Hypogonadism May Predict Vertebral Fracture in Patients With Chronic Glucocorticoid Exposure

Spine radiography
Researchers identified the risk factors associated with fragility fracture development in patients receiving glucocorticoids.

Hypogonadism is the principal risk factor for fragility fractures in men and women with chronic glucocorticoid (GC) exposure, according to study results published in RMD Open. In a cohort of patients with long-term GC use, fractures were significantly more common among postmenopausal women and men with low testosterone levels. Receiving GC boluses was also an independent risk factor for vertebral fractures.

In this cross-sectional study, researchers enrolled consecutive adult patients receiving chronic GC treatment for a rheumatologic autoimmune disease. Chronic GC use was defined as receiving at least 5 mg per day of prednisone or equivalent for more than 3 months. Patients provided their medical history and underwent clinical assessment. Bone mineral density of the lumbar spine, femoral neck, and total hip was assessed by dual-energy x-ray absorptiometry (DXA). Trabecular bone score was calculated using DXA lumbar spine images. Fracture Risk Assessment Tool (FRAX) scores were calculated for major osteoporotic fractures. Researchers obtained radiographs of the thoracic and lumbar spine to determine the presence of a vertebral fracture. Vertebral fracture was defined as a reduction of 20% or more in the anterior, middle, or posterior height of the vertebral body compared with adjacent, unaffected vertebrae. Logistic regression was used to identify correlates of vertebral fractures and other fragility fractures.

The study cohort included 127 patients (mean age, 61.5±17.9 years; mean duration of GC treatment, 47.7±68.9 months), among whom 80 (63%) were women. Overall, 36 patients (28%) had any fragility fracture and 21 (17%) had vertebral fracture. Compared with patients without vertebral fracture, those with vertebral fracture had greater mean age (68.0±12.8 vs 60.1±18.6 years, respectively; P =.02) and more frequently received GC boluses (57.1% vs 29.5%, respectively; P =.03). All women with vertebral fracture were postmenopausal, and approximately 60% of men with vertebral fracture had low testosterone levels (<250 ng/dL). Hypogonadal men also had more fragility fractures than those with normal testosterone levels (≥250 ng/dL; 50% vs 14%, respectively; P =.046).

In multivariate analyses, the principal risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; 95% CI, 1.85 to >100; P =.01) and having received GC boluses (OR, 3.45; 95% CI, 1.04-12.15; P =.01). The principal risk factors for any fragility fracture were hypogonadism (OR, 7.03; 95% CI, 1.47-38.37; P =.01) and a FRAX score greater than 20 for major osteoporotic fractures (OR, 7.08; 95% CI, 1.28-53.71; P =.02). Analyses were adjusted for age, body mass index, C-reactive protein, and sex.

Overall, hypogonadism was a significant risk factor for any fragility fracture in men and women with chronic GC exposure. Receiving GC boluses also substantially increased the risk for vertebral fracture.

Study limitations included its cross-sectional design, the absence of a control group, and the inclusion of patients with similar clinical characteristics.

“These results indicate the importance of evaluating the gonadal axis in these patients,” the researchers concluded. “In addition, our results highlight the need to evaluate preventive antiosteoporotic treatment…when receiving GC bolus(es).”


Florez H, Hernández-Rodríguez J, Carrasco JL, et al. Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses. Published online September 6, 2020. RMD Open. doi:10.1136/rmdopen-2020-001355