Lower SHBG concentrations tied to reduced fracture risk for men
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Key takeaways:
- Men with lower levels of SHBG in the UK Biobank were less likely to sustain any fracture during follow-up.
- Lower testosterone levels were associated with an increased fracture risk after adjusting for SHBG.
Men with lower concentrations of sex hormone-binding globulin may be less likely to sustain a fracture than those with higher levels, according to data published in The Journal of Clinical Endocrinology & Metabolism.
In an analysis of data from the UK Biobank, researchers examined associations between sex hormones and fracture risk among men. Both SHBG and testosterone levels were significantly associated with fracture risk, but the associations between SHBG and fractures were more robust than the link between testosterone and fractures, according to Louise Grahnemo, PhD, associate professor in the department of internal medicine and clinical nutrition, Institute of Medicine at Sahlgrenska Osteoporosis Centre and the Center for Bone and Arthritis Research at the Sahlgrenska Academy at University of Gothenburg in Sweden, and Claes Ohlsson, MD, PhD, professor and head of the department of internal medicine and clinical nutrition, Institute of Medicine at the Sahlgrenska Academy at University of Gothenburg.
“It is important to consider not only testosterone, but also SHBG when considering the risk of fractures in men,” Grahnemo and Ohlsson told Healio.
Researchers obtained serum total testosterone and SHBG levels from men who enrolled in the UK Biobank from 2006 to 2010. Free testosterone was calculated based on total testosterone, SHBG and fixed albumin levels. Incident fractures were collected until 2022 from hospital admission ICD-10 codes. Participants were divided into quintiles based on sex hormone levels.
There were 205,973 men with testosterone levels available, 190,607 participants with available SHBG concentrations and 189,585 men who had enough data for free testosterone to be calculated. During a median follow-up of 13.6 years, 5% of men had a fracture at any site.
In a model that adjusted for covariates, but not for SHBG, men in the lowest quintile for total testosterone concentration had a lower risk for any fracture (HR = 0.93; 95% CI, 0.88-0.98) and hip fracture (HR = 0.79; 95% CI, 0.69-0.91) than men in the highest quintile. Total testosterone level was not tied to a significant difference in forearm fracture risk. However, after adjusting for SHBG concentration, men in the lowest total testosterone quintile had a higher risk for any fracture (HR = 1.24; 95%, CI, 1.16-1.33), hip fracture (HR = 1.28; 95% CI, 1.08-1.51) and forearm fracture (HR = 1.51; 95% CI, 1.25-1.82) than men in the highest quintile.
In a fully adjusted model, men in the lowest quintile for calculated free testosterone had a higher risk for any fracture (HR = 1.27; 95% CI, 1.2-1.35), hip fracture (HR = 1.41; 95% CI, 1.2-1.66) and forearm fracture (HR = 1.4; 95% CI, 1.18-1.65) than men in the highest quintile.
Participants in the lowest quintile for SHBG had a lower risk for any fracture (HR = 0.71; 95% CI, 0.67-0.75), hip fracture (HR = 0.55; 95% CI, 0.47-0.65) and forearm fracture (HR = 0.62; 95% CI, 0.52-0.74) than men in the highest quintile. The findings were similar in a model adjusting for total testosterone level.
“The association between SHBG and fracture risk was not surprising, but the association was surprisingly strong,” Grahnemo and Ohlsson told Healio.
Grahnemo and Ohlsson said future studies should use Mendelian randomization and assess whether there are causal associations between sex hormone levels and fracture risk for men.
For more information:
Louise Grahnemo, PhD, can be reached at louise.grahnemo@gu.se.
Claes Ohlsson, MD, PhD, can be reached at claes.ohlsson@medic.gu.se.
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