Osteoprosis in Type 2 Diabetic Patients- a Cohort Study
It is becoming apparent that both type 1 and type 2 diabetes mellitus (DM) are associated with an increased risk for osteoporosis-associated fractures. A meta-analysis by Vestergaard showed that patients with type 1 DM have decreased bone mineral density (BMD) and increased fracture risk. This study noted a 6.9 relative risk of hip fracture, when the expected relative risk of fracture was only 1.4 based on the BMD. This finding suggests that the increased fracture risk is not entirely accounted for by the lower BMD. It has been demonstrated that the presence of diabetic microvascular complications, including ophthalmic, nephropathic, and neurological, lead to a higher risk of hip fracture in patients with type 1 DM. Unlike patients with type 1 DM, patients with type 2 DM have an average or higher BMD than age-matched controls. However, several studies have demonstrated that patients with type 2 DM have a higher risk of hip, proximal humerus, and foot fractures[2-4]. Data from the Women's Health Initiative Observational Study indicate that post-menopausal women with diabetes are at an increased risk of hip, foot, and spine fractures, and fractures overall. For a given BMD, diabetic bone appears to be less strong and therefore more likely to fracture[2, 6].
Insulin-like growth factor (IGF)-1, insulin, bone morphogenetic proteins and osteopreotegerin (OPG), serve as anabolic signals to promote bone formation[7-10]. Among these anabolic mediators, liver-derived IGF-1 is of particular interest since profound growth retardation, small bone size, low BMD and osteoporosis were reported in IGF-1 and IGF-1 receptor deficiencies. Furthermore, insulin was found to directly induce osteogenic action by increasing cell proliferation, differentiation, alkaline phosphatase activity and expression of type Ⅰcollagen and osteocalcin in human osteoblast-like MG-63 cells. Type 1 DM featuring low circulating insulin and IGF-1 levels usually occurs in young children prior to peak bone mass attainment, whereas type 2 DM is common in adults who have already attained peak bone mass.
Some possible humornal and cellular mechanism for diabetes related osteoporosis/fractures were proposed and summaried as the following, (1)Diabetes mellitus increases osteoclast function but decreases osteoblast function, thereby leading to accelerated bone loss, osteopenia and osteoporosis. (2)DM/hyperglycemia induces production of macrophage colony stimulating factor (MCSF), tumor necrosis factor (TNF)-α and receptor activator of nuclear factor-κB ligand (RANKL), all of which are osteoblast-derived activators of osteoclast proliferation and differentiation. (3) DM/hyperglycemia suppresses osteoblast proliferation and function, in part, by decreasing runtrelated transcription factor (Runx)-2, osteocalcin and osteopontin expressions. (4)Adipogenic differentiation of mesenchymal stem cells is increased as indicated by the overexpression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor (PPAR)-g, adipocyte fatty acid binding protein (aP2), adipsin and resistin. A decrease in neovascularization may further aggravate bone loss. (5)Bone quality is also reduced as a result of advanced glycation end products (AGE) production, which may eventually result in low impact or fragility fractures.
DM are associated osteoporosis/fracture. The underlying mechanism, especially of type 2 DM, mandates a DM-osteoporosis cohort to elucidate. In clinical practice, to developed preventive strategies from osteoporotic-fracture is also necessary.
Type 2 Diabetes Mellitus
|Study Design:||Observational Model: Cohort
Time Perspective: Cross-Sectional
- Osteoprosis in type 2 diabetic patients- a cohort study [ Time Frame: three years ] [ Designated as safety issue: No ]
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|National Taiwan University Hospital||Recruiting|
|Taipei, Taiwan, 100|
|Contact: Kuo Chin Huang, PhD 02-23123456 ext 66081 firstname.lastname@example.org|
|Principal Investigator:||Kuo Chin Huang, PhD||Department of Family Medicine, National Taiwan University Hospital|