Low BMD Linked to SHBG Levels in Postmenopausal Women With T2D

Blood sample tube for sex hormone binding globulin or SHBG test, diagnosis for abnormal testosterone level
Women with higher serum SHBG had an increased risk for osteoporosis, osteopenia, and fracture.

Among postmenopausal women with type 2 diabetes (T2D), higher serum sex hormone-binding globulin (SHBG) is associated with lower bone mineral density (BMD), according to study results published in the Annals of Translational Medicine.

The results indicated that women with higher serum SHBG had an increased risk for osteoporosis, osteopenia, and fracture.

The literature suggests that links exist between sex hormone concentrations and bone microarchitecture, but most research has been conducted in individuals without diabetes, although T2D is associated with greater risk for skeletal fragility. Researchers therefore aimed to assess whether levels of SHBG, follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone are correlated with BMD in postmenopausal women with T2D (N=214; mean age, 60.0 years; mean diabetes duration, 10.0 years; mean hemoglobin A1c, 7.8%) using retrospective data. Dual-energy x-ray absorptiometry was used to measure BMD at the lumbar spine (L2-L4), femoral neck, and total hip and the modified fracture risk algorithm (FRAX) tool determined 10-year probability of fracture. Sex hormone concentrations were tested by chemical luminescence assay.

Serum SHBG was inversely correlated with BMD at all measured skeletal sites (P <.002 for all). The results indicated that SHBG was a determinant of BMD at the lumbar spine (β=-0.199; P <.05) and total hip (β=-0.233; P <.05) after adjustment for several factors. The researchers also found that SHBG and estradiol levels were associated with major osteoporotic fracture (β=0.253 [P <.001] and β=-0.159 [P <.05], respectively). Serum SHBG level was the only sex hormone concentration that was a determinant of hip fracture (β=0.262; P <.001).

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In multivariable-adjusted logistic regression models, every standard deviation increase in SHBG concentration was linked to a 2% increase in the risk for osteoporosis/osteopenia (P =.017), while estradiol and testosterone had no association. Women with SHBG in the highest quartile (>6.935 µg/mL) had a 4.21 times higher risk for osteoporosis/osteopenia (P =.015) compared with women with concentrations in the lowest quartile (<3.069 µg/mL).

The researchers noted that given the study’s retrospective design, they could not assess changes in sex hormones and BMD over time. In addition, the number of fractures recorded was too small for statistical analyses.

“Longitudinal clinical studies are needed to confirm the role of SHBG in the bone health of postmenopausal women with [T2D],” the researchers wrote.

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Jing Y, Wang X, Yu J, et al. Associations of serum sex hormone binding globulin with bone mineral densities and higher 10-year probability of fractures in postmenopausal women with type 2 diabetes mellitus. Ann Transl Med. 2019;7(18):457.