Bone loss

Pasteurella multocida toxin (PMT) is the major pathogenic factor responsible for atrophic rhinitis, a disease which is characterized by bone loss in the nose of pigs. PMT is a 145 kDa single-chain exotoxin, which activates Goq protein (but not Gan) and stimulates phospholipase C 3. In addition, G12/i3 proteins and subsequently Rho pathways are activated. 

A common cause of PTH-dependent hypercalcemia results from benign, or occasionally malignant, enlargement of one or more parathyroid glands, a condition known as primary hyperparathyroidism (PHPT). Although many patients with PHPT present in an asymptomatic state that does not require medical intervention, some are afflicted with excess bone loss, kidney stones, or other complications. If patients are... 

Osteoporosis is a common condition, in which bone density is decreased as a consequence of an imbalance between bone formation (osteoblast) and bone loss (osteoclast). This leads to fragile bones, which are at an increased risk for fractures. The term porosis means spongy, which describes the large holes seen in these bones. 

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

Contain potential benefits for men in protection against age-related bone loss and increases in cholesterol levels, without displaying estrogenic proliferative effects in the prostate... 

Summary term for a number of steroid hormones and their precursors with differentiation-inducing activity in many tissues. As regards bone, three components are relevant cholecalciferol ( vitamin D ) 25-hydroxyvi-taminD3 (calcidiol) and 1,25-dihydroxy vitamin D3 (calcitriol). The latter is the biologically active form and increases both intestinal calcium absoiption and bone resorption. Vitamin D preparations are widely used for the treatment of osteoporosis. Daily supplementation with vitamin D reduces bone loss in postmenopausal women and hip fractures in elderly subjects. 

This illness is mainly characterized by an age-related bone loss. The detection of osteocalcin in bone was the starting point for a series of studies on the role of vitamin K-dependent proteins in bone development and maintenance and on possible supplemantation therapies. Epidemiologic studies found differences in the risk of hip fractures depending on the dietary vitamin K... 

Supplementation with high doses of vitamin K1 (1 mg/day for 14 days) or MK-4 (45 mg/day) resulted in decreased levels of undercarboxylated osteocalcin and increase of bone formation markers and in a significant reduction in bone loss, respectively. Using such high doses, any kind of effects besides vitamin K can not yet be ruled out and have to be further elucidated by long term studies. An overview can be found in a review by Palacios [4]. 

Potassium as a nutrient lowers blood pressure, prevents bone loss, and reduces the risk of kidney stones. Some of these effects are due to the loss of sodium in the urine when potassium is ingested. 

Studies have demonstrated that treatment with soy or phytoestrogen enriched diets is effective in conserving bone in rodent models of osteoporosis (Anderson and Gamer, 1998 Ishimi et al, 2000 Draper et al, 1997). The mechanism of action of phytoestrogens on bone health is unclear but several mechanisms including inhibition of bone resorption and stimulation of bone formation maybe involved (Fanti etal, 1998 Ishimi e/a/., 1999 Picherit eta/., 2000). Limited data from studies in postmenopausal women have indicated that phytoestrogen supplements have a small, beneficial effect on bone loss in the lumbar spine (Alekel et al, 2000 Potter et al, 1998 Somekawa et al, 2001). 

ALEKEL D L, ST GERMAIN A, PERESON C T, HANSON K B, STEWART J W, TODA T (2000) IsoflaVOne-rich soy protein isolate attenuates bone loss in the lumber spine of perimenopausal women. Am J Clin Nutr. 72 844-52. 

DRAPER C R, EDEL M J, DICK I M, RANDALL A G, MARTIN G B, PRINCE R L (1997) PhytOeStiOgenS reduce bone loss and resorption in oophrecfomized rats. J Nutr. 127 1795-9. 

The phytoestrogen genistein reduced bone loss in short-term ovariectomised rats. Osteoporosis Int. 8 274-81. 

J p (2000) Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. J Nutr. 130 1675-81. 

Horiuchi et al., 2000 Japanese postmenopause n = 85 Women with a high soy protein intake showed less bone loss and higher BMD at the lumbar spine Biomarkers urinary deoxypyridinoline (bone resorption) decreased... 

Alekel et al., 2000 American perimenopause n = 69 40 g soy protein (containing 80 mg isoflavones/day) over 6 months attenuates bone loss in the lumbar spine... 

Arjmandi et al., 1996 95 d old OVX rats 30 d soy protein with isoflavones (8 mg/d) starting at OVX Prevention of bone loss soy protein/isoflavones prevented the BMD losses in the femur and d lumbar vertebra after OVX... 

Arjmandi et al., 1998a,b 95 d old OVX rats 35 d casein diet after OVX, then 65 d soy protein with isoflavones (9 mg/d) No significant effect of soy protein in reversal of bone loss, assessed by BMD. Soy induced femoral lGF-1 mRNA and some increases in bone turnover markers... 

Harrison et al., 1998 10 week old OVX rats low calcium diet treatment starts 2 weeks after OVX Soy protein with isoflavones (6 mg/d) for 4 weeks Reduced bone loss (higher bone weight, higher calcium content) but no decrease of markers of bone turnover for the soy group... 

Table 6.4 Effect of pure isoflavones on OVX-induced bone loss in rodents...

Ishida et al., 1998 9 week old OVX rats calcium-deficient diet daidzin 10, 25, 50 mg/kg bw by gavage treatment for 28 d starting 7 d after OVX High dose genistin or daidzin prevented bone loss. Daidzin retarded femoral bone loss in a dose-dependent manner... 

Ishimi et al., 1999 8 week old OVX mice low calcium diet genistein (0.7 mg/d) treatment for 4 weeks Reduced bone loss by genistein although not as effective as estradiol... 

Uesugi et al., 2001 11 week old OVX rats tube feeding into the stomach isoflavone glycosides (25, 50 or 100 mg/kg/d) for 4 weeks Daidzin, glycitin and genistin each significantly prevented OVX-induced bone loss at 50 mg/kg/d and reduced urinary excretion of pyridinoline and deoxypyridinoline... 

Similar to the human studies, the animal studies are not entirely consistent, due to the different study designs (source and dose of soy protein/isoflavones time, method and length of administration age of rats, etc.). Nevertheless, a certain number of conclusions may be drawn. Overall, soy extracts or pure isoflavones show an osteoprotective effect in the ovariectomized rat model of menopausal bone loss. The time of administration is important and they must be given at the time of ovariectomy which allows prevention but not reversal of bone loss. Although the OVX-induced bone loss in the rat is a... 

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