Adrenocorticotropic Hormone Modulates Bone Mineral Density among Postmenopausal Saudi Women with Type 2 Diabetes Mellitus Irrespective of Osteoporosis Status
Authors: Al-Daghri Nasser M. , Sabico Shaun , Masoud Mohammad , Khattak Malak Nawaz Khan , Alokail Majed 
Published: April 2020

BackgroundThe pituitary gland secretes several hormones known to regulate the activity of other endocrine glands, hence the name “master gland”. Neuroendocrinology of bone is a new and emerging field based on the theory that pituitary hormones can directly affect bone remodeling and metabolism. Therefore, the present study aims to determine for the first time in a homogenous Arabian cohort, the associations of the major hormones of the anterior pituitary gland and other hormones with indices of bone mineral density among known T2DM (type 2 diabetes mellitus) and postmenopausal Saudi women, with or without osteoporosis.MethodsIn this cross‐sectional study, a total of 363 postmenopausal Saudi women [N=161 without osteoporosis, age (years) 54.7±7.6, BMI (body mass index) (kg/m2) 34.6±5.7; N=202 with osteoporosis, age 59.0±8.7, BMI 32.3±6.4] were randomly selected from the Osteoporosis Registry database of the Chair for Biomarkers of Osteoporosis (CBCD) in King Saud University, Riyadh, Saudi Arabia. Serum calcium was measured routinely. Parathyroid hormone (PTH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), testosterone, estrogen, prostaglandin and insulin‐growth factor 1 (IGF1) were measured using commercially available assay kits following manufacturers’ instructions. Serum 25(OH)D was measured using electrochemiluminiscence assay. Bone mineral density (BMD) and corresponding T‐scores were assessed using dual x‐ray absorptiometry (DXA).ResultsAge‐ and BMI‐adjusted comparisons revealed that levels of testosterone and estrogen were significantly lower in the osteoporosis group than those without (p‐values 0.05 and 0.02, respectively). Circulating ACTH levels were significantly higher in the osteoporosis group than their counterparts (p=0.002). In all subjects, FSH was inversely and significantly associated with T‐Score (spine) (R=−0.27; p<0.05) and BMD (femur) (R=−0.35; p<0.05). Post‐stratification, ACTH was significantly associated with BMD (spine) (R=0.62; p<0.05). No significant associations between hormones and BMD were seen in the non‐osteoporosis group. In all subjects and using stepwise linear regression, ACTH and IGF1 predicted 32% of the variance in T‐Score of the spine (p=0.002). Furthermore, ACTH and TSH predicted 29% of the variance in T‐Score of the femur (p=0.002). Lastly, ACTH and IGF1 predicted 37.4% of the variances observed in BMD (femur) (p=0.001).ConclusionAmong the anterior pituitary hormones, the stress hormone regulator, ACTH, seems to influence BMD the most, at least among Saudi women with T2DM, irrespective of osteoporosis status. An imbalance of this hormone may predispose T2DM individuals to decreased BMD and subsequent osteoporosis. Whether these findings apply to the non‐T2DM population needs further investigation.Support or Funding InformationDeanship of Scientific Research, Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
Stepwise regression analysis using T‐score and BMD as dependent variables

Dependent

Predictor

β

R2

P‐Value

T‐Score Spine

Model 2

0.320

0.002

ACTH

−3.07

0.003

IGF1

2.90

0.007

T‐Score Femur

Model 2

0.288

0.002

ACTH

−2.90

0.001

TSH

1.29

0.031

BMD Spine

None

BMD Femur left

Model 2

0.374

0.001

ACTH

−0.25

0.007

IGF1

0.45

0.029

BMD Femur Right

None