Osteoporosis drug therapy

Sunyecz JA, Weisman SM. The role of calcium in osteoporosis drug therapy. J Womens Health. 2005 14 180-192. 

Adequate calcium and vitamin D intake is essential in the prevention and treatment of osteoporosis. Calcium and vitamin D supplements to meet requirements should be added to all drug therapy regimens for osteoporosis. 

Treatment decisions regarding initiation of therapy for osteoporosis can be complex. Patients meeting criteria for osteoporosis (T-score below -2.5) or other high-risk patients with a history of osteoporotic fracture gain significant benefit from treatment. Drug therapy should be initiated in these patients. 

Because secondary osteoporosis causes play a significant role in men, any secondary cause (e.g., hypogonadism) should be excluded or treated before considering other drug therapy. 

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. 

Calcitonin therapy results in decreased bone resorption. Osteoclasts have calcitonin receptors and calcitonin inhibits their activity. Sodium fluoride stimulates bone formation by unknown mechanisms. In women with osteoporosis, fluoride therapy produced an increased bone mineral density but no reduction in the rate of vertebral fractures. Other drugs known as selective estrogen receptor modulators (raloxifene, droloxifene, idoxifene, and levormeloxifene) may provide an alternative to estrogen replacement therapy (Chapter 34). Administration of low doses of PTH [or recombinant PTH( 1 -34)] does not affect serum calcium concentration, promotes bone formation, and increases mineral density. This anabolic action of PTH is probably mediated by decreasing osteoblast apoptosis. 

Nonpharmacologic interventions alone are not always sufficient to prevent osteoporosis-related fractures, and drug therapy is often necessary. Table 88-6 describes the important aspects of the commonly prescribed medications for osteoporosis. The choice of pharmacotherapy depends on many individual patient-specific characteristics and preferences. Regardless of the medication selected, allpatients should receive adequate calcium and vitamin D intake. In order to optimally reduce fracture risk, all people should also implement lifestyle modifications that reduce faU risk. 

Hyperlipidemia, diabetes mellitus, and severe osteoporosis are relative contraindications for oral isotretinoin. The drug may very occasionally produce significant mood changes, depression, and other significant psychiatric adverse effects. Although relationship to drug therapy is controversial, current recommendations are that patients be counseled about and screened for depression during therapy. ... 

Exemestane is an irreversible aromatase inactivator that binds to the aromatase enzyme to block the production of estrogen from androgens. Exemestane is absorbed rapidly after oral administration, with a terminal half-life of 24 hours. The drug is eliminated primarily by the liver and feces, with less than 1% of the dose excreted unchanged in the urine. Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women who have had disease progression following tamoxifen therapy. Side effects include hot flashes, fatigue, osteoporosis/bone fractures, and flulike symptoms. 

The drug reduces fracture risk in postmenopausal women, but no fracture data are available in men. Lumbar spine BMD increases are higher than with any other osteoporosis therapy. Although wrist BMD is decreased, wrist fractures are not increased. 

Biskobing DM (2003) Novel therapies for osteoporosis. Expert Opin Invest Drugs 12 611-621... 

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. 

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