Shows Prolotherapy is Effective in the Treatment of
MRI-Documented Meniscal Tears)
Tell him you performed (or
received if you are the patient) Prolotherapy on the joint. Ask him
specifically if he sees regeneration of articular cartilage, menisci,
ligaments and any other structures? Do not be surprised when the
radiologist says, “yes.” Send us the films to be published in the
Journal of Prolotherapy. Perhaps then we can eliminate some of the
skepticism about Prolotherapy and people can receive the treatments they
really need, such as Prolotherapy. At least one of the myths that
prevails in the world of orthopedics, that articular cartilage does not
regenerate, will be dismissed once and for all. We can then rejoice
because people with pain will get the treatments they need. Perhaps
people everywhere will finally understand that cartilage can be
stimulated to repair, and that it is Prolotherapy that is needed to
regenerate articular cartilage.
BIBLIOGRAPHY
1. Sandell L, et al. Articular
cartilage and changes in Arthritis: Cell biology of osteoarthritis.
Arthritis Research & Therapy. 2001; 3(2):107-113.
2. Hamerman D. The biology of osteoarthritis. N Engl J Med. 1989;
320:1322-1330.
3. Goldring MB. Osteoarthritis and cartilage: The role of cytokines in
this disorder. Curr Rheumatol Rep. 2000;2:459-465.
4. Meachim G, et al. Cell counts of normal and osteoarthritic articular
cartilage in relation to the uptake of sulphate in vitro. Ann Rheum Dis.
1962;21:45-50.
5. Mankin HJ, et al. Biochemical and metabolic abnormalities in
articular cartilage from osteoarthritic human hips. II. Correlation of
morphology with biochemical and metabolic data. J Bone Joint Surg Am.
1971;53A:523-537.
6. Rothwell AG, et al. Chondrocyte multiplication in osteoarthritic
articular cartilage. J Bone Joint Surg Brit. 1973;55:588-594.
7. Ryu J, et al. Biochemical and metabolic abnormalities in normal and
osteoarthritc human articular cartilage. Arthritis Rheum. 1984;
27:49-57.
8. Sandy J, et al. In vivo and in vitro stimulation of chondrocyte
biosynthetic activity in early experimental osteoarthritis. Arthritis
Rheum. 1984;27:388-397.
9. Eyre D, et al. Biosynthesis of collagen and other matrix proteins by
articular cartilage in experimental osteoarthritis. Biochem J.
1980;188:823-837.
10. Lippiello L, et al. Collagen synthesis in normal and osteoarthritic
cartilage. J Clin Invest. 1977;59:593-600.
11. Sandell LJ, et al. Alternatively spliced type II procollagen mRNAs
define distinct populations of cells during vertebral development:
Differential expression of the amino-propeptide. J Cell Biol. 1991;
114:1307-1319.
12. Oganesian A, et al. Type IIA procollagen amino-propeptide is
localized in human embryonic tissues. J Histol Cytochem. 1997;45:
1469-1480.
13. Hering TM. Molecular biology of cartilage repair. In Osteoarthritic
Disorders Edited by Kuettner K, et al, Rosemont, Illinois: American
Association of Orthopaedic Surgeons, 1995;pp.329-340.
14. Altman R, et al. Development of criteria for the classification and
reporting of osteoarthritis. Arthritis Rheum. 1986;29:1039-1049.
15. Aigner T, et al. Differential expression of collagen types I, II,
II, and X in human osteophytes. Lab. Invest. 2005;73:236-243.
16. Matyas JR, et al. Gene expression of type II collagens in
chondro-osteophytes in experimental osteoarthritis. Osteoarthritis Cart.
1997;5:99-105.
17. Pottenger LA, et al. The effect of marginal osteophytes on reduction
of varus-valgus instability in osteoarthritic knees.
Arthritis Rheum. 1990;33:853-858.
18. Uchino M, et al. Growth factor expression in the osteophytes of the
human femoral head in osteoarthritis. Clin Orthop Rel Res.
2000;pp.119-125.
