Damaging Contributions to Cartilage and Glycosaminoglycan Processing

ANTIDEPRESSANTS  ENDANGER BONE and JOINTS

• Ray: Cyclic antidepressants may increase hip fracture risk. J of Manip Med (12/91):46
  

• Bockman RS et al: Steroid induced osteoporosis. Ortho Clin of N Amer 21(1):97
  
• Fries: Prednisone greatly increases fracture risk. J of Musculoskeletal Med (6/92):16
  
• Mitchell: [Steroid use causes osteo-degenerative arthritic hips]. Radiology 1987; 62(3):709
  
• Fessler: [Chronic steroid use leads to epidural lipomatosis.] Spine 1992; 17(2)
  

• Yoo: Suppression of proteoglycan synthesis in chondrocyte cultures derived from canine intervertebral disc. Spine 17(2):221-224
  
• Newman: Lancet 1985; pgs. 11-14
  
• VanDerKraan et al: High susceptibility of human articular cartilage glycosaminoglycan synthesis to changes in inorganic sulfate availability. J of Ortho Research 1990; 8(4):565-71
  
• Whittaker: Arthritis drugs actually cause cartilage destruction! Health & Healing 3(6):1-4
  

• Palmoski: Arthritis and Rheumatism 1985; 28:548;   DeVries: Arthritis and Rheumatism 1985; 28:922-9;   Laan: Arthritis and sciatica drug weakens vertebrae. Backletter 1994;9(2):22
  

• Glucosamine Sulfate
  
• Perna Canaliculus  (pure chondroitin sulfate)
  

• from green lipped mussel (shellfish); those allergic to shellfish should be cautious
  

Glucosamine Sulfate                   
may prevent degeneration & promote regeneration of cartilage
- improves mobility and relieves pain with significantly less side effects than NSAIDs
- has good tolerability
- maintains its good benefits even if there is an interruption in taking them compared with drug therapy which relieves pain only while taking the drug

• Glucosamine sulfate (GS) is a naturally occurring part of joint cartilage and forerunner for and stimulant of proteoglycan synthesis and the making of GAG which is necessary for development of the white fibrocartilage of the disc. Unlike NSAIDs which relieve symptoms of and, over time, accelerate the destruction of, degenerative joint and disc disease, glucosamine has been shown in experiments to slow the progression of the degenerative disease and promote repair of affected cartilage:
  
• Two similar yet separate experiments^6,7 were conducted and gained similar results: patients receiving GS improved by 71% compared to a placebo group.⁶ 
  
• A comparison⁸ of 2 groups --one receiving ibuprofen and one GS three times per day (total of 1500 mg) for 30 days--showed that the GS group reported less pain on rest, standing, and exercise. The GS group's improvement was more pronounced, lasting for a period of 6 to 12 wks after the treatment ended.
  
• In a double-blind study⁹ of people suffering from osteoarthritis of the knees compared a placebo group to a GS group. The GS group showed significant reduction in pain, joint tenderness, and swelling  treated with 1500 mg GS daily.
  
• Findings by electron micrographs of cartilage of persons receiving GS compared to a placebo¹⁰ show:
  
• Placebo results - typical of osteoarthritis;             GS results - more similar to healthy cartilage.
  
• GS is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In a clinical trial, GS was tested against ibuprofen. 35% of the ibuprofen group complained of adverse effects throughout the treatment, with seven dropping out of the study. Only six of the 100 patients in the GS group experienced adverse effects. Therefore, GS was as effective as ibuprofen.¹⁸
  
• GS is the preferred form of glucosamine (over GS HCl, for example) and the only form of glucosamine subjected to over 300 scientific investigations & 20 double-blind studies. ²⁹
  
• The absorption rate for GS is about 98%. ^24,25
  
• GS is extremely non-toxic, and its therapeutic margin is 10-30 times better than NSAIDs ²⁶ When taken orally, it is more effective than placebo and at least as effective as NSAIDs in relieving the symptoms of osteoarthritis. ²⁸
  
• 2% of 1500 patients were unable to tolerate GS: peptic ulcer and diuretic use were associated with increased risk of side effects, most commonly: gastric upset (3.5%), heartburn (2.7%), diarrhea and nausea (1%). ²⁷
  

