In the UK, over 250 000 patients take continuous oral glucocorticoids (GCs), yet no more than 14% receive any therapy to prevent bone loss, a major complication of GC treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double. This review, based wherever possible on clinical evidence, aims to provide easy-to-use guidance with wide applicability. A treatment algorithm is presented for adults receiving GC doses of 7.5 mg day(-1) or more for 6 months or more. General measures, e.g. alternative GCs and routes of administration, and therapeutic interventions, e.g. cyclical etidronate and hormone replacement, are recommended.

A UK Consensus Group on management of glucocorticoid‐induced osteoporosis: an update

Glucocorticoids are potent osteopenic agents, producing negative calcium and bone balance via actions at many sites. The most significant adverse effects of glucocorticoid drugs on the skeleton are probably a direct inhibition of matrix synthesis by the osteoblast, reductions in calcium absorption in both the gut and the renal tubule, and the production of hypogonadism, particularly in men. Reductions in bone density of 10-40% result, the loss being more marked in trabecular bone and in patients receiving a high cumulative dose of the steroid. Fractures occur in about 30% of individuals who take these drugs for an average of 5 years. Bone loss is reversible when glucocorticoid treatment is withdrawn. Bone density can also be increased by sex hormone replacement in those with demonstrable deficiency, by bisphosphonates, and possibly by vitamin D metabolites. All patients treated with glucocorticoids for more than 6 months should be considered for bone densitometry and be offered appropriate drug treatment if values are towards the lower end of the young normal range or if there is already evidence of fractures occurring after minimal trauma. With this approach, the significant morbidity associated with steroid osteoporosis might be substantially avoided.

Glucocorticoid osteoporosis--mechanisms and management.

Chronic inflammatory disorders such as inflammatory bowel diseases (IBD) affect bone metabolism and are frequently associated with the presence of osteoporosis. Bone loss is regulated by various mediators of the immune system such as the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6, or interferon-gamma. TNF-α, a master cytokine in human IBD, causes bone erosions in experimental models and these effects are exerted by osteoclasts. Other TNF-related cytokines such as receptor activator of nuclear factor kappa B (RANK), its ligand, RANKL, and osteoprotegerin are important mediators in inflammatory processes in the gut and are critically involved in the pathophysiology of bone loss. The awareness and early diagnosis of osteoporosis in states of chronic inflammation, together with applied therapies such as bisphosphonates, may be beneficial in inflammation-associated osteoporosis. Although several mechanisms may contribute to osteoporosis in patients with IBD and coeliac disease, inflammation as an important factor has so far been neglected. As key inflammatory mediators in IBD such as TNF-α are involved in the disease process both in gut and bone, we hypothesise that neutralisation of TNF-α could prove an efficient strategy in the treatment of inflammation-related osteoporosis in the future.

https://gut.bmj.com/content/gutjnl/57/5/684.full.pdf

Gut, inflammation and osteoporosis: basic and clinical concepts

More than half of all women and about one third of men will experience osteoporotic fractures during their lives. Although no symptoms occur prior to fracture, bone mineral density and other risk factors can be used to identify high-risk patients, and because effective interventions exist, many of these fractures are now preventable. The proportion of people who are affected, the mortality and morbidity resulting from osteoporotic fractures, and the major known risk factors are discussed. Greater attention should be given to measuring bone mineral density and identifying other risk factors to quantitate the degree of fracture risk among patients (with or without a history of previous fractures), because the consequences of fractures often are severe, and no symptoms other than fractures are associated with disease progression.

Osteoporosis. Frequency, consequences, and risk factors.

Objective

To evaluate the extent of and risk factors for bone loss in a population-based cohort of patients with rheumatoid arthritis (RA) receiving conventional health care.



Methods

In a longitudinal study, clinical data were collected and bone mineral density (BMD) measurements were performed at baseline and after 2 years. Dual-energy x-ray absorptiometry was used for hip and spine BMD measurements. At baseline, patients received advice about lifestyle adjustments and calcium and vitamin D supplementation; during the followup period they were treated with antirheumatic and bone-sparing drugs, according to clinical judgment.



Results

After a mean ± SD of 2.2 ± 0.2 years, 366 (298 women, 68 men) of the 488 patients who were examined at baseline were reexamined. At that time, 47.9% were current users of corticosteroids and 37.0% were using antiresorptive drugs (hormone replacement therapy, bisphosphonates, or calcitonin). The mean BMD reduction was −0.64% in the femoral neck, −0.77% in the total hip, and −0.29% in the spine at L2-4. BMD was increased at all measurement sites in current users of antiresorptive drugs (0.16–1.64%) but was decreased in patients using calcium and vitamin D alone (−1.99% to −1.39%) and in patients not using any osteoporosis treatment (−1.20% to −0.43%). Current use of corticosteroids was independently associated with increased risk for BMD loss in the total hip (odds ratio [OR] 2.63, 95% confidence interval [95% CI] 1.38–5.00) and spine at L2-4 (OR 2.70, 95% CI 1.30–5.63), whereas current use of antiresorptive drugs was associated with decreased risk for bone loss in the total hip (OR 0.43, 95% CI 0.20–0.89).



Conclusion

Results of this population-based, 2-year followup study indicate that adequate management of patients with RA, addressing both the rheumatic disease and osteoporosis, protects against bone loss.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/art.10408

Bone loss in patients with rheumatoid arthritis: Results from a population-based cohort of 366 patients followed up for two years

Although high doses of glucocorticoids are believed to cause bone loss, the effects of low glucocorticoid doses are still controversial. Our study examined the effects of low-dose glucocorticoids on the rate of bone loss at three appendicular bone sites. The study population was a cohort of elderly Japanese-Americans, 1094 women and 1378 men. The women were all postmenopausal. At the baseline examination the mean age of the women was 64 years (range 45–81), and the mean age of the men was 68 years (range 61–82). Glucocorticoid users (19 women and 21 men) had used oral systemic or inhaled glucocorticoids on a regular schedule for more than 1 month (mean use was 2.1 years for the women and 1.9 years for the men). The most common dose was equivalent to 5 mg/day of prednisone; fewer than 15% of users had taken doses equivalent to 10 mg/day or more. Changes in bone mass at the calcaneus, distal radius, and proximal radius were documented using bone densitometry at 1 to 2-year intervals over an 8-year period. The initial bone mass of the glucocorticoid users and controls was similar at the baseline examination. The subsequent loss rates among females during glucocorticoid use, however, were approximately double that of the controls. Among males, bone loss rates during glucocorticoid use were 2–3 times that of controls for the calcaneus and radius sites. The differences between glucocorticoid users and controls persisted after adjusting for confounding variables such as age and use of thiazides and estrogens. We conclude that users of low-dose glucocorticoids have increased rates of bone loss at appendicular sites among both elderly women and men.

J. K. Saito

Papers

Users of low-dose glucocorticoids have increased bone loss rates : a longitudinal study