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Increase in Osteoporosis Thought Due to Increase in DPP-4

Osteoporosis is a common disease that affects humans, especially postmenopausal women. Therefore, assessing risks and identifying potential targets for osteoporosis intervention is important for public health. There are many risk factors that are associated with osteoporosis. More evidence has shown that glucagon-like peptide-1 (GLP-1) has some contribution to bone metabolism.

Dipeptidyl peptidase-4 (DPP-4) degrades GLP-1 and also plays a crucial role in development of dyslipidemia, inflammation and insulin resistance, all of which have been associated with the pathogenesis of osteoporosis. However, no studies have been done on DPP-4 and its association with osteoporosis in postmenopausal women.

This was a cross-sectional population study of 744 postmenopausal women aged 47-76 years. Since DPP-4 is associated with hyperglycemia and impaired bone metabolism, to alleviate this confounding factor, the authors chose to evaluate its effects on postmenopausal women with normal glucose tolerance.

Patients’ information was collected through standard questionnaires administered by trained staff. Several tests were done to measure the participants’ baseline levels. The areal BMD (grams/cm2) were measured at the lumbar spine (L1-L4) and femoral neck by dual-energy X-ray absorptiometry (DXA) and diagnosis of osteoporosis was in accordance with the World Health Organization’s standard (T-score ≤ -2.5 SD).

Results showed that out of 744 participants, 140 participants (18.8%) had osteoporosis. DPP-4 activities were divided into quartiles and the prevalence of osteoporosis according increased as the DPP-4 activities increases. Data also showed that older subjects were more likely to have higher DPP-4 activities. Subjects with higher DPP-4 activities also show higher levels of BMI, TG, TC, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), lower active GLP-1, and BMD compared to subjects with lower DPP-4 activities. Partial correlation analysis showed that DPP-4 activities were positively associated with TC, HOMA-IR and was negatively correlated with active GLP-1 and BMD in these participants.

Although previous studies have suggested that DPP-4-inhibitors may have a protective effect on bone, the relationship between DPP-4 activity and bone metabolism is not clearly understood. From this study, the authors were able to observe that high DPP-4 activity is associated with a high bone turnover rate (lower BMD) and also increase in insulin resistance (higher level of HOMA-IR).

The authors suggested that elevated DPP-4 activity in postmenopausal women could be used as a marker or warning signal that predict the development of osteoporosis. Even though this might have some clinical significance for early identification for postmenopausal women with high risk for osteoporosis, more studies are warranted.

Practice Pearls:

  • Dipeptidyl peptidase-4 (DPP-4) degrades GLP-1 and also plays a crucial role in development of dyslipidemia, inflammation and insulin resistance, all of which have been associated with the pathogenesis of osteoporosis.
  • High DPP-4 activity is associated with a high bone turnover rate and the increase in insulin resistance.
  • Elevated DPP-4 activity in postmenopausal women is used as a marker or warning signal that predicts the development of osteoporosis.

Zheng T, Yang L, Liu Y, Liu H, Yu J, Zhang X, and Qin S. “Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of osteoporosis in postmenopausal women with normal glucose tolerance.” Journal of Clinical Endocrinology & Metabolism, 4 Aug 2015. Web. 7 Sep 2015.