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Secondary osteoporosis in patients with an osteoporotic fracture

https://doi.org/10.1016/j.berh.2009.09.006Get rights and content

Secondary osteoporosis is a common cause of osteoporosis, and there are many medical conditions associated with osteoporosis. Many of these present well before osteoporosis develops, and knowledge of these pre-existing conditions may influence the decision about whether to test and/or treat for osteoporosis. Men and premenopausal women with unexplained osteoporosis or a history of fragility fracture should undergo investigation for secondary osteoporosis. Postmenopausal women with risk factors for secondary osteoporosis should also be carefully evaluated. Beyond the well-recognised association with glucocorticoids, an increasing list of drugs has been implicated in causing bone loss and fractures. With appropriate consideration of secondary causes and relevant investigations, many of these conditions are preventable with newer therapies.

Section snippets

Glucocorticoids

Glucocorticoids are known to affect bone through multiple pathways, influencing both bone formation and bone resorption [1], [2], [3]. The most important effects appear to be on bone formation due to direct effects on cells of the osteoblastic lineage [3], although indirect effects related to sex steroid production are also important. The predominant effect of glucocorticoids is the inhibition of osteoblasts and osteoblast precursors, but increased osteoctye apoptosis has also been implicated

Aromatase inhibitors (AIs)

Aromatase inhibitors (AIs) are widely used as adjuvant therapy in postmenopausal women with estrogen receptor-positive breast cancer. AIs prevent androgen aromatisation, reducing circulating total oestrogens levels. Three AIs are commonly used in breast cancer, namely anastrozole, letrozole and exemestane. Their associated suppression of biologically available oestrogens has a deleterious effect on bone and postmenopausal women receiving AIs have increased bone resorption, decreased BMD and

Gonadotropin-releasing hormone agonists

Gonadotropin-releasing hormone (GnRH) agonists are commonly used to treat hormone-dependent cancers, for example, prostate and breast cancer. Using GnRH agonists to induce hypogonadism in males diagnosed with prostate cancer increases the risk of osteoporotic fracture [27], [28], *[29]. Shahinian et al [27]. studied the use of GnRH agonists or orchidectomy and the risk of fracture in 50 613 men aged over 66 years with prostate cancer 5 years after diagnosis. Males treated with GnRH agonists or

Antiepileptic drugs (AEDs)

A meta-analysis has shown that fracture risk in patients with epilepsy is 2 to 6 times higher than that in the general population [31]. The mechanisms are multifactorial and all types of antiepileptic drugs (AEDs) are potentially implicated. A large proportion of these fractures (35%) appear to occur in relation to seisures, although some may be caused by falls without seisures, since side effects of AEDs include sedation, dizziness and ataxia. Use of AEDs may also have direct effects on bone

Antidepressants

Recent studies have shown the role of the central nervous system in regulating bone remodelling. Antidepressant use has been related to an increased fracture risk, largely via increased falls risk and decreased BMD. However, the decrease in BMD has also been reported in patients with untreated depression *[36], [37], [38]. A case-control analysis and a self-controlled case series from the GPRD have shown that the use of anti-depressants is associated with increased risk of hip fracture [39].

Glitazones

Glitazones are a new class of oral agents for the treatment of type 2 diabetes. They have anti-diabetic effects through the activation of the nuclear receptor and transcription factor peroxisome proliferator-activated receptor-γ, which plays an important role in fatty acid metabolism. Glitazones appear to affect bone through an increase in bone marrow adiposity and decreased osteoblastogenesis, resulting in a decrease in bone formation. In addition, glitazones can affect the aromatase pathway,

Proton pump inhibitors (PPIs)

Proton pump inhibitors (PPIs) (e.g., omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole) are among the most commonly used drugs in the world. Their main action is a pronounced and long-lasting reduction of gastric acid production. Three large retrospective studies have suggested an association between long-term use of PPIs and an increased risk of fractures, particularly of the hip *[46], [47], [48]. A large nested case-control study using the General Practice Research

Inflammatory bowel disease

Crohn's disease and ulcerative colitis are two common types of chronic, relapsing, gastrointestinal disease and are associated with a significant morbidity and mortality, not just related to bowel manifestations. Large epidemiological studies have confirmed an increase in the risk of fracture of approximately 20–30% in these patients, with the risk being greater in those with Crohn's disease than in ulcerative colitis [49], [50]. Numerous studies have confirmed lower BMD [49], [50], [51];

Auto-immune Joint Disease and Bone Loss

Rheumatic diseases are amongst the most common causes of secondary osteoporosis. Even after excluding the use of therapeutic glucocorticoids as frequent contributors to bone loss, it is clear that rheumatoid arthritis (RA) and ankylosing spondylitis, in particular, are associated with excess fracture risk.

Studies in the late 20th century showed an approximate doubling of risk of vertebral and non-vertebral fracture in patients with RA even without the use of supplemental glucocorticoids [55],

Immobilisation including Stroke and Spinal Cord

The severity of bone loss with immobilisation is much greater than in postmenopausal osteoporosis. Fracture rates are substantially higher. After spinal cord injury, the incidence of fractures steadily increases. Several studies have reported incidence rates from 4% to –34% [74], [75], [76], *[77]. The studies with longest follow-up have the highest incidence rates. Zehnder[74] showed a fracture incidence of 1% per year during the first year after injury, with rates increasing to 4.6% per year

Acknowledgements

Dr Nigel Arden, Professor David M Reid and Professor Susan Ott for presentations at the First International Conference on Secondary Osteoporosis in Florence in 2007.

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