• Supplemented chondroitin sulfates work like naturally occurring chondroitins found in cartilage:
  

• The central event in osteoarthritis and degenerative disc disease is the loss of the proteoglycans from the disc. ³²
  
• Low GAG precedes degenerative disc disease; injured and adjacent discs show less GAG and increased collagen. ³³
  
• osteodegenerative arthritis shows increased release of GAG. ³⁴
  
• Arthrosis shows a loss of glycosaminoglycan. ³⁵
  
• Bucci reports that OSTEOARTHRITIS CAN BE REVERSED by chondroprotective agents - GAGs - if use of analgesics (aspirin, non-steroidal drugs) is minimal.¹ Further, he states that oral administration of GAGs is better than injection because constant higher levels can be maintained in the bloodstream instead of short periods of elevation by shots.
  
• Cole, Ghosh & Taylor wrote that mature beagle dogs, when given GAG over a 26 wk period, showed cartilage improvement.² These  findings  were  the  first  to suggest that GAG administration might  be  of value in management  of  degenerative disc disease.A 50% loss of GAG from rabbit articular cartilage when arthritis of the joint was reported in one study. This caused the cartilage matrix to be less capable of restoring the proteoglycan content of the cartilage and resulted in loss of joint stiffness and resistance to the compression.³
  
• In rabbits with osteoarthritis of the knee, injection of sulfated GAG inhibited enzymes that destroy cartilage and promoted repair of the defects. GAG had been found to increase proliferation of the hyaline cartilage of the hip joint in mice and the femoral condyles, femur and tibia of rabbits. Furthermore, Puhl and Dustmann induced regeneration of damaged cartilage in rabbits. ⁵
  
• 120 patients suffering from osteoarthritis of the knees and hips were either given oral chondroitin sulfates or a placebo. After three months, the group given the oral chondroitin in the morning and the evening reported a reduction in pain and pain movement. There were no reported side effects. In addition, there was a 60-day carry-over effect when administration was stopped. Results appeared within 2 to 8 weeks. ¹⁶
  
• 50 patients suffering from osteoarthritis of the knee were given oral chondroitin sulfate or a pain medication. Cartilage tissue samples were taken after three months of therapy. Results showed that the chondroitin group had repaired the cartilage to a significant degree. ¹⁵
  
• Eismont showed circulation into the disc when he reported that antibiotics reach the nucleus pulposus following 8 hours of intramuscular administration.⁴
  
• Dogs given GAG showed less osteophyte formation, less disc space narrowing, better disc injury repair, and prevention of experimental disc degeneration. ³⁶
  
• Trentham et al ¹⁹ (of Harvard University) report in Science on a new way to help rheumatoid arthritis (RA) sufferers: oral tolerization. This procedure involved a liquid solution of cartilage/collagen and orange juice. Dr. Trentham states that this seems to "teach" the body's immune system to stop inflaming the tissue around the joints. This appears to arrest the progress of RA. In a three month trial, 28 patients -- all of whom were taken off all other drugs -- got relief from RA; 4 went into remission. Thirty-one patients on a placebo became worse. Basically, this study finds that the immune system can be

