Low Parathyroid Hormone Levels Linked to Fracture Risk in Diabetic Women

The increase in risk is not associated with poor bone mineral density but rather poor bone formation. Bone quality is measured by both density and turnover, and serum parathyroid hormone (PTH) levels were seen as significantly correlated with lower levels of osteocalcin – a chemical indicator of bone turnover – in both men and women with type 2 diabetes.

However, while the correlation between lower PTH and osteocalcin was seen in diabetics of both sexes, only the diabetic women in the study were seen at elevated fracture risk independent of bone mineral density. The findings help tease apart the complex etiological relationship between type 2 diabetes and fracture risk.

Dr. Masahiro Yamamoto of the Shimane (Japan) University Faculty of Medicine, in a study by the same group of researchers, established recently that diabetic patients had an increased risk of vertebral fractures independent of bone mineral density (J. Bone Miner. Res. 2009;24:702-9).

For their current study, Dr. Yamamoto and colleagues recruited hospitalized diabetic patients (123 postmenopausal women between the ages of 45 and 80, and 132 men aged 50-82) and nondiabetic controls (189 women and 51 men), measuring PTH and osteocalcin levels and adjusting for age, body mass index, hemoglobin A_1c, creatinine, 25-hydroxyvitamin D, and lumbar bone mineral density.

Subjects and controls were divided into subgroups based on mean PTH and osteocalcin levels. Threshold values for women were 34.7 pg/mL for PTH and 18.1 ng/mL for osteocalcin, and for men, 24.1 pg/mL for PTH and 10.7 ng/mL for osteocalcin.

Diabetes patients of both sexes were seen to have lower PTH and osteocalcin levels than controls. Multivariate regression analysis showed that PTH levels of diabetes patients significantly correlated with osteocalcin levels for both men and women.

Postmenopausal diabetic women with lower PTH and osteocalcin levels had a significantly, 4.7-fold higher risk of fracture than did those with higher PTH and osteocalcin.

No increased vertebral fracture risk associated with lower PTH and osteocalcin was seen in diabetic men.

Dr. Yamamoto and colleagues wrote that, "In contrast to T2DM women, HbA_1c levels in T2DM men were significantly and inversely associated with osteocalcin levels after multivariate adjustment, suggesting that osteocalcin levels in T2DM men could be affected by improvement of glycemic conditions," which could help explain the difference in fracture risk.

The investigators listed several limitations of their study, including its small size and the fact that that it was not population based, allowing for the potential for selection bias. The diabetes cases may have represented people with more severe disease than is usual for Japan, they noted.

Dr. Yamamoto and colleagues also noted that they did not test for deficiencies of magnesium, which is known to modulate PTH secretion. Bone metabolic markers may have been affected by prior fractures, they acknowledged, and the influence of hormones, such as estrogen produced by adipose tissue, was not considered.