(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Spinal-Fractures

A 65-year-old man had surgery in June 1995 for femoral neuralgia. The plain films of the spine were normal at the time. In September of the same year, when he was beginning to walk gradually longer distances, he started experiencing back pain. Crush fractures of T8 and L2 were seen on plain films. His pain worsened, and he was admitted in December 1995. A third set of plain films disclosed fractures of all the vertebral bodies from T8 through L5, with increased density of the endplates of the same vertebras. Serum and urinary levels of calcium and phosphate were normal. Dual-energy X-ray absorptiometry demonstrated osteoporosis predominating in the trabecular bone. Evidence of increased bone resorption was seen on the histomorphometric study. Large amounts of dihydroxypyridinoline were found in the urine. Investigations for the classical causes of osteoporosis in males were unrewarding. Careful questioning revealed that the patient had been taking inhaled beclomethasone for seven years to treat chronic obstructive lung disease. Serum levels of cortisol and ACTH were low, consistent with a diagnosis of treatment-induced hypercorticism. To our knowledge, this is the first reported case of osteoporotic vertebral fractures in a male due to inhaled glucocorticoid therapy. Inhaled glucocorticoids are generally believed to induce only minimal systemic effects. However, decreased serum osteocalcin levels and increased urinary excretion of bone resorption markers have been reported in patients under inhaled beclomethasone therapy. Low spinal bone mineral density values correlated with the degree of pituitary-adrenal gland suppression as evaluated using the ACTH test have also been found in several groups of patients treated with inhaled glucocorticoids.

Topics: Administration, Inhalation; Administration, Topical; Aged; Anti-Inflammatory Agents; Beclomethasone; Glucocorticoids; Humans; Lumbar Vertebrae; Lung Diseases, Obstructive; Male; Osteoporosis; Radiography; Spinal Fractures; Thoracic Vertebrae

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors ( p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) ( p = 0.001), RCV ( p<0.0001) and SSI ( p = 0.001) were found to be significant predictors, but not trabecular BMD ( p = 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures.

Topics: Administration, Oral; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone and Bones; Bone Density; Epidemiologic Studies; Female; Humans; Osteoporosis; Prednisolone; Radius; Risk Factors; Spinal Fractures; Tomography, X-Ray Computed

Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p<0.05) and the trabecular bone density (p<0.01). Among patients > or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p<0.05), total bone mineral density (p<0.01) and cortical bone mineral density (p<0.01). Bone mineral density in the distal radius measured by pQCT and the vertebral bodies by axis QCT were correlated, regardless of whether systemic glucocorticoids were administered. Glucocorticoid administration not only decreases trabecular but also cortical bone mineral density. Since cortical bone provides strength and stiffness, it appears that the loss of cortical bone is responsible for the increased incidence of fracture seen in patients receiving systemic glucocorticoid therapy.

Topics: Aged; Asthma; Beclomethasone; Bone Density; Bone Resorption; Chronic Disease; Female; Glucocorticoids; Humans; Lumbar Vertebrae; Male; Outpatients; Predictive Value of Tests; Radius; Spinal Fractures; Tomography, X-Ray Computed

Osteoporosis is a major complication of long-term corticosteroid administration, but the magnitude of the effect in patients with chronic obstructive pulmonary disease (COPD) is not well defined. In a cross-sectional study, we evaluated the association between steroid use and vertebral fractures in 312 men, 50 yr of age or older, with COPD. Subjects were evaluated according to their corticosteroid use: Never Steroid Users (NSU) (n = 117), Inhaled Steroid Users (ISU) (n = 70), and Systemic Steroid Users (SSU) (n = 125). The prevalence of one or more vertebral fractures was 48.7% in the NSU group, 57.1% in the ISU group, and 63.3% in the SSU group. Compared with NSU, SSU were two times as likely to have one or more vertebral fractures: age-adjusted odds ratio (OR) = 1.80; 95% CI, 1.08 to 3.07. This relationship was primarily due to a strong association between continuous systemic steroid use and vertebral fractures: age-adjusted OR = 2.36; 95% CI, 1.26 to 4.38. In addition, fractures in SSU were more likely to be multiple and more severe. A weaker relationship existed between inhaled steroid use and vertebral fractures: age-adjusted OR = 1.35; 95% CI, 0.77 to 2.56 compared with NSU. These data indicate that vertebral fractures are common in older men with COPD; the likelihood of these fractures is greatest in those men using continuous systemic steroids.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-Agonists; Age Factors; Aged; Anti-Inflammatory Agents; Beclomethasone; Confidence Intervals; Cross-Sectional Studies; Evaluation Studies as Topic; Forced Expiratory Volume; Glucocorticoids; Humans; Logistic Models; Lung Diseases, Obstructive; Male; Middle Aged; Odds Ratio; Osteoporosis; Prednisone; Prevalence; Smoking; Spinal Fractures; Triamcinolone Acetonide; Vital Capacity