Abstract

Fracture risk associated with drugs: a search for candidate drugs in the same way as for candidate genes

Author(s): Peter Vestergaard

Oral corticosteroids increase fracture risk, while topical corticosteroids do not. The effect of the corticosteroids is probably linked to negative effects on calcium metabolism, with a negative calcium balance and effects on gonadal function. Insulin and oral antidiabetics, except glitazones, decrease fracture risk by countering the negative skeletal effects of diabetes. Glitazones appear to be associated with an increased risk of fractures, which is probably linked to their negative effects on bone cells. Antithyroid drugs per se decrease fracture risk by inducing euthyroidism. Some, but not all, antiepileptic drugs are associated with a very limited increase in fracture risk. The mechanisms probably relate to liver induction with vitamin D deficiency. Anxiolytics and neuroleptics are associated with a very limited increase in fracture risk, which is probably linked to the risk of falls. Among antidepressants, selective serotonin-reuptake inhibitors carry a larger increase in relative fracture risk than tricyclic antidepressants. Lithium is associated with a decrease in fracture risk, which may be the result of an effect on bone metabolism, but further research is required. Most, but not all, opioids are associated with an increase in fracture risk, which is probably due to an increased risk of falls owing to dizziness. Some, but not all, NSAIDs are associated with an increase in fracture risk, which is probably linked to dizziness. Proton-pump inhibitors are associated with an increased fracture risk, which is probably linked to decreased calcium absorption with secondary hyperparathyroidism, while histamine H2 receptor antagonists are associated with a decrease in fracture risk, although the mechanism of the latter is unknown. Histamine H1 receptor antagonists and oral contraceptives are not associated with significant changes in fracture risk.