Weak bones, fractures prevalent in Cushing’s syndrome: Analysis
Researchers ID urgent need for bone health assessment in these patients
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Weak bones and fragility fractures are highly prevalent among people with Cushing’s syndrome, a risk that persists even after achieving disease remission, according to a medical records analysis.
Despite these findings, less than half of this patient population had their bone health properly assessed and/or managed, the data showed.
“These findings identify an urgent need for improved awareness, assessment, and management of bone-health in this high-risk population and call for specific evidence-based practice guidelines,” the scientists wrote.
The study, “Clinical Practice Patterns in Bone Health Assessment and Management in Endogenous Cushing’s Syndrome,” was published in Clinical Endocrinology.
Up to half of Cushing’s patients develop osteoporosis
Endogenous Cushing’s syndrome occurs when the body produces excess cortisol. It’s usually caused by tumors of the pituitary gland (Cushing’s disease), adrenal glands, or, rarely, other organs (ectopic Cushing’s syndrome). Exogenous Cushing’s syndrome is caused by prolonged exposure to steroid medications that mimic natural cortisol.
Weakness in the bones is a common but frequently overlooked complication of Cushing’s syndrome. Up to half of patients develop osteoporosis, a bone disease characterized by thin, brittle bones resulting from reduced bone density. While osteoporosis is most commonly seen in people older than 50, it can occur in younger adults with Cushing’s.
Despite the high prevalence of bone disease in endogenous Cushing’s, specific guidelines for managing bone health are lacking. Current recommendations are primarily based on those for exogenous Cushing’s syndrome.
To fill this gap, scientists in the U.K. examined how clinicians assessed bone health and managed bone disease in Cushing’s syndrome patients in real-world settings.
“Our findings could support the development of specific evidence-based guidelines to improve bone health outcomes in this high-risk population,” the scientists wrote.
Less than half of patients underwent bone health testing at diagnosis
The team collected clinical data from 79 adults with endogenous Cushing’s syndrome. Sixty-four (81%) were diagnosed with Cushing’s disease, 13 (16%) had adrenal Cushing’s, and two (3%) had ectopic Cushing’s. Nearly all (81%) participants were women, of whom one-fourth (25%) were post-menopausal. All but two cases were treated surgically.
When researchers examined how clinicians assessed bone health by measuring vitamin D levels in blood, they found that about half of patients underwent testing at diagnosis (43%) and during a follow-up of nearly five years. (54%) Measuring vitamin D helps assess bone health because adequate vitamin D is necessary for proper calcium absorption and bone mineralization.
By comparison, clinicians measured calcium, phosphate, and ALP, a liver damage marker, more frequently at diagnosis (78.4% or more) and during follow-up (62% or more). Tests for parathyroid hormone, which can indirectly reflect bone health, were much less frequent at diagnosis (25.3%) and during follow-up (16.5%).
Test results showed that calcium, phosphate, and ALP levels were all within normal ranges. Vitamin D levels were adequate but tended toward the lower limit of normal, while parathyroid hormone levels were at the upper limit of normal.
When scientists examined how clinicians managed bone health at diagnosis, they found that 27.8% received calcium supplementation, 37.8% received vitamin D supplementation, and 7.6% received osteoporosis medications. Vitamin D use increased during follow-up to about half (47%) of the patient population.
Clinicians were more likely to assess bone health in patients with fractures. Most (71.4%) of these patients received calcium, vitamin D, or osteoporosis drugs. At diagnosis, one-fifth (21.4%) started osteoporosis medications, the use of which rose within the first year after remission (40%), but dropped during the second year and beyond (26.3%).
About one in five participants sustained fracture within 2 years
After primary treatment, bone density in the hip area increased within the first year, with minor improvements in the spine and total hip. Beyond the first year, bone density in all three bone regions declined slightly compared with the first-year tests.
Even so, when bone density was compared with what is expected for a person’s age and sex, the results steadily improved over time and were better after the first year than before treatment.
About one in five (17.7%) participants sustained a fracture within two years, with more than half sustaining multiple fractures. Fracture of the spine (vertebrae) was the most common, and over half were multiple vertebral fractures.
During the first year, six patients (7.6%) sustained new fragility fractures resulting from low-energy trauma, five of whom had a history of fractures. A similar number (7.6%) of new fractures, including two vertebral fractures, were sustained after the first year.
Our findings reveal a clear mismatch between high fracture burden and low clinical engagement in bone health assessment in endogenous [Cushing’s syndrome], reinforcing the need for targeted clinical guidelines to standardise assessment and support timely intervention.
Overall, 26 fragility fractures were recorded from diagnosis to a mean follow-up of 39.8 months (3.3 years). Of these, almost half (46.2%) occurred during follow-up, despite remission (normalized cortisol), “highlighting ongoing fracture risk,” the team noted.
Finally, the bone density in the lower spine at diagnosis was significantly lower in those treated with osteoporosis drugs than in those not treated, which likely contributed to the decision to treat, according to researchers.
Even though they began with lower bone density, those who received these medications showed a meaningful improvement in spinal bone density over time. After a follow-up of over five years, their bone density in the spine had improved to levels similar to those of individuals who did not receive these medications. Changes in hip bone density were similar between the two groups, the data indicated.
“Our findings reveal a clear mismatch between high fracture burden and low clinical engagement in bone health assessment in endogenous [Cushing’s syndrome], reinforcing the need for targeted clinical guidelines to standardise assessment and support timely intervention,” the researchers wrote.
