Osteoporosis drug-induced

Approximately one-third to one-half of osteoporosis cases in men and half of all cases in perimenopausal women are due to secondary causes.4 Common secondary causes in men include hypogonadism, glucocorticoid use, and alcoholism. The most common cause of drug-induced osteoporosis is glucocorticoid use. 

Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents. 

Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the isotretinoin population. While causality to isotretinoin has not been established, an effect cannot be ruled out. Physicians should use caution when prescribing isotretinoin to patients with a genetic predisposition for age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsants. 

Clinical trials have demonstrated that the use of the bisphosphonates, nasal calcitonin, or human rPTH combined with calcium and vitamin D supplementation is effective in preventing drug-induced osteoporosis. Thus, individuals receiving over the long term any medication that can induce osteomalacia should also take one of these compounds and have periodic bone density determinations. 

Corticosteroids are extremely useful in elderly patients who cannot tolerate full doses of NSAIDs. However, they consistently cause a dose- and duration-related increase in osteoporosis, an especially hazardous toxic effect in the elderly. It is not certain whether this drug-induced effect can be reduced by increased calcium and vitamin D intake, but it would be prudent to consider these agents (and bisphosphonates if osteoporosis is already present) and to encourage frequent exercise in any patient taking corticosteroids. 

Inhibits PTH-induced bone resorption [osteoporosis drug potential]... 

Toxicity Bleeding, osteoporosis, heparin-induced thrombocytopenia (HIT), hypersensitivity Bleeding, skin necrosis (if low protein C), drug interactions, teratogenic (bone dysmorphogenesis)... 

Long-term treatment with glucocorticosteroids results in a decrease in bone uptake. This phenomenon may not be explained as interference between a pharmaceutical and a radiopharmaceutical but by the drug-induced osteoporosis (Conklin et al. 1983). 

The application of 1,2S- OH)2D3, its analog la-OH-D3, and 25-OH-D3 to these diseases is, therefore, evident. Certainly l,25-(OH)2D3 or la-OH-D3 would be effective in renal osteodystrophy, hypoparath3 oidism, vitamin D dependency rickets, and drug induced osteomalacia. It is very promising as a treatment for various forms of osteoporosis. A review of the clinical literature related to this is beyond the scope of this chapter, but interested readers are directed elsewhere for this information... 

Miproxifene (TAT-59) is a prodrug of 4-hydroxy-tamoxifen that has been developed for tamoxifen-resistant carcinoma, but relatively little information has been published on this drug. Compared with tamoxifen, miproxifene inhibits estradiol-stimulated proliferation of MCF-7 cells at a threefold lower dose than that of tamoxifen, and of dimethyl-benzanthracene (DMBA)-induced rat mammary tumors at a dose tenfold lower than tamoxifen (Toko et al. 1990). In any event, in preclinical castrated rat models, it shows an endometrial stimulation activity that is similar to that of tamoxifen, which means it has limited potential use in the prevention or treatment of osteoporosis or cardiovascular disease (Shibata et al. 2000). Similarly, considering the preclinical findings of endometrial stimulation reported on GW5638 (Willson et al. 1997), it is likely that this new SERM belonging to the triphenylethylene family will be limited in clinical use to the treatment of advanced tamoxifen-resistant breast cancer once its efficacy is demonstrated in human clinical trials. 

Several drugs are known to affect calcium metabolism and to Induce calcium loss (42). Amongst these are the use of glucocorticoids and thyroid extract. The use of both of these drugs can lead to the development of osteoporosis. It Is less well known that several other... 

Qassification Idiopathic osteoporosis type 1, occurring in postmenopausal females type 11, occurring in senescent males and females (>70 y). Secondary osteoporosis associated with primary disorders such as Cushing s disease, or induced by drugs, e.g chronic therapy with glucocorticoids or heparin. In these forms, the cause can be eliminated. 

Finally, bisphosphonates have an important place in treatment of osteoporosis of all causes, including steroid-induced osteoporosis. Disodium etidronate, alendronate and clodronate all have potent effects to restore bone mass, and this effect persists for several years of therapy. Newer drugs such as zoledronic acid can be administered by infrequent (once-yearly) infusion, which can help compliance and reduce side effects. 

Metabolic changes over a long period may induce disease, e.g. thiazide diuretics (diabetes meUitus), adrenocortical hormones (osteoporosis), phenytoin (osteomalacia). Drugs may also enhance their own metabolism, and that of other drugs (enz5mie induction). 

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