This occurs by a decrease in osteoblastogenesis, and an increase in the apoptosis of mature osteoblasts and osteocytes. Glucocorticoids delay the maturation of immature stromal cells toward osteoblasts and inhibit the function of mature osteoblasts. Instead, glucocorticoids enhance adipogenesis, and this probably occurs at the expense of osteoblastic differentiation.
The effect is secondary to the induction of CAAT enhancer binding protein beta and CAAT enhancer binding protein delta, and of peroxisome proliferator-activated receptor gamma, which inhibits osteoblastic differentiation.
These effects suggest that glucocorticoids play a role in the trade of osteoblasts and adipocytes. This is confirmed further by the fact that Notch is induced by glucocorticoids and Notch inhibits osteoblastogenesis and enhances adipogenesis. Clinically, the early effects of glucocorticoids on bone resorption can be reversed by the administration of bisphosphonates, whereas the inhibitory effects on bone formation might be reversed by parathyroid hormone. In conclusion, glucocorticoids have profound effects on skeletal cells that lead to the development of osteoporosis.
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Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Related Articles. How Is Osteoporosis Treated? What Are the Benefits of Yoga for Osteoporosis? The Best Herbs for Osteoporosis.
What Are the Stages of Osteoporosis? Hyperthyroid or Hyperparathyroid? What's the Difference? Reverse osteoporosis and prevent bone loss with effective medication. What Causes Osteoporosis? How to Prevent Osteoporosis. How Hypoparathyroidism Is Treated. Physical Therapy for Osteoporosis. FRAX assessment has already been included in some guidelines at different steps of the treatment decision. Persistent inflammation is associated with bone loss as shown in longitudinal studies in patients with active RA or ankylosing spondylitis SpA.
In contrast, prospective open studies show that complete control of inflammation in parallel with clinical improvement and thus increased mobility is accompanied by the absence of bone loss. However, there is no evidence for a reduction in fracture risk with such a strategy, 60 and new epidemiological studies are mandatory in this matter.
Age, female gender, low BMI, history of falls and previous fractures, duration of menopause and smoking are associated with fracture risk in patients with GCs, similarly to how they are in primary osteoporosis. We have shown that prevalence of non-vertebral fractures is a strong determinant of the risk of having vertebral fractures in patients with RA, 61 implying that the individual's skeleton is already of inadequate strength to withstand the trauma of daily living.
Beyond GC use, these risk factors must be assessed in all patients, and all causes of secondary osteoporosis are added risk factors of fractures in patients with GCs. At the initiation of GC treatment, the patient's height must be measured, as height loss in the follow-up could be related to asymptomatic vertebral fractures. Biological tests are performed to screen for other causes of bone diseases.
There is no indication for assessment of biochemical markers of bone remodelling either at baseline or during follow-up, as bone turnover is consistently low in GC users. As the daily dose of GCs is a determinant of fracture risk, it must be constantly reviewed by considering both the reduction of the dose to the minimally active and alternative administration such as intra-articular injections.
The risk of falling should be assessed in particular in elderly patients, patients with painful joints of the lower limbs and patients with massive doses of GCs. Physical activity or mobilisation should be considered, adapted to the underlying condition. Attention to nutrition must be paid to prevent protein and calcium intake deficiencies. GC-treated patients may seldom be outdoors, and thus exposed more than the general population to vitamin D deficiency. There is no evidence of an advantage using calcitriol or alcalcidol, as there is a large variability of outcomes with these vitamin D metabolites over plain vitamin D.
Bisphosphonates and teriparatide have been assessed in prevention and treatment of GIOP. There are a number of issues regarding their efficacy. Thus the efficacy on fractures is mainly based on bridging data between the short-term change in BMD in patients with GCs, and the long-term change in BMD and reduction of fracture risk in patients with postmenopausal osteoporosis. Bisphosphonates are the more popular antiosteoporotic drugs. There was a 2. Attention has been paid recently to osteonecrosis of the jaw and atypical femoral fractures such as side effect of long-term administration of antiresorptive drugs in osteoporosis; these events are very rare, 70 71 but GC use is one of the identified risk factors.
