2097 Henry Tecklenburg Drive Localized Proliferant Injections of the Anabolic Hormones Growth Hormone and Testosterone Marc N. Dubick M.D. 2097 Henry Tecklenburg Drive Suite 203 West Charleston, SC 29414-5739 Prolotherapysc.com

But first a necessary review of Structural pain The enthesis Wound healing

Structural Pain Pain left when epidurals don’t work, surgery was not indicated or did not get rid of all the pain and diskogenic pain or radicular (nerve) pain is not the problem. Primarily involves: Degenerative joints, ligament and tendon degeneration/injury Muscle weakness/deconditioning Degeneration at the enthesis 9/16/2018

The Enthesis Attachment site of tendons and ligaments (TL) to bone This site creates a firm union by splaying out the fibers to create a larger surface area. The enthesis has 2-3 times the cross sectional area as the mid substance TL. 9/16/2018

The Enthesis 9/16/2018

Chronic Enthesis Injuries The consequence of chronic stress at enthesis is tissue micro trauma with altered or incomplete tissue repair. Orderly phased wound repair is absent or aborted in these areas of micro trauma because of hypoxia. Result of acute injuries that have not healed over time. This is enthesopathy or tendonosis. CHRONIC ENTHESIS INJURIES 9/16/2018

Wound Healing Three distinct phases that overlap in time. Inflammation Granulation Remodeling

Wound Healing has distinct phases that overlap in time.

Remodeling Phase To complete healing of LIGAMENTS Movement and loading of the tissue is critical Ligaments need movement from the beginning of the granulation phase There is period of vulnerability when the curve of wound healing is plotted against pain and ligament strength. Period of vulnerability is proportional to original severity of injury and expected demand.

Remodeling Phase To complete healing of TENDONS Movement and some loading of the tissue is critical to a good outcome Periods of stress need to be spaced with rest periods from 4 to 72 hours Stress needs to be incrementally increased Progressive stress is critical What is the balance between stress, rest and intensity?

Diagnosis and Treatment First and Foremost Make the correct diagnosis Combination of a complete HPI and thorough structural Physical Examination Careful listening often provides the diagnosis Imaging studies Local anesthetic injections DIAGNOSIS AND TREATMENT Sacroiliac pain Look--patient can't sit at all or for long on affected side Listen--Increased pain with driving, prolonged sitting or standing Frequent presenting symptom—”My knee buckles and I fall occasionally”. Failure of the Slip-Clutch Mechanism--due to posterior sacral ligament weakness and causes the knee to give way. Touch--pain pinpointed at the sacroiliac joint, inferior sacral boarder, leg length discrepency 9/16/2018

Initial Conservative Treatment Evaluation and treatment by Physical Therapy or Chiropractic Joint manipulation Stabilization exercises Core strengthening exercises Aerobic exercise Local anesthetic/steroid injection as a therapeutic/diagnostic measure Healthy diet/Nutritional supplements INITIAL CONSERVATIVE TREATMENT 9/16/2018

Treatment When Conservative Measures Fail: Proliferant Injections The iatrogenic stimulation of the wound healing and tissue repair process.

Three Types of Proliferant Injections Prolotherapy--Injection of a glucose based solution that stimulates new tissue formation via an intense inflammatory response Growth Hormone/Testosterone--Localized injections that directly stimulate healing on a cellular basis TREATMENT WHEN CONSERVATIVE MEASURES FAIL 9/16/2018

Indications for Proliferant Injections Chronic ligament and tendon weakness/laxity Chronic tendonosis or degenerative ligament changes/enthesopathies virtually anywhere in the body Continued joint instability despite frequent joint manipulations PROLOTHERAPY INDICATIONS 9/16/2018

Most Common Areas Treated Cervical, Thoracic, Lumbar Spine Sacroiliac Joints/Ligaments Shoulder, Elbow, Wrist Hip, Knee, Ankle, Foot Essentially at any ligament or tendon enthesis or in any joint/capsule 9/16/2018

hGH and Testosterone hGH—anabolic protein hormone—NOT A STEROID Recombinant human growth hormone (DNA origin) Manufactured from e. coli bacteria Testosterone—anabolic/androgenic steroid hormone Synthetic bioidentical hormone compounded in an aqueous form

Hormone Molecules aka ligands—molecules that are able to bind to other molecules and form new ones that serve biological purposes Signal triggering molecules that bind to a particular site on a target cell known as a receptor protein Secreted by specialized cells and carried by the circulatory system to their target organs Have cell wall receptors

hGH and Testosterone Intrinsic factors Vitally important for normal body function and wound healing Share many common pathways and stimulate the production of common cytokines necessary for wound healing Major impact likely in the first few minutes of wound healing The effect of the two together most probably outweighs the effect of each one individually

Cytokines A small protein released by cells that has a specific effect on the interactions between cells, on communications between cells or on the behavior of cells.

