Steroid-induced Osteoporosis

Ewa Sewerynek; Michal Stuss

Disclosures

Aging Health. 2012;8(5):471-477. 

In This Article

Treatment & Prevention of Glucocorticosteroid-induced Osteoporosis

Owing to a much lower mechanical bone strength than would appear to be the case from observing BMD and a significant increase in fracture risk, associated with the use of glucocorticoids, patients treated with this group of drugs require different rules of conduct. According to the recommendations of the American College of Rheumatology (ACR) from 2010,[39] the glucocorticoid dose and the duration of therapy should be reduced to a minimum, which is clinically effective in specific diseases, such as rheumatoid arthritis, asthma or others. The glucocorticoid dose reduction and shortening therapy duration minimizes the risk of fractures. Similar to the general recommendations for osteoporosis treatment, lifestyle modifications, consisting of regular physical activity including exercises with own body weight, fall prevention, smoking cessation, limiting alcohol, compensation of calcium deficiency to a total intake of 1200–1500 mg/day and control of vitamin D3 alteration of 25-hydroxyvitamin D3 concentration are also very important. A recommended preventive dose of vitamin D3 is 800–1000 IU per day. However, due to its impaired metabolism associated with chronic steroid treatment those patients can often require much higher doses of vitamin D3.[40] Monitoring patient's height and BMD is also essential in glucocorticoid therapy. The ACR recommends radiological or morphometric assessment of the spine in patients receiving 5 mg or more of prednisolone daily. Before starting treatment, the assessment of global fracture risk based on the presence of other known coexisting risk factors beyond steroids, such as low BMI, parental hip fracture, current smoking, consumption of more than 3 units of alcohol a day and a significant decrease in BMD should also be considered.[39] American College of Rheumatology recommendations distinguish two groups of patients:

  • Premenopausal women and men under 50 years of age;

  • Postmenopausal women and men over 50 years of age.

Clinical data on this first group of patients are very scarce because of difficulties in fracture risk assessment, owing to the lack of reliable tools. The popular FRAX calculator was not designed to assess fracture risk in premenopausal women and men under the age of 40 years. There are no clear guidelines of conduct in the first group of patients without prevalent osteoporotic fractures and individual approaches are thus recommended. For patients with osteoporotic fractures receiving ≥5 mg prednisolone or equivalent for more than a month, it is recommended to start treatment with bisphosphonates of proven effectiveness in gluococorticoid-induced osteoporosis, such as alendronate or risedronate, and if steroid dose is ≥7.5 mg, zoledronic acid should also be considered. If treatment with glucocorticoids is continued for a period of 3 months then, regardless of the dose, the patient should receive one of four treatment options: alendronate, risedronate, zoledronate or teriparatide, with anabolic effects on bone. Another problem is the issue of fertility and reproduction. Osteoporosis requires long-term use of drugs that have not been tested on pregnant women, and their influence on fetus growth and fertility has not been studied. For this reason, preferred forms of treatment in this group of patients include agents with a shorter half-life. In addition, the inclusion criteria for antiosteoporotic treatment in women planning to get pregnant are alleviated. According to the ACR, steroid treatment in this group of women should be limited to 3 months only with doses of ≥7.5 mg of prednisolone or equivalent and recommended, concomitant administration of alendronate, risedronate or teriparatide.[39]

The patients in the second group of the ACR recommendations should be divided into three subgroups, depending on the established global fracture risk, calculated on the basis of well proven algorithms, such as FRAX (low, medium or high fracture risk). Among patients with low or medium fracture risk, it is recommended to start therapy with alendronate, risedronate or zoledronate, if steroid administration exceeds 3 months and daily dose is ≥7.5 mg of prednisolone or equivalent. However, in patients with an average risk of fracture, it is also advisable to administer alendronate and risedronate if steroid daily dose is <7.5 mg of prednisolone or equivalent and the patient has been treated for ≥3 months. Patients with high fracture risk should receive one out of the following three drugs: alendronate, risedronate or zoledronate, if they use steroids in a dose of <5 mg/day, even for <1 month, and when they receive >5 mg glucocorticoids per day, we should also consider teriparatide administration.[39]

The ACR do not recommend other forms of treatment, such as denosumab, strontium ranelate, hormone replacement therapy, testosterone, etidronate, ibandronate, calcitonin or raloxifene among others, for the absence of sufficient data, regarding their efficacy in the treatment of glucocorticoid-induced osteoporosis, although there are some promising positive reports in the literature.[41–45] In addition, ACR recommendations do not indicate any superiority of these drugs over others, despite the available data from head-to-head trials in the literature.[46–48] In patients receiving subcutaneous teriparatide doses of 20 µg/day, increases in lumbar spine BMD was much higher and vertebral fractures were prevented in a more effective way than in the group receiving oral alendronate at dose of 10 mg per day after 36 months of therapy.[46,48] In another study,[47] the effectiveness of zoledronate, administered once a year, was compared with that of risedronate in a dose of 5 mg/day orally. After 12 months of treatment, in the group treated with zoledronate, a greater increase in BMD of the spine and hip was observed than in the group of patients on risedronate. The antifracture efficacy of both treatments was comparable.[19]

It is also worth mentioning that fracture risk calculators reveal a number of limitations. For example, FRAX takes into account hip BMD only. In effect of glucocorticoid use, there is a large loss of trabecular bone, especially in the vertebral spine, which contains higher amounts of this form of bone tissue than the hip. This can cause underestimated fracture risks. Bisphosphonates are drugs of proven antifracture effectiveness, but their use may be associated with side effects, such as gastrointestinal problems when orally administered or flu-like symptoms when administered intravenously.[49–51] The vast majority of severe complications, such as atrial fibrillation or osteonecrosis of the jaw, appear very rarely and the direct relationship between their occurrence and the use of bisphosphonates is controversial.[52–54]

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