Buccal hygiene procedures should be implemented to prevent any local increased risk of infection. Whether these rare events can change the duration of anti-resorptive treatments in long-term GC users needs further studies. Bisphosphonates should be used cautiously in premenopausal women, as they cross the placenta; appropriate contraception must be used if necessary and preference given to a short bone half-life bisphosphonate.
The use of administrative databases offers the opportunity to assess a huge number of patients, taking into account the methodological issues related to these studies retrospective design, lack of details in patient characteristics, absence of confirmation of the diagnosis of fractures, etc. There is so far no study of denosumab on GIOP.
In a subgroup analysis of a month study of patients with RA still active although they were receiving methotrexate treated with denosumab, BMD increases were similar in patients with and without GCs.
GIOP is a condition where the principal cause of bone loss is reduction in bone formation. This is the rationale for using teriparatide, a parathyroid hormone peptide producing anabolic skeletal effects by stimulation of bone formation. More importantly, a significantly lower number of vertebral fractures was observed: 0. There are a number of guidelines published by different national societies and colleges, on use of pharmacological treatment in GIOP, which vary somewhat.
Adherence to antiosteoporotic treatment may be low in some patients who are already taking multiple medications, and should be assessed regularly. Height loss can be related to vertebral fractures, sometimes asymptomatic because of the analgaesic property of GCs.
We should not go on neglecting fracture risk in patients with GCs. This risk must be assessed in all patients at the initiation of prolonged GC therapy. The treat-to-target strategy focusing on low disease activity is effective on bone loss in RA. New epidemiological data are needed to assess the benefit of such a strategy on fracture incidence. Competing interests: None. Provenance and peer review: Commissioned; externally peer reviewed.
Data sharing statement: No additional data are available. National Center for Biotechnology Information , U. RMD Open. Published online Apr 8. Karine Briot and Christian Roux. Author information Article notes Copyright and License information Disclaimer.
Correspondence to Professor Christian Roux; rf. This article has been cited by other articles in PMC. Abstract Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the first cause in young people. Key messages. Role of underlying inflammation In the general population, even small elevations of C reactive protein within the normal range increase non-traumatic fracture risk.
Bone effects of GCs The predominant effect of GCs on bone is the impairment in bone formation figure 1. Open in a separate window. Figure 1. Indirect effects of GCs Earlier, emphasis had been placed on the effects of GCs on calcium metabolism, because of decrease of gastrointestinal absorption of calcium and induction of renal calcium loss.
Differential sensitivity to GCs There is great variability of side effects of GCs among individuals, including bone loss, for largely unknown reasons. Epidemiology The risk of fractures is increased by twofold in patients with GCs, and the risk of vertebral fractures is even higher. Dose effect In epidemiological studies, the increased risk of fractures is observed even at low doses of prednisone, that is, 2.
Prior versus current GCs use Ever use of GCs is associated with an increased risk of hip fracture, and this justifies the assessment of osteoporosis and fracture risk in all patients.
BMD loss BMD loss is an immediate consequence of the introduction of GCs and affects the trabecular bone ie, spine more than it does the cortical bone ie, femur. Assessment of fracture risk Role of BMD There is a mismatch between BMD data and fracture data in patients receiving GCs because of the disparity related to the alteration of bone quality. Role of underlying disease Persistent inflammation is associated with bone loss as shown in longitudinal studies in patients with active RA or ankylosing spondylitis SpA.
Role of patient characteristics Age, female gender, low BMI, history of falls and previous fractures, duration of menopause and smoking are associated with fracture risk in patients with GCs, similarly to how they are in primary osteoporosis. Treatment General measures At the initiation of GC treatment, the patient's height must be measured, as height loss in the follow-up could be related to asymptomatic vertebral fractures. Pharmacological treatment Bisphosphonates and teriparatide have been assessed in prevention and treatment of GIOP.
Follow-up Adherence to antiosteoporotic treatment may be low in some patients who are already taking multiple medications, and should be assessed regularly. Conclusion We should not go on neglecting fracture risk in patients with GCs. Footnotes Competing interests: None. References 1. Kok C, Sambrook PN. Secondary osteoporosis in patients with an osteoporotic fracture.
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