Bone Turnover Lower Among Men With Type 2 Diabetes Mellitus, A1c Greater Than 7%

Bird bone tissue. Coloured scanning electron micrograph (SEM) of cancellous (spongy) bone from a starling’s (Sturnus vulgaris) skull. This tissue, found in the interior of bones, is characterised by a honeycomb arrangement of trabeculae (columns) and spaces. This honeycomb structure provides support and strength to the bone. Magnification: x25 when printed 10 centimetres wide
Study authors identified whether the hemoglobin A1c threshold level where reduction in bone turnover begins.

The following article is part of our coverage of the Endocrine Society’s annual meeting (ENDO 2021) that is being held virtually from March 20-23, 2021. Endocrinology Advisor‘s staff will report on the top research in hormone science and clinical care. Check back for the latest news from ENDO 2021.


For men with type 2 diabetes mellitus (T2DM), an A1c of at least 7% appears to be the threshold for lower bone turnover no matter which medications are in use, according to research recently presented at the Endocrine Society’s ENDO 2021 conference, held virtually from March 20 to 23, 2021.

Participants were recruited from 2 clinical trials in 2 separate Veteran Affairs health centers. This study included 217 men aged 35 through 65 years (mean age, 55), with an average BMI of 36.15 kg/m (standard deviation [SD], 6.44), and average A1c of 6.1% (SD, 1.5). In this cohort, 32.7% of participants (n=71) was previously diagnosed with T2DM.

High-performance liquid chromatography was used to measure A1c; liquid chromatography/mass spectrometry (LC/MS) was used to measure estradiol and testosterone; enzyme-linked immunosorbent assay was used to measure sclerostin and bone turnover markers, including osteocalcin and C-telopeptide of type 1 collagen (CTx); and dual energy x-ray absorptiometry was used to assess bone mineral density.

A1c values were used to classify participants into 4 categories (group 1, <6%; group 2, 6.1%-6.5%; group 3, 6%-6.7%; group 4, >7%). Analysis of variance was used to compare the different A1c categories and simple regression analysis was used to assess correlations.

Study authors found significant negative correlations between A1c and osteocalcin (Pearson correlation coefficient [r], -0.32; P <.001) and CTx (r, -0.32; P <.001). Participants in group 4 exhibited lower bone turnover markers compared with groups 1, 2, and 3 (group 4, 4.04 ng/mL [SD, 2.64]; group 1, 6.53 ng/mL [SD, 3.18]; group 2, 5.99 ng/mL [SD, 3.16]; group 3, 6.09 ng/mL [SD, 3.16]; P =.002), as well as lower CTx (group 4, 0.19 ng/mL [SD, 0.12]; group 1, 0.34 ng/mL [SD, 0.17]; group 2, 0.32 ng/mL [SD, 0.18]; group 3, 0.28 ng/mL [SD, 0.14]; P =.0002).

All A1c categories showed comparable sclerostin levels. Participants with T2DM had lower osteocalcin than participants with A1c of 7% or lower (3.95 ng/mL [SD, 2.68] vs 6.34 ng/mL [SD, 2.77]; P =.007), as well as lower CTx (0.18 ng/mL [SD, 0.13] vs 0.31 ng/mL [SD, 0.15]; P <.001). After adjusting for medications, this correlation maintained statistical significance (P =.003). Areal bone mineral density did not vary significantly between men with T2DM compared with others in the study after adjustments for baseline weight, age, and testosterone.

The study authors concluded that men with T2DM who have an A1c level of 7% or greater showed decreased bone turnover regardless of medication use.

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Joad SS, Gregori G, Russo V, et al. Hemoglobin A1c of 7% is the threshold for bone impairment in men with type 2 diabetes mellitus. Presented at: ENDO 2021; March 20-23, 2021. Session P11.