Effects of Traditional Chinese Medicine on Bone Loss in SAMP6: A Murine Model for Senile Osteoporosis

Abstract

In healthy adults, the amount of bone formation approximately balances the amount of bone resorption. In aged individuals, the balance shifts to favor bone resorption, which can result in debilitating diseases such as osteoporosis. Osteoporosis is a skeletal disorder characterized by compromised bone strength, and predisposes a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality. 1)Osteoporosis is regarded as a heterogeneous disorder with multiple causes. It is roughly divided into two distinct types. Type I, known as postmenopausal osteoporosis, occurs in women after menopause. Type II, senile osteoporosis, occurs in both old men and women. Ovariectomy has been extensively used as an experimental model for postmenopausal osteoporosis, while senescence-accelerated mice P6 (SAMP6) can be used as a senile osteoporosis model.2) These mice exhibit a significant decrease in bone mineral density (BMD) and bone formation. It was demonstrated by using light microscopy and histomorphometric method that both osteoclastogenesis and osteoblastogenesis decreased in SAMP6.3) Recently, we found that the osteoblasts showed degenerative changes and the number of osteoblasts decreased, while the mast cells in bone marrows significantly increased in SAMP6 at 2 and 5 months of age. These findings indicated that the lower bone mass in SAMP6 was mainly due to the reduction of osteoblast formation. 4) However, the pathogenesis of senile osteoporosis has not fully been elucidated.Despite numerous investigations, the treatment and prevention of osteoporosis remain unsolved problems. Several agents such as estrogens and selective estrogen receptor modulators, bisphosphonates, calcitonin (CT) and parathyroid hormone (PTH) have been used clinically in the treatment of the disease. Traditional Chinese medicine has developed its own unique system during a period of 3000 years and has recently been reevaluated in the clinical field.5) Chinese medicines are known to have low toxicity and are suitable for long-term administration compared to chemically synthesized medicines. Several Chinese medicines are claimed to be effective in treatment of osteoporosis. By measuring BMD and serum hormone levels, Sassa et al. found that Hochu-ekki-to could elevate the serum level of ovarian hormone and prevent the bone loss in ovariectomized animals.6) Berberine, an isoquinoline alkaloid, could inhibit BMD decrease in both male and female SAMP6.7) It was morphologically demonstrated that Hachimi-jio-gan, Juzentaiho-to and Unkei-to were effective in preventing bone loss induced by ovariectomy in rats.8) However, no data are available as to the recovery of bone loss in SAMP6 by any of these Chinese medicines. In order to evaluate the effects of traditional Chinese medicine on senile osteoporosis, we examined whether Hachimi-jio-gan, Juzen-taiho-to or Unkei-to could prevent the bone loss in SAMP6. MATERIALS AND METHODS Traditional Chinese MedicinesDried extract powder of the traditional Chin...

Comparative Effects of Milk and Soymilk on Bone Loss in Adult Ovariectomized Osteoporosis Rat

“…The serum total cholesterol and triglyceride levels were determined by enzymatic assays (Richmond, 1973; Tamaoku et al, 1982). The serum PTH and estradiol levels were measured using immunoradiometric assay kit as reported before (Chen et al, 2005).…”

Effects of Hachimi-jio-gan Extract on Intestinal Absorption of Calcium in Ovariectomized Mice and Stimulation of RANKL-induced Osteoclast Differentiation of Raw264.7 Cells by Lipopolysaccharide

“…That is, as shown by the MRT ab values of calcium, the rate and is in accordance with previous clinical usage and studies [12][13][14] . For example, Hidaka et al 13) showed that Unkei-to, Hachimi-jiogan, and Juzen-taiho-to are as effective as 17ß-estradiol in preventing the development of bone loss in OVX rats, while Chen et al 15) determined that Hachimi-jio-gan and Juzen-taiho-to are effective in preventing bone loss in SAMP6 mice.…”

“…Mice were randomly divided into two groups of sham-operated (SHAM) and OVX mice. After the mice were anesthetized by ether, SHAM mice were bilaterally nonovariectomized, but the OVX group was bilaterally ovariectomized as previously described [12][13][14][15][16][17] . The mice had free access to food and water during the conditioning period of 4 weeks.…”

“…[12][13][14][15][16][17] The ovariectomized (OVX) animal model is considered appropriate for investigating problems related to postmenopausal bone loss, a primary risk factor for osteoporosis. O'Loughlin and Morris 12) showed that the impairment of intestinal calcium absorption following ovariectomy is not a result of decreased circulating 1,25-dihydroxyvitamin D or intestinal responsiveness to 1,25-dihydroxyvitamin D, but results from estradiol stimulating intestinal calcium absorption probably by a direct effect on the intestine.…”

“…It is believed that Hachimi-jio-gan enhances physical activity and promotes renal function 14) . Furthermore Hachimi-jiogan has been clinically used in treating gynecological diseases and postmenopausal symptoms [14][15][16][17] , such as severe hot flushes, insomnia, muscle aches and pains, formication, fatigue, palpitations and mood swings. Additionally, Hidaka et al 15) showed that Unkei-to, Hachimi-jio-gan, and Juzen-taiho-to are as effective as 17ß-estradiol in preventing the development of bone loss in OVX rats, and Chen et al 17) indicated that Hachimi-jio-gan and…”