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How to prevent glucocorticoid-induced osteoporosis

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ABSTRACTWhen prescribing glucocorticoids for long-term treatment, physicians should take steps to prevent osteoporosis, a common and serious side effect of these drugs.

KEY POINTS

  • Glucocorticoids have both direct and indirect effects on bone cells, and they both suppress bone formation and promote resorption.
  • Patients who need glucocorticoids should receive the lowest effective dose for the shortest possible time. They should also be advised to undertake general health measures, including stopping smoking, reducing alcohol intake, exercising daily, and taking in adequate amounts of calcium and vitamin D.
  • Bisphosphonates and teriparatide (Forteo) are approved for treating glucocorticoid-induced osteoporosis, but adherence to guidelines for managing this condition is far from optimal.


 

References

Although glucocorticoid drugs such as prednisone, methylprednisolone, and dexamethasone have many benefits, they are the number-one cause of secondary osteoporosis. 1 When prescribing them for long-term therapy, physicians should take steps to prevent bone loss and fractures.

Being inexpensive and potent anti-inflammatory drugs, glucocorticoids are widely used to treat many diseases affecting millions of Americans, such as dermatologic conditions, inflammatory bowel disease, pulmonary diseases (eg, asthma, chronic obstructive pulmonary disease, interstitial lung disease), renal diseases (eg, glomerulonephritis), rheumatologic disorders (eg, rheumatoid arthritis, lupus, vasculitis, polymyalgia rheumatica), and transplant rejection.

This article discusses the mechanisms of glucocorticoid-induced bone loss and guidelines for preventing and treating it.

GLUCOCORTICOIDS PROMOTE BONE LOSS DIRECTLY AND INDIRECTLY

The pathophysiology of glucocorticoid-induced osteoporosis is much more complicated than was previously thought.

The older view was that these drugs mostly affect bone indirectly by inhibiting calcium absorption, causing secondary hyperparathyroidism. Indeed, they do inhibit calcium absorption from the gastrointestinal tract and induce renal calcium loss. However, most patients do not have elevated levels of parathyroid hormone.

Now, reduced bone formation rather than increased bone resorption is thought to be the predominant effect of glucocorticoids on bone turnover, as these drugs suppress the number and the activity of osteoblasts.

Direct effects on bone

Glucocorticoids directly affect bone cells in a number of ways—eg, by stimulating osteoclastogenesis, decreasing osteoblast function and life span, increasing osteoblast apoptosis, and impairing preosteoblast formation. 2

Glucocorticoids also increase osteocyte apoptosis. 3 Osteocytes, the most numerous bone cells, are thought to be an integral part of the “nervous system” of bone, directing bone-remodeling units to locations where repair of bone microfractures or removal of bone is needed. Osteocyte apoptosis caused by glucocorticoids may disrupt the signaling process, resulting in increased osteoclast activity in an area of apoptotic osteocytes and the inability to directly repair bone, thus impairing the bone’s ability to preserve its strength and architecture. Such disruption may affect bone quality and increase the risk of fracture independent of any decrease in bone mineral density. 4

Direct molecular effects

Glucocorticoids have been found to:

  • Block the stimulatory effect of insulin-like growth factor 1 on bone formation 5
  • Oppose Wnt/beta-catenin signaling, resulting in decreased bone formation 6
  • Affect stromal cell differentiation, shunting cell formation towards more adipocyte formation so that fewer osteoblasts and chondrocytes are formed, resulting in less bone formation
  • Increase levels of receptor activator of nuclear factor kappa (RANK) ligand and macrophage colony-stimulating factor and decrease levels of osteoprotegerin, resulting in increased osteoclastogenesis and increased bone resorption 7
  • Decrease estrogen, testosterone, and adrenal androgen levels, which also have adverse effects on bone cells. 8

Inflammatory diseases also affect bone

Furthermore, many patients taking glucocorticoids are already at risk of osteoporosis because many of the diseases that require these drugs for treatment are associated with bone loss due to their inflammatory nature. In rheumatoid arthritis, RANK ligand, one of the cytokines involved in inflammation, causes bony erosions and also causes localized osteopenia. The malabsorption of calcium and vitamin D in inflammatory bowel disease is a cause of secondary osteoporosis.

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