References:
1. Bucci LR:  Reversal of osteoarthritis by nutritional intervention. ACA J of Chiropractic (11/90): 69-72.
2. Cole TC, Ghosh P, Taylor TKF: Arteparon modifies proteoglycan turnover in the intervertebral disc. British J of Bone and Joint Surgery 1988; 70B(1):166 .
3. Lowther DA: The effect of compression and tension on the behavior of connective tissues. Aspects of Manipulative Therapy, Churchill Livinstone 1985:16-21.
4. Eismont FL et al: Antibiotic penetration into rabbit nucleus pulposus. Spine 12(3): 254-6.
5. Wilhelmi, Maier: Experimental studies on the effects of drugs on cartilage. Ciba Geigy Documenta Geigy, Basle, Switzerland, 1982.
6. D'Ambrosio E et al:  Glucosamine sulfate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 1981;2:504-8
7. Crolle G, D'Este E:  Glucosamine sulphate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin 1980;7:104-9
8. Vaz: Double-blind clinical evaluation of relative efficacy of glucosamine sulphate in the management of osteoarthritis of knee in out-patients. Curr Med Res Opin '82;8:145-9.
9. Pujalte JM et al: Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthritis." Curr Med Res Opin 1980;7:110-14
10. Drovanti A et al: Therapeutic activity of oral glucosamine sulfate in osteoarthritis: a placebo-controlled, double-blind investigation. Clin Ther 1980;3:260-72
11. Benedikt H: Glycosaminoglycans and derivatives for treatment of arthritis. Chiropractic Products 1997; May: 92-95
12. Soldani G, Romangnoli J: Experiment and clinical pharmacology of glycosaminoglycan (GAGS). Drugs in Experimental and Clinical Research 1991; 18(1):81-85.
13. Rovetta G: Galactosaminoglycuronglycan sulphate (matrix) in therapy of tibiofibular osteoarthrosis of the knee. Drugs in Experimental and Clin Research 1991; 18(1):53-57.
14. Pruden JF, Balassa LL: The biological activity of bovine cartilage preparations. Seminars in Arthritis and Rheumatism 1974; 3(4):287+.
15. Pepitone VR: Chondroprotection with chondroitin sulfate. Drugs in Experimental and Clinical Research 1991; 17(1):3-7.
16. Olivero U et al: Effects of treatment with matrix on elderly people with chronic articular degeneration. Drugs in Experimental and Clincal Research 1991; 17(1):45-51.
17. Wellburn M: Shotgun approach may quell arthritis, rheumatism, and back pain! J of Arthritis Research 1994; Sept:15-22.
18. Fassender HM et al: Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis and Cartilage 1994; 2(1):61-69.
19. Trentham DE et al: Effects of oral administration of Type II collagen on rheumatoid arthritis. Science 1993; 261
20. "Chicken bone protein aids arthritis sufferers, scientist says." Dallas Morning News 24 September 1993:sec. A, p. 6.
21. Theodosakis J, Adderly B, Fox B: The Arthritis Cure. New York: St. Martin's Press, 1997: 55.
22. Sullivan MX, Hess WC: Cystine content of finger nails in arthritis. JBJS 1935; 16:185-8.
23. Senturia BD: Results of treatment of chronic arthritis and rheumatoid conditions with colloidal sulphur. JBJS 1934; 16:119-25.
24. Setnikar I et al: Pharmacokinetics of glucosamine in man. Arzneim Forsch 1993; 43(1):1109-13.
25. Setnikar I et al: Pharmacokinetics of glucosamine in the dog and man. Arzneim Forsch 1986; 36(4):729-35.
26. Arzneim Forsch 1991; 41:542-5
27. Pharmatherapeutica 1982; 3:157-68
28. Reicht A, Forster KK, FIscher M et al: Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. Arzneimittle-Foschung 1994; 44(1):75-80
29. Murray MT: Irrefutable evidence: glucosamine sulfate proven superior over other forms of glucosamine and chondroitin sulfate. Vital Communications, Inc.
30. Aitman: Arthritis and Rheumatism 1991; 31(1)
31. Hutton et al: Analysis of chondroitin sulfate in lumbar intervertebral discs at two different stages of degneration as assessed by discogram. J of Spinal Disorders 1997; 10(1)
32. Bishop PB, Bray RC: Abnormal joint mechanics and the proteoglycan composition of normal and healing rabbit medial collateral ligament. JMPT 1994; 16(5):300-5
33. Melrose, Ghosh, Taylor, Osti, Vernon-Roberts: A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the anulus fibrosus. Journal of Orthopedic Research, vol. 10
34. Ratliffe: Increased release of matrix componenets from articular cartilage in experimental canine osteoarthritis. J of Orthopedic Research, vol. 10
35. Olsen: Acta Orthop Scand 1989; 60(1):23-25

36. Internaional Society for the Study of the Lumbar Spine. Proceedings published by Saunders. 1990:13.

Disclaimer:  No claims are being made, either expressed or implied, that these products will cure disease, replace prescribed medications, or replace sound advice from a physician.