Cellular Mechanisms of Estrogen on Cartilage
Dr Tanko from Denmark summarized three decades of medical research in an article published in 2008 in Climacteric entitled, " Review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage." (8) The authors state, " Estrogen receptors have been identified in articular chondrocytes from various animals and humans." They conclude: "The effects of estrogen on articular cartilage further corroborate the due consideration of estrogen therapy for maintaining not only bone but also cartilage health in postmenopausal women." . (8)
Animal Studies
Estrogen Replacement in Monkeys Prevents OA
A
study published in Arthritis Rheumatism 2002 entitled,"Effects
of long-term estrogen replacement therapy on osteoarthritis severity in
monkeys", by Dr Ham from the University of Minnesota, examined estrogen
replacement therapy (ERT) on the severity of osteoarthritis
(OA) of the knee joint in postmenopausal female monkeys (after surgical
removal of the ovaries).(7)
After three years of estrogen treatment, using Premarin, the monkeys were sacrificed and knee joints examined histologically. The authors found that cartilage lesions of osteoarthritis (OA) were significantly less severe in the animals given estrogen replacement (ERT) compared with those in the control group. The authors concluded," These results demonstrate that long-term estrogen replacement (ERT) significantly reduces the severity of osteoarthritis (OA).(7)
Ovarectomized Mice Treated with Estrogen
A 2006 study by Tanko from Denmark published in Arthritis Rheumatism found that estrogen prevented joint and cartilage degradation in an animal model with mice. This article was entitled,"Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation."(9) The authors found that "treatment of the animals with estrogen counters the acceleration of type-two collagen degradation and these benefits can be maximized by early initiation after menopause. The protective effect of estrogen seems to involve direct inhibition of the catabolic function of chondrocytes." (9)
Pig Studies
Similarly in pigs, researchers found estrogen prevents cartilage degradation. This study was published by Claassen from Germany in 2002 Annals of Anatomy, entitleded, " The effect of estrogens and dietary calcium deficiency on the extracellular matrix of articular cartilage in GÃ ¶ttingen miniature pigs." (10) Their study investigated how estrogen deficiency affects the articular cartilage . They found that in animals with estrogen deficiency, the articular cartilage underwent degradation, i.e. similar changes to those observed in physiologically aging cartilage.(10)
Electron Microscope Study of Estrogen Deficiency Induced Arthritis in the Guinea Pig
A guinea pig study by Dr Dai from China was published in the Chinese medical Literature, in 2005, entitled,"The relationship of the expression of estrogen receptor in cartilage cell and osteoarthritis induced by bilateral ovariectomy in guinea pig." (11)
The authors used the scanning electron microscope (SEM) and transmission electron microscope (TEM) to analyze cartilage degeneration in joints after ovariectomy, which produces estrogen deficiency in the animals. The authors looked at estrogen receptors and serum levels of estrogen. They indeed found estrogen receptors (ER) in the cartilage of the guinea pigs. They also found Joint Cartilage degeneration detected by electron microscopy at 6 weeks, with severe degenerative lesions at 12 weeks after removal of ovaries compared to the control group. The author concludes that , "bilateral ovariectomy in the guinea pig leads to severe osteoarthritis ".(11)
Ovarectomized Sheep Treated With Estradiol Implants
Published in 1997 in Osteoarthritis Cartilage, a study entitled," Biochemical effects of estrogen on articular cartilage in ovariectomized sheep" by Dr AS Turner from Colorado State University, looked at estrogen replacement with estradiol implants in ovarectomized sheep.(12) After twelve months, the articular cartilage from the knee joints were carefully evaluated. Ovarectomy, with its attendant estrogen deficiency had a significant deleterious effect on articular cartilage. Treatment with estradiol, a bioidentical hormone, reversed these deleterious effects, and maintained structural integrity of the joints. (12)
Another sheep study published in 2005 in Osteoarthritis Cartilage, entitled, "Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage iNOS", by Dr MA Cake MA from Australia examined the effect of estrogen depletion (ovariectomy) on articular cartilage of the joints, and the production nitric oxide synthase (iNOS). (13)
At 26 weeks after removal of the ovaries, the joints were studied histologicaly, and amounts for nitric oxide (NO) studied. In the estrogen deficient animals, cartilage thickness was reduced, along with arthritic changes and upregulated nitric oxide production. (13) The authors conclude, "estrogen depletion caused regional thinning of femoro-tibial cartilage, with biomechanical and histological changes suggestive of a disturbance in proteoglycan and collagen."(13)
Animal Model Summary Paper
