The Endocrine Society's 97th Annual Meeting & Expo:

Does Type 2 Diabetes Affect Bone Quality?

Whether bone quality, distinct from bone density, differs in postmenopausal women with vs without type 2 diabetes was the question addressed by Joshua Nicholas Farr, PhD, in his March 5, 2014, presentation at the Endocrine Society Annual Meeting in San Diego, California. Dr. Farr is an Assistant Professor of Medicine at the Mayo Clinic, Rochester, MN.

Fractures in Patients with Type 2 Diabetes
Risk of fractures is higher in patients with type 2 diabetes, despite higher body mass index and bone mineral density—factors that typically protect against fractures. Unfortunately, it is difficult to recapitulate this paradox in animal models. Since areal bone mineral density and the fracture risk assessment tool underestimate fracture risk in patients with type 2 diabetes, whether critical aspects of bone quality, distinct from areal bone mineral density, influence bone strength and contributes to the higher fracture risk is of interest. 

Measuring Bone Quality
Progress in understanding how bone material properties might be altered in type 2 diabetes has been greatly hampered by the invasive nature of the direct measures needed to quantify these properties, rendering routine clinical assessment of bone material properties impractical. Recent advances in microindentation technology, however, have now made it safe to quantify an index of bone material properties with minimal discomfort.

Bone Microindentation Testing
A hand-held microindentation instrument called the OsteoProbe® (Active Life Scientific Inc., Santa Barbara, CA) measures bone material strength index at the midshaft of the nondominant anterior tibia. The impact mechanism creates a force driving the probe into bone, while a displacement transducer measures indentation distance increase from impact. This rise in indentation distance is then converted by a computer to bone material strength index.

In addition to the new device, bone microarchitecture can be measured using high-resolution peripheral quantitative computed tomography, which provides a noninvasive bone biopsy of the distal radius and tibia.

Study Objectives

  • To determine whether bone material strength index, bone imaging parameters (derived from DXA and high-resolution peripheral quantitative computed tomography), and/or bone turnover are altered in patients with type 2 diabetes compared to age-matched, nondiabetic controls.
  • To examine associations of bone material strength index with duration of type 2 diabetes and circulating levels of glycated hemoglobin.

Patient Characteristics
Subjects with (n=30) and without type 2 diabetes (n=30) were comparable in age, current smoking status, daily alcohol intake, number of previous fractures, and height. They differed significantly in weight and body mass index.

Results
Adjusted for body mass index, measurements using high-resolution peripheral quantitative CT of the distal radius did not differ between controls and patients with type 2 diabetes. Though consistent with previous studies, cortical porosity was approximately 37% higher in patients with type 2 diabetes. These findings can be generalized to extend to African-American women with type 2 diabetes, who also have higher cortical porosity than controls.

In patients with type 2 diabetes and fragility fracture, cortical porosity was also found to be significantly greater than in subjects without diabetes.

Unadjusted bone material strength index was 12% lower in patients with type 2 diabetes, and adjusted for body mass index; the index was 11% lower in these patients. Differences remained significant following further adjustment for hypertension and diabetic complications.

Unadjusted DXA regional areal bone mineral density was significantly greater in patients with type 2 diabetes in six of seven regions, including total body. When adjusted for body mass index, no significant differences were observed between patients and controls. 

These studies were confined to women; however, and were limited by small sample sizes.

The Working Hypothesis of Reduced Bone Quality and Increased Fracture Risk in Type 2 Diabetes
Our current understanding of the pathogenesis of skeletal fragility in type 2 diabetes mellitus suggests a working hypothesis, whereby poor glucose control leads to increases in advanced glycation endproducts (AGEs) that exert negative effects on osteoblasts. These negative effects on osteoblasts result in reduced bone formation. This defect in bone formation subsequently results in low bone turnover, which prolongs the lifespan of type I collagen in bone, leaving it particularly vulnerable to damage from increased AGEs. Ultimately, this vicious cycle may contribute to reduced bone quality and increased fracture risk.

Summary
The present study was the first demonstration, using an in vivo index of bone material strength, of compromised bone material properties in patients with type 2 diabetes. The results confirm previous studies demonstrating low bone turnover in these patients, and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. "The skeleton needs to be recognized as another important target tissue subject to diabetic complications,” concluded Dr. Farr.

Future Considerations
Four questions need to be addressed in further studies:

  1. Does measuring an index of bone material properties and/or cortical porosity enhance the identification of subjects with type 2 diabetes at increased risk of fragility fractures?
  2. Are the findings comparable between men and women?
  3. Does bone material strength index and cortical porosity deteriorate more rapidly over time in patients with type 2 diabetes than in nondiabetic subjects?
  4. Do circulating hormonal (for example, estrogen and testosterone) and biochemical (for example, bone turnover markers and advanced glycation end products) parameters predict longitudinal changes in bone material strength index and cortical porosity?

 

March 13, 2015

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