IGF-1 may be useful marker of bone health in Cushing’s disease

Lower IGF-1 levels found in young people with low bone density in study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Young people with Cushing’s disease who have low bone density also tend to have low levels of insulin-like growth factor 1 (IGF-1), a signaling molecule that’s known to play key roles in bone development, a new study shows.

“Our study found that a higher IGF-1 index was independently and significantly associated with [a] decreased prevalence of low bone mass in young [Cushing’s disease] patients,” the researchers wrote.

According to the team, these findings highlight the potential role of IGF-1 in the mechanisms underlying the lack of bone mass associated with Cushing’s disease.

They also “support the exploration of this pathway in therapeutic agent development” in osteoporosis — a disease that weakens bones and is common in people with the rare disorder — the team wrote.

The study, “Association of IGF-1 Level with Low Bone Mass in Young Patients with Cushing’s Disease,” was published in the International Journal of Endocrinology.

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Looking for biomarkers to monitor bone health

Cushing’s disease is caused by a tumor in the brain’s pituitary gland that ultimately leads to the excessive production of the stress hormone cortisol; high cortisol levels are responsible for the disease’s symptoms.

Bone problems are a common feature of Cushing’s, with many patients experiencing low bone density or osteoporosis, in which bones become more porous than normal, increasing the risk of fractures. Recognizing changes in bone density and providing early treatment can help reduce the risk of more serious complications, such as fractures.

It can be challenging, however, for clinicians to identify such changes without advanced imaging equipment.

Now, a team of scientists at Fudan University, in China, sought to identify markers of low bone density in people with Cushing’s disease. To that end, they conducted a study to find biomarkers that could be easily measured to help monitor bone health.

“On account of the scarcity of data and pressing open questions concerning risk evaluation and management of osteoporosis, we performed a well-powered study to identify the related factors associated with low bone mass in young [Cushing’s disease] patients at the time of diagnosis,” the researchers wrote.

The scientists analyzed data from 153 people with Cushing’s disease, comprising 33 men and 120 women. The patients ranged in age from 13 to 49, and none of the women had gone through menopause, when menstrual periods permanently cease.

Based on imaging tests, slightly fewer than half of the patients (48.37%) were found to have low bone density. Researchers then conducted a battery of statistical tests looking for factors that were significantly associated with reduced bone density.

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Link found between low bone mass, lower levels of IGF-1

Initial tests showed that patients with poor bone density tended to have higher blood pressure and cortisol levels, as well as higher levels of cholesterol and creatinine, a marker of kidney damage.

Patients with low bone density also were more likely to be male. Women with low bone mass tended to have higher levels of the male sex hormone testosterone. These associations are broadly in line with previous research on bone density in Cushing’s disease.

Initial tests also showed that patients with low bone mass tended to have lower levels of IGF-1. In further statistical models, where researchers controlled for many of the other factors, they found a statistically significant positive correlation between IGF-1 and bone density — in other words, patients with higher IGF-1 levels also tended to have higher bone density, and vice versa.

When researchers divided patients into several groups based on IGF-1 levels, they found that patients with the highest IGF-1 levels also were the ones who had the lowest prevalence of low bone density (23.81%). Conversely, the prevalence of low bone mass was highest among those with the lowest IGF-1 levels (68.29%).

Collectively, according to researchers, these data suggest that IGF-1 may be a useful marker to assess bone density in Cushing’s patients.

“The decrease in IGF-1 might be a risk factor for low bone mass in [Cushing’s disease] patients,” the team wrote, though they stressed that, from these data alone, it’s unclear whether low IGF-1 levels might be a cause or consequence of low bone density in Cushing’s.

The team highlighted a need for further investigation into the biological role of IGF-1 in regulating bone health in Cushing’s disease.