In 2008, Dr Sniekers of the Netherlands summarized all preceding animal studies in a report published in Osteoarthritis Cartilage, entitled," Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment - a systematic approach." (14)
Dr Tanko from Denmark summarized three decades of medical research in an article published in 2008 in Climacteric entitled, " Review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage." (8) The authors state, " Estrogen receptors have been identified in articular chondrocytes from various animals and humans." They conclude: "The effects of estrogen on articular cartilage further corroborate the due consideration of estrogen therapy for maintaining not only bone but also cartilage health in postmenopausal women." . (8)
Animal Studies
Estrogen Replacement in Monkeys Prevents OA
After three years of estrogen treatment, using Premarin, the monkeys were sacrificed and knee joints examined histologically. The authors found that cartilage lesions of osteoarthritis (OA) were significantly less severe in the animals given estrogen replacement (ERT) compared with those in the control group. The authors concluded," These results demonstrate that long-term estrogen replacement (ERT) significantly reduces the severity of osteoarthritis (OA).(7)
Ovarectomized Mice Treated with Estrogen
A 2006 study by Tanko from Denmark published in Arthritis Rheumatism found that estrogen prevented joint and cartilage degradation in an animal model with mice. This article was entitled,"Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation."(9) The authors found that "treatment of the animals with estrogen counters the acceleration of type-two collagen degradation and these benefits can be maximized by early initiation after menopause. The protective effect of estrogen seems to involve direct inhibition of the catabolic function of chondrocytes." (9)
Pig Studies
Similarly in pigs, researchers found estrogen prevents cartilage degradation. This study was published by Claassen from Germany in 2002 Annals of Anatomy, entitleded, " The effect of estrogens and dietary calcium deficiency on the extracellular matrix of articular cartilage in GÃ ¶ttingen miniature pigs." (10) Their study investigated how estrogen deficiency affects the articular cartilage . They found that in animals with estrogen deficiency, the articular cartilage underwent degradation, i.e. similar changes to those observed in physiologically aging cartilage.(10)
Electron Microscope Study of Estrogen Deficiency Induced Arthritis in the Guinea Pig
A guinea pig study by Dr Dai from China was published in the Chinese medical Literature, in 2005, entitled,"The relationship of the expression of estrogen receptor in cartilage cell and osteoarthritis induced by bilateral ovariectomy in guinea pig." (11)
The authors used the scanning electron microscope (SEM) and transmission electron microscope (TEM) to analyze cartilage degeneration in joints after ovariectomy, which produces estrogen deficiency in the animals. The authors looked at estrogen receptors and serum levels of estrogen. They indeed found estrogen receptors (ER) in the cartilage of the guinea pigs. They also found Joint Cartilage degeneration detected by electron microscopy at 6 weeks, with severe degenerative lesions at 12 weeks after removal of ovaries compared to the control group. The author concludes that , "bilateral ovariectomy in the guinea pig leads to severe osteoarthritis ".(11)
Ovarectomized Sheep Treated With Estradiol Implants
Published in 1997 in Osteoarthritis Cartilage, a study entitled," Biochemical effects of estrogen on articular cartilage in ovariectomized sheep" by Dr AS Turner from Colorado State University, looked at estrogen replacement with estradiol implants in ovarectomized sheep.(12) After twelve months, the articular cartilage from the knee joints were carefully evaluated. Ovarectomy, with its attendant estrogen deficiency had a significant deleterious effect on articular cartilage. Treatment with estradiol, a bioidentical hormone, reversed these deleterious effects, and maintained structural integrity of the joints. (12)
Another sheep study published in 2005 in Osteoarthritis Cartilage, entitled, "Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage iNOS", by Dr MA Cake MA from Australia examined the effect of estrogen depletion (ovariectomy) on articular cartilage of the joints, and the production nitric oxide synthase (iNOS). (13)
At 26 weeks after removal of the ovaries, the joints were studied histologicaly, and amounts for nitric oxide (NO) studied. In the estrogen deficient animals, cartilage thickness was reduced, along with arthritic changes and upregulated nitric oxide production. (13) The authors conclude, "estrogen depletion caused regional thinning of femoro-tibial cartilage, with biomechanical and histological changes suggestive of a disturbance in proteoglycan and collagen."(13)
Animal Model Summary Paper
In 2008, Dr Sniekers of the Netherlands summarized all preceding animal studies in a report published in Osteoarthritis Cartilage, entitled," Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment - a systematic approach." (14)
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