Glucocorticoid-Induced Osteoporosis: Mechanisms and Therapeutic Approach

To evaluate mandibular bone changes by comparing the fractal dimension (FD), mandibular cortical width (MCW), and panoramic mandibular index (PMI) on panoramic radiographs in patients using intravenous corticosteroids versus controls.

In total, 60 patients were divided into 2 groups: 30 patients receiving intravenous corticosteroid treatment and 30 age- and sex-matched healthy people as the control group. Panoramic radiographs of all patients were evaluated. FD was measured in 4 regions: the subcortical area in the condyle, the area superior to the angle of the mandible, the alveolar bone distal to the mandibular left second premolar root, and the alveolar bone mesial to the mental foramen. MCW and PMI were calculated to assess cortical thickness.

The FD values in the condyle, angle of the mandible, and mental foramen region were significantly lower in the corticosteroid group (P ≤ .011), but there was no significant difference in the second premolar area (P = .101). MCW values were significantly lower in the corticosteroid group (P < .001). There was no significant difference in PMI between the groups (P = .544).

The FD and MCW values of the patients using corticosteroids can be helpful in quantitatively and objectively evaluating osseous changes in patients receiving intravenous corticosteroids.

The IDO/kynurenine pathway is now established as a major regulator of immune system function. The initial enzyme, indoleamine 2,3-dioxygenase (IDO1) is induced by IFNγ, while tryptophan-2,3-dioxygenase (TDO) is induced by corticosteroids. The pathway is therefore positioned to mediate the effects of systemic inflammation or stress-induced steroids on tissue function and its expression increases with age. Disorders of the musculoskeletal system are a common feature of ageing and many of these conditions are characterized by an inflammatory state. In inflammatory arthritis and related disorders, kynurenine protects against the development of disease, while inhibition or deletion of IDO1 increases its severity. The long-term regulation of autoimmune disorders may be influenced by the epigenetic modulation of kynurenine pathway genes, with recent data suggesting that methylation of IDO may be involved. Osteoporosis is also associated with abnormalities of the kynurenine pathway, reflected in an inversion of the ratio between blood levels of the metabolites anthranilic acid and 3-hydroxy-anthranilic acid. This review discusses evidence to date on the role of the IDO/kynurenine pathway and the highly prevalent age-related disorders of osteoporosis and rheumatoid arthritis and identifies key areas that require further research.

The aim of this study was to examine the prevalence of osteoporosis, osteopenia, and bone mineral density (BMD) less than the expected range based on age in patients with systemic lupus erythematosus (SLE) in a tropical region of Brazil and the relationship between reduced BMD and several associated factors, especially the SLE disease damage index (SDI). We scored 159 patients with creatinine clearance of 60 mL/min or more for SDI, which was modified by excluding the osteoporosis item. For postmenopausal women and men older than 50 yr, T-scores identified osteopenia (<−1.0 and >−2.5) and osteoporosis (≤−2.5). For all patients, a Z-score of −2.0 or less identified BMD less than the expected range for age. Other variables that influence BMD were studied. The prevalence of osteoporosis, osteopenia, and BMD less than the expected range for age was 28%, 54%, and 29.6%, respectively. The Z-scores were significantly lower in patients with a modified SDI ≥ 1 (mean ± standard deviation [SD] = −1.45 ± 1.18) compared with patients with a modified SDI = 0 (mean ± SD = −0.94 ± 1.01; p = 0.01). The lowest Z-score had a significant association with postmenopausal status (p = 0.038) and significant correlations with the duration of glucocorticoid (GC) usage (p = 0.033, r = −0.17), the cumulative amount of GC (p = 0.000, r = −0.28), and parathyroid hormone levels (p = 0.003, r = −0.24). A multiple linear regression revealed that the modified SDI (p = 0.003) and the cumulative amount of GC (p = 0.006) had significant independent associations with the lowest Z-score. In conclusion, a BMD less than the expected range for age occurs frequently in Brazilian patients with SLE independent of the renal failure. The patients with greater SDIs had lower Z-scores, which suggests a direct association between chronic inflammation from disease and a reduced BMD.

We studied 265 men (mean age 56.4 years; range 18–83 years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate (RIS) in patients either commencing (prednisolone 7.5 mg/day or equivalent) (prevention arm, n = 88) or continuing glucocorticoid therapy (treatment arm, n = 177).

Patients received either a single ZOL 5 mg infusion or RIS 5 mg oral daily at randomization, along with calcium (1000 mg) and vitamin D (400–1200 IU). Primary endpoint: difference in percentage change from baseline in bone mineral density (BMD) at the lumbar spine (LS) at 12 months. Secondary endpoints: percentage changes in BMD at total hip (TH) and femoral neck (FN), relative changes in bone turnover markers (β-CTx and P1NP), and overall safety.

In the treatment subpopulation, ZOL increased LS BMD by 4.7% vs. 3.3% for RIS and at TH the percentage changes were 1.8% vs. 0.2%, respectively. In the prevention subpopulation, bone loss was prevented by both treatments. At LS the percentage changes were 2.5% vs. − 0.2% for ZOL vs. RIS and at TH the percentage changes were 1.1% vs. − 0.4%, respectively. ZOL significantly increased lumbar spine BMD more than RIS at Month 12 in both the prevention population (p = 0.0024) and the treatment subpopulation (p = 0.0232) in men. In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum β-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced β-CTx at all time-points, and P1NP at Month 3 (p = 0.0297) only. Both treatments were well tolerated in men, albeit with a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL.

Once-yearly ZOL preserves or increases BMD within 1 year to a greater extent than daily RIS in men receiving glucocorticoid therapy.