Osteoporosis thiazide diuretics

Thiazide diuretics decrease urinary calcium excretion and may decrease bone turnover. However, their effects on bone mineral density and fracture rates have not been studied in controlled trials. Thiazide diuretics are not recommended solely for potential beneficial effects in osteoporosis. 

Prescribing thiazide diuretics solely for osteoporosis is not recommended but is a reasonable choice for patients with osteoporosis who require a diuretic and for patients on glucocorticoids with a 24-hour urinary calcium excretion >300 mg. 

Several studies have shown that thiazide diuretics prevent calcium loss in bones, which may improve bone density and protect against osteoporosis. Preliminary research also suggests that diuretics are helpful in preventing stroke. Lurther studies are needed to confirm these findings. 

Glucocorticoid treatment for arthritis or other ailments can very quickly produce a form of osteoporosis caused by the inhibition of bone formation [334]. In such cases, the decrease in bone mass may be as much as 10-20%, but examination of trabecular bone reveals a much greater (30-40%) decrease in this component of bone [335]. Combination therapies with vitamin D and bisphosphonates, calcitonin or fluoride can be effective [336]. Therapy employing vitamin D or 1,25-(OH)2D3, the latter being highly calcaemic, should also include serum calcium monitoring and the use of thiazide diuretics as appropriate. 

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). 

B Unlike other diuretics, furosemide at high infusion rates is associated with ototoxicity. Ototoxicity may occur with all loop diuretics, but the frequency is less with bumetanide and it has not been reported with torsemide. In addition, hypocalcemia is a side effect also experienced with loop diuretics and not with thiazide diuretics. In contrast, hydrochlorothiazide decreases urinary excretion of calcium, which may result in an elevation of serum calcium levels. Thus, thiazide diuretics may potentially reduce the risk of osteoporosis and be beneficial in postmenopausal women. 

Women receive the same benefits from antihypertensive therapy as men. However, ACE inhibitors and ARBs are contraindicated in women who intend to become pregnant because they are teratogenic. Thiazide diuretics may be especially beneficial in postmenopausal women with osteoporosis because they cause retention of calcium and have been shown to positively affect bone mineral density. Women tend to have higher rates of drug-related adverse effects than men. 

Thiazide diuretics increase urinary calcium resorption. A 10-year retrospective study of 83,728 women demonstrated fewer fractures among patients currently taking thiazides." A prospective trial demonstrated maintenance of BMD at the spine and hip over a 3-year period with low-dose hydrochlorothiazide, with a greater effect seen in women." Prescribing thiazide diuretics solely for osteoporosis is not recommended, but is a reasonable choice for the patient with osteoporosis who requires a diuretic. 

Thiazide diuretics, which reduce urinary excretion of Ca, sometimes are employed to treat calcium nephrolithiasis and may be useful for the treatment of osteoporosis see Chapter 61). Thiazide diuretics also are a mainstay for treatment of nephrogenic diabetes insipidus, reducing urine volume by up to 50%. The mechanism of this paradoxical effect remains unknown. Since other hahdes are excreted by renal processes similar to those for Cl", thiazide diuretics may be useful for the management of Br" intoxication. 

ADVERSE EFFECTS AND PRECAUTIONS Adverse effects of diuretics see Chapter 28) determine tolerance and adherence. Erectile dysfunction is a troublesome adverse effect of thiazide diuretics physicians should inquire specifically regarding its occurrence. Albeit uncommon, gout may be a consequence of the hyperuricemia induced by these diuretics. Either of these adverse effects is reason to consider alternative therapies. Hydrochlorothiazide may cause rapidly developing, severe hyponatremia in some patients. Thiazides inhibit renal Ca " excretion, occasionally leading to hypercalcemia although generally mUd, this can be more severe in patients subject to hypercalcemia, such as those with primary hyperparathyroidism. The thiazide-induced decreased Ca excretion may be used therapeutically in patients with osteoporosis or hypercalciuiia. 

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). 

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