Review
Drug-induced Osteoporosis: Mechanisms and Clinical Implications

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Abstract

Drug-induced osteoporosis is common and has a significant impact on the prognosis of patients suffering from chronic debilitating diseases. Glucocorticoids are the drugs causing osteoporotic fractures most frequently, but osteoporosis with fractures is observed also in women treated with aromatase inhibitors for breast cancer, in men receiving anti-androgen therapy for prostate cancer, in postmenopausal women treated with high doses of thyroxine, and in men and women treated with thiazolinediones for type 2 diabetes mellitus. Bone loss with fractures also occurs in patients treated with drugs targeting the immune system, such as calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, anticonvulsants, loop diuretics, heparin, oral anticoagulants, and proton pump inhibitors.

Section snippets

Glucocorticoids

Glucocorticoids are used in the treatment of inflammatory and autoimmune diseases, neoplasias, and following organ transplantation. Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. The central mechanism of action of glucocorticoids is decreased bone formation, secondary to impaired osteoblastic differentiation and function.1 However, during the initial phases of glucocorticoid exposure, bone resorption is increased, explaining an early bone loss.2

Psychotropic and Anticonvulsant Therapy

Selected drugs with central nervous system effects may alter skeletal metabolism. This has clinical relevance because patients taking these drugs are often elderly and frail, with a propensity to fall and, consequently, to fracture.

Heparin

Heparin is effective in the prevention and treatment of venous thromboembolism. In vitro, heparin inhibits the differentiation and function of osteoblasts.51 In vivo, heparin decreases bone formation and increases bone resorption, the latter by inhibiting the expression of osteoprotegerin, a decoy receptor for receptor activator of nuclear factor–kappa B ligand.51

In pregnant women, up to one third of patients placed on heparin have a significant decrease in BMD, with fractures occurring in only

Calcineurin Inhibitors

Calcineurin inhibitors are immunosuppressants used in combination with glucocorticoids in patients undergoing organ transplantation. In vitro, cyclosporine and tacrolimus inhibit osteoclastogenesis and bone resorption.63 However, in vivo, these drugs cause bone loss due to markedly increased bone resorption.64 Changes in T-cell cytokine production and altered vitamin D metabolism with secondary hyperparathyroidism may contribute to the effects of calcineurin inhibitors. Furthermore, it is not

Proton Pump Inhibitors

Proton pump inhibitors are commonly used in the treatment of diseases of the upper gastrointestinal tract. In vitro, the inhibition of proton pumps on the osteoclast ruffled border may decrease bone resorption.72 However, proton pump inhibitors decrease intestinal calcium absorption, increasing bone resorption in vivo. Proton pump inhibitors decrease BMD at the lumbar spine and hip, and increase the risk of vertebral and nonvertebral fragility fractures, depending on drug dose and duration of

Conclusions

Drugs routinely used for treatment of multiple diseases have detrimental effects on the skeleton. Awareness of this clinical problem is limited, and consequently, preventive measures are often not undertaken. Adequate monitoring of bone health and therapeutic intervention are recommended when drugs with an adverse bone safety profile are used, particularly in patients with additional risk factors for osteoporosis.

Acknowledgment

The authors thank Mary Yurczak for secretarial assistance.

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    Funding: This work was supported by MIUR and Centro di Ricerca sull'Osteoporosi-University of Brescia/EULO (A. Giustina).

    Conflict of Interest: Dr. Mazziotti has nothing to declare. Dr. Canalis reports receiving consulting or lecture fees from Eli Lilly, GlaxoSmithKline, Novartis, and Amgen. Dr. Giustina reports receiving consulting or lecture fees from Abiogen, Eli Lilly, GlaxoSmithKline, Merck, Amgen, and Stroder. No pharmaceutical industry funds were received for the preparation of the manuscript or related research.

    Authorship: Each author has participated in the writing of the manuscript and has seen and approved the submitted version. Further, each author has been involved in the conception and design of the study and the analysis of the data.

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