19. Colao A, et al. Reversibility of joint thickening in acromegalic
patients: an ultrasonography study. Journal of Clinical Endocrinology
and Metabolism. 1998;83:2121-2125.
20. Colao A, et al. Twelve months of treatment with octreotide-LAR
reduces joint thickness in acromegaly. European Journal of
Endocrinology. 2003;148:31-38.
21. Barkan A. Acromegalic arthropathy and sleep apnea. Journal of
Endrocrinology. 1997;155:S41-S44.
22. Chrisman OD. The effect of growth hormone on established cartilage
lesions. Clinical Orthopedics. 1975;107:232-238.
23. Sledge CB. Growth hormone and articular cartilage. Federation
Proceedings. 1973;32:1503-1505.
24. Smith R, et al. Growth hormone stimulates insulin-like growth factor
actions on adult articular chondrocytes. Journal of Orthopaedic
Research. 1989;7:198-207.
25. Werther G, et al. Visual demonstration of growth hormone receptors
on human growth plate chondrocytes. Journal of Clinical Endocrinology &
Metabolism. 1990;70:1725-1731.
26. Mankin H. The effect of aging on articular cartilage. Bull New York
Acad. Med. 1968;44:545-552.
27. Elliott H. Studies on articular cartilage. Am J Anat. 1936;58:
127-145.
28. Telhag H. DNA synthesis in degenerated and normal joint cartilage in
full-grown rabbits. Acta Orthop. Scandinavica. 1973;44: 604-610.
29. Rothwell A, et al. Chondrocyte multiplication in osteoarthritis
Articular Cartilage. Journal of Bone and Joint Surgery. 1973;55B:
588-594.
30. O’Driscoll S. Current concepts review- The healing and regeneration
of articular cartilage. Journal of Bone and Joint
Surgery. 1998;80:1795-1812.
31. Redman S, et al. The cellular responses of articular cartilage to
sharp and blunt trauma. Osteoarthritis and Cartilage. 2004;12: 106-116.
32. Mankin H. The response of articular cartilage to mechnical injury.
Journal of Bone and Joint Surg Am. 1982;64:460-466.
33. Lane J, et al. Anaerobic and aerobic metabolism in articular
cartilage. Journal of Rheumatology. 1977;4:334-342.
34. Schwartz R, et al. The effect of environmental pH on
glycosaminoglycan metabolism by normal articular human
chondrocytes. J Lab and Clin Med. 1976;87:198-205.
35. Smith T, et al. Role of growth hormone in glycosaminoglycan
synthesis by articular cartilage. Nature. 1975;253:269-271.
36. Guerne P, et al. Growth factor responsiveness of human articular
chondrocytes in aging and development. Arthritis and Rheumatism.
1994;38:960-968.
37. Hauser R, et al. Prolo Your Pain Away! Third Edition. Beulah Land
Press, 2007;p.32.
38. Hackett G. Joint stabilization. American Journal of Surgery. 1955;
89:968-973.
39.
Reeves K. Prolotherapy: present and future applications in soft
tissue pain and disability. Physical Medicine and Rehabilitation Clinics
of North America. 1995;6:917-925.
40. IBID. Randomized prospective double-blind placebo-controlled study
of dextrose Prolotherapy for knee osteoarthritis with or without ACL
laxity. Alt Ther Health Med. 2000;6(2):37-46.
41. IBID. Randomized, prospective, placebo-controlled double-blind study
of dextrose Prolotherapy for osteoarthritic thumb and finger (DIP, PIP,
and trapeziometacarpal) joints: evidence of clinical efficacy. J Altern
Complement Med. 2000;6(4):pp.311-320.
42. Hauser R, et al.
A retrospective study on dextrose Prolotherapy for
unresolved knee pain at an outpatient charity clinic in rural Illinois.
Journal of Prolotherapy. 2009;1:11-21.
43. Hauser R, et al. Standard clinical X-ray studies document cartilage
regeneration in five knees after Prolotherapy. Journal of Prolotherapy.
2009;1:22-28.
|
Prolotherapy
Our
Prolotherapy Books - 
POWER
OVER PAIN