Questions to be answered How can hGH and testosterone help when epidurals don’t work, surgery was not indicated or did not get rid of all the pain and diskogenic pain or radicular (nerve) pain is not the problem ? Where and how do hGH and testosterone work in stimulating or aiding wound healing and tissue repair ? 9/16/2018

hGH and testosterone play key roles in regulating cell functions Stimulation of protein synthesis Releasing signaling molecules Altering cell wall flexibility Modify pain perception Adjustment of blood flow at wound site Occur in time periods ranging from a few seconds to 24 hours hGH and testosterone play key roles in regulating cell functions

hGH Regulates key metabolic processes and specifically those related to protein synthesis Action achieved through the stimulation of the Growth Hormone Receptor and the IGF-1 pathway Many effects on growth and metabolism mediated indirectly by control of the synthesis of other growth factors A gene, activated by hGH has been discovered that is critical for the body’s tissues to heal and regenerate Not as much research on cellular specifics as with testosterone—all cells appear to be involved, but particularly the macrophages

Testosterone Changes cell wall flexibility Influences cellular adhesions Influences cell-cell interactions Increases local blood supply by changing the voltage dependent ion channels ! Stimulates production of cytokines and other peptides to help direct acute inflammation Decreases the pain of injections by stimulation of the GABA receptors Potent effect on the remodeling phase of wound healing, where it stimulates collagen deposition

HGH Studies Reduction in wound healing times, morbidity, mortality in severe burn patients--systemic Improvement in healing of donor skin grafts—applied topically Healing of iatrogenic bone defects in animal studies--systemic Stimulation of forearm muscle mass—locally injected Enhanced reparative collagen deposition during wound healing in healthy older men--systemic 9/16/2018

PROLIFERANT INJECTIONS: THE IATROGENIC STIMULATION OF THE WOUND HEALING AND TISSUE REPAIR PROCESS

INJECTION CONCEPT Needling a dysfunctional area to iatrogenically create a wound, with resultant bleeding and the initiation of the wound healing cascade. Injection of anabolic hormones, hGH and testosterone in supra-physiologic doses that will jump start the healing process on a cellular basis and markedly enhance the arriving intrinsic hormones, platelets, growth factors, etc. Will negate the possible negative effect of low intrinsic testosterone, which could slow healing

Patient Selection Patients need good healing capacity and motivation to improve Avoid individuals with: Primary discogenic pain Chronic illness, true fibromyalgia, immunocompromised Bedridden with chronic pain Alcohol, drug, or tobacco abusers Malnourished Secondary gain issues Need other proliferants for active professional athletes 9/16/2018

Case History 25 y.o. healthy female with 1 month hx of right sided low back pain which occurred acutely while playing tennis. Hx of previous back injury 6 yrs. Past after falling down 3 steps. Chiropractic treatment for 3 weeks resolved the problem Top flight HS athlete who holds the SCISA record for hurdles

Initial Treatment for First Month Chiropractic care since injury Physical Therapy evaluation performed—diagnosis of right sacroiliac joint dysfunction—treatment followed Imaging studies—normal No improvement after one month of Chiropractic and Physical Therapy

H & P Right Sacroiliac joint and L5-S1 facet dysfunction Moderate to severe right hip capsule laxity Pubic symphysis asymmetry Right hip adductor tendinitis/tendinosis at attachments on anterior ischium and inferior pubic ramus

Initial InjectionTreatment Local anesthetic/ Anti-inflammatory injection right sacroiliac joint, L4-5, L5-S1 facet joint capsules Results—short term significant pain relief Injection procedure performed under fluoroscopic guidance as are all of my injections

Treatment Plan Series of hGH/testosterone/procaine injections to sacroiliac joints/ligaments, L4-5, L5-S1 facet joint capsules, right hip capsule, right hip adductors, pubic ligaments. Three injections planned per body area (not all at same sitting)

Results During 1st injection, excellent tissue density found at pubic ligaments, left sacroiliac joint and ligaments, L4-5 facet capsule and these areas were no longer treated. After a series of injections, with each area being treated 3 times, patient reported no pain and minimal ligament/joint weakness was found by treating chiropractor. Two months following procedures, patient began running and has not slowed down since. Now 2 years post treatment and is 100% improved, exercising and receiving maintenance joint mobilization

Rational for this unusual unilateral injury—High Hurdles

hGH/Testosterone study IRB approval Prospective Outcome Study: The Treatment of Chronic Enthesopathies of Ligaments and Tendons with Localized Growth Hormone and Testosterone Injections 2 year study 100 participants

Hypothesized Benefits of hGH/testosterone Average three injections per body area Minimal pain Rapid onset of healing and joint stability Ability to use large volumes of injectate Safe solution