Osteoporosis Immobilization

Ethylestrenol (4 mg p.o. daily) is an anabolic steroid that is used to promote weight gain to combat tissue depletion, anemia and to overcome the catabolic effects of corticosteroids, osteoporosis, immobilization, and debilitation. Ethylestrenol enhances the production of erythropoietin by the kidneys and hence increases the red blood cell mass and volume (see Figure 95). Ethylestrenol may retain electrolytes and fluid and hence may become detrimental in patients with severe cardiac and renal diseases. Ethylestrenol is contraindicated in prostatic hypertrophy with obstruction and severe types of cancer (see also Table 8). 

These results indicated osteoporosis. In this condition, which often appears secondary to another pathology such as an endocrinopathy, chronic renal failure or following long term immobilization, bone architecture is normal hut its mass is reduced relative to its volume, that is there is normal mineralization hut the amount of osteoid matrix is reduced. Treatment is with bone resorption inhibitors such as the bisphosphonate group of drugs, for example alendronate. 

Bone loss causing secondary osteoporosis may be accelerated by a number of factors such as the use of corticosteroids, smoking and immobilization. 

Novo Nordisk showed in the synthesis of (-)-Ormeloxifene (48), a drug candidate for the treatment and prevention of osteoporosis, that the enzymatic asymmetric hydrolysis of potential intermediates can be carried out using Candida rugosa lipase (CRT) immobilized on Accurel (Scheme 15) [74]. Racemic czs-hexanoate mc-46 was subjected to enzymatic hydrolysis in aqueous acetonitrile and gave the phenol ds-(3R,4S)-47 in 95% ee. This transformation is a nice example to demonstrate that the enzyme can recognize and use remote stereocenters. The reaction was run on a 10 g scale, and it was even possible to recycle hexanoate (3S,4R)-46. Simple recovery of the immobilized enzyme by... 

Following initiation of anti hypertensive therapy with thiazide diuretics, transient hypercalcemia has been seen in over one-third of patients (87). Two percent of patients receiving long-term thiazide diuretics administration had persistent hypercalcemia (68). In the elderly (especially women), combined administration of thiazides with vitamin 0 supplements (for osteoporosis) can have synergistic effects on the elevation of serum calcium levels resulting in severe hypercalcemia (69). Similarly, if the patient is predisposed to hypercalcemia (IHPT, 2HPT or immobilization), thiazides can precipitate significant and sustained hypercalcemia (68,70). 

The mechanism responsible for osteoporosis resulting from immobilization is not clear. One theory suggests that muscular activity stimulates osteoblastic activity in the bone. Another theory proposes that the rate of bone destruction is accelerated in osteoporosis. In immobilized innervated rat limb, there is an increased destruction in the matrix, reflected by a more rapid turnover of [ " C]glycine into the soft tissue. The increased turnover of amino acids into the protein of soft tissue is paralelled by an increased turnover by the calcium in the bone and the in the chondroitin sulfate. 

Health Hints for Preventing Bone Fractures. Every safe measure for the prevention of osteoporosis should h)e considered, because bone fractures are painful, incapacitating, and costly and immobilization of the patient during recovery may result in other serious problems, such eis further weakening of bones, formation of blood clots, and atrophy of muscles. Some practical recommendations for normal, healthy people follow ... 

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