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Thursday, 26 November 2015

Glucose levels tied to bone turnover in diabetics

NEW YORK (Reuters Health) - Blood glucose changes may alter bone turnover and have detrimental effects on bone health in diabetics, according to Danish researchers.
As Dr. Jakob Starup-Linde told Reuters Health by email, "Our findings suggest that the bone turnover is dependent on plasma glucose levels in patients with diabetes. Thus, glycemic variability may cause the diabetic bone disease with high fracture rates in spite of normal to increased bone mineral density."
In a November 7 online paper in Bone, Dr. Starup-Linde of Aarhus University Hospital and colleagues note that fracture risk is increased in diabetics. This is 7-fold increased risk in type 1 diabetes (T1D) and 1.4-fold increased risk in patients with type 2 diabetes (T2D).
Oral ingestion of glucose causes an acute decrease in bone turnover markers, and thus glucose levels may affect bone turnover in diabetes. To investigate further, the team examined blood samples from 98 T1D patients and 96 T2D patients. These had been taken in non-fasting conditions in the morning.
There were lower bone turnover markers in patients with T2D than T1D. In particular this was true of P-Procollagen type 1 amino terminal propeptide (P1NP), p-osteocalcin (OC), and s-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL).
In addition, s-osteoprotegerin (OPG) was higher in T2D but P-C-terminal cross-linked telopeptide of type-I collagen (CTX), p-fibroblast growth factor-23 (FGF-23), p-sclerostin, and p-undercarboxylated osteocalcin (ucOC) were similar in both groups.
Increasing non-fasting glucose levels were inversely related to p-CTX, p-P1NP, p-OC, and p-ucOC and directly related to s-OPG. This was the case in simple linear and multiple linear regressions adjusted for factors influencing bone turnover markers including hemoglobin A1c (HbA1c).
"We found," the investigators continue, "that the p-glucose levels were correlated negatively with bone turnover markers and positively with s-OPG in patients with T1D whereas p-glucose levels were only positively correlated with s-OPG in patients with T2D."
"Bone turnover in patients with diabetes," they add, "may fluctuate in the same manner as p-glucose and disrupt the remodeling process, which may decrease bone quality, if removal of old bone is interrupted and the remodeling not complete."
"The practical implications of the study," the researchers conclude, "are that glucose fluctuations need to be taken into account and not just average glucose levels when measuring bone turnover markers in patients with diabetes."
Commenting on the findings by email, Dr. Fernando Rivadeneira of University Medical Center Rotterdam, the Netherlands, told Reuters Health, "This well-conducted study provides additional evidence supporting the contention (we and others have made previously) that the skeletal complications consisting of higher fracture risk despite relatively higher (bone mineral density) observed in patients with type 2 diabetes mellitus, are related to the inhibition of the physiological remodeling (resorption and formation) process needed for bone repair."
Dr. Rivadeneira, who is an associate professor of musculoskeletal genomics, added, "Their study also shows that this deleterious process is not just about high glucose levels; the study also pinpoints clear differences across biochemical markers between patients with type 1 and type 2 diabetes. Noteworthy are those differences in markers like vitamin D and those from the OPG-RANK-RANKL pathway, which (pending further scrutiny) should be considered for the differential treatment and prevention of skeletal complications, depending on the type of diabetes of the patient."
The European Union Framework Programme 7 and the Familien Hede Nielsens Fund partially supported this research. The authors reported no disclosures.

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