Glucocorticoid-induced osteoporosis (GIO)
Long-term term glucocorticoid therapy may have devastating consequences in terms of loss of bone density and increased fracture risk. Any patient being started on oral glucocorticoid therapy with the intent to treat for more than 3 months should be considered for bone density testing and bone-protective medication. Table 9 shows the guidelines of the American College of Rheumatology for the prevention and treatment of GIO.Monitoring treatment
The ultimate indicator of efficacy for osteoporosis therapy is reduction of fracture risk. In clinical trials, this is done by comparing fractures rates in a group receiving active medication compared to placebo. For individual patients in clinical practice, BMD is normally used as a surrogate measurement of changes in bone strength and fracture risk in response to therapy. An increase or stabilization of BMD is associated with reduction in fracture risk [ although other measures of bone qualities, particularly changes in bone turnover markers are correlated to changes in fracture risk as well. Patients started on pharmacologic therapy are typically retested in 1–2 years in order to be sure there has been no loss of BMD, and retested at longer intervals once response to therapy has been shown. Patients at very high risk for bone loss, such as those on glucocorticoid therapy, may need to be tested as often as every 6 months, until stability of bone mass has been demonstrated.Discontinuation of treatment
It is intuitive that pharmacologic therapy should be continued as long as fracture risk is high, and stopped when that is no longer the case. Prolonged therapy adds to patient cost and inconvenience, and possibly increases the risk of drug toxicity due to longer exposure. Clinical trials and knowledge of drug mechanisms of action are helpful in predicting the likely outcome of discontinuation, and suggestive of appropriate measures for follow-up. Discontinuing estrogen, raloxifene, or calcitonin therapy is likely to be associated with rapid loss of therapeutic effect and subsequent bone loss due to sex hormone deficiency and/or aging. Therefore, patients at high risk for fracture who stop these drugs should probably soon be started on another anti-fracture drug. Bisphosphonates, having a strong affinity for bone and a long bone half-life, have been shown to have persistence of suppression of bone turnover for months to years after cessation of therapy. This suggests that patients who have been taking an oral bisphosphonates for years may continue to benefit from drug effects for a long time after discontinuation, with the duration of persistent effect varying according to the pharmacological properties of the bisphosphonate used. With teriparatide, there is evidence that discontinuation may be quickly followed by bone loss, which can be prevented by initiating bisphosphonate therapy.Nonresponders
In clinical trials, the overwhelming majority of patients treated for osteoporosis with antiresorptive or anabolic medication stabilize or increase BMD and benefit from a reduction in fracture risk. In clinical practice, approximately 10% of elderly patients treated with a bisphosphonate have been shown to lose BMD , defined as a BMD decrease more than the Least Significant Change (LSC) at a 95% level of confidence, a value that can be calculated for each bone densitometry center. Medical evaluation of these BMD losers revealed a previously unrecognized contributing factor, or secondary cause of osteoporosis in about 50%. Although there is no universal consensus on the definition of non-response to therapy, defining nonresponse in terms of BMD loss more than the LSC is a useful tool in clinical practice, and is cause for further medical investigation. Common causes for nonresponse include poor adherence (not taking medication or not taking it correctly), calcium or vitamin D deficiency, and comorbidities (diseases, conditions or medication that impair drug effect or are associated with osteoporosis) [46].When to refer to an osteoporosis specialist
The care of osteoporosis patients crosses all medical specialty lines. Primary care specialists and most medical subspecialists may justifiably claim the right to manage osteoporosis in their patients, and do it well. In a small percentage of patients with unusual clinical presentations, intolerance to standard medications, or poor response to therapy, additional expertise may be required. Table 10 shows established guidelines for referral to an osteoporosis specialist(published with permission in writing from:http://www.clinicalmolecularallergy.com)
