Menopause bone loss

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... 

Muldoon SB University of Florida, Gainesville, FL Association of menopausal bone loss with blood lead levels in women National Institute of Environmental Health Sciences... 

Many centers continue to examine this and other SERMs, for example in countering menopausal bone loss (16), in the hope that they can take the place of tamoxifen and provide a means of avoiding the risks of such complications as endometrial cancer, cataract, and stroke (17-19). 

Figure 20.8 illustrates the four basic drug effect patterns when the input or output parameter changes with an exponential time course. As an example of this type of disease progress model, consider postmenopausal osteoporosis reflected by the net loss of bone mass after the menopause. Bone loss may be due to decreased formation or increased resorption of bone. Figure 20.9 illustrates the time course of bone mass change due to increased bone loss and the effect of administering a drug to reduce that loss. For example, raloxifene has been shown to be beneficial in women with postmenopausal osteoporosis (11). The pattern of increase in bone mineral density observed after treatment with raloxifene or placebo resembles the curves shown in Figure 20.10. However, the treatment duration in this dataset was too short to identify the actual mechanism of raloxifene effect on disease progress.

NOTE Studies in the 1980s determined that large doses of fluoride do not protect from osteoporosis (Sect. 10.2.3), or decrease the incidence of bone fractures. It appears that increased fluoride in the diet inhibits osteoblast activity more than osteoclast activity women on fluoride supplements suffer from more bone fractures, not less. Fluoride therapy for osteoporosis was popular in the 1980s, but the reports published after 1990 reduced enthusiasm for this treatment and it is not now recommended for post-menopausal bone loss. 

M. McClung, B. Clemmesen, and A. Daifotis Alendronate prevents po.st-menopausal bone loss in women without osteoporosis. Annals of Internal... 

The rate of bone loss commonly accelerates at menopause due to a decline in trophic sex hormone production, especially when a bone-healthy lifestyle is not practiced. In older studies, approximately 10% to 25% of bone loss was documented in the decade after menopause. Bone loss then slows to 8% to 12% per decade, a rate that was similar to that of older men. This accelerated loss has not been demonstrated in most of the placebo groups who were taking calcium and vitamin D supplements in recently conducted randomized controlled trials. 

Many women experience substantial calcium losses due to rapid bone turnover after the menopause. Hence, intake of calcium that would cause the calcium balance to remain positive should be increased to - 1500 mg per day (Heaney etal. 1978). Apart from the menopause, bone loss in the elderly results probably also from malabsorption of calcium (Ireland and Fordtran 1973, Gallagher etal. 1979). In addition, other factors that are common in the elderly may threaten their nutritional status, including social isolation, impaired cognition, or the physical inability to either obtain or prepare food (Barrett-Connor 1989). 

In general, peak bone mass occurs between 30 and 40 years of age (3,6) and is dependent on genetic factors as well as proper intake of calcium, maintenance of quality nutrition, and participation in weight-bearing exercise (6). Thereafter, peak bone mass progressively declines at the rate of 0.3 to 0.5% of cortical bone per year (3). After menopause, bone loss is accelerated (2% per year in the spine) (6) for a period of 5 to 10 years because of the loss of estrogen. This can result in up to a 30% decrease in bone mineral density. 

Long-term morbidity associated with menopause includes accelerated bone loss and osteoporosis (see Chap. 3 Osteoporosis ). 

Tamoxifen is discussed in Chap. 61, Breast Cancer raloxifene is discussed in Chap. 3, Osteoporosis. Raloxifene decreases bone loss in recently menopausal women without affecting the endometrium and has estrogen-like actions on lipid metabolism. It may exacerbate vasomotor symptoms, and it increases the risk of venous thromboembolism and stroke. 

Osteoporosis is a consequence of the reduction of skeletal mass caused by an imbalance between bone resorption and bone formation. The loss of gonadal function and aging are the two main factors that contribute to the development of osteoporosis. Around the fourth or fifth decade of life, men and women lose bone at a rate of 0.3-0.5% per year. After menopause, the rate of bone loss increases to 10% a year (Nordin et al. 1990 Riggs et al. 1986,1998). The bone loss due to estrogen withdrawal is associated with increments in both bone resorption as well as in bone formation, with the former exceeding the latter. This indicates the birth of new BMUs or an increase in the lifespan of cur-... 

Nordin BE, Need AG, Chatterton BE, Horowitz M, Morris HA (1990) The relative contributions of age and years since menopause to postmenopausal bone loss. J Clin Endocrinol Metab 70 83-88... 

Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK (2003) Bone loss and bone size after menopause. N Engl J Med 349 327-334... 

Prevention of postmenopausal osteoporosis Initiate with lowest dose as soon as possible after menopause. Adjust dosage if necessary. Discontinuation may reestablish natural rate of bone loss. 

A 2-year randomized, double-blind, placebo-controlled trial in 301 healthy postmenopausal women demonstrated that by increasing the Ca intake of women previously habituated to inadequate intakes (i.e., extremely low = <400 mg Ca/day or low = >400 to <650 mg Ca/ day), the bone loss that characteristically occurs during postmenopause can be attenuated or even halted (Dawson-Hughes et al., 1990). The protective effects of Ca were dependent on the anatomical site, years since menopause, and the source of supplemental Ca used. Early postmenopausal women (<5 years) generally experience a more accelerated rate of bone loss compared to women >6-year postmenopausal, in whom the rapid rate of bone loss finally slows. The subjects were randomized to... 

An AI of Ca and vitamin D is essential for retarding the rate of systemic bone loss that occurs naturally as a consequence of aging and declining hormone levels (e.g., menopause). Declining BMD can lead to osteopenia. 

A number of different ways of administering oe-strogens have been widely used for post-menopausal replacement therapy, usually abbreviated HRT. Each of these is effective in prevention of vasomotor symptoms and protection from bone loss, and studies have shown significant reductions in risk of vertebral and hip fracture. 

The replacement of old bone tissue with new tissue is a natural phenomenon in healthy humans leading to an increase in bone mass. However, with further aging, reduced bone mass naturally becomes more predominant, with the rate at which bone loss occurs far exceeds that at which replacement occurs. The loss of bone tissue and its associated elevated incidence of osteoporosis tend to increase after menopause. A number of pharmaceuticals have been developed to slow this... 

Other target organs for the action of 1,25-dihydroxyvitamin D include the kidneys, bone, muscle,vwand skin. The hormone promotes reabsorption of both Ca2+ and inorganic phosphate by kidney tubules. In bone it binds to a specific receptor where it promotes the mobilization of calcium ions. This effect may result in part from stimulation of calcium-activated ATPase of the outer membrane of bone cells. Dissolution of bone also requires the presence of parathyroid hormone (PTH), the 83-residue hormone secreted by the parathyroid gland. In women past the age of menopause and in elderly men the production of 1,25-dihydroxyvitamin D decreases.w This may be a cause of the serious bone loss (osteoporosis) frequently observed. Treatment with 1,25-dihydroxyvitamin D3 or a synthetic analog seems to be helpful to such individuals. /Xy See also Chapter 30, Section A,5. 

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